http://www.reproductivecloning.net
http://www.roslin.ak.uk
http://www.bioethics.net
http://www.icta.org
http://www.all.org
http://www.gene-watch.org/
http://www.genome.gov/pages/education/illustration_of_cloning.htm
http://www.ornl.gov/sci/techresources/Human_Genome/publicat/primer/fig11a.html
http://www.genome.gov/pages/education/illustration_of_cloning.htm
http://www.gallup.com/poll/137357/Four-Moral-Issues-Sharply-Divide-Americans.aspx
http://en.wikipedia.org/wiki/Cloning
http://learn.genetics.utah.edu/content/cloning/
http://www.theguardian.com/science/cloning
http://www.genome.gov/25020028
http://www.debate.org/opinions/is-human-cloning-wrong
http://library.thinkquest.org/24355/data/reactions/proconmain.html
http://civilliberty.about.com/od/internationalhumanrights/f/human_cloning.htm
http://www.resolve.org/about/the-stem-cell-and-cloning-debate.html
http://www.chiff.com/science/cloning.htm
http://www.youtube.com/watch?v=unSf2cDsCcE
http://www.youtube.com/watch?v=T6NTlcJEJGA
http://www.youtube.com/watch?v=jLy-tYq8qV0
http://www.cloneorgans.com/pros-and-cons-of-cloning/20/
http://healthresearchfunding.org/pros-cons-human-cloning/
http://thefarnsworths.com/science/cloning.htm
Cloning Is Unethical
Leon R. Kass, "Defending Life and Dignity: How, Finally, to Ban Human Cloning," The Weekly
Standard, vol. 13, February 25, 2008. Copyright © 2008, News Corporation, Weekly Standard.
All rights reserved. Reproduced by permission.
"The ban [on cloning] deserves the support of all."
Leon R. Kass is Harding Professor of Social Thought at the University of Chicago and former
chairman of the President's Council on Bioethics. In the following viewpoint, Kass writes that
human cloning is an unethical practice. The duplication and destruction of embryos—even for
medical good—violates the sanctity of life, he argues. Moreover, he alleges that reproductive
cloning robs children of the right to descend from a mother and father and paves the way to
"manufactured" babies. And with advancements in stem cell research that do away with the
need for embryos altogether, therapeutic cloning is no longer justified, he maintains.
As you read, consider the following questions:
1. How does the author describe the arguments for therapeutic cloning?
2. How have scientists worked their way around therapeutic cloning, as stated by Kass?
3. What does the author recommend in his proposed ban against reproductive cloning?
In his [2008] State of the Union address President [George W.] Bush spoke briefly on matters of
life and science. He stated his intention to expand funding for new possibilities in medical
research, to take full advantage of recent breakthroughs in stem cell research that provide
pluripotent stem cells without destroying nascent human life. At the same time, he continued,
"we must also ensure that all life is treated with the dignity that it deserves. And so I call on
Congress to pass legislation that bans unethical practices such as the buying, selling, patenting,
or cloning of human life."
As in his previous State of the Union addresses, the president's call for a ban on human cloning
was greeted by considerable applause from both sides of the aisle. But Congress has so far
failed to pass any anti-cloning legislation, and unless a new approach is adopted, it will almost
certainly fail again.
Fortunately, new developments in stem cell research suggest a route to effective and sensible
anti-cloning legislation, exactly at a time when novel success in cloning human embryos makes
such legislation urgent. Until now, the cloning debate has been hopelessly entangled with the
stem cell debate, where the friends and the enemies of embryonic stem cell research have
managed to produce a legislative stalemate on cloning. The new scientific findings make it
feasible to disentangle these matters and thus to forge a successful legislative strategy. To see
how this can work, we need first to review the past attempts and the reasons they failed.
Three Important Values
Three important values, differently weighted by the contending sides, were (and are) at issue in
the debates about cloning and embryonic stem cells: scientific and medical progress, the
sanctity of human life, and human dignity. We seek to cure disease and relieve suffering
through vigorous research, conducted within acceptable moral boundaries. We seek to protect
vulnerable human life against destruction and exploitation. We seek to defend human
procreation against degrading reproductive practices—such as cloning or embryo fusing—that
would deny children their due descent from one father and one mother and their right not to
be "manufactured."
Embryonic stem cell research pits the first value against the second. Many upholders of the
sanctity of human life regard embryo destruction as unethical even if medical good may come
of it; many partisans of medical research, denying to nascent human life the same respect they
give to life after birth, regard cures for disease as morally imperative even if moral harm may
come of it. But the deepest challenge posed by cloning has to do not with saving life or avoiding
death, but with human dignity, and the cloning issue is therefore only accidentally bound up
with the battle about stem cell research. Yet both parties to the stem cell debate happily turned
the cloning controversy into the life controversy.
The faction favoring embryonic stem cell research wanted to clone embryos for biomedical
research, and touted cloning's potential to produce individualized (that is, rejection-proof) stem
cells that might eventually be used for therapy. Its proposed anti-cloning legislation (the
Kennedy-Feinstein-Hatch bill) would ban only "reproductive cloning" (cloning to produce
children) while endorsing the creation of cloned human embryos for research. Such cloning-forbiomedical-research its proponents originally called "therapeutic cloning," hoping that the goal
of "therapy" would get people to overcome their repugnance for "cloning." But when that
strategy backfired, they disingenuously denied that the cloning of embryos for research is really
cloning (they now call it, after the technique used to clone, SCNT, somatic cell nuclear transfer).
They also denied that the product is a human embryo. These Orwellian [like the "doublespeak"
of the totalitarian government described in George Orwell's 1984] tactics succeeded in
confusing many legislators and the larger public.
The faction opposed to embryonic stem cell research wanted to safeguard nascent human life.
Its proposed anti-cloning legislation (the Weldon-Stupak bill in the House, the BrownbackLandrieu bill in the Senate) would ban all human cloning—both for reproduction and for
biomedical research—by banning the initial step, the creation of cloned human embryos. (This
is the approach I have favored, largely because I thought it the most effective way to prevent
the production of cloned children.) But most of the bill's pro-life supporters cared much more
that embryos not be created and sacrificed than that children not be clones. Accordingly, they
sought to exploit the public's known opposition to cloning babies to gain a beachhead against
creating embryos for destructive research, which practice, although ineligible for federal
funding, has never been illegal in the United States. Initially, this strategy worked: In the
summer of 2001, the Weldon-Stupak bill passed the House by a large bipartisan majority. (It has
been passed again several times since.) But momentum was lost in the Senate, owing to delays
caused by [the terrorist attacks of] 9/11 and strong lobbying by the pro-stem cell forces, after
which time an impasse was reached, neither side being able to gain enough votes to close
debate....
Another Chance to Act
Fast forward to 2008. We are in the last year of the Bush presidency. Despite the president's
numerous calls for action, we remain the only major nation in the high-tech world that cannot
summon itself to ban human cloning, thanks to the standoff over the embryo issues.
Fortunately, science has given Congress another chance to act. In the last six months, the
scientific landscape has changed dramatically. On the one hand, the need for anti-cloning
legislation is now greater than ever; on the other hand, there are reasons why a new approach
can succeed.
Here is what's new. After the 2005 Korean reports of the cloning of human embryos turned out
to be a fraud, many said that human cloning could not be achieved. Yet late in 2007 Oregon
scientists succeeded for the first time in cloning primate embryos and growing them to the
blastocyst (5-7-day) stage, and then deriving embryonic stem cells from them. More recently,
other American scientists, using the Oregon technique, have reported the creation of cloned
human embryos. The age of human cloning is here, and the first clones, alas, do not read "made
in China."
On the stem cell front, the news is decidedly better. In the last two years, several laboratories
have devised methods of obtaining pluripotent human stem cells (the functional equivalent of
embryonic stem cells) without the need to destroy embryos. The most remarkable and most
promising of these approaches was reported by both Japanese and American scientists
(including Jamie Thompson, the discoverer of human embryonic stem cells). It is the formation
of human (induced) pluripotent stem cells (iPSCs) by means of the reprogramming (also called
de-differentiation) of somatic cells. Mature, specialized skin cells have been induced to revert
to the pluripotent condition of their originating progenitor.
The therapeutic usefulness of this approach has also been newly demonstrated, by the
successful treatment of sickle cell anemia in mice. Some iPSCs were derived from skin cells of
an afflicted mouse; the sickle cell genetic defect in these iPSCs was corrected; the treated iPSCs
were converted into blood-forming stem cells; and the now-normal blood-forming stem cells
were transferred back into the afflicted mouse, curing the disease.
Scientists have hailed these results. All parties to the stem cell debates have noted that the
embryonic-stem-cell war may soon be over, inasmuch as science has found a morally
unproblematic way to obtain the desired pluripotent cells. But few people have seen the
implications of these developments for the cloning debate: Cloning for the purpose of
biomedical research has lost its chief scientific raison d'etre. Reprogramming of adult cells
provides personalized, rejection-proof stem cells, of known genetic make-up, directly from
adults, and more efficiently than would cloning. No need for human eggs, no need to create
and destroy cloned embryos, no need for the inefficient process of deriving stem cell colonies
from cloned blastocysts. Ian Wilmut himself, the British scientist who cloned Dolly the sheep,
has abandoned his research on cloning human embryos to work with reprogrammed adult cells.
Another effect of this breakthrough is that the value for stem cell research of the spare
embryos that have accumulated in IVF [in vitro fertilization] clinics has diminished considerably,
defusing the issue of the ban on federal funding of such research. Why work to derive new
stem cell lines from frozen embryos (of unknown quality and unknown genetic composition,
and with limited therapeutic potential owing to transplant immunity issues) when one can work
with iPSCs to perfect the reprogramming approach and avoid all these difficulties?
A Triple-pronged Approach
That's not the only way the new scientific landscape changes the policy and legislative pictures.
We are now able to disentangle and independently advance all three of the goods we care
about. First, it now makes great sense to beef up federal support for regenerative medicine,
prominently featuring ramped-up work with iPSCs (and other non-embryo-destroying sources
of pluripotent human stem cells). The timing is perfect. The promise is great. The potential
medical payoff is enormous. And the force of example for future public policy is clear: If we
exercise both our scientific wit and our moral judgment, we can make biomedical progress,
within moral boundaries, in ways that all citizens can happily support.
Second, we should call for a legislative ban on all attempts to conceive a child save by the union
of egg and sperm (both taken from adults). This would ban human cloning to produce children,
but also other egregious forms of baby making that would deny children a link to two biological
parents, one male and one female, both adults. This approach differs from both the KennedyFeinstein-Hatch and the Brownback-Landrieu bills, yet it could—and should—gain support from
people previously on both sides. It pointedly neither endorses nor restricts creating cloned
embryos for research: Cloning embryos for research is no longer of such interest to scientists;
therefore, it is also no longer, as a practical matter, so important to the pro-life cause.
Moreover, the prohibited deed, operationally, should be the very act of creating the conceptus
(with intent to transfer it to a woman for pregnancy), not, as the Kennedy-Feinstein-Hatch bill
would have it, the transfer of the proscribed conceptus to the woman, a ban that would have
made it a federal offense not to destroy the newly created cloned human embryos. The ban
proposed here thus deserves the support of all, regardless of their position on embryo
research.
Third, the time is also ripe for a separate bill to defend nascent life, by setting up a reasonable
boundary in the realm of embryo research. We should call for a (four- or five-year) moratorium
on all de novo creation—by whatever means—of human embryos for use in research. This
would block the creation of embryos for research not only by cloning (or SCNT), the goal of the
Brownback-Landrieu anti-cloning bill, but also by IVF. Such a prohibition can now be defended
on practical as well as moral grounds. Many human embryonic stem cell lines exist and are
being used in research; 21 such lines, still viable, are available for federally funded research,
while an even greater number are being studied using private funds. The new iPSC research,
however, suggests that our society can medically afford, at least for the time being, to put aside
further creation of new human life merely to serve as a natural resource and research tool. We
can now prudently shift the burden of proof to those who say such exploitative and destructive
practices are absolutely necessary to seek cures for disease, and we can require more than
vague promises and strident claims as grounds for overturning the moratorium.
Morally and strategically speaking, this triple-pronged approach has much to recommend it. It
is at once more principled, more ambitious, and more likely to succeed than its predecessors.
By addressing separately the cloning and embryo-research issues, we can fight each battle
exactly on the principle involved: defense of human procreation or defense of human life. By
broadening the first ban to include more than cloning, we can erect a barrier against all
practices that would deny children born with the aid of reproductive technologies the ties
enjoyed by children conceived naturally. By extending the second ban to cover all creation of
life solely as an experimental tool, we can protect more than merely embryos created by
cloning. We would force everyone to vote on the clear principles involved: Legislators would
have to vote yea or nay on both weird forms of baby-making and the creation of human life
solely for research, without bamboozling anyone with terminological sleights of hand. And by
combining these legislative restrictions with strong funding initiatives for regenerative
medicine, we can show the American people and the world that it is possible to vigorously
pursue the cures all dearly want without sacrificing the humanity we rightly cherish.
Politically as well, this triple-pronged approach is a winner for all sides. Because the latest
science has made creating embryos for research unnecessary and inefficient by comparison
with reprogramming, we have the chance to put stem cell science on a footing that all citizens
can endorse. Indeed, in return for accepting a moratorium on a scientific approach that is not
very useful (creation of new embryos for research), scientists could exact large sums in public
support for an exciting area of science. With pro-lifers as their biggest allies, they could obtain
the research dollars they need—and their supposed enemies would write the biggest checks.
Meanwhile, at the very time the latest science has made affronts to human procreation—
cloning, but not only cloning—more likely and even imminent, pro-lifers and scientists can
come together to ban these practices in America, as they have already been banned in the rest
of the civilized world, without implicating the research debate at all.
In an election year, Congress will be little moved to act quickly on these seemingly low priority
items. Moreover, the partisans who have produced the current impasse may still prefer to keep
things at stalemate, the better to rally their constituents against the other side. But we can ill
afford to be complacent. The science is moving very rapidly. Before the end of the summer [of
2008], we may well hear of the cloning of primate babies or perhaps even of a human child.
Now is the time for action, before it is too late.
Religious Views of Cloning Do Not Agree
Bob Sullivan, “Religions Reveal Little Consensus on Cloning,” MSNBC.com, 2005. Copyright ©
2005 by Bob Sullivan. Reproduced by permission.
Bob Sullivan is a technology consultant for MSNBC, an Internet news service. He is the winner
of the prestigious 2002 Society of Professional Journalists Public Service Award. In the following
selection he explains the views of the major religions toward cloning. Members of these
religions do not agree among themselves as to whether human cloning is wrong or not, Sullivan
notes. People opposed to therapeutic cloning believe that destruction of a human embryo
during research is murder; but, as Sullivan writes, most Jews do not believe that, nor do they
believe cloning is "playing God." Catholics and conservative Christians generally oppose all
human cloning. Views among other Christians—as well as among Buddhists, Hindus, and
Muslims—are diverse, and some have no religious objection even to reproductive cloning. As
Sullivan reports, a 2004 survey has shown that the majority of Americans base their attitude
toward cloning on their individual opinions rather than on religious dogma.
The debate over whether scientists are "playing God" has probably never been more real than
now, as humans consider calling forth the spark of life, seemingly without divine intervention.
However, a confused population looking for clear ethical wisdom on cloning might be
disappointed: Beyond issuing a general call for caution, the world's spiritual leaders hardly
speak with one voice on the cloning debate.
What would Jesus do? Or Buddha? Or the Dalai Lama? The announcement of sheep-clone Dolly
in 1997 sent many religious leaders to the pulpit. Others scrambled through religious texts
looking for guidance. There were plenty of swift condemnations.
But as the realities and limitations of science have removed some of the haze surrounding
cloning, the philosophical and religious debates have also come into focus.
Today, conservative Christians are still unmoved from their blanket opposition to all cloning.
Other faiths have found room in their traditions for therapeutic cloning—the use of cloned cells
for research and health reasons, but not for breeding humans. Some even find ethical room for
the cloning of humans.
But in almost every case, the religious debate is still open-ended. Other than opposition to the
more sinister possibilities, such as the creation of "spare-parts" humans, there is hardly
consensus about the ethics of cloning. In the absence of a central teaching authority, akin to
the Roman Catholic Church's Congregation for the Doctrine of the Faith, many religious scholars
are still openly debating the pros and cons of a powerful new science that could bring as much
potential for hope as for horror.
Three Basic Questions
The discussion eventually wraps itself around three central questions: Would cloning somehow
corrupt traditional family relationships and lineage? Is destruction of a fertilized embryo during
research murder? And perhaps more fundamentally, does cloning meddle with God's universe
in a way that humans shouldn't?
Picking a position on cloning is actually an exercise in revisiting basic religious beliefs, says
Courtney Campbell, director of the Program for Ethics, Science and the Environment at Oregon
State University.
For example, most Jews and Muslims don't consider a fertilized embryo to have full human
status, which essentially gives a green light to therapeutic cloning research. In that sense, the
discussion about therapeutic cloning tends to follow lines similar to the debate over stem cell
research and, ultimately, abortion.
"Thinking about cloning ought to require traditions to go back and think through basic tenets,
such as does life really begin at conception," Campbell said. "You can't avoid that question."
To most faithful, answering such deep questions requires study of religious texts. Some people
might think thousand-year-old writings would offer little guidance on 21st-century scientific
morality, but that's not true, says Rabbi Edward Reichman, assistant professor of philosophy
and history at Yeshiva University Einstein College of Medicine.
"The (Jewish) law is relevant to any imaginable technology," he said. "When you apply the law
to a new technology, you can seek direct precedent, or you can ... seek to distill a principle of
the law that applies.
"With evolution, Darwin, Copernicus, it was fundamentally the same. It was an unknown thing
one couldn't have dreamed of when the law was written, but where the principles applied."
Jewish law is squarely on the side of medical research that has potential to save and preserve
life, Reichman said. As a result, Jewish scholars are generally among the most vocal religious
leaders in support of therapeutic cloning.
"The Jewish faith generally welcomes new technologies and sciences in as much as they can
benefit the world, especially medicine. We do not necessarily perceive all advances as stepping
on God's toes," he said.
Christian Views Are Diverse
But that's exactly the interpretation arrived at by Roman Catholic scholars after examining the
Bible and Canon Law. Back in 1987, the church became the leading voice against human cloning
of any kind. In a document called "Donum Vitae," Roman Catholics were told that cloning was
"considered contrary to the moral law, since (it is in) opposition to the dignity both of human
procreation and of the conjugal union."
The church still holds that position, which is also supported by conservative Christians such as
Southern Baptists. However, there is great diversity of opinion among other Christian
denominations, and even within those denominations.
Oregon State's Campbell compiled the most comprehensive look at religious perspectives in
1997, for the National Bioethics Advisory Commission appointed by then-President Bill Clinton.
Campbell used a simple traffic-light system to classify the religious points of view: Catholics and
Southern Baptists issue clear red lights on both therapeutic and human cloning. But among
"mainline" Protestants such as the Lutheran and Episcopal faiths, Campbell found some green
and yellow lights.
"Some traditions and leading figures in conservative Protestantism who were opposed to
human cloning for reproductive reasons have come to see that given the ambiguity about their
own views about the status of embryonic life, and given the potential for health benefits, they
could be opposed to reproductive cloning, but affirm therapeutic cloning," Campbell said. The
main reason, Campbell says, is the tradition of emphasizing individual choice over central
dogma.
Buddhism: Yes and No
Some other faiths are even harder to pin down. For example, there is no stated position among
Buddhists on cloning, so scholars like Campbell are left only to interpret the tradition's precepts
on their own.
Buddhism might be willing to accept cloning, Campbell said, because it represents a leap in
modern science and self-understanding that could be considered a path to enlightenment. On
the other hand, the Eightfold Path prohibits harm to any sentient beings, which could be seen
in the destruction of cells necessary to perform cloning research. Campbell's judgment: a yellow
light on the issues raised by human cloning, and a flashing red light on other implications of
cloning research.
Damien Keown, professor at Goldsmiths College in London and perhaps the best-known expert
on possible Buddhist responses to cloning, generally agreed. He said the tradition doesn't have
the same kind of fundamental moral opposition that can be found in Christian faiths. Buddhists
already believe in non-sexual reproduction, for example, since Buddhism teaches that life can
come into being through supernatural phenomenon like spontaneous generation. "Life can thus
legitimately begin in more ways than one," he said.
"For Christians, to bring into being a new human or animal life by cloning as opposed to normal
sexual reproduction is to 'play God' and usurp the power of the creator. This is not a problem
for Buddhism, because in Buddhism the creation of new life is not seen as a 'gift from God,'"
Keown said in a recent paper. "For this reason the technique in itself would not be seen as
problematic."
Buddhism sees human individuality as a mirage, so adherents wouldn't share some of the other
philosophical complaints that Western thinkers have about cloning, as it pertains to devaluing
an individual's personality or character by creating copies.
But that hardly means Buddhists will welcome clones. On more practical grounds, Buddhism
promotes ultimate respect to every sentient being, and that generally includes cells born out of
research. Destroying such cells, even in research on animal cloning, runs contrary to Buddhist
teaching.
"It is hard to see what purposes—scientific or otherwise—can justify the dehumanization that
results when life is created and manipulated for other ends," Keown said. "We should not
forget that Ian Wilmut, the creator of Dolly [the cloned sheep], failed 276 times before Dolly
was conceived."
Hindu and Muslim Views Vary
Hindu religious scholars have issued flashing red lights, according to Campbell—which means
they are calling for a temporary pause to provide time to think, but have not issued an outright
objection of human cloning.
A Hindu's sense of the world and the relationship between people and Creator is very different
from Western traditions, so Hindus also wouldn't have the same fundamental objection to
"playing God" that Christians might. But there are plenty of concerns about the desire for greed
and power that might be served by aggressive scientists who call for cloning.
Diversity among Muslims makes an authoritative description of Islamic thought on cloning
nearly impossible. Dr. Abdulaziz Sachedina, University of Virginia professor and a leading U.S.
scholar on Muslim thought regarding cloning, believes that most Muslims will eventually agree
that scientists wouldn't have discovered cloning if Allah hadn't willed it. So cloning for the
purpose of enhancing the chances of procreating within a solid family structure will be
"regarded as an act of faith in the ultimate will of God as the Giver of all life."
But he's hardly without opponents. Nasser Farid Wasel, Egypt's Mufti, said in 1999 that cloning
clearly contradicts Islam. Other muftis have gone further, saying scientists who clone are doing
Satan's work.
Dr. Ibrahim B. Syed, director of the Islamic Research Foundation International and an
outspoken cloning supporter, says such absolute statements from religious leaders only serve
to complicate the conversation.
"Anything new, just as a reaction, they oppose it," Syed said. "Our religious leaders have little
knowledge of evolving technologies." But the problem works both ways, he conceded. "The
scientists don't know anything about religious beliefs, often."
Science vs. Religion
Scientific advances have shaken religious beliefs to their roots repeatedly through the ages.
Charles Darwin did it. Copernicus did it. And now, companies like Advanced Cell Technologies
are doing it.
But as much as religious leaders want to push scientists to think more about the morality of
their work, scientists are pushing religious leaders back to the basic tenets of their faiths, where
they scramble to make sense of a world teetering on the razor's edge of irreversible change.
While it might be a frightening moment, it's also a grand opportunity, Campbell said.
"Science can be a spur to creative and innovative theological thought," he said. "And I think
what is a crying need is for the church to be a forum for discussion with engaged dialogue
between science and religion, and be a venue for civic conversation."
In the debate over cloning, will religious views ultimately matter? Already, some scientists are
working faster than ethicists on cloning. And at least in the United States, there is an open
question about the weight given to religious leaders' opinions on cloning.
Four out of five people said they opposed cloning in a survey conducted [in 2004] for the Pew
Forum on Religion and Public Life and the Pew Research Center for the People and the Press.
But only one in four Catholics and one in three Protestants cited religious beliefs as the main
reasons for their opposition. Pollsters say many Americans pride themselves on developing
their own opinions rather than consulting religious dogma—which means that the key decisions
on cloning are much more likely to be made in the House of Representatives than in a house of
God.
Research Cloning Should Be Allowed but Not Reproductive Cloning
Christiane Nüsslein-Volhard, "Manipulating the Human Embryo," USA Today, January 2011, pp.
30-33. Copyright © by the Society for the Advancement of Education. All rights reserved.
Reproduced by permission.
"Rules must serve to prevent misuse, but they also should not unduly inhibit medical research
that is guided by the ethical principle to help and cure existing human beings."
In the following viewpoint, Christiane Nüsslein-Volhard argues that regulations are needed to
govern medical technologies such as embryonic stem cell research, in vitro fertilization, and
cloning. These regulations, contends Nüsslein-Volhard, should be based on reality, not fiction;
they should be guided by science but decided on by society through its elected officials. Based
on a biology-based definition of the beginning of a human being, regulations that prohibit
reproductive cloning while allowing research cloning would be reasonable, asserts NüssleinVolhard. According to her, such regulations would prevent misuse but would not impede
important medical research that can help existing human beings. Christiane Nüsslein-Volhard is
a German biologist who won the Albert Lasker Basic Medical Research Award in 1991 and the
Nobel Prize in physiology or medicine in 1995 for her research on the genetic control of
embryonic development. She is the author of Coming to Life: How Genes Drive Development,
from which this viewpoint is excerpted.
As you read, consider the following questions:
1. According to Nüsslein-Volhard, Paracelsus's recipe for the creation of the Homunculus
calls for sperm to be incubated in a concoction of what?
2. According to Nüsslein-Volhard, what is the second reason that cloning does not work
efficiently for the actual reproduction and breeding of animals?
3. In what important way do mammalian embryos differ from those of chickens or frogs, as
stated by the author?
Genes and embryos have become the subject of intense public discussion, as the achievements
and scientific discoveries in the fields of embryology and genetics not only increase our
knowledge, but open up new possibilities to influence human life in a principally novel way. In
addition, these achievements give rise to speculations and scenarios that indeed would change
the world substantially should they ever be realized. Although several medical applications of
new technologies, in particular gene technology, now are widely accepted, there is a
widespread fear of the dangers of unpredictable consequences of such technologies.
Embryos Are at the Center of Debate
At the center of these debates is the issue of the extent to which human embryos should be
manipulated in vitro and whether to interfere with their genetic constitution. Among different
countries, the regulations relating to this issue are diverse, ranging from very restrictive, for
instance in Germany and Ireland, to quite permissive in the United Kingdom and Sweden.
What exactly is the issue? Since 1978, it has been possible to fertilize human eggs outside the
female body and cultivate the embryos in vitro for a short while before they are transferred
back into the uterus to achieve pregnancy. The current procedure for this in vitro fertilization
yields surplus embryos that are not transferred back. This opens up the possibility to use these
embryos for medical research rather than discarding them. For instance, embryonic stem cell
cultures could be obtained that could be used to develop therapies for several severe diseases.
By genetic screening of such early embryos, congenital diseases could be avoided, even
eradicated. However, according to the generally accepted moral conviction of our culture,
every human being possesses dignity and, therefore, must not be used solely for the benefit of
others. Opponents and supporters of embryo research share this moral position. The conflict
therefore does not concern the acceptance of human dignity and protection, but rather the
moral status of the early embryo.
From which point on is a human embryo a human being? Are the very early embryos human
beings, which have to be protected just like growing embryos during pregnancy, or is their
moral status different, and gradually changing until birth? The view of such a graded increase in
status in many ways does reflect our natural feeling, which is manifested by our customs of
birth control and laws of abortion. This difference in status is the bone of contention. The
German law of 1990, for instance, defines the beginning of a human being at fertilization, while
others consider the actual time of implantation into the female organism as crucial. In the U.K.
[United Kingdom], in vitro is allowed until the 14th day. A human being becomes a legal person
only by birth.
Although the criteria used for the definitions rely on biological events, they are not a scientific,
but a moral, issue. Dignity, right to life, and protection are not biological, but moral categories.
Therefore, these issues should be decided not by scientists but by our society as a whole
through our political representatives. The big differences among nations even of very similar
cultural backgrounds indicate that there is no single correct solution. However, in order to
guarantee efficient research, we need clear regulations that are respected widely. The legal
definition of the beginning of a human being should be reasonable, plausible, and consistent. It
is at this point where scientific knowledge and judgment may help by describing grades and
steps of embryonic development. It also is the obligation of scientists to reveal the potential
applications and consequences of embryonic research. As there are conflicting moral issues—
such as the right to life on the one hand and the pain and suffering caused by yet untreatable
diseases on the other—these regulations demand great care and foresight and will have longlasting consequences to our societies.
Utopias of Human Creation
Using early human embryos for medical therapy merely is part of the debate. Additional issues
include the ability to interfere with the processes of reproduction, and diagnostic procedures
such as the selection, or even the genetic manipulation, of children with desired attributes. A
particularly controversial issue is that of cloning. It is remarkable that, in this debate, or rather
in the representation of this debate by the media, there is little or no distinction between what
is real, what is plausible, and what is utterly utopian. Sometimes the impression is conveyed
that science not only could accomplish anything we desire, but actually would test the limits of
the possible without any ethical considerations. This attitude is not new. There is a long
tradition on both sides: blind belief in scientific progress and its flip side, the utter distrust in
science.
Utopias of man creating man have existed since antiquity, handed down through the
generations by way of myths and religions. Even though most people would acknowledge that
the creation of woman from Adam's rib or the creation of Pallas Athena from Zeus's head are
meant purely as symbols, things look different if such ideas are supported by contemporary
biological theories. A good example from the Middle Ages is the recipe of the creation of the
Homunculus (Latin for little human) by Paracelsus of Hohenheim, a scholar of alchemy and
various other sciences in the 16th century. The story of the Homunculus is based on the popular
idea of preformation, which prevailed for a long time. This idea implies that the sperm already
harbors a completely formed human being, a Homunculus, which unfolds in the mother's body
in the way a plant's seed would develop in the earth. Paracelsus's 1537 "recipe" replaces the
mother's organism with an artificial medium. The sperm is incubated in a concoction of horse
dung, urine, and other ingredients, and kept warm inside a pumpkin. According to Paracelsus, a
small human being would appear within 40 days, provided that the process was undertaken in
secrecy.
While the Homunculus story belongs to the realm of fantasy, British writer Aldous Huxley's
utopia of human creation as described in his 1932 novel Brave New World often is considered
to be rather realistic—at least if it is not possible right now, it is seen to be possible in the near
future. Huxley imagines a procedure by which embryos can be made to form buds, such that
from one embryo several identical copies can develop. These cloned embryos then are to be
raised in bottles that serve as a kind of artificial uterus. The realism of his story is buttressed by
Huxley's detailed description of the physical and technical difficulties of the uterus machine.
Most striking perhaps is his conjecture that the conditions under which the clones mature can
be manipulated to program the desired attributes of these parentless beings. In Huxley's time,
the conditions of human and mammalian development were known in broad strokes only, and
the nature and biochemical function of genes were not known at all. Yet, it is even more
remarkable that there are people who take Huxley's ideas as present or future truth rather than
as the fiction that they are.
Research from Animals to Humans
While our understanding of the general processes involved in human development has been
aided by research on model organisms, such as the mouse, procedures discussed for
application in humans are based on research on domestic animals. Artificial fertilization as well
as genetic diagnosis of single embryonic cells have been developed and studied in cattle. The
original idea was to use genetic diagnosis to predetermine the sex of a calf in order to produce
predominantly female cattle for milk or male cattle for meat, depending on the breed. The
procedure rarely is used, though, because it is so complicated.
For artificial fertilization, hormone treatment of the cow stimulates the production of
supernumerary [i.e., extra] eggs. Then the eggs are removed from the ovary and placed in a
culture dish where they are mixed either with the sperm, or where the sperm is injected
directly into the eggs. After a few days, when the fertilized egg has divided several times, the
embryo is reimplanted into the mother cow. For genetic diagnosis, prior to implantation, one or
two cells are removed from the embryo and its chromosomes are analyzed. The removal of one
or even two cells at this stage does not harm the embryo, and it will develop normally after
implantation.
The first experiments in cloning by nuclear transplantation were conducted in the 1960s on
amphibia. Researchers were interested in determining whether all body cells maintain all genes
that are necessary to create a healthy animal. The first mammal to be cloned was a sheep
called Dolly. Breeders' interest in cloning lies in multiplying genetically identical animals that
have proven to have particular desired properties. This also is the basis for the wide use of
cloning in crops. However, plants are not cloned by cell nucleus transfer but rather by taking
layers and cuttings for plant reproduction, a quite natural event propagating genetically
identical plants.
During the procedure of animal cloning, the nucleus of an egg cell is removed and replaced by a
nucleus taken from a body cell of a chosen animal. In rare cases, a blastocyst will develop and,
even rarer still, this blastocyst will give rise to a healthy animal. Such a cloned animal carries the
same genotype as the donor animal from which the nucleus originated. Even though cloning
has been accomplished in several animals—among them cows, sheep, and mice—the success
rate is extremely low. In most cases, the clone's development is sooner or later interrupted,
resulting in frequent miscarriages and stillbirths.
While these attempts at cloning animals have provided a satisfactory answer to the question of
whether the set of genes remains complete in body cells, cloning does not work efficiently for
the actual reproduction and breeding of animals. There are several reasons for this. First, the
body cells from which the nuclei are taken may have accumulated too many mutations. During
normal development, special cells from the germ line produce the offspring. These cells are well
protected, leading to fewer mutations than body cells. Second, the developmental potential of
body cells is restricted because their genes are wrapped in special proteins and partially
modified. These restrictions would have to be reversed completely during contact with the
cytoplasm of the egg. This reprogramming apparently takes place only rarely. A probable third
reason is that, in the egg, the chromosomes are not always distributed in an orderly fashion
after the nuclear transfer. Whatever the reasons may be, the fact is that cloning by nuclear
transfer is successful only in very rare cases. Presently, it is unpredictable how the procedure
could be made more efficient and safe.
Human Reproductive Cloning Has Been Roundly Rejected
Cloning a human means creating a person with exactly the same genotype as an already
existing person—a belated twin, as it were. To construct such an embryo, the nucleus of a body
cell would have to be transferred to an egg cell from which its own nucleus had been removed.
Yet, as previously stated, cloning animals with this procedure only rarely produces healthy
animals. In Dolly's case, more than 200 eggs had to be treated before success was achieved.
This rate is much too low to justify even the slightest attempt at cloning a human being. With
humans, vastly different safety requirements are appropriate than those for domestic animals.
While it is a moot point to debate the ethical implications of a procedure that, although
theoretically possible, in reality cannot be performed successfully—at least not for the time
being—human imagination still has stirred up extensive ethical discussions on the issue of
cloning. Biologically speaking—apart from the extremely low success rate and frequent mishaps
predicted to go with this procedure—the fact that a cloned child would have no parents creates
a high level of discomfort. In addition, the motivation for a desire to "double" oneself or
somebody else does not bode well for the child's welfare. Therefore, on ethical grounds alone,
attempts at cloning of human beings (reproductive cloning) have been rejected by scientists
and researchers all over the world. In many countries it even has been rendered illegal....
When the Embryo Requires Protection
Still, the crucial issue remains: When does a human embryo have to be protected against
destruction and use for other purposes? As mentioned, it is not the task of the scientists to
decide this question, but rather that of society as a whole, and the differences in political
opinions reflect by no means a discrepancy of the opinions of scientists in different countries.
Nevertheless, in defining the moral status of the embryo, the classical arguments of ethicists
and philosophers often are based on pieces of biological evidence, which sometimes prove to
be highly debatable if inspected more closely from the view of modern biology. For instance, a
widely accepted dogma argues that human life is a continuous process, starting with
fertilization, which does not display any sharp transitions—and during which nothing
substantial is being added that would justify a change in status. Another argument states that
the zygote—with its complete genetic constitution—also would hold the complete potential to
develop into a human being.
Now, it is quite clear that a chicken or frog embryo starting with fertilization has the potential,
even without motherly protection, to develop continuously until hatching. In the case of
mammals—and thus humans—however, the embryo has to implant into the uterus of the
mother to be able to develop further. The zygote alone only has the potential to form a
blastocyst that then has to hatch from the egg case in order to implant into the uterus and
begin the next stage of development.
Biologically speaking, this is a marked transition and there almost is nothing more
discontinuous than such a process in which the embryo is placing itself in direct and immediate
cellular contact with another individual. In the fertilized egg, the genetic program is complete.
For its realization, though, the intensive interaction—the symbiosis with a second organism, the
mother—is required. This is indispensable and cannot be provided by surrogates. Only at birth,
the growing human being has become a separated, independent organism that breathes with
its own independent metabolism. Certainly, the born human being still has much need of
attention and protection, but it now is fed from the outside and, therefore, in case of necessity,
can survive without the mother. There is no debate that, at this stage, it is a human being with
all rights.
Rules That Do Not Impede Medical Research Are Needed
As already mentioned, it is remarkable that the issue of embryo protection is treated in such a
different manner in different countries. This reflects the difficulty in compromising between
extreme positions. It would be most desirable if one could agree on rules guiding embryonic
research that are based on plausible and reasonable grounds. Science is international and
progress in the long run depends on equal and just conditions for scientific research. Such rules
certainly must serve to prevent misuse, but they also should not unduly inhibit medical
research that is guided by the ethical principle to help and cure existing human beings.
In addition to the scientific quality of the intended research, it should be required that sufficient
animal experiments have been carried out in order to guarantee a reasonable rate of success to
make a procedure practicable in humans. Also, the laws should prevent those embryos
manipulated in vitro—for example chimeras with embryonic stem cells, or those that have been
constructed by nuclear transfer—from being implanted into a female organism to start
pregnancy. Such a regulation also would prohibit reproductive cloning of humans. The most
important factor, however, is to proceed with care and ensure that possible contributions of
medical research to reduce pain and suffering are not prohibited for fear of misuse.
Creating Embryos for Research Is Wrong
Christian Life Resources, "A Primer on Human Cloning," April 2009. Copyright © 2009. All rights
reserved. Reproduced by permission.
"All therapeutic cloning must be condemned."
Christian Life Resources (CLR) is a Wisconsin-based organization that seeks to educate people
about the biblical value and sanctity of human life. In the following viewpoint, CLR says that all
cloning is wrong because it is not mankind's right to create life. However, somatic cell nuclear
transfer, or therapeutic cloning, in which embryos are created and then destroyed, is worse
than reproductive cloning, because in the latter the intent is not to destroy life, but to create it.
According to CLR, therapeutic cloning should be condemned.
As you read, consider the following questions:
1. According to Christian Life Resources, therapeutic cloning is also known as what?
2. According to the author, what are some of the ways that the term "soul" is defined?
3. According to Christian Life Resources, what are some of the disorders that cloned
animals tend to have?
Cloning moved from the arena of movie-scripting to reality in 1997. It was in that year that
Nature journal announced Scottish scientists had cloned a sheep named Dolly. The worldwide
scientific, religious, political, ethical and moral implications of cloning continue to spread since
then.
Human cloning produces the genetic duplication of another human. The genetic code is copied
deliberately from one person to make another person with the same genetic material. A cloned
embryo is a twin of its donor—essentially at an earlier stage of life. It is human and has only one
parent with the same genetic makeup as that parent.
Three Types of Cloning
1) Recombinant DNA Cloning (AKA [also known as] "recombinant DNA technology"; "DNA
cloning"; "molecular cloning"; "gene cloning")
This type involves the transfer of a DNA fragment from one organism to a self-replicating
genetic element. The DNA of interest can then be propagated in a foreign host cell. This type of
cloning creates fewer ethical concerns since it involves the cloning of DNA rather than the
cloning of a human being.
2) Reproductive Cloning (AKA "somatic cell nuclear transfer" [SCNT])
This technology generates an animal with the same nuclear DNA as another living or previously
existing animal. SCNT bypasses sexual [re]production by creating embryos without fertilization.
The nucleus of a cell which contains genetic materials is taken and implanted into a hollowedout egg deprived of a nucleus. The reconstructed egg is treated with chemicals or electric
current to stimulate cell division. The cloned embryo is then transferred into a female's womb
(or an artificial womb) until the clone is born. This process is already being tested on human
subjects as well as animals.
A high rate of death, deformity, and disability is associated with this form of cloning. Dolly was
cloned after 276 attempts.
3) Therapeutic Cloning (AKA "embryo cloning"; "clone and kill")
This type involves the production of human embryos solely for research use. To date, cloned
embryos are used and destroyed within 14 days of existence.
Scientists harvest embryonic stem cells which can generate into any type of specialized cell in
the human body. These stem cells are extracted from the embryo after five days' division. The
extraction destroys (kills) the young embryo's life, raising grave ethical concerns from lifeaffirming organizations such as Christian Life Resources.
In November 2001, ACT (Advanced Cell Technologies), a Massachusetts biotech company,
announced the first cloning of human embryos for therapeutic research. This breakthrough had
limited success: 3 of 8 eggs actually divided and only one divided into 6 cells before the cloning
ended.
The Issue Is Intent
Since all human cloning is reproductive (it duplicates [the] genetic code of the donor to make a
new human life), the issue is really the intention for that life. The intent of reproductive cloning
is to bring about a live birth; the intent of therapeutic cloning is to harvest the stem cells of the
5-7 day-old embryo and use those stem cells for therapeutic purposes.
Only God Should Create Life
God, in His Word, provides clear principles dealing with human life:
God alone has authority over life and death.
See now that I myself am He! There is no god besides me. I put to death and I bring to life.
(Deuteronomy 32:39)
The LORD brings death and makes alive. (1 Samuel 2:6)
Man has the responsibility to preserve and protect human life.
And for your lifeblood I will surely demand an accounting. I will demand an accounting from
every animal. And from each man, too, I will demand an accounting for the life of his fellow
man. Whoever sheds the blood of man, by man shall his blood be shed; for in the image of God
has God made man. (Genesis 9:5,6)
The commandments, "Do not commit adultery," "Do not murder," "Do not steal," "Do not
covet," and whatever other commandment there may be, are summed up in this one rule:
"Love your neighbor as yourself." (Romans 13:9)
Speak up for those who cannot speak for themselves. (Proverbs 31:8)
Human life is present long before birth. In fact, human life and accountability for sin are evident
at the earliest stages of life.
Surely I have been a sinner from birth, sinful from the time my mother conceived me. (Psalm
51:5)
Before I formed you in the womb I knew you, before you were born I set you apart. (Jeremiah
1:5)
These passages direct mankind to respect God's authority over life and death. We do not have
the right to assume God's authority for ourselves, but rather have the responsibility to protect
human life, even from its earliest stages.
Other Cloning Risks
There is always the concern that human life will become a commodity rather than appreciated
as a blessing from God. When the true value of human life is diminished, it is possible to
rationalize and justify actions that are otherwise considered unethical and harmful. The reality
is that some already determine that a "potential cure" has a greater value than an existing
human life. The risk is that this immoral attitude will spread as the value of human life
continues to diminish.
The intent of therapeutic cloning is to destroy human lives within the first week of life. In spite
of claims that this will benefit mankind, there is no justification in God's Word for such action.
Therefore, all therapeutic cloning must be condemned.
Reproductive cloning is done in the same manner, but for a completely different intent. The
goal of sustaining a human life is commendable and more desirable than the planned
destruction of those lives, but the inherent risks involved in the cloning process make it hard to
justify as a God-pleasing procedure. When considering the very low success rates and the
subsequent destruction of the young lives that are considered "failures," this procedure as well
cannot be supported or encouraged.
Clones Also Have Souls
The term "soul" is defined in many ways. For some it is an "inner strength" for others it is
simply used as a figure of speech, but for Christians it is the part of a person, given by God, that
lives eternally. It joins with the physical body at the beginning of life, and separates from the
body at physical death.
Although God's Word does not specifically address the issue of clones, we do know that there is
no life apart from the presence of a soul. If a human clone is alive, then we conclude that the
living human being, regardless of how his/her life began, is a living being because there is a soul
present. More importantly, we must conclude that a clone is equally in need of a Savior from
sin and therefore will want to share the Gospel message of salvation with him/her.
Do not be afraid of those who kill the body but cannot kill the soul. Rather, be afraid of the one
who can destroy both soul and body in hell. (Matthew 10:28)
As the body without the spirit is dead, so faith without deeds is dead. (James 2:26)
Cloned Animals
A tadpole was first cloned in 1952. Sheep, goats, carp, cows, mice, pigs, cats, rabbits, and gaur
[a wild ox] have since been cloned by nuclear transfer technology. In 2003, a horse, white-tailed
deer and mule were cloned. An Afghan hound dog, named Snuppy, was cloned in South Korea
in 2005. The world's first extinct mammal, a subspecies of a mountain goat known as a
Pyrenean ibex, was cloned using tissue samples from one found dead in early 2000; the kid,
born in January 2009, died 9 minutes after birth due to malformed lungs. In April 2009 the first
cloned camel was born in the United Arab Emirates.
Some species are more resistant to SCNT and cloning experiments have failed with monkeys
and chickens.
Research involving cloning is very expensive and many institutions can receive lucrative funding
for research. Cloning has had a high rate of failures, miscarriages and stillbirths. The rate of
"success" of cloned offspring is less than 10 percent. For example, 841 horse embryos were
created and only two dozen lived past their first week.
At this time, cloned animals tend to have immune dysfunction, aggressive behavior and
increased rates of infection, tumor growth and other disorders. Studies of cloned mice show
early death rates. Cloned calves also died prematurely and were disproportionately large in
size. Australia's first cloned sheep died suddenly and mysteriously having appeared healthy.
Human Cloning in the United States
The U.S. House of Representatives has passed legislation twice to ban both therapeutic
cloning—taking the life of a human at the embryonic stage in order to extract stem cell lines—
and reproductive cloning for the purpose of creating babies with genomes identical to a living
person....
On March 9, 2009, President Barack Obama signed an executive order to lift restrictions on the
federal funding of embryonic stem cell research. In comments made at the signing, Obama
stated his administration would develop "strict guidelines" to avoid human cloning
experimentation for human reproduction, because its misuse or abuse cannot be tolerated.
Despite assurances by Obama that the government never "opens the door" for human cloning,
critics say stem cell research can lead to the cloning process....
The American Medical Association and the American Association for Advancement of Science
issued a formal statement against human reproductive cloning. However, cloning for
therapeutic reasons is gaining momentum in the scientific and medical world.
Cloning Facts and Fictions
Excerpted from Frankenstein's Footsteps: Science, Genetics, and Popular Culture, by Jon Turney.
Copyright ©1998 by Jon Turney. Reprinted with permission from Yale University Press.
In the following selection, Jon Turney describes how fictional portrayals of cloning and other
forms of human gene alteration shape the public's response to actual scientific developments
in the field. Public confusion has been heightened, Turney believes, by writings such as In His
Image, a 1978 book in which American science journalist David Rorvik claimed that he had
assisted in the cloning of a human being. Rorvik's book blurred the line between fact and
fiction, Turney asserts, just as imaginary scenarios of human cloning spawned by the factual
reports of the successful 1997 cloning of a sheep have done. On the other hand, Turney points
out that fiction can also be a useful way of framing ethical questions raised by scientific
research into controversial areas such as cloning. Turney is the author of Frankenstein's
Footsteps: Science, Genetics, and Popular Culture, from which the following is excerpted. He is
also a senior lecturer in science communication in the department of science and technology
studies at University College, London.
Cloning has long been one of the possibilities used to symbolise the powers of new biological
technology. To some extent, this began with Aldous Huxley's vision in Brave New World, but it
really emerged as a recurrent motif in debate in the late 1960s and early 1970s. The contention
over fact and fiction was then crystallised by a book published by the US science journalist
David Rorvik in 1978. In the book, In His Image, Rorvik claimed he had assisted in the cloning of
a human being. He presented his story as fact, and provided extensive references to back up his
claim that such a feat was possible. The claim was strongly denied by scientists, most notably by
the British biologist Derek Bromhall, who was angry that his own work had been cited, and
provided a convincing demolition of the scientific credibility of the story. Bromhall also accused
Rorvik of presenting fiction as fact out of greed, glossing over his own claim about his motives
in his epilogue where he expressed the hope that many readers will be persuaded of the
possibility, perhaps even the probability of what I have described and benefit by this 'preview'
of an astonishing development whose time ... has apparently not yet quite come. And if this
book, for whatever reason, increases public interest and participation in decisions related to
genetic engineering then I will be more than rewarded for my efforts.
Here, Rorvik seemed to admit that the book was an attempt to exploit the difficulties scientists
have in responding to claims like his. By deliberately blurring the boundary between fact and
fiction, he hoped to provoke public discussion. In that he succeeded, aided considerably by the
welter of scientific denunciation. Although the book was condemned as a literary confidence
trick, it was widely read. What was, in truth, a badly written novel, with copious discussion of
bioethics culled from the academic literature, became a Literary Guild selection, and the US
paperback rights were sold for a quarter of a million dollars.
In addition, Rorvik's earlier non-fiction collection on the biological revolution was republished in
paperback, and the controversy spawned numerous newspaper and magazine articles, at least
one conventional popular non-fiction book on cloning and a British television documentary.
Although this programme generally supported the view that the book was a hoax, the preview
article in the Radio Times, replete with references to Huxley, concluded that "in one sense ... it
doesn't matter if it is true or not ... as the chronology demonstrates, 'if it be not now, yet it will
come. The readiness is all'. We live in a brave new world."
With this kind of response, Rorvik seemed justified in believing that his deliberate blurring of
genre boundaries would be effective in stimulating debate. Other writers at the time were
pursuing the issues [raised by biotechnology] in fiction, but not getting this kind of attention.
Consider, for example, a science fiction novel of the near future by the well-regarded Australian
author George Turner, who has a character observe:
As a group, biologists are the most dangerous men alive. The bomb we've learned to live with
and pollution we will handle. But biologists!
What they have achieved since the sixties is enough to put the fear of hellfire into Jehovah
himself. Artificial inovulation, the gerontological drugs, brain regrowth and the mechanics of
gene manipulation—these are already with us, imperfect and unready but with us.
They are only the beginning.
Consider the implications, and retch.
This is a rather stronger condemnation of contemporary biological research than anything
offered by Rorvik, but it is the latter's book which is still remembered, at least when journalists
look up their cuttings to write another article on cloning.
Using Fictions to Frame a Debate
The succession of bursts of publicity about cloning show how different parties to the debates
about the future implications of biological science treat the role of fictions in these debates in
different ways. Some commentators explicitly acknowledge the importance of a fictional
tradition in offering symbolic possibilities which dramatise a wider range of concerns about
experimental biology. Consider, for example, one notable later media flurry about cloning,
when Jerry Hall and colleagues at George Washington University in the US made the front page
of the New York Times in 1993 with experiments aimed at producing multiple embryos from a
single in vitro fertilised egg. The lengthy reports which followed in Time and Newsweek both
emphasised the distance between what Hall and colleagues had achieved and the many
fictional uses of cloning. Under the heading 'Clone Hype', Newsweek's main report made
continual references both to Rorvik's book and to stories about cloned dinosaurs and multiple
Hitlers to stress what the work was not about. Time took a very similar line, while emphasising
that the work had created a worldwide sensation, and that 77 per cent of Americans polled that
week wanted to see such research either temporarily halted or banned outright. Their reporter
observed that the actual research reported 'seems, in many ways, unworthy of the hoopla.' And
the magazine made a point of showing how many of the bioethicists who contributed comment
to the wider press coverage of the story were offering scenarios that went well beyond existing
technology. This suggestion was underlined with a separate article on 'Cloning classics',
summarising fictions about the subject from Brave New World to Fay Weldon's 1989 novel The
Cloning of Joanna May. The article opened with the observation that, 'When it comes to dealing
with cloning, ethicists and science-fiction writers have almost identical job descriptions.'
The outpouring of concerned commentary which followed Hall's announcement was relatively
short-lived. But the most recent episode in the cloning saga evoked a longer-running debate.
The cover of Nature for 27 February 1997 depicted a Scottish-bred sheep, known as Dolly, over
the headline 'A flock of clones'. By the time Nature appeared, the story had already been widely
previewed in the general media, following a British Sunday newspaper's exclusive the previous
weekend. The birth of Dolly was taken as a signal that cloning of adult mammals, and hence
humans, was now a real technological possibility.
A team at the Roslin Institute in Edinburgh, working with colleagues from a local biotechnology
firm, had perfected techniques which allowed nuclei from adult cells to be fused with eggs to
produce a new individual genetically identical to the original adult. Their success rate was very
low, one lamb from 277 fusions, but they did succeed. The enormous volume of comment that
followed ... [had] two particularly prominent features ... which I want to highlight. One was the
apparently strongly felt urge, both among media writers and, as opinion polls had already
suggested, much of the public, that something must be done to stop human cloning. The other
was, as Nature's own editorial argued, that the widespread feeling that governments had been
'caught napping by clones' was an indictment of all the policy-makers, ethical advisers and
technology foresight panels who are supposed to be keeping an eye on science and technology.
This shows, perhaps, one ultimate limitation of the urge to dismiss particular possibilities which
have become the focus of concern about the direction biology may be taking as fictions. The
paradoxical result in Dolly's case was that she was the realisation of an idea which had been
discussed for more than half a century, yet her advent in the flesh was treated as an enormous
surprise. Newsweek suggested that
Twenty years ago, when only the lowly tadpole had been cloned, bioethicists raised the
possibility that scientists might some day advance the technology to include human beings as
well. They wanted the issue discussed. But scientists assailed the moralists' concerns as
alarmist. Let the research go forward, the scientists argued, because cloning human beings
would serve no discernible scientific purpose. Now the cloning of humans is within reach, and
society as a whole is caught with its ethical pants down.
If so, it was not for want of trying on the part of some commentators. But this time, although
there were still respectable arguments why human cloning was unlikely ever to be possible—
which some scientists were quick to point out—there was a widely shared determination that
the possibility should be considered seriously. Those who responded to Dolly, from President
Bill Clinton on down, the former with his call for a report 'within 90 days' from his advisers,
wanted to understand more clearly what human cloning might mean.
How the Public Understands Fictions
Although it was widely recognised that cloning was still mainly a symbol for a broader set of
technologies, that there were important issues relating to the industrial use of animals
connected with Dolly's future as a drug incubator, and that cloned humans would probably not
be identical to their genetic forebears, it was the prospect of an end to biological individuality
which really caught media audiences' attention. Fictional scenarios abounded as writers tried to
help readers think through the possible implications. Time magazine, for example, which like
Newsweek again made cloning its cover story, ran a four-page article on future ethical problems
built around a series of tableaux from a hospital cloning laboratory of the future. To top that, it
rounded off its special report on Dolly with a tongue-in-cheek science fiction story by Douglas
Coupland. The magazine seemed to be taking seriously its suggestion in 1993 that ethicists and
science fiction writers had similar jobs.
This seems to suggest that creating fictions about the possible outcomes of applying biological
technology to people is a legitimate contribution to debate. Both literary creation and scenario-
spinning by bioethicists are ways of alerting society to possibilities which merit discussion
before they are realised—certainly a view writers tend to share. Scientists, though, are not so
sure. One stance they adopt more commonly is to argue that the public is unable to distinguish
fact from fiction. Non-scientists, it is suggested, interpret metaphorical warnings literally.
Writers must therefore take responsibility for portraying well-intentioned science in a negative
light. Commenting on films in the Frankenstein tradition, the distinguished British geneticist
Paul Nurse suggests that 'the real dilemma comes when the freedom of the artist to produce
what they like has to be combined with the fact that these productions are taken by the public
to be an absolutely true portrayal of science'. His British colleague Ruth McKernan agreed that
'the line between science fantasy as entertainment and science fact needs to be drawn more
clearly'.
This kind of assertion radically oversimplifies the relations between media and audiences, fact
and fiction, and the range of stories available at any one time. 'Factual' stories are always
framed in some way which is intended as a guide to interpretation—one reason for the
journalistic invocations of Frankenstein or Brave New World. But this does not mean that the
suggestion that some piece of science is 'like' Frankenstein's project or 'reminiscent' of Brave
New World is taken literally. Both literary criticism and media studies demand that we take a
more sophisticated view of what goes on when diverse audiences assimilate a complex set of
messages about science.
Cloning Research Would Not Benefit Humans
Reprinted from "Little Lamb, Who Made Thee?" by Kevin T. Fitzgerald, America, March 29,
1997, by permission of the author.
Kevin T. Fitzgerald argues in the following viewpoint that human cloning research should be
banned as it would be of no benefit. Human cloning is too risky for its human subjects; it will
not replace a dead or dying child, nor will it ease the pressure of reproductive choices, he
contends. Furthermore, Fitzgerald asserts that cloning humans for their organs is manipulative
and diminishes the value of a human being. Fitzgerald is a research professor in molecular
genetics at Loyola University's Cardinal Bernardin Cancer Center in Chicago.
As you read, consider the following questions:
1. According to Fitzgerald, what are some of the possible benefits of cloning research?
2. In the author's opinion, what may change people's minds about the desirability of
human cloning research?
3. Why is human cloning research too risky, in Fitzgerald's view?
The news that an adult sheep had been successfully cloned has created one common reaction:
increasing anxiety about what our societies should and should not do in the face of the dizzying
pace of scientific advances.
Even the scientific community itself was caught by surprise, because cloning an adult mammal
was thought to be unattainable in the near future, if achievable at all. The surprise quickly
changed to excitement as researchers considered the potential benefits this powerful new
technology could bring.
Surprise and Excitement
What caused such surprise and excitement? First, the surprise. The key breakthrough was the
successful reactivation of all the genes required for the development of a new organism in a
cell taken from adult tissue that had silenced many of these genes. Cells that perform the
specialized tasks of a particular tissue or organ express only those genes necessary for the
function of that tissue or organ—in this case sheep mammary tissue. But using one of these
cells the researchers of the Roslin Institute in Edinburgh, Scotland, were able to stimulate the
genes of this cell so that they could initiate the developmental process of creating a new
individual animal.
Second, the excitement. By employing this technique, scientists may be able to clone
endangered species in order to delay or prevent extinction, or study the processes of
mammalian development to investigate the potential for organ regeneration and repair, or
discover the mechanisms controlling mammalian gene activation so that genes inappropriately
turned on or off in cancer may be reset to their normal levels of activity. Another possibility is
the application of this technique to the cloning of humans. It is this startling possibility that has
been the focus of much of the recent public discussion.
Now that the cloning of a mammalian adult has been achieved in one species, the consensus is
that it could also be achieved in humans. But the vast majority of scientists, ethicists,
theologians and politicians have publicly stated that there should be at least a moratorium on
human cloning research, if not an outright ban. Public opinion polls have mirrored this
response. Yet the more troubling question persists: Within a few years' time, will the medical
and reproductive possibilities of human cloning be enticing enough to change public opinion
and initiate research into the application of this technology to humans?
These fears are well founded. Research on human cloning would involve substantial risks to the
health and welfare of the initial clones, because any research specific to human cloning would
eventually have to be carried out on human beings. Moreover, there are the broader societal
risks already raised in the public discussion surrounding this issue: the increasing objectification
and devaluation of human life (e.g., children viewed as products rather than gifts), the pressure
on women and couples to have their own genetically related children and the rebirth of
eugenics programs seeking to create super- or sub-human populations. Considering the gravity
of these risks, are there presently any compelling reasons for pursuing human cloning?
Several scenarios have been proposed as potentially justifying the use of cloning technology on
humans. In general they fall into three categories: producing a clone in order to save the life of
an individual who requires a transplant; making available another reproductive option for
people who wish to have genetically related children but face physical or chronological
obstacles preventing conception through intercourse alone; cloning a child who is dying from a
tragic accident or a non-genetic disease in order to create another genetically identical child.
No Reason for Research
A few general responses can be made to the above proposals. First, from a scientific
perspective, solutions to these problems are already possible and are already the focus of
current animal research. There is no reason, then, to start the more ethically problematic
research into human cloning. Second, and more importantly, social and psychological problems
cannot and should not be reduced to genetic or biological solutions. Human cloning will not
replace a child, and it will not remove the existing pressures on people making reproductive
choices. Finally, cloning a human being solely for the purpose of supplying organs or tissue
makes it, at a minimum, a mere instrument for manipulation and negates the human identity of
the clone.
But these discussions bring to the surface many of the deep-seated concepts and images
people have about who we are and how we are to live together. Fortunately, the JudeoChristian tradition can offer these discussions three important contributions. It brings careful
and thoughtful convictions concerning the nature and purpose of human existence, a long
history of practical care for the needs of the global human family and a strong appreciation for
the contributions of science. Since scientific discoveries will continue to come at an increasingly
rapid pace, these benefits are needed now more than ever, as are the cautions they contain.
Therapeutic Cloning of Human Embryos Should Be Tolerated
Shane Ham, "The Promise of Therapeutic Cloning," Progressive Policy Institute Backgrounder,
July 5, 2001. Reproduced by permission.
Shane Ham is a senior policy analyst for the Progressive Policy Institute, a research and
education institute that promotes progressive politics geared to the Information Age.
Reproductive cloning is a risky and morally debatable scientific pursuit, and public fears about
cloning in general stem from this ethically unsettling manner of human reproduction.
Therapeutic cloning, on the other hand, does not involve bringing cloned embryos to term.
Instead, therapeutic cloning utilizes stem cells from donated or discarded embryos to create
new treatments for severe ailments. By using cloned cells, for example, doctors could overcome
immune system reactions that have made such practices as organ and tissue transplants so
problematic. Such unique and promising treatments are a worthwhile endeavor, and therefore
Congress and the president should show their support for therapeutic cloning, even as they
rightly continue to ban reproductive cloning.
We are living in the golden era of medical research. Almost every week a major advance is
announced in the scientific journals, and [in February 2001] researchers reached a watershed in
human history when they published the complete human genome, a catalog of our DNA.
Despite the promise of breakthroughs in the near future that could help all of us lead longer
and healthier lives, medical research is not immune to political pressure. The Progressive Policy
Institute (PPI) [in June 2001] released a report detailing the political pressure being exerted by
President [George W.] Bush to halt research into stem cells—the "universal clay" of biology that
can turn into any type of tissue and potentially cure a number of diseases, from Alzheimer's to
diabetes, that kill 3,000 Americans every day. Now President Bush and Republican leaders in
Congress are indicating that they want to interfere with another line of research that could save
millions of lives: therapeutic cloning.
It is important to distinguish between two distinct kinds of cloning: therapeutic cloning and
reproductive cloning. Therapeutic cloning is not cloning in the sense most people use the term,
namely using technology to create a person who is a genetically identical copy of someone else.
That type of cloning is reproductive cloning, and is rightfully subject to a moratorium.
Therapeutic cloning, on the other hand, seeks only to derive stem cells from a cloned embryo.
The embryo is created by cloning DNA taken from a donor, which can be gathered by simply
swabbing the inside of one's cheek, and transferring it into an unfertilized donor egg. The
embryo then divides into a tiny clump of about 100 cells, and the stem cells are then derived to
be used to create any kind of tissue, from nerve cells to arteries to organs.
Aiding Organ Transplants
The potential therapies that may be developed from therapeutic cloning are significant. Under
current medical technology, patients who need organ transplants face two grave dangers: that
a matching organ from a donor will not be found in time, and if an organ is found, that it will be
rejected by the patient's immune system as a foreign invader. To get around the rejection risk,
patients must have their immune systems suppressed, which in itself presents a grave danger,
as it leaves the patient susceptible to any number of infections that people with normal
immune systems do not need to worry about. (Indeed, suppression of the immune system is
what makes AIDS such a lethal disease.)
Therapeutic cloning has the potential to change all of that. Since embryonic stem cells are
capable of becoming any kind of tissue, researchers hope to learn to grow entire organs from
scratch in a laboratory, eliminating the need to wait for organ donors. If the stem cells that
create the organ are cloned from the patient, medical researchers believe that the patient's
body will not recognize the organ as a foreign object; with no risk of rejection, there would be
no need for dangerous immunological suppression. Therapeutic cloning, therefore, may
significantly reduce the risks involved with stem cell therapies derived from non-related
embryos, and save millions of lives.
The Current Ban
Federal funding for therapeutic and reproductive cloning is currently banned by the Dickey
amendment, which specifies that funds cannot be used for "the creation of a human embryo or
embryos for research purposes." Though this language applies to therapeutic and reproductive
cloning, it is not specific to cloning; it also bans federal funding for any other methods of
creating an embryo, including combining a sperm and an egg in a laboratory setting, if it is done
for research purposes. In March 1997, President [Bill] Clinton extended the Dickey amendment
ban on cloning [which applied to the Department of Health and Human Services (HHS)] to all
federal agencies, without distinguishing between reproductive and therapeutic cloning. He also
called for a voluntary moratorium on cloning by privately funded researchers. Despite the
media attention surrounding the issue in the wake of Dolly, the famous sheep that was the first
live clone, the National Bioethics Advisory Commission in June 1997 supported a temporary
moratorium on reproductive cloning, but did not recommend against therapeutic cloning and
did not recommend a permanent ban.
Many prominent scientists ... and bioethicists ... who oppose reproductive cloning still strongly
favor therapeutic cloning for research based on its tremendous potential to ease human
suffering.
There [have been] a number of bills in Congress that address the issue of human cloning. The
House Energy and Commerce Committee's Subcommittee on Health held a hearing [in 2001] on
the two leading proposals. H.R. 1644, authored by Reps. Dave Weldon (R-Fla.) and Bart Stupak
(D-Mich.), would ban all human cloning under any circumstances. H.R. 2172, authored by Reps.
Jim Greenwood (R-Pa.) and Peter Deutsch (D-Fla.), would ban reproductive cloning, but allow
therapeutic cloning as long as researchers register with the federal government and attest to
their understanding that cloned embryos are not to be implanted for pregnancy. The
Greenwood-Deutsch bill would also place a ten year ban on reproductive cloning. At the
hearing, HHS Deputy Secretary Claude Allen did not take a position on the two bills, but made
clear that President Bush supports a total ban on all cloning. Following the hearing, House
Republican Conference Chairman J.C. Watts (R-Okla.) declared a total ban on all cloning to be a
top priority for the party.
An Ethical Form of Cloning
The reasons for having a moratorium on reproductive cloning are fairly clear. Changing the way
humans have reproduced for millions of years raises a host of ethical questions which society is
only now beginning to consider. Moreover, reproductive cloning is still an unproven and
extremely unsafe technique. Though a small number of animals have been successfully cloned,
for every clone that is born there are dozens more unsuccessful clones that are either
miscarried or seriously malformed. It is unclear at this stage whether even those "successful"
clones are truly successful; there is evidence to suggest that cloned organisms suffer from
significant developmental and health problems. The temporary moratorium on reproductive
cloning, therefore, is entirely appropriate.
Therapeutic cloning, on the other hand, does not engender the same safety and ethical
concerns. While therapeutic cloning does involve the creation of an embryo, the derivation of
stem cells from cloned embryos is the same as the derivation from leftover embryos, and any
cloned human embryos would be created with the express permission of the donor and the
express understanding that the embryo would be used for stem cell derivation only, not for
implantation. Many prominent scientists (such as Rudolf Jaenisch) and bioethicists (such as
Arthur L. Caplan) who oppose reproductive cloning still strongly favor therapeutic cloning for
research based on its tremendous potential to ease human suffering.
What Should Be Done
Some critics of therapeutic cloning contend that the temptation to implant cloned embryos will
be too great, and the birth of a human clone would be inevitable. The Greenwood-Deutsch
legislation addresses that concern by providing severe criminal penalties—up to 10 years in
prison—for researchers who implant embryonic clones. This safeguard should be sufficient to
deter those who can be deterred; for those who are determined to create a human clone
despite the legal impediments, even a total ban on creating embryonic clones will not stop
them. (And no ban passed by Congress can stop scientists in other countries from reproductive
cloning.) The potential reward in advanced therapies for dreaded diseases more than justifies
the risk.
Though cloning is still a new science and caution is warranted, there is no need to close off a
promising avenue of scientific inquiry because of justified fears of reproductive cloning.
Therefore, PPI recommends the following steps to let this vital research go forward:
1. Congress should pass, and President Bush should sign, the Greenwood-Deutsch bill (H.R.
2172) to ban reproductive cloning for 10 years.... [this bill never left the Senate]
2. President Bush should revise the executive ban on federal funding for cloning to allow
funding for therapeutic cloning while continuing to ban funding for reproductive cloning. When
President Clinton issued his order barring federal agencies from supporting human cloning, he
acted out of prudent intent to slow the scientists until bioethicists and policymakers had a
chance to consider the implications of cloning. In the accompanying legislation Clinton sent to
Congress, he asked for a five-year sunset period on the ban in order to force reconsideration of
cloning when more information was available.... With legal prohibitions and funding bans firmly
in place against reproductive cloning, there is no reason to continue the ban on federal funds
for research into therapeutic cloning.
3. Congress should repeal the Dickey amendment and allow HHS and the National Institutes of
Health (NIH) to fund research in therapeutic cloning. While Clinton's ban extended the Dickey
amendment to all agencies, repealing that ban would not benefit researchers unless the Dickey
amendment is repealed. The primary source of funding for biomedical research is NIH, a
division of HHS, and the Dickey amendment is a rider on the HHS appropriations bill. To ensure
that scientists have the resources they need to conduct their important research, the Dickey
amendment must be repealed. NIH could then change their guidelines to allow funding for
research using stem cells derived from embryos created through asexual cloning for research
purposes (somatic nuclear transfer), while still confining funding for research on stem cells
derived from embryos created sexually (by combining eggs with sperm) to those derived from
excess in vitro fertilization embryos which would otherwise be discarded.
It is entirely appropriate to be skeptical about powerful new technologies, and to take a
collective pause to consider the next step. The United States did so with cloning. But now that
we have a clearer picture of the risks and a firm understanding that reproductive cloning should
not take place now, if ever, we should move forward cautiously with therapeutic cloning to see
if it can live up to its promise.... We must not close the door on this important medical research
because of fears about reproductive cloning. With [hoped for legal] safeguards ... and the
oversight inherent in federal funding, research into therapeutic cloning can go forward under
the bright light of public scrutiny and perhaps, one day in the future, save lives.
Cloning Is Ethical
Jacob M. Appel, "Should We Really Fear Reproductive Human Cloning?" Huffington Post, April
6, 2009. Reproduced by permission.
"I don't believe that we should be so quick to greet cloning technology with a permanent
injunction."
Jacob M. Appel is a bioethicist and medical historian. He also writes fiction that explores
biomedical ethics. In the following viewpoint, Appel argues that the promises of human cloning
should not be dismissed and deserve an unbiased evaluation. While the potential of birth
defects and long-term health complications currently remains high, the author insists that
human cloning is inevitable and thus laws and safeguards must be set in place to protect
children born through the procedure. Appel contends that research and efforts for human
cloning should not be stopped, but must proceed with caution.
As you read, consider the following questions:
1. Why does Appel question President Barack Obama's position on human cloning?
2. How does the author view cloning children for organ donation?
3. What is Appel's opinion of parents cloning a child who has died?
In his remarks lifting the ban on the federal funding of embryonic stem cell research [in March
2009], President [Barack] Obama took pains to distinguish research cloning from reproductive
cloning. According to the President, "the use of cloning for human reproduction" is "dangerous,
profoundly wrong, and has no place in our society, or any society," and he promised to ensure
that "our government never opens the door" to such a practice. What the President did not do
was to explain precisely why he opposes reproductive cloning. Is his opposition solely based
upon the health risks that cloning techniques, such as somatic cell nuclear transfer, may impose
upon children born as a result of this novel technology? Or does he believe that human
reproductive cloning ought to be prohibited even if it could someday be rendered as safe—or
safer—than other forms of procreation? To some who oppose reproductive cloning, as polls
consistently suggest that a majority of Americans still do, these questions may seem purely
academic: As long as our society adopts the right policy, one might argue, why concern
ourselves with whether we are doing so for the wrong reasons or even for conflicting reasons?
The reality of the legislative debates preceding state cloning bans—from California's 1997
prohibition to the statute enacted [in April 2009] in Montana—is that much antagonism to
reproductive cloning appears to reflect an inchoate, emotional and often illogical repugnance
to the practice on the part of lawmakers, rather than well-reasoned and well-articulated
opposition. What is actually needed is an unbiased assessment of both the perils and promises
of cloning humans.
Most evidence suggests [that] reproductive human cloning, at the present time, would pose
serious dangers to any children so produced. The frequency of birth defects and long-term
health complications in cloned animals remains exceedingly high. These genetic disorders likely
result from programming errors due to what biologists call "imprinting," and arise when the
double sets of maternally- or paternally-derived genes in the embryo "speak" simultaneously.
While scientists are currently working on reprogramming techniques, which would prevent
these errors, the feasibility of such efforts remains largely uncertain. What is far clearer is that,
if society's only objection to reproductive cloning is the danger that the technology poses to the
offspring, then research to render human cloning safe should be pursued vigorously.
The most obvious benefit of reproductive cloning—if it could be rendered safe—would be as a
source of transplantable tissues and organs. I certainly do not mean to suggest that cloned
children would have any fewer human rights or should be treated any differently than noncloned children. Quite the contrary: Much as children conceived in "test tubes" are morally and
legally indistinguishable from children conceived in utero, any moral approach to reproductive
cloning would ensure that clones were treated with the same respect and dignity as any other
identical twins. However, parents frequently decide to produce additional offspring in order to
provide matching bone-marrow donors for their critically-ill children. Pediatric kidney donations
between living siblings takes place in many nations. For a family with a dying child, the prospect
of using cloning to create a potential donor with a set of perfectly-matched genes—and
ultimately, two healthy, lovable children—might be a godsend. The ethics surrounding such
procedures are highly complex. Nobody should believe otherwise. However, one should never
mistake the complexity of making a decision for its underlying morality. Certainly, there is a
wide difference between believing that the possibilities of human cloning should be
approached with wisdom and considerable caution, as do I, and deciding a priori that such
potentially therapeutic opportunities should be dismissed out of hand. I cannot imagine that
President Obama's remarks were intended to mean that, if reproductive cloning could be
rendered safe for both mother and baby, and if it could save the life of a desperate sibling, it
would still be profoundly wrong.
Only a Matter of Time
Individuals may wish to clone children for many additional reasons: some that strike
mainstream society as highly reasonable, others that strike us as rather peculiar. Infertile
couples might use the technology to produce children with some of their own DNA. A family
who has lost a child in an accident might find some solace in cloning their lost son or daughter;
the second kid would, of course, be a distinct human being from the first, with its own identity,
but the sense of continuity experienced by the mourning parents might provide comfort
nonetheless. The Raëlian Church has pursued cloning technology for religious purposes. As long
as a scientific consensus exists that cloning is a health threat to the offspring, these individuals
should not be permitted to risk bringing a severely disabled child into the world. I think most
reasonable people would agree that when the health of children is at stake, we should set the
safety bar high and take few unnecessary risks. However, if the time comes when scientists
conclude that reproductive cloning can be conducted without a threat to the health of the
offspring, then the burden will fall upon opponents to explain precisely why such a practice
threatens human dignity or societal welfare. The cry of "we don't like it"—which has been used
to justify opposing every aspect of human enlightenment from women's suffrage to gay
equality—will simply not be a sufficient answer.
What has been lost in the rush to condemn reproductive cloning wholesale has been any
meaningful effort to protect future children created through such a procedure. Whether the
practice is legal or not in the United States, it will likely be only a matter of time before some
determined scientist, somewhere in the world, creates a cloned human being. We need clear
laws to establish the relationship between the supplier of the cloned DNA and the resulting
progeny (e.g. Are they siblings? Parent and child? What are the clone's inheritance rights?) We
require guarantees that, if genetic defects do arise in such children as a result of cloning,
treatment for these conditions will be covered by private health insurance. And we need
careful regulation and funding to ensure that the procedure is rendered safe—if that can be
done—before cloned embryos are brought to term. In short, we need legislation to ensure that
any future cloned men and women will be treated with the dignity and humanity that they
deserve.
In an ideal world, human reproductive cloning would be safe, legal and rare. I say rare because
my guess is that the majority of people, myself included, would have little desire to raise cloned
offspring. After all, it is now possible to clone pets—but few of us would choose to spend a
spare $150,000 on such a venture. Yet thirty-eight years after James Watson's seminal essay,
"Moving Toward the Clonal Man," called for increased public debate on this promising and
perplexing subject, I don't believe that we should be so quick to greet cloning technology with a
permanent injunction. Instead, what human reproductive cloning requires at the moment is a
yellow light, telling us to proceed with extreme caution, until we know with confidence
whether the technology can ever be used to produce healthy babies.
The Ethics of Cloning: An Overview
Aaron D. Levine, Cloning: A Beginner's Guide. Oxford, U.K.: OneWorld, 2007. Copyright © Aaron
D. Levine 2007. Reproduced by permission.
An assistant professor in the School of Public Policy at Georgia Tech, Aaron D. Levine writes
about the ways in which ethics debates influence ongoing research in emerging biotechnology
fields. Specifically, he has assessed the impact of government policies on embryonic stem cell
research worldwide. Levine is the author of Cloning: A Beginner's Guide and editor of States and
Stem Cells: The Policy and Economic Implications of State-Funded Stem Cell Research.
The science of cloning will almost inevitably shape human existence as we know it from this
point forward. With cloning for food and therapeutic purposes being pursued with some level
of success and the cloning of humans looming on the horizon, it is important that individuals
participate in informed debate about the ethical implications of this technology.
Comprehending the science of cloning is essential to understanding how cloning will shape the
future, and this understanding will aid everyone in weighing the potential costs and benefits of
this groundbreaking technology.
Cloning technology was invented during the twentieth century and now is poised to help define
the twenty-first. Almost everyone has heard of Dolly, the cloned sheep born in 1996 but what
about the rapid progress made since then? Scientists now count horses, cows, cats, and dogs
among the many animals they can clone. This progress raises a host of questions. Are you
comfortable drinking milk or eating meat from a cloned cow? Should we clone extinct or
endangered species? Will the April 2005 birth of Snuppy, the world's first cloned dog, usher in a
new era of cloned pets? Should we clone embryos to generate embryonic stem cells and help
develop medical therapies? And perhaps the most important question of all: when, if ever, will
this progress lead to the first cloned human?
Creating an Informed Debate
Although scientists are nearly unified in their opposition to cloning humans for reproductive
purposes, on-going research toward other goals makes this likely, if not inevitable. For the most
part, this research is driven by the hope that cloning technology will have significant health
benefits, perhaps leading to transplantation therapies that use embryonic stem cells specifically
tailored to individual patients. Of course, if a cloned human is ever born, the desire for fame
will almost certainly play a role. Looking back to the media frenzy surrounding the birth of the
first test tube baby in 1978 or the clamor surrounding the birth of Dolly, it is not hard to
imagine the furor that a cloned human baby would generate.
By and large, cloning is not what you see in the movies.
As modern biotechnology is increasingly applied to humans, it raises important questions for
society to address. Should we, perhaps in the relatively near future, allow infertile couples or
single mothers to use cloning technology to try to produce a child? Should we, in the longer
term, permit parents to use cloning technology not just to have children, but to have children
with specific genetic modifications or enhancements? Debates on cloning technology and its
implications are, all too often, hijacked by advocates or opponents who skew the science to fit a
particular view. Although the details of cloning research are complex, the general technique is
not particularly difficult to understand. And understanding this general technique and its
consequences is more than enough to participate fully in these important debates and to see
through the many myths clouding discussions of cloning.
The Science of Cloning
Cloning is, at its most basic level, reproduction without sex. "Sex" does not refer to the act of
intercourse but to sexual reproduction—the joining of genetic material from two parents into
an embryo that may, if development goes well, give rise to a new adult organism. All humans
alive today were born through sexual reproduction; a single sperm from the male joined with
an egg from the female, creating an embryo with half its genetic material derived from each
parent. This mixing of genetic material introduces an element of chance into reproduction,
ensuring that children differ genetically from their parents. In cloning, offspring are genetically
identical to their single parent. Such offspring are the products of "asexual" reproduction.
Cloning, rather than relying on the merging of egg and sperm, uses the genetic material or DNA
from a single cell. This cell is joined to an egg from which the DNA has been removed. Next, this
construct is coaxed to develop as if it were a newly fertilized egg. If development proceeds
normally, the resulting organism will be genetically identical to the single donor. In this case,
reproduction no longer generates new combinations of genetic material but faithfully
duplicates previously existing ones.
Although mammals do not normally reproduce asexually, nature does provide a close analogy:
identical twins. Roughly one out of every 250 human births results in identical twins—siblings
that are genetically identical. Because a cloned child would be genetically identical to its DNA
donor, it can be helpful to imagine cloning as a form of delayed twinning. If cloning technology
were perfected and applied to humans, the birth of a cloned human would not be altogether
unlike the birth of identical twins but instead of a few minutes separating the two births, there
could be many years.
Scientists speculate that a cloned human and his or her parent would typically be less similar
than identical twins. This is because the environment plays an important role in development.
Identical twins usually share much of the same environment, while a cloned human and his or
her genetic parent often would not. Identical twins develop in the same uterus and usually
grow up in the same household. In contrast, a cloned human would probably be carried in a
different womb and grow up in a different household from its genetic parent. The cloned child
would also be born into a world that had changed significantly. The importance of
environmental influences has led bioethicists who have considered the possibility of human
cloning to focus on its unpredictability. It is not clear that a child cloned from Mozart or
Pavarotti would grow up to perform or even appreciate music.
Human vs. Animal Cloning
Humans have not been cloned and few plausible reasons exist to clone humans for
reproductive purposes. Some have suggested that cloning might provide a means for infertile
parents to have a genetically related child. However, fertility research seems likely to lead to
other, more effective and less controversial, approaches to treat the few couples for whom this
last resort might be necessary. Others have suggested cloning may be justified when a child
dies young; believing parents would deserve a chance to bring their lost loved one back to life.
But many think this would lead to disappointment all round. Due to environmental influences,
the cloned child would not be the same as the deceased child he or she was ostensibly
replacing. Furthermore, the new child, forever competing against an idealized memory, might
face unreasonable expectations. In the end, neither parents nor child would prosper.
Cloning matters because it is on the verge of affecting daily life around the world and its
importance will only grow with time.
Because human cloning seems remote and is generally undesired, cloning science today focuses
primarily on animal research. In animals bred for human use, such as cows, pigs, and horses,
the advantages of asexual reproduction are significant. The element of chance central to sexual
reproduction frustrates animal breeders and livestock producers. When mating a prize-winning
stud to promising mare, horse breeders aren't excited by the chance that the resulting foal will
randomly receive the parents' worst genes: they want to propagate the genes that turned the
stud into a champion, in the hope of producing future winners. Cloning, by allowing breeders to
produce genetic replicas of valuable animals, makes this process more efficient. For horse
racing, this efficiency comes at a steep price, as cloned horses are currently forbidden from
participating in officially sanctioned races. These sorts of restrictions don't apply to pigs or
cows, which are bred to produce meat and milk for consumers, rather than for competition.
Not surprisingly, livestock breeders, particularly in the United States, have shown interest in
using this technology to make their operations more productive and more profitable.
Hollywood Cloning Myths
By and large, cloning is not what you see in the movies. It is not photocopying; or at best it is
like using a slow and blurry photocopier—so slow, that by the time the copy is made, the
original has changed. If you cloned your dog today, there wouldn't be an exact replica running
around and barking tomorrow, as suggested in the Arnold Schwarzenegger hit The Sixth Day.
Rather, you would create an embryo that could potentially be transferred into the womb of a
surrogate mother. Nine weeks later, if all went well, a puppy would be born. This puppy would
be genetically identical to your dog but, obviously, much younger. It might look like its parent
had looked as a puppy but it would experience a different environment and, perhaps, mature
differently.
Movies such as Multiplicity, in which an overworked contractor clones himself to help cope with
his busy life, ignore the time delay essential to cloning. In this case, the movie's premise, while
entertaining, is absolutely wrong. The clones, rather than helping out at work and around the
house, would be a burden. They would be infants, not adults as portrayed in the movie, and like
any human infants would need nearly constant attention. As any parent can tell you, adding a
baby (or several) to your family is not a good strategy for gaining extra time.
Nor does cloning bring back the long-dead. Cloning technology, at least at its current efficiency
levels, requires a significant amount of biological material. For living animals, it is simple to take
a sample and preserve this material: Dolly, for instance, was cloned from frozen cells. However,
finding enough genetic material presents a significant hurdle to cloning long-extinct species. For
now, the cloning of dinosaurs, as seen in Jurassic Park and its successors, is no more than a
scientific pipe dream. That said, scientists have made progress in cloning endangered species
and some believe cloning may offer a promising conservation strategy. Attempts to clone
recently extinct animals, such as the Tasmanian tiger, where preserved biological material may
still exist, remain a possibility.
As we shall see, cloning is not easy. When Dolly was born, she was the only success in 277
attempts. Success rates have improved but the procedure remains inefficient. Many cloned
embryos fail to develop, and when development does start, a variety of abnormalities are seen.
Even in the most efficient operations, only a minority of the original cloned embryos develop to
term and go on to lead healthy lives. At the moment, this inefficiency limits the usefulness of
animal cloning for commercial purposes. It also raises the ire of animal rights activists, who
complain that the technology produces deformed animals. Obviously, these inefficiencies
would need to be overcome before scientists could even begin to consider cloning humans for
reproductive purposes.
Cloned Animals for Food
Cloning matters because it is on the verge of affecting daily life around the world and its
importance will only grow with time. Animal cloning will revolutionize food production in the
coming years and may, by turning animals into biological factories, revolutionize
pharmaceutical production as well. Moving from animals to humans, cloning technology may, if
some expectations prove true, radically alter medicine, leading the way to an era of
personalized transplant therapies. Finally, in the longer term, it opens the door to the cloning
(and potential genetic engineering) of humans, perhaps changing the very essence of what it
means to be a human being.
A growing scientific consensus suggests that milk and meat from cloned animals, or at least
from their progeny, are safe for human consumption. In December 2006, the U.S. Food and
Drug Administration announced preliminary plans to allow products from cloned livestock into
the food supply. If finalized, such a ruling could have dramatic effects. Scientists can clone
several important farm animals, including cows and pigs, but only a small number of cloned
animals—none destined for consumption—live on American farms today. One industry insider
has estimated that within twenty months of a ruling allowing products from cloned animals into
the food supply, American farms would be covered with hundreds of thousands of clones. This
could occur despite widespread consumer discomfort with the very idea of eating products
from cloned animals.
Thus far, the United Kingdom and most other European countries have shown more caution
regarding the introduction of cloned animal products into the food supply. If, as appears likely,
the United States approves these products first, it could contribute to continued trade wars.
Although cloning does not necessarily include genetic modification, some cloned products will
almost certainly also be genetically modified. Thus, trade in cloned products could get tangled
in the on-going debate on the import of genetically modified organisms; a number of countries
have limited their imports of agricultural products from nations where genetic modification is
prevalent.
When Dolly was cloned in 1996, the research was primarily funded by a biotechnology firm that
aimed to revolutionize the way drugs are produced.... The basic idea is to create, through
cloning, genetically modified sheep or cows that produce therapeutic compounds, such as
insulin or growth hormone, in their milk. Pharmaceutical companies could isolate these
valuable compounds from the milk for a fraction of the cost of traditional manufacturing
methods. The milk would not be intended for human consumption and would probably be
discarded after the therapeutics had been isolated. This technique, known as "pharming,"
offers potential economic benefits for drug companies and has taken off since Dolly's birth.
Numerous cows have been bred to produce therapeutics in their milk and some scientists are
exploring the possibility of harvesting drugs from other body fluids, including urine. Pharming
raises a number of concerns, including the risk of drug-producing animals accidentally entering
the food supply. Although the risks may be remote, even those of us unfazed by drinking milk
from a cloned cow wouldn't be pleased to find out the milk was significantly enriched with a
prescription medicine.
The Future of Cloning
While cloned animals that produce therapeutic compounds already exist, the creation of cloned
human embryos to facilitate medical therapies remains in the future and raises serious ethical
questions. Many scientists are optimistic that cloning will, one day, regularly be used to create
stem cells genetically matched to specific patients. These cells could, potentially, help treat a
range of debilitating conditions, such as type 1 diabetes and Parkinson's disease. Because the
cells would be genetically matched to the individual patient, they might avoid the immune
rejection problems that complicate transplant therapies today. This potential therapeutic
technique is controversial, however, because deriving these patient-matched stem cells, using
currently envisioned approaches, would require the creation of a cloned human embryo. At five
days of age, the stem cells would be isolated from the embryo and the developmental process
halted. Dramatic advances toward this vision of regenerative medicine were reported by a
group of researchers based in South Korea, but in late 2005 the veracity of this work was called
into question: today, it is clear that most, if not all, these advances were fraudulent. Despite
this set-back, many scientists believe the vision remains promising and "therapeutic cloning" is
being pursued by scientists around the world.
Cloning also matters because, given the field's current trajectory, it is part of our shared future.
From the food supply to the medicine cabinet, cloning technology is poised to change the way
we live. But these changes are controversial. Each of us can and should participate in the
debates that will shape the role cloning plays in the future. Before you say "yuck" to drinking
milk from cloned cows or rush off to save your dog's DNA in preparation for eventual cloning,
take the time to learn a bit about the science. Although cloning is fairly simple, misinformation
is prevalent. Understanding the science behind cloning will help make these debates more
meaningful and their outcomes more satisfactory for everyone.
Introduction to Cloning: Opposing Viewpoints
"The ability to routinely write the 'software of life' will usher in a new era in science, and with it,
new products and applications such as advanced biofuels, clean water technology, food
products, and new vaccines and medicines." —J. Craig Venter, American pioneer in genomic
research
On May 20, 2010, an article appeared in the online version of the prestigious Science magazine
announcing the creation of man-made life. Led by J. Craig Venter, a team of researchers
reported "the design, synthesis, and assembly" of a modified version of a bacteria that typically
lives in the lungs of cattle and goats. On the same day that Venter's article was published,
President Barack Obama requested that the newly formed Presidential Commission for the
Study of Bioethical Issues (PCSBI) look at the ethical implications of "synthetic biology," the field
of science encompassing Venter's bacterial creation. A week later, a US congressional
committee held a hearing on the same topic. The significant interest in synthetic biology lies in
its extraordinary potential to benefit mankind. However, like cloning, synthetic biology has
many ethical concerns. What is synthetic biology? The website SyntheticBiology.org, created by
students and faculty members at Harvard University and the Massachusetts Institute of
Technology, asserts that synthetic biology refers to both:


the design and fabrication of biological components and systems that do not already
exist in the natural world, and
the redesign and fabrication of existing biological systems.
English scientists Andrew Balmer and Paul Martin offer a simpler explanation for synthetic
biology. According to the scientists, synthetic biology is "the deliberate design of biological
systems and living organisms using engineering principles."1 Still, another explanation of
synthetic biology, provided by the PCSBI, contrasts synthetic biology with standard biology.
According to the PCSBI, "whereas standard biology treats the structure and chemistry of living
things as natural phenomena to be understood and explained, synthetic biology treats
biochemical processes, molecules, and structures as raw materials and tools to be used in novel
and potentially useful ways, often quite independent of their natural roles."2
Synthetic biology has been made possible through advances in scientists' knowledge about
genes and by the availability of advanced technologies that allow scientists to manipulate genes
in the laboratory. Each year since James Watson and Francis Crick described the structure of
DNA in 1953, scientists' knowledge of genes has steadily risen. From the early knowledge that
genes are composed of varying sequences of four different molecules of DNA—adenosine (A),
thymine (T), cytosine (C), and guanine (G)—scientists have been able to elucidate the entire
genetic sequence of several living organisms, including humans. Today, scientists use gene
synthesizers to either replicate gene sequences found in nature or to create novel genes by
stitching As, Ts, Cs, and Gs together in ways not found in nature.
To make their synthetic bacteria, Venter and his team replicated genes from a bacterium called
Mycoplasma mycoides, which causes lung infections in cattle and goats. After tweaking some of
the genes to create new sequences, they then transplanted them into an enucleated cell (a cell
with its nucleus removed) of a closely related bacterium. An article in the Economist
highlighting the importance of this achievement said that Venter had "created a living creature
with no ancestor" and a "Rubicon had been crossed." According to the Economist, "synthetic
biology makes it possible to conceive of a world in which new bacteria (and eventually, new
animals and plants) are designed on a computer and then grown to order." This ability says the
Economist, "would prove mankind's mastery over nature in a way more profound than even the
detonation of the first atomic bomb."3
Venter's work and other applications of synthetic biology so far have involved the creation of
novel microorganisms, particularly medicine-producing and fuel-producing microbes. For
instance, synthetic biology is being used to produce the antimalarial drug artemisinin.
According to the World Health Organization (WHO), artemisinin-based combination therapy is
the best treatment available for malaria, a disease that kills millions of people in the developing
world every year. Artemisinin is produced naturally by the plant Artemisia annua. However, the
plant is hard to grow and artemisinin yields are low. These factors led synthetic biologist Jay
Keasling from the University of California, Berkeley, to focus his research on the creation of
microbes that can quickly and inexpensively produce bulk quantities of artemisinin. In a 2009
article about Keasling's artemisinin project in the New Yorker magazine, Michael Specter noted
that "Keasling realized that the tools of synthetic biology, if properly deployed, could dispense
with nature entirely, providing an abundant new source of artemisinin." Keasling also told
Specter that artemisinin shouldn't be the end of the story, "we ought to be able to make any
compound produced by a plant inside a microbe ... you need this drug: O.K., we pull this piece,
this part, and this one off the shelf. You put them into a microbe, and two weeks later out
comes your product."4
At the congressional hearings on synthetic biology, Keasling also described another important
application of synthetic biology with which he is involved. Keasling is the chief executive officer
and vice president of the Fuels Synthesis Division at the Joint BioEnergy Institute (JBEI) in
Emeryville, California. Researchers at the JBEI are exploring the potential of synthetic biology to
produce plant-based fuels, i.e., biofuels, which can replace gasoline and other transportation
fuels. The JBEI researchers have been developing procedures to produce these biofuels from
Keasling's novel artemisinin-producing microbe. Keasling and his team at the JBEI hope to
produce enough biofuels to make a significant dent in the United States' reliance on foreign
sources of oil.
The production of medicines and biofuels using engineered microorganisms may not seem
frightening. However, many people looking beyond these initial applications see synthetic
biology as deeply troubling research. In its report, the PCSBI noted that synthetic biology's
critics "express concerns about 'playing God,' threatening biodiversity and the organization and
natural history of species, demeaning and disrespecting the meaning of life, and threatening
long-standing concepts of nature."5
In 2008 the Hastings Center, a nonpartisan, nonprofit bioethics research institute, began a
project to examine the ethical concerns about synthetic biology. Gregory E. Kaebnick, a
research scholar at the center and one of the lead researchers on the project, testified at the
US congressional hearings on synthetic biology. According to Kaebnick, synthetic biology raises
two different types of concerns. First, it raises concerns about potential risks and consequences
to the natural world of creating new life-forms. Second, it raises intrinsic concerns dealing with
whether or not the creation of synthetic organisms is a good or a bad thing in and of itself,
aside from the consequences. These intrinsic concerns, according to Kaebnick, are the same
concerns many people have about reproductive cloning. They feel it is wrong, regardless of the
benefits.
Many of the ethical concerns about synthetic biology were expressed in the days after Venter's
May 20, 2010, Science article was published. Several media reports from the United States and
England contained quotes from ethics professor Julian Savulescu, from the University of Oxford,
and David King, director of the organization Human Genetics Alert. Savulescu said, "Venter is
creaking open the most profound door in humanity's history, potentially peeking into its
destiny. He is not merely copying life artificially or modifying it by genetic engineering. He is
going towards the role of God. Creating artificial life that could never have existed." David King
said, "What is really dangerous is these scientists' ambitions for total and unrestrained control
over nature, which many people describe as 'playing God.'"6 Christian commentator Chuck
Colson elaborated on King's thoughts by adding, "even if our intentions are pure and our
standards are rigorous, we humans are neither as smart nor as competent as our God-like
pretensions make us feel. Fallen, finite man often finds ways to turn yesterday's nightmare
scenario into tomorrow's headline. In a world where bridges collapse, oil rigs blow up, and cars
suddenly accelerate, God-like control isn't only hubris, it's pure fantasy. The only real way to
avoid the unthinkable is not to try and play God in the first place. But that would require the
kind of humility that Venter and company reject out-of-hand."7
In an interview with the BBC on the day his article was published, Venter responded to critics'
claims that he was playing God. According to Venter, the term "playing God" comes up every
time there is a new medical or scientific breakthrough associated with biology. But says Venter,
"'playing God' has been a goal of humanity from the earlier stages to try to control nature—
that's how we got domesticated animals. This is the next stage in our understanding. It is a baby
step in our understanding of how life fundamentally works and maybe how we can get some
new handles on trying to control these microbial systems to benefit humanity." 8
A year later, Venter was still getting asked whether he was "playing God." In a story for 60
Minutes in June 2011, Steve Kroft asked Venter whether he was acting with hubris and was
irresponsible as some had charged. Venter responded, "I can tell you what we're doing is safe.
There's no way that I can guarantee that other people that use these tools will do intelligent,
safe experiments with it. But I think the chance of evil happening with this and somebody even
trying to do deliberate evil would be pretty hard." Kroft then asked Venter if he was "playing
God," and Venter responded, "We're not playing anything. We're understanding the rules of
life."9
Synthetic biology has not elicited the same kind of response that cloning has from the religious
community. Unlike cloning, to which the religious community is generally vehemently opposed,
synthetic biology has some support. For instance, theologian Nancey Murphy from the Fuller
Theological Seminary in Pasadena, California, was quoted in the Wall Street Journal as saying
that synthetic biology "is very much within divine mandate."10 Furthermore, an article in the
national Catholic weekly magazine America attributed the Vatican newspaper L'Osservatore
Romano as saying, "Venter's creation has produced 'an interesting result,' which could have
many applications, but the new technology 'must have rules just like everything that lies at the
heart of life.'" The America article also quoted Cardinal Angelo Bagnasco, president of the
Italian bishops' conference, as saying that the development of the first synthetic cell was a
"further sign of human intelligence, which is a great gift of God." However, with intelligence
comes responsibility, he said. Therefore, any intellectual or scientific advancement "must
always measure up to an ethical standard."11
As synthetic biology expands and scientists' achievements are registered, the ethical concerns
surrounding this field will likely increase as well. However, it is questionable whether ethical
concerns of synthetic biology will achieve the same level that cloning has, unless scientists try
to recreate human life. Biotechnological advances that can be seen as meddling in the creation
of human life generally elicit the most passionate debates. In Opposing Viewpoints: Cloning,
scientists, theologians, ethicists, legal scholars, and many others contribute their thoughts on
the controversial issue of cloning.
Cloning
The moral issues posed by human cloning are profound and have implications for today and for
future generations. Today's overwhelming and bipartisan House action to prohibit human
cloning is a strong ethical statement, which I commend. We must advance the promise and
cause of science, but must do so in a way that honors and respects life.
—President George W. Bush, July 31, 2001
We must not say to millions of sick or injured human beings "go ahead and die and stay
paralyzed because we believe ... a clump of cells is more important than you are."
—Representative Jerrold Nadler (D-NY), July 2001
The Human Genome Project defines three distinct types of cloning. The first is the use of highly
specialized deoxyribonucleic acid (DNA) technology to produce multiple, exact copies of a single
gene or other segment of DNA to obtain sufficient material to examine for research purposes.
This process produces cloned collections of DNA known as clone libraries. The second kind of
cloning involves the natural process of cell division to create identical copies of the entire cell.
These copies are called a cell line. The third type of cloning, reproductive cloning, is the one
that has received the most attention in the mass media. This is the process that generates
complete, genetically identical organisms such as Dolly, the famous Scottish sheep cloned in
1996 and named after the entertainer Dolly Parton (1946-).
Cloning may also be described by the technology used to perform it. For example, the term
recombinant DNA technology describes the technology and mechanism of DNA cloning. Also
known as molecular cloning, or gene cloning, it involves the transfer of a specific DNA fragment
of interest to researchers from one organism to a self-replicating genetic element of another
species such as a bacterial plasmid. (See Figure 8.1: Bacterial plasmid.) The DNA under study
may then be reproduced in a host cell. This technology has been in use since the 1970s and is a
standard practice in molecular biology laboratories.
Just as GenBank is an online public repository of the human genome sequence, the Clone
Registry database is a sort of "public library." Used by genome sequencing centers to record
which clones have been selected for sequencing, which sequencing efforts are currently under
way, and which are finished and represented by sequence entries in GenBank, the Clone
Registry may be freely accessed by scientists worldwide. To effectively coordinate all of this
information, a standardized system of naming clones is essential. The nomenclature used is
shown in Figure 8.3: Standardized clone names.
Cloning Genes
Molecular cloning is performed to enable researchers to have many copies of genetic material
available in the laboratory for the purpose of experimentation. Cloned genes allow researchers
to examine encoded proteins and are used to sequence DNA. Gene cloning also allows
researchers to isolate and experiment on the genes of an organism. This is particularly
important in terms of human research; in instances where direct experimentation on humans
might be dangerous or unethical, experimentation on cloned genes is often practical and
feasible.
Cloned genes are also used to produce pharmaceutical drugs, insulin (a pancreatic hormone
that regulates blood glucose levels), clotting factors, human growth hormone, and industrial
enzymes. Before the widespread use of molecular cloning, these proteins were difficult and
expensive to manufacture. For example, before the development of recombinant DNA
technology, insulin used by people with diabetes was extracted and purified from cow and pig
pancreases. Because the amino acid sequences of insulin from cows and pigs are slightly
different from those in human insulin, some patients experienced adverse immune reactions to
the nonhuman "foreign insulin." The recombinant human version of insulin is identical to
human insulin so it does not produce an immune reaction.
Figure 8.4: Cloning DNA in plasmids shows how a gene is cloned. First, a DNA fragment
containing the gene being studied is isolated from chromosomal DNA using restriction enzymes.
It is joined with a plasmid (a small ring of DNA found in many bacteria that can carry foreign
DNA) that has been cut with the same restriction enzymes. When the fragment of
chromosomal DNA is joined with its cloning vector (cloning vectors, such as plasmids and yeast
artificial chromosomes, introduce foreign DNA into host cells), it is called a recombinant DNA
molecule. Once it has entered into the host cells, the recombinant DNA can be reproduced
along with the host cell DNA.
Another molecular cloning technique that is simpler and less expensive than the recombinant
cloning method is the polymerase chain reaction (PCR). PCR has also been dubbed "molecular
photocopying" because it amplifies DNA without the use of a plasmid. Figure 6.5: Polymerase
chain reaction (PCR) shows how PCR is used to generate a virtually unlimited number of copies
of a piece of DNA.
A collection of clones of chromosomal and vector DNA (a small piece of DNA containing
regulatory and coding sequences of interest) is called a library. Because there is no apparent
order signifying the original positions of the cloned pieces on the uncut chromosome, to show
that two particular clones are next to each other in the genome, libraries of clones containing
partly overlapping regions are constructed. Figure 8.5 displays how, by dividing the inserts into
smaller fragments and determining which clones share the same DNA sequences, clone libraries
are constructed.
Reproductive Cloning
Another way to describe and classify cloning is by its purpose. Organismal or reproductive
cloning is a technology used to produce a genetically identical organism—an animal with the
same nuclear DNA as an existing, or even an extinct, animal.
The reproductive cloning technology used to create animals is called somatic cell nuclear
transfer (SCNT). In SCNT scientists transfer genetic material from the nucleus of a donor adult
cell to an enucleated egg (an egg from which the nucleus has been removed). This eliminates
the need for fertilization of an egg by a sperm. The reconstructed egg containing the DNA from
a donor cell is treated with chemicals or electric current to stimulate cell division. Once the
cloned embryo reaches a suitable stage, it is transferred to the uterus of a surrogate (female
host), where it continues to grow and develop until birth. Figure 8.6: Reproductive cloning
shows the entire SCNT process that culminates in the transfer of the embryo into the surrogate
mother and ultimately the birth of a cloned animal.
Organisms or animals generated using SCNT are not perfect or identical clones of the donor
organism or "parent" animal. The clone's nuclear DNA is identical to the donor's, but some of
the clone's genetic materials come from the mitochondria in the cytoplasm of the enucleated
egg. Mitochondria, the organelles that serve as energy sources for the cell, contain their own
short segments of DNA called mtDNA. Acquired mutations in the mtDNA contribute to
differences between clones and their donors and are believed to influence the aging process.
Dolly the Sheep Paves the Way for Other Cloned Animals
In 1952 scientists transferred a cell from a frog embryo into an unfertilized egg, which then
developed into a tadpole. This process became the prototype for cloning. Ever since, scientists
have been cloning animals. The first mammals were also cloned from embryonic cells in the
1980s. In 1997 cloning became headline news when, after more than 250 failed attempts, Ian
Wilmut (1944-) and his colleagues at the Roslin Institute in Edinburgh, Scotland, successfully
cloned a sheep, which they named Dolly. Dolly was the first mammal cloned from the cell of an
adult animal, and since then researchers have used cells from adult animals and various
modifications of nuclear transfer technology to clone a range of animals, including a gaur,
sheep, goats, cows, horses, mules, oxen, deer, mice, rats, pigs, cats, dogs, and rabbits.
To create Dolly, the Roslin Institute researchers transplanted a nucleus from a mammary gland
cell of a Finn Dorsett sheep into the enucleated egg of a Scottish blackface ewe and used
electricity to stimulate cell division. The newly formed cell divided and was placed in the uterus
of a blackface ewe to gestate. Born several months later, Dolly was a true clone—genetically
identical to the Finn Dorsett mammary cells and not to the blackface ewe, which served as her
surrogate mother. Her birth revolutionized the world's understanding of molecular biology,
ignited worldwide discussion about the morality of generating new life through cloning,
prompted legislation in dozens of countries, and launched an ongoing political debate in
Congress.
Dolly was the object of intense media and public fascination. She proved to be a basically
healthy clone and produced six lambs of her own through normal sexual means. Before her
death by lethal injection in February 2003, Dolly had been suffering from lung cancer and
arthritis. An autopsy (postmortem examination) of Dolly revealed that, other than her cancer
and arthritis, she was anatomically like other sheep.
In February 1997 Don Wolf and his colleagues at the Oregon Regional Primate Center in
Beaverton successfully cloned two rhesus monkeys using laboratory techniques that had
previously produced frogs, cows, and mice. It was the first time that researchers used a nuclear
transplant to generate monkeys. The monkeys were created using different donor blastocysts
(early-stage embryos), so they were not clones of one another—each monkey was a clone of
the original blastocyst that had developed from a fertilized egg. Neither of the cloned monkeys
survived past the embryonic stage.
An important distinction between the process that created Dolly and the one that produced the
monkeys was that unspecialized embryonic cells were used to create the monkeys, whereas a
specialized adult cell was used to create Dolly. The Oregon experiment was followed closely in
the scientific and lay communities because, in terms of evolutionary biology and genetics,
primates are closely related to humans.
In 2000 the Oregon researchers succeeded when one of four embryos created by splitting an
early-stage embryo and implanting the pieces into mother animals survived. The survivor was
named Tetra, from the Greek prefix for the number four. Researchers and the public speculated
that if monkeys could be cloned, it might become feasible to clone humans.
In May 2001 BresaGen Limited, an Australian biotechnology firm, announced the birth of that
country's first cloned pig. The pig was cloned from cells that had been frozen in liquid nitrogen
for more than two years, and the company used technology that was different from the process
used to clone Dolly the sheep. The most immediate benefit of this new technology was to
improve livestock—cloning enables breeders to take some animals with superior genetics and
rapidly produce more. Biomedical scientists were especially attentive to this research because
of its potential for xenotransplantation—the use of animal organs for transplantation into
humans. Pig organs genetically modified so that they are not rejected by the human immune
system could prove to be a boon to medical transplantation.
During that same year the first cat was cloned, and the following year rabbits were successfully
cloned. In January 2003 researchers at Texas A&M University reported that cloned pigs
behaved normally—as expected for a litter of pigs—but were not identical to the animals from
which they were cloned in terms of food preferences, temperament, and how they spent their
time. The researchers explained the variation as arising from the environment and epigenetic
(not involving DNA sequence change) factors, causing the DNA to line up differently in the
clones. Epigenetic activity is defined as any gene-regulating action that does not involve
changes to the DNA code and that persists through one or more generations, and it may explain
why abnormalities such as fetal death occur more frequently in cloned species.
In May 2003 a cloned mule—the first successful clone of any member of the horse family—was
born in Idaho. The clone was not just any mule, but the brother of the world's second fastest
racing mule. Named Idaho Gem, the cloned mule was created by researchers at the University
of Idaho and Utah State University. The researchers attributed their success to changes in the
culture medium they used to nurture the eggs and embryos.
In August 2003 scientists at the Laboratory of Reproductive Technology in Cremona, Italy, were
the first to clone a horse. Cesare Galli et al., the Italian scientists, describe their cloning
technique in "Pregnancy: A Cloned Horse Born to Its Dam Twin" (Nature, vol. 424, no. 6949,
August 7, 2003).
The mule was cloned from cells extracted from a mule fetus, whereas the cloned horse's DNA
came from her adult mother's skin cells. There were other differences as well. The University of
Idaho and Utah State University researchers harvested fertile eggs from mares, removed the
nucleus of each egg, and inserted DNA from cells of a mule fetus. The reconstructed eggs were
then surgically implanted into the wombs of female horses. In contrast, Galli et al. harvested
hundreds of eggs from mare carcasses, cultured the eggs, removed their DNA, and replaced it
with DNA taken from either adult male or female horse skin cells.
In May 2004 the first bull was cloned from a previously cloned bull in a process known as serial
somatic cell cloning or recloning. Before the bull, the only other successful recloning efforts
involved mice. Chikara Kubota, X. Cindy Tian, and Xiangzhong Yang, the successful research
team, describe their techniques in "Serial Bull Cloning by Somatic Cell Nuclear Transfer" (Nature
Biotechnology, vol. 22, no. 6, June 2004). Their effort was also cited in the Guinness Book of
World Records as the largest clone in the world.
At the close of 2004 a South Korean research team reported cloning macaque monkey
embryos, which would be used as a source of stem cells. Conservationists then focused
research efforts on cloning rare and endangered species. In April 2005 Texas A&M University
announced the first successfully cloned foal in the United States. That same month, Korean
scientists at Seoul National University cloned a dog they dubbed "Snuppy." In May 2005
Embrapa, a Brazilian agricultural research corporation, reported the creation of two cloned
calves from a Junquiera cow, which is an endangered species. In 2006 ferrets were cloned using
somatic cell nuclear transfer.
Cloning Endangered Species
Reproductive cloning technology may be used to repopulate endangered species such as the
African bongo antelope, the Sumatran tiger, and the giant panda, or animals that reproduce
poorly in zoos or are difficult to breed. In January 2001 scientists at Advanced Cell Technology
(ACT), a biotechnology company in Massachusetts, announced the birth of the first clone of an
endangered animal, a baby bull gaur (a large wild ox from India and Southeast Asia). The gaur
was cloned using the nuclei of frozen skin cells taken from an adult male gaur that had died
eight years earlier. The skin cell nuclei were joined with enucleated cow eggs, one of which was
implanted into a surrogate cow. The cloned gaur died from an infection within days of its birth.
That same year scientists in Italy successfully cloned an endangered wild sheep. Cloning an
endangered animal is different from cloning a more common animal because cloned animals
need surrogate mothers to be carried to term. Furthermore, the transfer of embryos is risky,
and researchers are reluctant to put an endangered animal through the rigors of surrogate
motherhood, so they opt to use nonendangered domesticated animals whenever possible.
Cloning extinct animals is even more challenging than cloning living animals because the egg
and the surrogate mother used to create and harbor the cloned embryo are not the same
species as the clone. Furthermore, for most already extinct animal species such as the woolly
mammoth or the dinosaur, there is insufficient intact cellular and genetic material from which
to generate clones. In the future, carefully preserving intact cellular material of imperiled
species may allow for their preservation and propagation.
In April 2003 ACT announced the birth of a healthy clone of a Javan banteng, an endangered
cattlelike animal native to Asian jungles. The clone was created from a single skin cell, taken
from another banteng before it died in 1980, which had remained frozen until it was used to
create the clone. The banteng embryo gestated in a standard beef cow in Iowa.
Born on April 1, 2003, the cloned banteng developed normally, growing its characteristic horns
and reaching an adult weight of about 1,800 pounds (816 kg). As of 2008, he was in good health
at the San Diego Zoo. Hunting and habitat destruction reduced the number of banteng, which
once lived in large numbers in the bamboo forests of Asia, by more than 75% from 1983 to
2003. In "Ecological-Economic Models of Sustainable Harvest for an Endangered but Exotic
Megaherbivore in Northern Australia" (Natural Resource Modeling, vol. 20, no. 1, March 2007),
Corey J. A. Bradshaw and Barry W. Brook report that in 2007 a population of between 8,000
and 10,000 banteng lived on an isolated peninsula in northern Australia.
In August 2005 the Audubon Nature Institute in New Orleans, Louisiana, reported that two
unrelated endangered African wildcat clones had given birth to eight babies. These births
confirmed that clones of wild animals can breed naturally, which is vitally important for
protecting endangered animals on the brink of extinction.
Reproductive Human Cloning
In December 2002 a religious sect known as the Raelians made news when their private
biotechnology firm, Clonaid, announced that they had successfully delivered the world's first
cloned baby. The announcement, which could not be independently verified or substantiated,
generated unprecedented media coverage and was condemned in the scientific and lay
communities. At least some of the media frenzy resulted from the beliefs of the Raelians—
namely, the sect contends that humans were created by extraterrestrial beings. As of 2008,
Clonaid boasted about the creation of five cloned babies, but it had not yet offered any proof of
their existence.
Clonaid's announcement brought attention to the fact that several laboratories around the
world had embarked on clandestine efforts to clone a human embryo. For example, in 2002
Panayiotis Zavos (1944-), a U.S. fertility specialist, claimed to be collaborating with about two
dozen international researchers to produce human clones. Another doctor focusing on fertility
issues, Severino Antinori (1945-), attracted media attention when he maintained that hundreds
of infertile couples in Italy and thousands in the United States had already enrolled in his
human cloning initiative. As of 2008, neither these researchers nor anyone else had offered
proof of successful reproductive human cloning.
Therapeutic Cloning
Therapeutic cloning (also called embryo cloning) is the creation of embryos for use in
biomedical research. The objective of therapeutic cloning is not to create clones but to obtain
stem cells. Stem cells are "master cells" capable of differentiating into multiple other cell types.
This potential is important to biomedical researchers because stem cells may be used to
generate any type of specialized cell, such as nerve, muscle, blood, or brain cells. Many
scientists believe that stem cells can not only provide a ready supply of replacement tissue but
also may hold the key to developing more effective treatments for common disorders such as
heart disease and cancer as well as degenerative diseases such as Alzheimer's and Parkinson's.
Researchers believe that in the future it may be possible to induce stem cells to grow into
complete organs.
Advocates of therapeutic cloning point to other treatment benefits such as using stem cells to
generate bone marrow for transplants. They contend that scientists could use therapeutic
cloning to manufacture perfectly matched bone marrow using the patient's own skin or other
cells. This would eliminate the problem of rejection of foreign tissue associated with bone
marrow transplant and other organ transplantation. Stem cells also have the potential to repair
and restore damaged heart and nerve tissue. Furthermore, there is mounting evidence to
suggest that stem cells from cloned embryos have greater potential as medical treatments than
stem cells harvested from unused embryos at fertility clinics, which are created by in vitro
fertilization and remain, even with the growing use of adult stem cells (which are generally
limited to differentiating into different cell types of their tissue of origin), the major source of
stem cells for research. Figure 8.7: Heart muscle repair with adult stem cells shows how adult
stem cells may be used to repair damaged heart muscle. These prospective benefits are among
the most compelling arguments in favor of cloning to obtain embryonic stem cells.
Stem cells used in research are harvested from the blastocyst after it has divided for five days,
during the earliest stage of embryonic development. Many people regard human embryos as
human beings or at least as potential human beings and consider their destruction, or even
using techniques to obtain stem cells that might imperil their future viability, as immoral or
unethical.
Jose B. Cibelli et al. of the ACT report in "Somatic Cell Nuclear Transfer in Humans: Pronuclear
and Early Embryonic Development" (e-biomed: The Journal of Regenerative Medicine, vol. 2,
2001) that they created a cloned human embryo, and, unlike groups that had claimed to have
done this before, they published their results. In the press release "Advanced Cell Technology,
Inc. (ACT) Today Announced Publication of Its Research on Human Somatic Cell Nuclear
Transfer and Parthenogenesis" (November 25, 2001, http://www.advancedcell.com/pressreleases/), the ACT boasts that this achievement offers "the first proof that reprogrammed
human cells can supply tissue" and is a vital first step toward the objective of therapeutic
cloning—using cloned embryos to harvest embryonic stem cells able to grow into replacement
tissue perfectly matched to individual patients. To clone the human embryos, Cibelli et al.
collected women's eggs and removed the genetic material from the eggs with a thin needle. A
skin cell was inserted inside each of eight enucleated eggs, which were then chemically
stimulated to divide. Just three of the eight eggs began dividing, and only one reached six cells
before cell division ceased.
In 2003 a Chinese research team led by Ying Chen reported that it had made human embryonic
stem cells by combining human skin cells with rabbit eggs. Their accomplishment was published
in "Embryonic Stem Cells Generated by Nuclear Transfer of Human Somatic Nuclei into Rabbit
Oocytes" (Cell Research, vol. 13, no. 4, August 2003). The researchers removed the rabbit eggs'
DNA and injected human skin cells inside them. The eggs then grew to form embryos containing
human genetic material. After several days the embryos were dissected to extract their stem
cells.
In 2004 Woo Suk Hwang et al. of the Seoul National University reported in "Evidence of a
Pluripotent Human Embryonic Stem Cell Line Derived from a Cloned Blastocyst" (Science, vol.
303, no. 5664, March 12, 2004) that they had successfully cloned healthy human embryos,
removed embryonic stem cells, and grown them in mice. In January 2006, following a long
investigation, Seoul National University concluded that the research reported in Science had
been fabricated. As a result, the journal retracted this article along with another article,
"Patient-Specific Embryonic Stem Cells Derived from Human SCNT Blastocysts" (Science, vol.
308, no. 5729, June 17, 2005), by Hwang et al. In May 2006 Hwang was charged with fraud,
embezzlement, and violating South Korea's country's bioethics statutes
In 2005 Wilmut was granted a license by the British government to clone human embryos to
generate stem cell lines to study motor neuron disease (MND). Wilmut and his colleagues are
working to clone embryos to generate stem cells that would in turn become motor neurons
with MND-causing gene defects. By observing the stem cells growth into neurons, the
researchers hope to discover what causes the cells to degenerate. Their research involves
comparing the stem cells with healthy and diseased cells from MND patients to gain a better
understanding of the illness and to test potential drug treatments.
Human reproductive cloning remains illegal in Britain but therapeutic cloning is allowed on an
approved basis. The license granted to Wilmut and his colleagues is the second one granted by
Britain's Human Fertilisation and Embryology Authority.
In July 2006 Deepa Deshpande et al. restored movement to paralyzed rats using a new method
that demonstrates the potential of embryonic stem cells to restore function to humans
suffering from neurological disorders. They published their results in "Recovery from Paralysis
in Adult Rats Using Embryonic Stem Cells" (Annals of Neurology, vol. 60, no. 1, July 2006). Even
though clinical trials in humans are still years away, the results of this research represent an
important advance in the quest for a cure for paralysis and other neurological disorders.
In October 2006 Kevin A. D'Amour et al. reported in "Production of Pancreatic HormoneExpressing Endocrine Cells from Human Embryonic Stem Cells" (Nature Biotechnology, vol. 24,
October 2006) developing a process to turn human embryonic stem cells into pancreatic cells
that can produce insulin and other hormones.
Three studies—Volker Schächinger et al.'s "Intracoronary Bone Marrow-Derived Progenitor
Cells in Acute Myocardial Infarction," Ketil Lunde et al.'s "Intracoronary Injection of
Mononuclear Bone Marrow Cells in Acute Myocardial Infarction," and Birgit Assmus et al.'s
"Transcoronary Transplantation of Progenitor Cells after Myocardial Infarction"—describing the
use of stem cells in the treatment of heart disease were published in the New England Journal
of Medicine (vol. 355, no. 12, September 21, 2006). The studies produced conflicting results:
Schächinger et al. reported benefits for patients who had suffered myocardial infarction (heart
attack). Lunde et al. found no benefit from stem cell treatment of such patients. Assmus et al.
studied patients with chronic heart failure, who did show improvement after treatment. In the
editorial "Cardiac Cell Therapy—Mixed Results from Mixed Cells" in the same issue of the
journal, Anthony Rosenzweig writes that the three studies "provide a realistic perspective on
this approach while leaving room for cautious optimism and underscoring the need for further
study."
Rick Weiss indicates in "Stem Cell Work Shows Promise and Risks" (Washington Post, October
23, 2006) that research conducted at the University of Rochester Medical Center using nerve
cells grown from human embryonic stem cells to treat rats afflicted with Parkinson's disease
produced mixed results. The treatment reduced the animals' symptoms, but caused tumors in
the rodents' brains. The researchers acknowledged their work showed both the promise and
risks associated with stem cell treatments.
Research Promises Therapeutic Benefits without Cloning
In "Homologous Recombination in Human Embryonic Stem Cells" (Nature Biotechnology, vol.
21, no. 3, March 2003), Thomas P. Zwaka and James A. Thomson report that they used human
embryonic stem cells to splice out individual genes and substituted different genes in their
place. Their accomplishment was heralded as a first step toward the goal of regenerating parts
of the human body by transplanting either stem cells or tissues grown from stem cells into
patients. Zwaka and Thomson used electrical charges and chemicals to make the cells'
membranes permeable; the cells allowed the customized genes to enter, and they then found
and replaced their counterparts in the cells' DNA.
The ability to make precise genetic changes in human stem cells could be used to boost their
therapeutic potential or make them more compatible with patients' immune systems. Some
researchers assert that the success of this bioengineering feat might eliminate the need to
pursue the hotly debated practice of therapeutic cloning, but others caution that such research
could heighten concerns among those who fear that stem cell technology will lead to the
creation of "designer babies," which are bred for specific characteristics such as appearance,
intelligence, or athletic prowess.
Karin Hübner et al. report in "Derivation of Oocytes from Mouse Embryonic Stem Cells"
(Science, vol. 300. no. 5623, May 23, 2003) that they transformed ordinary mouse embryo cells
into egg cells in laboratory dishes. The researchers selected from a population of stem cells the
ones that bore certain genetic traits suggesting the potential to become eggs. They then
isolated those in laboratory dishes. Eventually, the cells morphed into two kinds of cells,
including young egg cells. The eggs matured normally and appeared to be healthy in terms of
their appearance, size, and gene expression. When cultured for a few days, the eggs also
underwent spontaneous division and formed structures resembling embryos, a process called
parthenogenesis. This finding implies that the eggs were fully functional and likely could be
fertilized with sperm.
Once refined, this technology could be applied to produce egg cells in the laboratory that would
enable scientists to engineer traits into animals and help conservationists rebuild populations of
endangered species. It offers researchers the chance to observe mammalian egg cells as they
mature, a process that occurs unseen within the ovary. The technology also offers an
unparalleled opportunity to learn about meiosis (reduction division), the process of cell division
during which an egg or sperm disgorges half of its genes so it can join with a gamete of the
opposite sex. There are many potential medical benefits as well. For example, women who
cannot make healthy eggs could use this technology to ensure healthy offspring.
Like many new technologies, transforming cells into eggs simultaneously resolves existing
ethical issues and creates new ones. For example, because the embryonic stem cells
spontaneously transformed themselves into eggs, this procedure overcomes many of the
ethical objections to cloning, which involves creating offspring from a single parent. However, it
also paves the way for the creation of "designer eggs" from scratch and, if performed with
human cells, could redefine the biological definitions of mothers and fathers.
Sawako Ina et al. explain in "Expression of the Mouse Aven Gene during Spermatogenesis,
Analyzed by Subtraction Screening Using Mvh-Knockout Mice" (Gene Expression Patterns, vol.
3, no. 5, October 2003) that they observed male mouse embryonic stem cells that developed
spontaneously, with some cells actually becoming germ cells. When the researchers
transplanted the germ cells into testicular tissue, the cells underwent meiosis and formed
sperm cells. One possible medical application of this technology would be to assist couples who
are infertile because the male cannot produce healthy sperm. One of the ethical issues that
might arise would be the potential for two men to both be biological fathers of a child. Another
is the potential to generate a human being who never had any parents using two laboratorygrown stem cells, one transformed into a sperm and the other into an egg. Many ethicists
advise consideration of such issues before permitting human experimentation.
In "Growth Factors Essential for Self-Renewal and Expansion of Mouse Spermatogonial Stem
Cells" (Proceedings of the National Academy of Sciences, vol. 101, no. 47, November 23, 2004),
Hiroshi Kubota, Mary R. Avarbock, and Ralph L. Brinster of the University of Pennsylvania
School of Veterinary Medicine indicate that they used cells from mice to grow sperm progenitor
cells in a laboratory culture. Known as spermatogonial stem cells, the progenitor cells are
incapable of fertilizing egg cells but give rise to cells that develop into sperm. The researchers
transplanted the cells into infertile mice, which were then able to produce sperm and father
offspring that were genetically related to the donor mice.
This breakthrough has many potential applications, including developing new treatments for
male infertility and extending the reproductive lives of endangered species. Researchers will
also attempt to genetically manipulate the sperm cells grown in a culture medium and then
implant the cells into animals. In this way they could introduce new traits into laboratory
animals and livestock, such as disease resistance. This culture technique offers researchers
additional opportunities to investigate the potential of spermatogonial stem cells as a source
for adult stem cells to replace diseased or injured tissue.
New Methods Obtain Stem Cells without Destroying Embryos
According to Young Chung et al., in "Embryonic and Extraembryonic Stem Cell Lines Derived
from Single Mouse Blastomeres" (Nature, vol. 439, no. 7073, January 12, 2006), embryonic
stem cell cultures can be derived from single cells of mouse embryos. Irina Klimanskaya et al.
describe in "Human Embryonic Stem Cell Lines Derived from Single Blastomeres" (Nature, vol.
444, no. 7118, November 23, 2006) a technique for removing a single cell—called a
blastomere—from a three-day-old embryo with eight to ten cells and using a biochemical
process to create embryonic stem cells from the blastomere. The method of removing a cell
from the embryo is much like the technique used for preimplantation genetic diagnosis, which
is performed to screen the cell for genetic defects. Klimanskaya et al. note that human
embryonic stem cell lines derived from a single blastomere were comparable to lines derived
with conventional techniques. Even though the researchers assert that the new method "will
make it far more difficult to oppose this research," opponents of stem cell research contend
that the new technique is morally unacceptable because even a single cell removed from an
early embryo may have the potential to produce a life.
Another technique reported in 2006 can obviate the need for embryonic stem cells. Erika Check
notes in "Simple Recipe Gives Adult Cells Embryonic Powers" (Nature, vol. 442, no. 7098, July 6,
2006) that researchers in the United Kingdom discovered the gene, called nanog, that is the key
to "reprogramming" adult cells back to an embryonic state. The reprogramming of adult cells
using nanog may make it possible for scientists to generate cells that specialize and develop
into every type of cell in the body without the controversial use of human embryonic stem cells.
The ACT notes in the press release "Advanced Cell Technology Develops First Human Embryonic
Stem Cell Line without Destroying an Embryo" (June 21, 2007,
http://www.advancedcell.com/pressrelease/advanced-cell-technology-develops-first-human-e
mbryonic-stem-cell-line-without-destroying-an-embryo) that at the fifth annual meeting of the
International Society for Stem Cell Research in Australia in 2007 it announced that it had
successfully produced a human embryonic stem cell line without destroying an embryo. The
technique, which involved removing blastomeres from embryos, was similar to that used for
preimplantation genetic diagnosis. The stem cells were genetically normal and differentiated
into various cell types including blood cells, neurons, heart cells, cartilage, and other cell types
with significant therapeutic potential. In February 2008 Young Chung et al. reported in "Human
Embryonic Stem Cell Lines Generated without Embryo Destruction" (Cell Stem Cell, vol. 2, no. 2,
February 7, 2008) the creation of fully functional liver cells from embryonic stem cells, and in
December 2008 Shi-Jiang Lu et al. described success in "Biological Properties and Enucleation of
Red Blood Cells from Human Embryonic Stem Cells" (Blood, vol. 112, no. 12, December 1, 2008)
in transforming human embryonic stem cells into red blood cells. This is a tremendous stride
because it may be possible to use this technique to produce blood for transfusion, which is
often in short supply due to a lack of donors.
In "Breakthrough of the Year: Reprogramming Cells" (Science, vol. 322, no. 5909, December 19,
2008), Gretchen Vogel reports that scientists had successfully transformed human skin cells
into stem cells. By observing this process, researchers are gaining insight into how cells grow,
change, and transform. It is hoped that reprogrammed cells such as these may prove useful in
helping physicians treat disease by using the patients' own cells.
Opinions Shape Public Policy
Even though it is widely believed that stem cell research is the key to developing effective
treatment for a range of serious and chronic diseases, public policy issues, especially funding for
stem cell research, have been shaped by a heated moral controversy that pits scientific
advancement against the sanctity of life. Opposition to stem cell research, and federal funding
for it, arises from the concern that it may involve destroying human life contained in embryonic
stem cells and the fear that embryos might be created solely for use in research, which could
result in their destruction. President George W. Bush (1946-) was strongly opposed embryonic
stem cell research, characterizing it as a moral hazard, because he considered the destruction
of human embryos morally wrong. He also expressed the belief that embryonic stem cell
research might lead to human cloning.
According to the White House press release "President Discusses Stem Cell Research" (August
9, 2001, http://www.whitehouse.gov/news/releases/2001/08/20010809-2.html), Bush
announced in August 2001 his decision to allow federal funds to be used for research on
existing human embryonic stem cell lines as long as the derivation process (which begins with
the removal of the inner cell mass from the blastocyst) had already been initiated, and the
embryo from which the stem cell line was derived no longer had the possibility of development
as a human being. The president established the following criteria that research studies must
meet to qualify for federal funding:


The stem cells must have been drawn from an embryo created for reproductive
purposes that was no longer needed for these purposes.
Informed consent must have been obtained for the donation of the embryo and no
financial inducements provided for donation of the embryo.
These criteria limited research to only 21 cell lines that had been created before August 9,
2001, and effectively banned federal funding for hundreds of embryonic stem cell lines,
including some that carried genetic mutations for specific conditions and diseases that
scientists wanted to study in the hope of finding cures. Many people argue that because
embryonic stem cells are not, in fact, embryos, research on such cells should be allowed.
Others, such as President Bush, believe that any research that creates or destroys human
embryos at any stage, such as creating new embryos through cloning or destroying an embryo
to create a stem cell line, should not be allowed. Despite Bush's ban of federal funding, such
research remained legal as long as private funding was used.
In January 2002 the Panel on Scientific and Medical Aspects of Human Cloning was convened by
the National Academy of Sciences; the National Academy of Engineering; the Institute of
Medicine Committee on Science, Engineering, and Public Policy; and the National Research
Council, Division on Earth and Life Studies Board on Life Sciences. Following the panel, the
report Scientific and Medical Aspects of Human Cloning (2002,
http://www7.nationalacademies.org/cosepup/Human_Cloning.html) was issued that called for
a ban on human reproductive cloning.
The panel recommended a legally enforceable ban with substantial penalties as the best way to
discourage human reproductive cloning experiments in both the public and private sectors. It
cautioned that a voluntary measure might be ineffective because many of the technologies
needed to accomplish human reproductive cloning are widely accessible in private clinics and
other organizations that are not subject to federal regulations.
The panel did not, however, conclude that the scientific and medical considerations that justify
a ban on human reproductive cloning are applicable to nuclear transplantation to produce stem
cells. In view of the potential to generate new treatments for life-threatening diseases and
advance biomedical knowledge, the panel recommended that biomedical research using
nuclear transplantation to produce stem cells be permitted. Finally, the panel encouraged
ongoing national discussion and debate about the range of ethical, societal, and religious issues
associated with human cloning research.
In February 2002 the American Association for the Advancement of Science (2008,
http://archives.aaas.org/docs/resolutions.php?doc_id=425), the world's largest general
scientific organization, affirmed a legally enforceable ban on reproductive cloning, but stated its
support for therapeutic cloning using nuclear transplantation methods under appropriate
government oversight. Similarly, the American Medical Association, a national physicians'
organization, addresses in "Human Cloning" (March 17, 2008, http://www.amaassn.org/ama/pub/category/4560.html) many of the issues associated with human
reproductive cloning. It also cautions that human cloning failures could jeopardize promising
science and genetic research and prevent biomedical researchers and patients from realizing
the potential benefits of therapeutic cell cloning.
According to the White House press release "President Bush Calls on Senate to Back Human
Cloning Ban" (April 10, 2002, http://www.whitehouse.gov/news/releases/2002/04/200204104.html), in April 2002 President Bush called on the U.S. Senate to back legislation banning all
types of human cloning. In his plea to the Senate, Bush said:
Science has set before us decisions of immense consequence. We can pursue medical research
with a clear sense of moral purpose or we can travel without an ethical compass into a world
we could live to regret. Science now presses forward the issue of human cloning. How we
answer the question of human cloning will place us on one path or the other.... Human cloning
is deeply troubling to me, and to most Americans. Life is a creation, not a commodity.... Our
children are gifts to be loved and protected, not products to be designed and manufactured.
Allowing cloning would be taking a significant step toward a society in which human beings are
grown for spare body parts, and children are engineered to custom specifications; and that's
not acceptable.... I believe all human cloning is wrong, and both forms of cloning ought to be
banned, for the following reasons. First, anything other than a total ban on human cloning
would be unethical. Research cloning would contradict the most fundamental principle of
medical ethics, that no human life should be exploited or extinguished for the benefit of
another.
On September 25, 2002, Elias A. Zerhouni (1951-;
http://olpa.od.nih.gov/hearings/107/session2/testimonies/stemcelltest.asp), the director of
the National Institutes of Health (NIH), testified before the Senate Appropriations
Subcommittee on Labor, Health and Human Services, and Education in favor of advancing the
field of stem cell research. Zerhouni exhorted Congress to continue to fund both human
embryonic stem cell research and adult stem cell research simultaneously to learn as much as
possible about the potential of both types of cells to treat human disease. He observed that
many studies that do not involve human subjects must be performed before any new therapy is
tested on human patients. These preclinical studies include tests of the long-term survival and
fate of transplanted cells, as well as tests on the safety, toxicity, and effectiveness of the cells in
treating specific diseases in animals. Zerhouni promised that trials using human subjects, the
clinical research phase, would begin only after the basic foundation had been established.
Despite Zerhouni's impassioned plea and subsequent efforts by Congress to reverse limitations
on embryonic stem cell research, President Bush vetoed such attempts, and, at the close of
2008, U.S. law continued to ban federal funding of any research that might harm human
embryos.
While campaigning for the office of president Barack Obama (1961-) pledged to lift the ban on
federal funding for embryonic stem cell research. On March 9, 2009, shortly after entering
office in January, he did so by an executive order. Despite President Obama's reversal of
President Bush's policy on embryonic stem cell research, for some research Congress would still
need to overturn the Dickey-Wicker amendment, which has been included in the fiscal
spending bills each year since 1996 and prohibits federal funding of any research that creates or
destroys human embryos. The amendment was set to remain in place until the fiscal year
ended September 2009, leaving it up to Congress to either act to either overturn it or continue
it with the next spending bill. Without President Bush to veto such a change, as of March 2009,
those in favor of embryonic stem cell research were exhorting Congress to overturn the
amendment.
Moral and Ethical Objections to Human Cloning
The difficulty and low success rate of much animal reproductive cloning (an average of just 1 or
2 viable offspring result from every 100 attempts) and the as-yet-inadequate understanding
about reproductive cloning have prompted many scientists to deem it unethical to attempt to
clone humans. Many attempts to clone mammals have failed, and about one-third of clones
born alive suffer from anatomical, physiological, or developmental abnormalities that are often
debilitating. Some cloned animals have died prematurely from infections and other
complications at rates higher than conventionally bred animals, and some researchers
anticipate comparable outcomes from human cloning. Furthermore, scientists cannot yet
describe or characterize how cloning influences intellectual and emotional development. Even
though the attributes of intelligence, temperament, and personality may not be as important
for cattle or other primates, they are vital for humans. Without considering the myriad
religious, social, and other ethical concerns, the presence of so many unanswered questions
about the science of reproductive cloning has prompted many investigators to consider any
attempts to clone humans as scientifically irresponsible, unacceptably risky, and morally
unallowable.
People who oppose human cloning are as varied as the interests and institutions they support.
Religious leaders, scientists, politicians, philosophers, and ethicists argue against the morality
and acceptability of human cloning. Nearly all objections hinge, to various degrees, on the
definition of human life, beliefs about its sanctity, and the potentially adverse consequences for
families and society as a whole.
In an effort to stimulate consideration of and debate about this critical issue, the President's
Council on Bioethics examined the principal moral and ethical objections to human cloning in
Human Cloning and Human Dignity: An Ethical Inquiry (July 2002,
http://www.bioethics.gov/reports/cloningreport/fullreport.html). The council's report
distinguished between therapeutic and reproductive cloning and outlined key concerns by
trying to respond to many as yet unresolved questions about the ethics, morality, and societal
consequences of human cloning.
The council determined that the key moral and ethical objections to therapeutic cloning
(cloning for biological research) center on the moral status of developing human life.
Therapeutic cloning involves the deliberate production, use, and destruction of cloned human
embryos. One objection to therapeutic cloning is that cloned embryos produced for research
are no different from those that could be used in attempts to create cloned children. Another
argument that has been made is that the ends do not justify the means—that research on any
human embryo is morally unacceptable, even if this research promises cures for many dreaded
diseases. Finally, there are concerns that acceptance of therapeutic cloning will lead society
down a slippery slope to reproductive cloning, a prospect that is almost universally viewed as
unethical and morally unacceptable.
The unacceptability of human reproductive cloning stems from the fact that it challenges the
basic nature of human procreation by redefining having children as a form of manufacturing.
Human embryos and children may then be viewed as products and commodities rather than as
sacred and unique human beings. Furthermore, reproductive cloning might substantially
change fundamental issues of human identity and individuality, and allowing parents
unprecedented genetic control of their offspring may significantly alter family relationships
across generations.
The council concluded that "the right to decide" whether to have a child does not include the
right to have a child by any means possible, nor does it include the right to decide the kind of
child one is going to have. A societal commitment to freedom does not require use or
acceptance of every technological innovation available.
Legislation Aims to Completely Ban Human Cloning
On February 27, 2003, the U.S. House of Representatives voted to outlaw all forms of human
cloning. The legislation prohibits the creation of cloned human embryos for medical research as
well as the creation of cloned babies. It contains strong sanctions, imposing a maximum penalty
of $1 million in civil fines and as many as 10 years in prison for violations. The measure did not
pass in the Senate, which was closely divided about whether therapeutic cloning should be
prohibited along with reproductive cloning. In early February 2003 President Bush issued a
policy statement that strongly supported a total ban on cloning. In the Senate two bills were
introduced: S. 245 was a complete ban intended to amend the Public Health Service Act to
prohibit all human cloning, and S. 303 was a less sweeping measure that also prohibited cloning
but protected stem cell research. S. 245 was referred to the Senate Committee on Health,
Education, Labor, and Pensions and S. 303 was referred to the Senate Committee on the
Judiciary. As of 2008, neither bill, nor any comparable proposed legislation, has emerged from
the Senate committees.
Even though nearly all lawmakers concur that Congress should ban reproductive cloning, many
disagree about whether legislation should also ban the creation of cloned human embryos that
serve as sources of embryonic stem cells. Many legislators agree with scientists that stem cells
derived from cloned human embryos have medical and therapeutic advantages over those
derived from conventional embryos or adults. Those who oppose the legislation calling for a
total ban assert that the aim of allowing research is to relieve the suffering of people with
degenerative diseases. They say that the bill's sponsors are effectively thwarting advances in
medical treatment and biomedical innovation.
Supporters of the total ban contend that Congress must send an unambiguous message that
cloning research and experimentation will not be tolerated. They consider cloning immoral and
unethical, fear unintended consequences of cloning, and feel they speak for the public when
they assert that it is not justifiable to create human embryos simply for the purpose of
experimenting on them and then destroying them.
On May 24, 2005, the House passed H.R. 810, the Stem Cell Research Enhancement Act of
2005, which would have permitted federal funding for embryonic stem cell research on cells
"derived from human embryos that have been donated from in vitro fertilization clinics, were
created for the purposes of fertility treatment, and were in excess of the clinical need of the
individuals seeking such treatment." The Senate passed the bill on July 18, 2006, and the
following day President Bush vetoed the bill.
In June 2007 the Executive Office of the President issued a Statement of Administrative Policy
(June 6, 2007, http://www.whitehouse.gov/omb/legislative/sap/110-1/hr2560sap-h.pdf)
reiterating the president's unequivocal opposition to all forms of human cloning. The statement
asserted that if legislation permitting the creation, development, or destruction of human
embryos for research purposes was presented to the president, then "his senior advisors would
recommend that he veto the bill." According to the White House press release "Executive
Order: Expanding Approved Stem Cell Lines in Ethically Responsible Ways" (June 20, 2007,
http://www.whitehouse.gov/news/releases/2007/06/20070620-6.html), that same month the
president issued an executive order requiring the secretary of health and human services and
the NIH director to issue a plan describing the conditions under which stem cell research may
be conducted "so that the potential of pluripotent stem cells can be explored without violating
human dignity or demeaning human life."
In his January 2008 State of the Union address, President Bush affirmed that there would be
continuing federal financial support for nondestructive stem cell research (research in which
human embryos are not harmed) while calling on Congress to pass legislation to ban practices
such as the buying, selling, patenting, or cloning of human life. Between 2007 and 2008
Congress considered three bills— H.R. 2560, H.R. 2564, and S. 812—to amend the Federal Food,
Drug, and Cosmetic Act to prohibit human cloning. H.R. 2560 was defeated and the others were
referred to the Subcommittee on Crime, Terrorism, and Homeland Security and the Committee
on the Judiciary, respectively.
After President Bush left office in January 2009, President Obama lifted the ban on federal
funding for all embryonic stem cell research on lines other than those President Bush approved
(those created before August 9, 2001). Without President Bush to veto bills such as H.R. 810,
the Stem Cell Research Enhancement Act of 2005, President Obama stated that he hoped
Congress would also act to allow such funding to go forward. Despite his strong support of
embryonic stem cell research, when issuing the executive order, President Obama stated that
under no circumstances should the funding for embryonic stem cell research be used to explore
human cloning.
State Human Cloning Laws
As of 2008, 15 states had enacted legislation that addresses human cloning. California was the
first state to ban reproductive cloning in 1997. Since then, 12 other states—Arkansas,
Connecticut, Indiana, Iowa, Maryland, Massachusetts, Michigan, Rhode Island, New Jersey,
North Dakota, South Dakota, and Virginia—have passed laws prohibiting reproductive cloning.
Arizona's and Missouri's legislation addresses the use of public funds for cloning, and
Maryland's prohibits the use of state stem cell research funds for reproductive cloning and
possibly therapeutic cloning, depending on the interpretation of the statute. Louisiana also
enacted legislation that prohibited reproductive cloning, but the law expired in July 2003. The
laws of Arkansas, Indiana, Iowa, Michigan, North Dakota, and South Dakota also prohibit
therapeutic cloning. Virginia's legislation may be interpreted as a complete ban on human
cloning; however, it is unclear because the law does not define the term human being, which is
used in the definition of human cloning. Rhode Island's law does not prohibit cloning for
research, and California's and New Jersey's laws specifically permit cloning for the purpose of
research.
California Leads the Way in Stem Cell Research
Though some states specifically ban human cloning, state funding of stem cell research was
supported by many individual states even when federal funds were not available. In 2002 the
California state legislature passed a law encouraging therapeutic cloning. Even though there
were no provisions for funds in the law, the move was interpreted as support for the research.
In 2004 stem cell research advocates offered voters a sweeping ballot measure—Proposition
71—to make public funding available to support stem cell research and therapeutic cloning.
Proposition 71 was championed by Robert Klein, a wealthy real estate developer and father of a
child with diabetes who might benefit from the research. It also received considerable financial
support from the Microsoft founder Bill Gates (1955-) to finance campaign advertising and
lobbying.
In November 2004 Californians approved Proposition 71, a ballot measure with the potential to
make the state a leader in human embryonic stem cell research. Proposition 71 enabled the
state to create a state agency called the California Institute for Regenerative Medicine (CIRM;
http://www.cirm.ca.gov/). The proposition prohibits reproductive cloning but funds human
cloning projects designed to create stem cells and allocates $3 billion over 10 years in research
funds. Those supporting the legislation hoped that stem cell research would become the
biggest, most important, and most profitable medical advancement of the twenty-first century.
The legislation's supporters intended to use the funds to attract top researchers to the state,
making California the epicenter of groundbreaking, lifesaving, and potentially lucrative medical
research.
The CIRM was officially established in 2005. An independent oversight committee composed of
public officials governs the CIRM. These officials are appointed on the basis of their experience
earned in California's leading public universities, nonprofit academic and research institutions,
patient advocacy groups, and the biotechnology industry. The CIRM funds biomedical research
based in California that focuses on developing diagnostics and therapies and on other vital
research that will lead to life-saving medical treatments. By 2007 the CIRM
(http://www.cirm.ca.gov/info/grants.asp) had approved 253 research grants totaling more than
$635.8 million, making CIRM the largest source of funding for embryonic and pluripotent stem
cell research in the world.
According to the Henry J. Kaiser Foundation
(http://www.statehealthfacts.org/comparetable.jsp?ind=112&cat=2), as of January 2008, 12
states had established state funding for stem cell research facilities, with seven, including
California, specifically including funding for embryonic stem cell research.
Public Opinions about Stem Cell Research and Cloning
According to Gallup poll data, in 2007 nearly two-thirds of Americans believed using stem cells
derived from human embryos in medical research is morally acceptable. Figure 8.8: Public
opinion on the moral acceptability of embryonic stem cell research, 2002-07 reveals that the
percentage of Americans that considers stem cell research morally acceptable had increased
from 52% in 2002 to 64% in 2007.
The percentage of Americans that deemed stem cell research morally acceptable in 2007 varies
by political philosophy, with support highest among liberals (84%) and moderates (69%),
compared to conservatives (48%). (See Table 8.2: Public opinion on the moral acceptability of
embryonic stem cell research by political philosophy, May 2007.) The Gallup poll also finds
attitudes about federal funding for medical research that uses embryonic stem cells has
changed, with 22% of survey respondents in 2007 indicating that they prefer the government
place no restrictions on government funding of stem cell research, compared to 11% in 2005.
(See Table 8.3: Public opinion on the extent to which the federal government should fund
embryonic stem cell research, selected years 2004-07.) The 2007 Gallup poll also finds that
most Americans (64%) disapproved of President Bush's decision to veto a bill that would have
expanded federal funding for embryonic stem cell research. (See Table 8.4: Public opinion on
whether the President should veto a bill expanding federal funding for embryonic stem cell
research, 2007.)
Even though Americans continue to feel that it is morally unacceptable to clone humans, public
support for cloning animals increased slightly from 31% in 2001 to 36% in 2007. (See Figure 8.9:
Public opinion on the moral acceptability of cloning humans and animals, 2001-05.) Like stem
cell research, which is favored by more liberals than conservatives, more liberals (55%) than
conservatives (28%) consider cloning animals morally acceptable. (See Table 8.2: Public opinion
on the moral acceptability of embryonic stem cell research by political philosophy, May 2007.)
The Human Genome Project
When the full map of the human genome is known ... we shall have passed through a phase of
human civilisation as significant as, if not more significant than, that which distinguished the
age of Galileo from that of Copernicus, or that of Einstein from that of Newton. ... We have
crossed a boundary of unprecedented importance. ... There is no going back. ... We are walking
hopefully in the scientific foothills of a gigantic mountain range.
—Ian Lloyd, Official Record, British House of Commons, 1990
In 1953 James D. Watson (1928-) and Francis Crick (1916-2004) described the double helical
structure of deoxyribonucleic acid (DNA). Their molecular DNA structure was published in
"Molecular Structure of Nucleic Acids: A Structure for Deoxyribose Nucleic Acid" (Nature, vol.
171, no. 4356, April 25, 1953), an article that was only two pages long. Despite the brevity of
this article, it ushered in a new age of discovery in genetics and laid the foundation for the
sequencing of the human genome.
The word genome was derived from two words: gene and chromosome. In the 21st century the
term genome is widely understood to be the entire complement of genetic material in the cell
of an organism. A genome is composed of a series of four nitrogenous (containing nitrogen, a
nonmetallic element that constitutes almost four-fifths of the air by volume) DNA bases:
adenine (A), guanine (G), thymine (T), and cytosine (C). In each organism these bases are
arranged in a specific order, or sequence, and this order constitutes the genetic code of the
organism. In humans the genome is composed of approximately 3 billion bases. In 2001 a first
draft sequence of the entire human genome was completed and made available to the public
for study and research. The Human Genome Project (HGP) of the National Human Genome
Research Institute, which is part of the National Institutes of Health (NIH), completed the full
human genome sequence in April 2003.
Laying the Groundwork for the Sequencing of the Human Genome
During the 1960s and 1970s the techniques that would enable the study of molecular genetics
were developed. In 1964 the American virologist Howard Temin (1934-1994) worked with
ribonucleic acid (RNA) viruses and discovered that Crick's central tenet—that DNA makes RNA
and that RNA makes protein—did not always hold true. In 1965 Temin described the process of
reverse transcriptase—that genetic information in the form of RNA can be copied into DNA. The
enzyme called reverse transcriptase used RNA as a template for the synthesis of a
complementary DNA strand. Throughout the 1960s the American biochemists Robert W. Holley
(1922-1993), Har Gobind Khorana (1922-), and Marshall Nirenberg (1927-2010), along with the
American molecular geneticist Philip Leder (1934-), all contributed to deciphering the genetic
code by determining the DNA sequence for each of the 20 most common amino acids. Holley,
Khorana, and Nirenberg were awarded the 1968 Nobel Prize in Physiology or Medicine.
The American biochemist Paul Berg (1926-) created the first recombinant DNA in 1972, and his
work paved the way for isolating and cloning genes. Recombinant DNA is formed by combining
segments of DNA, frequently from different organisms. In 1975 the British molecular biologist
Sir Edwin Southern (1938-) developed a method to isolate and analyze fragments of DNA that is
still being used. Known as the Southern blot analysis, it is a procedure for separating DNA
fragments by electrophoresis (a technique that separates molecules based on their size and
charge) and identifying a specific fragment using a DNA probe. Figure 7.1: Southern blot
analysis shows how the Southern blot analysis is performed. It is used in genetic research,
forensic examinations of DNA evidence in legal proceedings, and clinical medical practice.
In 1977 the British biochemist Frederick Sanger (1918-), whose many accomplishments have
been acknowledged by two Nobel Prizes in Chemistry in 1958 and 1980, and his colleagues
developed techniques to determine the nucleic acid base sequence for long sections of DNA. In
1978 the American biologists Hamilton O. Smith (1931-) and Daniel Nathans (1928-1999) and
the Swiss molecular geneticist Werner Arber (1929-) were awarded the Nobel Prize in
Physiology or Medicine for an array of discoveries made during the 1960s, including the use of
restriction enzymes, which ignited the biotechnology field. Restriction enzymes recognize and
cut specific DNA sequences. That same year restriction fragment length polymorphisms (DNA
sequence variants) were discovered. Figure 7.2: The identification of single nucleotide
polymorphisms (SNPs) in soybean DNA shows two single nucleotide polymorphisms—single
base changes between homologous DNA fragments.
By using these new genetic techniques, researchers were able to identify several genes for
serious human disorders during the 1980s. In 1982 the American molecular biologist James F.
Gusella (1952-) and his colleagues at Harvard University began studying patients with
Huntington's disease and determined that the gene for this degenerative, neuropsychiatric
disorder was located on the short arm of chromosome 4. That same year a gene for
neurofibromatosis type 1 was found on the long arm of chromosome 17. Neurofibromatoses
are a group of genetic disorders that cause tumors (most of which are not malignant) to grow
along various types of nerves and can affect the development of nonnervous tissues such as
bones and skin. The disorder may also result in developmental abnormalities such as learning
disabilities.
In 1985 the American biochemist Kary B. Mullis (1944-) and his colleagues at the Cetus
Corporation in California pioneered the polymerase chain reaction, a fast, inexpensive
technique that amplifies small fragments of DNA to make sufficient quantities available for DNA
sequence analysis—that is, determining the exact order of the base pairs in a segment of DNA.
Because it enabled researchers to make an unlimited number of copies of any piece of DNA, it
was dubbed "molecular photocopying," and in 1993 Mullis was awarded the Nobel Prize in
Chemistry for this tremendous breakthrough in gene analysis. By 1987 automated sequencers
were developed, enabling even more rapid sequencing and analysis on large segments of DNA.
Figure 7.3: Steps in a polymerase chain reaction (PCR) shows the steps involved in a polymerase
chain reaction.
In 1985 the Canadian molecular geneticist Lap-Chee Tsui (1950-) and his colleagues mapped the
gene responsible for cystic fibrosis, the most common inherited fatal disease of children and
young adults in the United States, to the long arm of chromosome 7. The gene for cystic fibrosis
was discovered in 1989, and it was determined that three missing nucleic acid bases occurred in
the altered gene of 70% of patients with cystic fibrosis.
The mutations associated with Duchenne muscular dystrophy were identified in 1987. This
gene is located close to the gene for chronic granulomatous disease (an X-linked autosomal
recessive disorder that, if left untreated, is fatal in childhood) on the short arm of the X
chromosome. In 1990 the American geneticist Mary-Claire King (1946-) found the first evidence
that a gene on chromosome 17 (now known as BRCA1) could be associated with an inherited
predisposition to breast and ovarian cancer.
The discoveries and technological advances made by researchers during the 1970s and 1980s
gave rise to modern clinical molecular genetics. The study of chromosome structure and
function, called cytogenetics, produced methods to view distinct bands on each chromosome.
Figure 7.4: Cytogenetic map of human chromosomes is a cytogenetic map of human
chromosomes. Cytogenetic studies are applied in three broad areas of medicine: congenital
(from birth) disorders, prenatal diagnosis, and neoplastic diseases (cancer).
The Birth of the Human Genome Project
The first meetings to discuss the feasibility of sequencing the human genome were organized
by Robert Louis Sinsheimer (1920-), a molecular biologist and chancellor of the University of
California (UC), Santa Cruz, and were held on campus in 1985. The idea of sequencing the
human genome generated excitement among the many well-known researchers in
attendance—they considered the undertaking to be the "Holy Grail" of molecular biology. The
following year Congress began to consider the feasibility of human genome research. However,
Congress did not decide to fund the project until 1988, after it concluded that the
establishment of administrative centers accountable to Congress could effectively manage key
aspects of the project, such as databases, sharing of research findings and materials, and
cultivating new technologies. The initial funding from Congress was $17.2 million to the NIH
and $10.7 million to the U.S. Department of Energy's (DOE) Office of Health and Environmental
Science, with progressive increases over the next several years. (See Table 7.1: U.S. Human
Genome Project funding, fiscal years 1988-2003.)
The allocation of these funds incited an impassioned debate. Opponents argued that the
financial and human resources devoted to the "big science" of the human genome project
would divert research funds from vital scientific and biomedical research and that most of the
sequence was of little biological interest and no medical utility. Other detractors warned that
the sheer size of the human genome would impede completion of the project within a
reasonable time frame without the creation of entirely new research methods and
technologies. The project was launched despite considerable opposition, and most of these
concerns were dispelled during the project's early years.
In 1988 Congress provided funding to the NIH and the DOE to "coordinate research and
technical activities related to the human genome." The NIH established the Office of Human
Genome Research in September 1988. The following year the office was renamed the National
Center for Human Genome Research (NCHGR). Watson served as its enthusiastic champion and
director until April 1992. Larry Thompson of the National Human Genome Research Institute
explains in "Background Paper on Internal Educational Activities at the National Human
Genome Research Institute" (June 10, 2002, http://www.genome.gov/10005291) that following
Watson's appointment, the NIH and the DOE committed 5% of the project's budget to address
ethical, legal, and social issues that arose from the study of the human genome. This ambitious
undertaking constituted the largest bioethics program, in terms of funding and human
resources, in the world.
In "About the Human Genome Project" (August 19, 2008,
http://www.ornl.gov/sci/techresources/Human_Genome/project/about.shtml), Human
Genome Project Information describes the ambitious goals of the HGP when it began in 1990.
The overarching HGP goals were to:
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Identify all the approximately 20,000 to 25,000 genes in human DNA
Determine the sequences of the 3 billion chemical base pairs that make up human DNA
Store HGP findings and other information in databases
Improve tools for data analysis
Transfer related technologies to the private sector
Effectively address the ethical, legal, and social issues that might arise from the project
International genomic research was also under way in Italy, England, France, Germany, Japan,
and other countries. For example, in 1987 the Italian National Research Council launched a
genome research project, and the United Kingdom began its project in February 1989. An
international group of geneticists founded in 1989 the Human Genome Organization (HUGO) in
Switzerland. Many international collaborations had already been forged as individual scientists
exchanged information in their quests for genetic links to disease. HUGO developed an
international framework to coordinate research projects and prevent wasted resources through
duplication, creating a culture of sharing data. In 1990 the European Commission initiated a
two-year human genome project. The Soviet Union funded its genome research project that
same year.
In April 1990 the initial planning stage of the HGP was completed with the publication of the
joint research plan Understanding Our Genetic Inheritance: The Human Genome Project—The
First Five Years, Fiscal Years 1991-1995
(http://www.ornl.gov/sci/techresources/Human_Genome/project/5yrplan/summary.shtml).
Just two years into the five-year plan, Watson resigned from his leadership position with the
NCHGR because he vehemently disagreed with NIH decisions about the commercialization,
propriety, and legality of patenting human gene sequences. Watson maintained that data from
the HGP should be in the public domain and freely available to all scientists as well as to the
public. In April 1993 Francis S. Collins (1950-) was named the director.
Many prominent researchers sided with Watson against the patenting and commercialization
of HGP data. In 1996 scientists at leading research institutions throughout the world agreed to
submit their findings and genome sequences to GenBank, a genome database maintained by
the NIH. In a resounding and unanimous move, they required the publication of any submitted
sequence data on the Internet within 24 hours of its receipt by GenBank. This action ensured
that gene sequences were in the public domain and could not be patented.
Worming Away
Even though sequencing the human genome was the principal objective, the HGP also sought
to sequence the genomes of other organisms. These other organisms served as models,
enabling researchers to test and refine new methods and technologies that helped identify
corresponding genes in the human genome. Table 7.2: Model organisms sequenced is a list of
some of the model organisms, including the roundworm, sequenced during the course of the
HGP, along with the dates the sequences were published and the number of bases in each
organism.
At Cambridge University, the British molecular biologist Sydney Brenner (1927-) was studying
the nematode worm Caenorhabditis elegans. By 1989 Brenner and his colleagues had
successfully produced a map of the entire Caenorhabditis elegans genome. The map consisted
of multiple overlapping fragments of DNA, arranged in the correct order, and Brenner's
research team printed the worm's genome on postcard-sized pieces of paper.
Watson believed the genomes of smaller organisms would not only help refine research
methods and the technology but also provide valuable sources of comparison once the human
genome project was under way. The worm map convinced Watson that Caenorhabditis elegans
should be the first multicellular organism to have its complete genome accurately sequenced.
When the worm-sequencing project began in 1990, the first automatic sequencing machines
had just become available from Applied Biosystems, Inc. The sequencing machines enabled the
worm pilot project to meet its objective of sequencing 3 million bases in three years. Equally
important, the worm project demonstrated that the technology could scale up—that is, more
machines and more technologists could produce more sequences faster.
A Decade of Accomplishments: 1993 to 2003
When the HGP began in September 1990, its projected completion date was 2005, at a cost of
$3 billion for just the U.S. portion of the research. Ever-improving research techniques—
including the use of restriction fragment length polymorphisms, which is described in detail in
Figure 7.5: Restriction fragment length polymorphism analysis (RFLP analysis), as well as the
polymerase chain reaction, bacterial and yeast artificial chromosomes, and pulsed-field gel
electrophoresis—accelerated the progress of the project. The HGP researchers finished the
mapping two years earlier than scheduled, and U.S. scientists spent just $2.7 billion.
Even though the HGP was truly a collaborative, international effort, most of the sequencing
work was performed at the Whitehead Institute for Medical Research in Massachusetts, the
Baylor College of Medicine in Texas, the University of Washington, the Joint Genome Institute
in California, and the Sanger Centre in the United Kingdom. Along with U.S government
funding, the HGP was supported by the Wellcome Trust, a charitable foundation in the United
Kingdom.
Public and Private Initiatives Compete
The NIH (March 25, 2010, http://www.nih.gov/about/almanac/organization/NHGRI.htm) notes
that in 1993 the NCHGR established a Division of Intramural Research, which was charged with
developing genome technology research of specific diseases. By 1996 eight NIH institutes and
centers had also collaborated to create the Center for Inherited Disease Research to study the
genetics of complex diseases. In 1997 the NCHGR gained full institute status at the NIH,
becoming the National Human Genome Research Institute (NHGRI). The following year a third
five-year plan, "New Goals for the U.S. Human Genome Project: 1998-2003," was published in
Science (vol. 282, no. 5389, October 23, 1998).
The mid-1990s also saw the birth of a privately funded genomics effort led by the American
geneticist J. Craig Venter (1946-). Venter had been working in a laboratory at the NIH when he
decided to concentrate his sequencing efforts not on the genome itself, but on the gene
products—that is, messenger RNAs produced by each cell. Besides the genes themselves, the
genome is composed of a much larger amount of DNA whose function is as yet unknown. This
portion of the genome is often referred to as "junk DNA," although it is possible that its true
value has not yet been determined. Venter eventually left the NIH to establish The Institute for
Genomic Research (TIGR), a private, nonprofit organization aimed at collecting and interpreting
vast numbers of expressed sequence tags. (Expressed sequence tags are random fragments of
complementary DNAs derived from the information in the RNAs, which contain all the
information that is actually expressed in a given cell type.) In July 1995 TIGR published the first
sequenced genome of the bacteria Haemophilus influenzae. (See Table 7.2: Model organisms
sequenced.)
The international partners in the genome project met in Bermuda in February 1996 at a
strategy meeting sponsored by the Wellcome Trust. There they created the "Bermuda
Principles," a set of conditions that govern access to data, including the standard that sequence
information be released into public databases within 24 hours. To adhere to this agreement,
participating scientists were to deposit base sequences into one of three databases within 24
hours of sequencing completion. The data contained in the three databases were exchanged
daily. Because these were public databases, access to the stored sequences was free and
unrestricted. The agreement was extended to data on other organisms at a meeting later that
same year.
In May 1998 Venter announced that he was allying with the Perkin-Elmer Corporation to form a
new company that would compete directly with the public effort to sequence the entire human
genome by 2001. The new company would become Celera Genomics. Venter planned to take a
different approach from the one used by the HGP. Instead of the map-based, gene-by-gene
approach taken by the HGP, his firm planned to break the genome into random lengths, and
then sequence and reassemble it. This method saved time by eliminating the mapping phase,
but it required robust computing capabilities to reassemble the human genome, which includes
many repeated sequences. Venter's approach relied on the use of a supercomputer and 300
high-speed automatic sequencers manufactured by the Perkin-Elmer Corporation; it was the
precursor to the large-scale genomics studies that have become standard.
The competition between public and private initiatives began in earnest. Within one week of
the launch of the private initiative, the Wellcome Trust increased its funding to the Sanger
Centre to step up the production of raw sequence. In response to this increased support, the
Sanger Centre revised its objective by aiming to sequence a full one-third of the entire genome
rather than just one-sixth. The race between the public and private projects was on, and the
milestones of the sequencing project came ever more rapidly.
Venter's firm energized the publicly funded project and inspired intensified efforts. HGP
investigators feared that if their efforts were perceived as slow and inefficient, the HGP would
lose congressional support and funding. The threat of genomic information ending up solely in
the hands of a private firm was simply unacceptable to the researchers. When Celera entered
the race to sequence the human genome, it changed the landscape of the field. Celera resolved
to make its data available only to paying customers and planned to patent some sequences
before releasing them.
The publicly funded HGP released sequence information quickly both to provide the scientific
community with timely data that were immediately usable and to place identified sequences
beyond the reach of commercial companies wishing to patent them or charge for access to the
data. The leadership of the HGP echoed the sentiments that had prompted Watson's
resignation. It contended that patenting the human sequence was unethical and delayed the
timely application of genomic information to medical disorders. Even though the HGP staunchly
opposed privileged access to the data, to speed completion of the project it had agreed to grant
Celera specific rights to the data generated by the collaborative effort between the two groups.
The First Draft of the Completed Human Genome
In April 2000 Celera announced that it was prepared to present the first draft of the human
genome. Not unexpectedly, scientists and the public eagerly anticipated this "first look" at the
human genome. Even though geneticists and other scientists could better comprehend the
mechanics and the future implications of this endeavor than the general public, the significance
of this achievement was evident to professionals and lay people alike. The professional
literature and the mass media had successfully communicated the importance of this
achievement, and it was understood that knowledge of the human genome held the key to the
singularity of the human species. Furthermore, it was widely assumed that this information
would be the basis for unprecedented advances in medicine and biomedical technology.
In "Rival Demands Sink Genome Alliance Plans" (Nature, vol. 404, no. 6774, March 9, 2000),
Natasha Loder explains that all hopes for continuing cooperation and collaboration between
the HGP and Celera were dashed when a letter from the Wellcome Trust was released to the
public. The letter described the HGP's concerns about Celera's intent to have its commercial
rights extended to research applications and to publish data from the collaborative efforts
under its name alone. Celera termed the release of the letter as unethical, and in a media
interview Venter described it as "a low-life thing to do." The anger and bitterness between the
two groups was not resolved and each vowed to publish the data separately.
In February 2001 the first working draft of the human genome was published in special issues of
the journals Nature (vol. 409, no. 6822, February 15, 2001) and Science (vol. 291, no. 5507,
February 16, 2001). Nature detailed the initial analysis of the descriptions of the sequence
generated by the HGP, and Science contained the draft sequence reported by Celera. Nature
said its choice to publish the HGP data reflected its traditional preference for publicly funded
research. Science editors Barbara R. Jasny and Donald Kennedy lauded Venter's group in the
editorial "The Human Genome," writing "his colleagues made it possible to celebrate this
accomplishment far sooner than was believed possible."
One of several surprises from the first draft was that previous estimates of gene number
appeared to have been wildly inaccurate. Most pregenome project estimates predicted that
humans had as many as 60,000 to 150,000 genes. The first draft of the complete genome
sequence indicated that the true number of genes required to make a human being was less
than 40,000. (The current estimate is between 20,000 and 25,000 genes.) By comparison, yeast
have 6,000 genes, fruit flies have 14,000, roundworms have 19,000, and the mustard weed
plant has 26,000. Another surprise was the observation that humans share 99.9% of the
nucleotide code in the human genome. Notably, human diversity at the genetic level is encoded
by less than a 0.1% variation in DNA.
First Draft Is Headline News
In June 2000 the White House press release "President Clinton Announces the Completion of
the First Survey of the Entire Human Genome"
(http://www.ornl.gov/sci/techresources/Human_Genome/project/clinton1.shtml) predicted
some of the anticipated medical outcomes of the project. These included the ability to:

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Alert patients that they are at risk for certain diseases. Once scientists discover
which DNA sequence changes in a gene can cause disease, healthy people can be
tested to see whether they risk developing conditions such as diabetes or
prostate cancer later in life. In many cases, this advance warning can be a cue to
start a vigilant screening program, to take preventive medicines, or to make diet
or lifestyle changes that may prevent the disease.
Reliably predict the course of disease. Diagnosing ailments more precisely will
lead to more reliable predictions about the course of a disease. For example, a
genetic fingerprint will allow doctors treating prostate cancer to predict how
aggressive a tumor will be. New genetic information will help patients and
doctors weigh the risks and benefits of different treatments.
Precisely diagnose disease and ensure the most effective treatment is used.
Genetic analysis allows us to classify diseases, such as colon cancer and skin
cancer, into more defined categories. These improved classifications will
eventually allow scientists to tailor drugs for patients whose individual response
can be predicted by genetic fingerprinting. For example, cancer patients facing
chemotherapy could receive a genetic fingerprint of their tumor that would
predict which chemotherapy choices are most likely to be effective, leading to
fewer side effects from the treatment and improved prognoses.
Developing new treatments at the molecular level. Drug design, guided by an
understanding of how genes work and knowledge of exactly what happens at the
molecular level to cause disease, will lead to more effective therapies. In many
cases, rather than trying to replace a gene, it may be more effective and simpler
to replace a defective gene's protein product. Alternatively, it may be possible to
administer a small molecule that would interact with the protein to change its
behavior. This is the strategy behind a drug in development for chronic
myelogenous leukemia, which targets the genetic flaw causing the disease. It
attaches to the abnormal protein caused by the genetic flaw and blocks its
activity. In preliminary tests, blood counts returned to normal in all patients
treated with the drug.
That same month BBC News (June 26, 2000, http://news.bbc.co.uk/1/hi/sci/tech/807126.stm)
compiled assessments of the achievement by the world's premier scientists and politicians.
Venter spoke for many researchers when he said, "I think we will view this period as a very
historic time, a new starting point." Michael Dexter of the Wellcome Trust echoed Venter's
sentiments when he ventured, "This is the outstanding achievement not only of our lifetime,
but in terms of human history. I say this, because the Human Genome Project does have the
potential to impact on the life of every person on this planet." Randy Scott, the president of
Incyte, another private firm involved in genomics research, predicted that "the availability of
genome sequence is just the beginning. Scientists now want to understand the genes and the
role they play in the prevention, diagnosis and treatment of disease." Mike Stratton of the
Cancer Genome Project was equally optimistic when he said that "it would surprise me
enormously if in 20 years the treatment of cancer had not been transformed." Sanger, the
pioneer of DNA sequencing, expressed the collective awe of the scientific community when the
HGP was completed earlier than anticipated. He admitted, "I never thought it would be done as
quickly as this."
The U.S. media celebrated the achievement with a flood of press releases and features. Efforts
were also made to explain this monumental accomplishment to the public and to educate
students. The DOE Human Genome Program provided a wealth of information about the HGP
and its findings on the Internet. Figure 7.6: From DNA to humans is an example of the
information the DOE made available to the public. Figure 7.7: Projected national benefits of
genomics research presents some of the potential environmental benefits of the HGP, including
reducing the impact of climate change and development of sustainable energy sources that
may be realized in the future.
Puffer Fish and Mouse Genomes Are Sequenced
In July 2002 the DOE Joint Genome Institute (JGI), operated by the Lawrence Berkeley National
Laboratory, the Lawrence Livermore National Laboratory, and the Los Alamos National
Laboratory, announced the draft sequencing, assembly, and analysis of the genome of the
Japanese puffer fish Fugu rubripes. The Fugu Genome Project was initiated in 1989 in
Cambridge, England, and in November 2000 the International Fugu Genome Consortium was
formed, headed by the JGI. During 2001 the puffer fish genome was sequenced and assembled
using the whole genome method pioneered by Celera. The puffer fish was the first vertebrate
genome to be publicly sequenced and assembled in this manner and the first vertebrate
genome published after the human genome. According to the JGI (2011, http://genome.jgipsf.org/Takru4/Takru4.home.html), puffer fish have the smallest known genomes among
vertebrates (animals with bony backbones or cartilaginous spinal columns—fish, reptiles, birds,
and mammals, including humans). The puffer fish sequence has about the same number of
genes as the considerably larger human genome, but is more compact because it contains
relatively little of the junk DNA present in the human genome sequence.
Comparison of the human and puffer fish genomes enabled investigators to predict the
existence of nearly 1,000 previously unidentified human genes. Even though the function of
these additional genes is as yet unknown, they contribute to the complete catalog of human
genes. Ascertaining the existence and location of genes helped scientists begin to describe how
they are regulated and function in the human body. Of the more than 30,000 puffer fish genes
identified, the vast majority of human genes have counterparts in the puffer fish, with the most
significant differences in genes of the immune system, metabolic regulation, and other
physiological systems that are not alike in fish and mammals.
On December 5, 2002, the first draft of the sequence of the mouse genome was published in
Nature (vol. 420, no. 6915). The mouse genome findings were deemed among the most
important in terms of their comparability with humans. Mice and humans have about the same
number of genes—approximately 20,000—and DNA base pairs—mice have 2.5 billion and
humans have approximately 3 billion. More importantly, about 90% of genes associated with
medical disorders in humans have counterparts in mice. This finding means that mice are
especially well suited for studying diseases that afflict humans and for testing therapeutic
treatments for disease.
The HGP Is Completed
After the publication of a first-draft human genome in 2001, researchers continued to fill in the
blanks and produce a complete and accurate sequence. In January 2003 another milestone in
the human genome sequencing effort was reported: the fourth human chromosome—
chromosome 14, the largest one to date, with 87 million base pairs—had been sequenced.
Roland Heilig et al. published their findings in "The DNA Sequence and Analysis of Human
Chromosome 14" (Nature, vol. 421, no. 6923, February 6, 2003). They found two genes that are
vital for immune responses on chromosome 14 and about 60 genes that, when defective,
contribute to disorders such as spastic paraplegia and Alzheimer's disease.
In a remarkable coincidence that made the crowning achievement of the HGP even more
poignant, the completion of the sequencing of the human genome occurred during the same
year slated for celebrations of the 50th anniversary of the discovery of the DNA double helix.
On April 14, 2003, the International Human Genome Sequencing Consortium, which is directed
by the DOE and the NHGRI, announced in the press release "All Goals Achieved: New Vision for
Genome Research Unveiled" (http://www.genome.gov/11006929) the successful completion of
the HGP more than two years earlier than had been anticipated. The consortium included
scientists at 20 sequencing centers in China, France, Germany, Great Britain, Japan, and the
United States.
Nature, the same journal that had published the groundbreaking discoveries of Watson and
Crick 50 years earlier, hailed the era of the genome in a special edition dated April 24, 2003
(vol. 422, no. 6934). As had been the practice since the inception of the HGP, the entirety of
sequence data generated by the HGP was immediately entered into public databases and made
freely available to the scientific community throughout the world, with no restrictions on its use
or redistribution. The data are used by researchers in academic settings and industry, as well as
by commercial firms that provide information services to biotechnologists.
In "All Goals Achieved," the DOE and the NHGRI describe the international effort to sequence
the 3 billion DNA base pairs in the human genome as "one of the most ambitious scientific
undertakings of all time," comparing it to feats such as splitting the atom or traveling to the
moon. Collins proudly declared that "the Human Genome Project has been an amazing
adventure into ourselves, to understand our own DNA instruction book, the shared inheritance
of all humankind. All the project's goals have been completed successfully—well in advance of
the original deadline and for a cost substantially less than the original estimates." In the same
press release Eric Steven Lander (1957-), the director of the Whitehead Institute/Massachusetts
Institute of Technology Center for Genome Research, predicted the postgenomic era when he
asserted, "The Human Genome Project represents one of the remarkable achievements in the
history of science. Its culmination this month signals the beginning of a new era in biomedical
research. Biology is being transformed into an information science, able to take comprehensive
global views of biological systems. With knowledge of all the components of the cells, we will
be able to tackle biological problems at their most fundamental level."
Collins urged the scientific community not to rest on its laurels in the wake of this triumph,
saying, "With this foundation of knowledge firmly in place, the medical advances promised
from the project can now be significantly accelerated." The April 24, 2003, issue of Nature
detailed the challenges researchers will face in the postgenomic era as they seek to employ the
HGP data to treat disease and improve public health. Recommendations included collaborative
efforts to produce:

New tools to allow discovery in the not-too-distant future of the genetic contributions
to frequently occurring diseases, including diabetes, heart disease, and mental illnesses
such as schizophrenia.



Improved methods for the early detection of disease and to enable timely treatment
when it is likely to be effective.
New technologies able to sequence the entire genome of any person affordably, ideally
for less than $1,000.
Wider access to tools and technologies of "chemical genomics" to enhance
understanding of biological pathways and accelerate pharmaceutical and other
treatment research.
Along with the special commemorative issue of Nature, the April 11, 2003, edition of Science
(vol. 300, no. 5617) ran articles that described the HGP and detailed the multidisciplinary DOE
plan dubbed "Genomes to Life," which aimed to use HGP data to understand the ways in which
microbes can provide opportunities to develop clean energy, reduce climate change, and clean
the environment.
The HGP Revises Its Estimate
In the October 2004 press release "International Human Genome Sequencing Consortium
Describes Finished Human Genome Sequence" (http://www.genome.gov/12513430), the
NHGRI reduced its estimate of the number of human genes from between 30,000 to 35,000 to
between 20,000 and 25,000. The refined human genome sequence, published in "Finishing the
Euchromatic Sequence of the Human Genome" (Nature, vol. 431, no. 7011, October 21, 2004),
was the most complete version to date. According to HGP scientists, it covered 99% of the
gene-containing parts of the human genome, identified nearly all known genes, and was 99.9%
accurate.
Dawn of the Postgenomic Era
In "Potential Benefits of Human Genome Project Research" (October 9, 2009,
http://www.ornl.gov/sci/techresources/Human_Genome/project/benefits.shtml), Human
Genome Project Information enumerates many of the potential benefits of HGP research.
Besides its role in the practice of molecular medicine, other uses of HGP data and applications
of human and other genomic research include:



Microbial genomics—using bacteria to create new energy sources such as biofuels and
safe, efficient toxic waste cleanup; enhancing understanding of how microbes cause
disease; and protecting workers and the public from threats of biological and chemical
terrorism and warfare. (See Figure 7.9 below.)
Risk assessment—measuring the risks and health problems caused by exposure to
radiation, carcinogens (cancer-causing agents), and mutagenic chemicals; and reducing
the probability of heritable mutations.
Archaeology, anthropology, evolution, and human migration—comparing the genomes
of humans and other organisms such as mice has already identified similar genes
associated with diseases and traits; improving the understanding of germline (cells that
give rise to eggs or sperm) mutations; studying migration based on female genetic
inheritance; examining mutations on the Y chromosome to trace lineage and migration
of males; and comparing the DNA sequences of entire genomes of different microbes to
enhance the understanding of the relationships among the three domains of life:
archaebacteria (cells that do not contain nuclei), eukaryotes (cells that contain nuclei),
and prokaryotes (single-celled organisms without nuclei).


DNA forensics—identifying crime victims, potential suspects, and catastrophe victims
through examination of DNA; confirming paternity and other family relationships;
clearing people wrongly accused of crimes; identifying and protecting endangered
species; detecting bacterial and other environmental pollutants; matching organ donors
and recipients for transplant programs; and determining pedigrees for animals and
plants.
Agriculture and livestock breeding—developing healthier and stronger crops and farm
animals that can resist insects, disease, and drought; creating safer pesticides; growing
more nutritious produce; incorporating vaccines into food products; and redeploying
plants such as tobacco for use in environmental cleanup programs.
Figure 7.9: Projected solutions to energy challenges arising from genomics research
Molecular Medicine
The HGP and the technological advances it has produced have moved the field of molecular
medicine forward with extraordinary speed. Ivan C. Gerling, Solomon S. Solomon, and Michael
Bryer-Ash assert in "Genomes, Transcriptomes, and Proteomes: Molecular Medicine and Its
Impact on Medical Practice" (Archives of Internal Medicine, vol. 163, no. 2, January 27, 2003)
that the HGP will not only influence the way science is conducted but will also advance the
clinical practice of medicine. The researchers credit the HGP for the technological advances that
enable preclinical detection (recognition of disease before its earliest biochemical or visible
expression). Gerling, Solomon, and Bryer-Ash foresee increasing accuracy and ease of
preclinical detection, as well as the ability to predict disease based on three fundamental levels
of biologic determination:



The genomic DNA constitution of the individual (the genome) is unchanged from the
moment of conception, except for some isolated, local mutations
The transcribed messenger RNA complement (the transcriptome)
The full range of translated proteins (the proteome)
Gerling, Solomon, and Bryer-Ash posit that the environment influences gene expression and
modifies gene products in ways that initiate, accelerate, or slow progress of disease-causing
processes. This does not change the genome, but it does change the transcriptome and the
proteome. Technological advances that occurred during the 1990s and the first few years of the
first decade of the 21st century have provided the tools to perform the comprehensive
molecular analyses needed to examine not only the genome but also the transcriptome and
proteome. Using new technologies will dramatically increase understanding at the molecular
level of the mechanisms of disease development.
Haplotype Mapping Project
In October 2002 an international effort to develop a haplotype map of the human genome was
launched. A haplotype is a set of alleles (particular forms of genes) or markers on one of a pair
of homologous chromosomes, and a haplotype map will show human genetic variation. The
premise of the International HapMap Project was that within the human genome different
genetic variants within a chromosomal region (haplotypes) occur together far more frequently
than others. Based on common haplotype patterns (combinations of DNA sequence variants
that are usually found together), the haplotype map simplifies the search for medically
important DNA sequence variations and offers new understanding of human population
structure and history.
Given that any two people are 99.9% identical genetically, understanding the 0.1% difference is
important because it helps explain why one person may be more susceptible to a certain
disease than another. Researchers can use the HapMap to compare the genetic variation
patterns of a group of people known to have a specific disease with a group of people without
the disease. Finding a certain pattern more often in people with the disease identifies a
genomic region that may contain genes that contribute to the condition. Researchers hope that
identifying single nucleotide polymorphisms (SNPs), which are specific positions in the genome
sequence that are occupied by one nucleotide in some copies and by a different nucleotide in
others, will enable them to identify the alleles that are associated with increased or decreased
susceptibility to common diseases, such as asthma, heart disease, or psychiatric illness. Figure
7.10: Most single nucleotide polymorphism (SNP) variation occurs within all groups shows that
most SNP variation (about 85%) occurs within all populations.
Researchers hypothesize that differences between haplotypes may be associated with varying
susceptibility to disease. As such, they indicate that mapping the haplotype structure of the
human genome may be the key to identifying the genetic basis of many common disorders. The
HapMap project serves as a resource for studying the genetic factors that contribute to
variation in response to environmental factors, in susceptibility to infection, and in the
identification of genetic variants that are associated with the effectiveness of, and adverse
responses to, drugs and vaccines.
To create a haplotype map, researchers must have enough SNPs to be sure that regions
containing disease alleles have been found and that regions not containing disease alleles can
be excluded from further consideration. The HapMap enables researchers to study the genetic
risk factors underlying a wide range of disorders. For any given disease, researchers may
perform an association study by using the HapMap tag SNPs to compare the haplotype patterns
of a group of people known to have the disease to a group of people without the disease. If the
association study finds a specific haplotype more frequently in those with the disease,
researchers scrutinize the precise genomic region in their search for the specific genetic variant.
By mid-2005 a draft of the HapMap, consisting of 1 million markers of genetic variation, was
released. The first draft of the HapMap enabled researchers to analyze the human genome in
ways that were not possible with the human DNA sequence alone. Second-generation data
from the project were released in July 2006 and provided a denser map that enables scientists
to narrow gene discovery more precisely to specific regions of the genome. The first- and
second-generation HapMaps analyzed data from 270 people from four different populations:
Yoruba in Ibadan, Nigeria; Japanese in Tokyo, Japan; Han Chinese in Beijing, China; and people
with north and west European ancestry living in Utah.
In September 2010 the International HapMap 3 Consortium published a third generation of the
HapMap in "Integrating Common and Rare Genetic Variation in Diverse Human Populations"
(Nature, vol. 467, no. 7311). The third-generation HapMap is the largest survey of human
genetic variation performed as of January 2011 and contains data from 1,184 people from a
total of 11 different populations, the four original populations and seven additional
populations: people with African ancestry living in the southwestern United States; people with
Chinese ancestry in Denver, Colorado; Gujarati Indians in Houston, Texas; Luhya people in
Webuye, Kenya; Maasai people in Kinyawa, Kenya; people with Mexican ancestry in Los
Angeles, California; and Italians in Tuscany, Italy. Because the third-generation HapMap looked
at 1.6 million SNPs in approximately 500 samples from the four original populations and over
650 samples from the seven new populations, it was able to detect rarer variants than those
identified in the two previous HapMaps. Writing in Nature, the International HapMap 3
Consortium concludes, "This expanded public resource of genome variants in global
populations supports deeper interrogation of genomic variation and its role in human disease,
and serves as a step towards a high-resolution map of the landscape of human genetic
variation."
The Future of Genomic Research
Established by the NHGRI in September 2003, the Encyclopedia of DNA Elements (ENCODE)
Project (January 4, 2011, http://www.genome.gov/10005107) aims to develop efficient ways to
identify and locate all the protein-coding genes, nonprotein-coding genes, and other sequencebased functional elements contained in the human DNA sequence. This ambitious undertaking
has created an enormous resource for researchers seeking to use and apply the human
sequence to predict disease risk and to develop new approaches to prevent and treat disease.
The ENCODE Project entails three phases: a three-year pilot project phase that began in
September 2003, a second technology development phase that parallels phase 1, and a planned
production phase. In "The ENCODE (ENCyclopedia Of DNA Elements) Project" (Science, vol. 306,
no. 5696, October 22, 2004), the ENCODE researchers describe their plans to build a "parts list"
of all sequence-based functional elements in the human DNA sequence. The researchers hope
to identify as-yet-unrecognized functional elements. During the pilot phase they developed and
tested ways to efficiently identify functional elements. They focused on 44 DNA targets, which
together cover 30 million base pairs (about 1% of the human genome). The target regions were
strategically selected to provide a representative cross section of the entire human genome
sequence. The conclusions from the pilot phase, which ended in 2006, were published in
"Identification and Analysis of Functional Elements in 1% of the Human Genome by the
ENCODE Pilot Project" (Nature, vol. 447, no. 7146, June 14, 2007). The ENCODE researchers
describe the human genome as an "elegant but cryptic store of information" and report that
their analyses provide a "rich source of functional information ... of the human genome" and
that the pilot phase constituted "an impressive platform for future genome exploration
efforts." During the second phase the researchers worked to develop new technologies to apply
to the ENCODE Project. In the press release "Researchers Expand Efforts to Explore Functional
Landscape of the Human Genome" (October 9, 2007, http://www.genome.gov/26023194), the
NHGRI states that it awarded grants totaling more than $80 million over the next four years to
fund the production phase of the project.
Susan E. Celniker et al. observe in "Unlocking the Secrets of the Genome" (Nature, vol. 459, no.
7249, June 18, 2009) that free access to not only the human genome but also to the genomes
of five model organisms—Escherichia coli, yeast (Saccharomyces cerevisiae), worm
(Caenorhabditis elegans), fly (Drosophila melanogaster), and mouse (Mus musculus)—has
provided new insights into how the information encoded in the genome produces complex
multicultural organisms. The pilot and first phases of the ENCODE analysis produced new
insights, pointed out the complexity of the biology, and raised new questions. In 2007 the
NHGRI expanded the human ENCODE project to include the entire genome and initiated the
model organism ENCODE (modENCODE) project to catalog the genomic elements of the worm
and fly, which share similarities with other organisms, even humans. The advantage of
cataloging these genomes is that they are small enough to be thoroughly examined using
currently available technologies. Celniker et al. opine that the modENCODE results "will add
value to the human ENCODE effort by illuminating the relationship between molecular and
biological events. In the future, these data will provide a powerful platform for characterizing
the functional networks that direct multicellular biology, thereby linking genomic data with the
biological programs of higher organisms, including humans." Figure 7.11: The modENCODE
project, 2010 shows the kind of genomic and other data the modENCODE project makes
available online. The figure depicts how users of the electronic database can access the
chromosome arm genomic sequence of a specific species, such as D. melanogaster (small fruit
flies) and C. elegans (roundworms).
Another NHGRI initiative is the creation of publicly available libraries, such as the NIH Chemical
Genomics Center, which collects and catalogs data about chemical compounds for scientists
who are engaged in developing chemical probes and charting biological pathways. These
chemical compounds have many promising applications in genomic research. For example, their
ability to enter cells readily makes them natural vehicles for pharmaceutical drug development
and drug delivery system design. An endeavor of this size and scope requires significant
financial and human resources, and the NHGRI is planning to use technologies such as roboticenabled, high-output screening to create large libraries containing up to a million chemical
compounds.
The United Kingdom's Wellcome Trust, along with Canadian funding organizations and the
global pharmaceutical company GlaxoSmithKline, established the charitable organization
Structural Genomics Consortium in April 2003 to round out international efforts in structural
genomics. Structural genomics is the systematic, high-volume generation of the threedimensional structure of proteins. The goal of examining the structural genomics of any
organism is the complete structural description of all proteins encoded by the genome of that
organism. These descriptions are important for drug design, diagnosis, and treatment of
disease. Like the HGP and the Chemical Genomics Center, the Structural Genomics Consortium
is placing all the protein structures in public databases where scientists throughout the world
may access them.
In "Dynamic Timeline" (February 4, 2010, http://www.genome.gov/25019887), the NHGRI
illustrates some of the research challenges and accomplishments of the postgenomic era.
Besides the HapMap project and the DOE's "Genomes to Life," it describes the 2006 launch of
The Cancer Genome Atlas (TCGA, http://cancergenome.nih.gov/wwd/program/), a network of
over 150 researchers at dozens of institutions across the United States that is mapping the
genomic changes in more than 20 tumor types in an effort to create a resource for use in
developing new strategies to prevent, diagnose, and treat cancer.
In October 2008 the TCGA reported the first results of its large-scale, comprehensive study of
glioblastoma (GBM), the most common form of brain cancer. TCGA researchers described in
"Comprehensive Genomic Characterization Defines Human Glioblastoma Genes and Core
Pathways" (Nature, vol. 455, no. 7216, October 23, 2008) the discovery of new genetic
mutations and other types of DNA alterations with potential implications for the diagnosis and
treatment of GBM. In January 2010 TCGA researchers detailed in "Integrated Genomic Analysis
Identifies Clinically Relevant Subtypes of Glioblastoma Characterized by Abnormalities in
PDGFRA, IDH1, EGFR, and NF1" (Cancer Cell, vol. 17, no. 1, January 19, 2010) four distinct
subtypes of GBM and reported that each subtype responded differently to chemotherapeutic
and radiation therapies. Even though these research findings cannot be immediately translated
into clinical practice, they may lead to more individualized treatments based on patients'
genomic alterations. The TCGA indicates in "Scientific Publications" (2010, Scientific
Publications, http://cancergenome.nih.gov/publications/scientific.asp) that in 2010 alone its
researchers published 21 articles describing their research findings in peer-reviewed science
and medical journals.
According to the NHGRI, in "2006: Initiatives to Establish the Genetic and Environmental Causes
of Common Diseases Launched" (April 10, 2006, http://www.genome.gov/25520287), two
other disease-related initiatives were established in 2006. The NIH Genes and Environment
Initiative (GEI) analyzes genetic variation among people with specific diseases and develops
technology to effectively monitor the environmental exposures that interact with genetic
variations to cause or trigger disease. The second initiative was a public-private partnership
called Genetic Association Information Network (GAIN), which was based on the assumption
that by working together, public and private scientists would progress faster than either could
working alone. GAIN aimed to determine the genetic contributions to common diseases. GAIN
researchers conducted genome-wide association studies that focused on psychiatric disorders,
psoriasis (a common skin disorder), Crohn's disease (an inflammatory bowel disease), breast
and prostate cancers, and diabetes. Funded by Pfizer Global Research and Development, this
initiative concluded at the close of 2008.
Reproductive Cloning
Human reproductive cloning should not now be practiced. It is dangerous and likely to fail. The
panel therefore unanimously supports the proposal that there should be a legally enforceable
ban on the practice of human reproductive cloning. For this purpose, we define human
reproductive cloning as the placement in a uterus of a human blastocyst derived by the
technique that we call nuclear transplantation.
—Committee on Science, Engineering, and Public Policy Board on Life Sciences, Scientific and
Medical Aspects of Human Reproductive Cloning (2002)
AAAS endorses a legally enforceable ban on efforts to implant a human cloned embryo for the
purpose of reproduction. The scientific evidence documenting the serious health risks associated
with reproductive cloning, as shown through animal studies, make it unconscionable to
undertake this procedure. At the same time, we encourage continuing open and inclusive public
dialogue, in which the scientific community is an active participant, on the scientific and ethical
aspects of human cloning as our understanding of this technology advances.
—American Association for the Advancement of Science Statement on Human Cloning,
February 14, 2002
The Human Genome Project defines three distinct types of cloning. The first is the use of highly
specialized deoxyribonucleic acid (DNA) technology to produce multiple, exact copies of a single
gene or other segment of DNA to obtain sufficient material to examine for research purposes.
This process produces cloned collections of DNA known as clone libraries. The second kind of
cloning involves the natural process of cell division to create identical copies of the entire cell.
These copies are called a cell line. The third type of cloning, reproductive cloning, is the one
that has received the most attention in the mass media. This is the process that generates
complete, genetically identical organisms such as Dolly, the famous Scottish sheep cloned in
1996 and named after the entertainer Dolly Parton (1946-).
Cloning may also be described by the technology that is used to perform it. For example, the
term recombinant DNA technology describes the technology and mechanism of DNA cloning.
Also known as molecular cloning, or gene cloning, it involves the transfer of a specific DNA
fragment of interest to researchers from one organism to a self-replicating genetic element of
another species such as a bacterial plasmid. (See Figure 8.1: Bacterial plasmid.) The DNA under
study may then be reproduced in a host cell. This technology has been in use since the 1970s
and is a standard practice in molecular biology laboratories.
According to Christina Ullman ("Cloning" in Genes & Society Graphics, Genetics & Public Policy
Center at Johns Hopkins University with support from the Pew Charitable Trusts, 2008,
http://www.dnapolicy.org/resources/cloning_infographic_final.pdf, accessed October 11, 2010)
displays and describes the differences between different types of cloning. This graphic
depiction was developed by the Johns Hopkins University's Genetics and Public Policy Center of
the Phoebe R. Berman Bioethics Institute with support from the Pew Charitable Trusts. Also
presented are some of the current and potential applications of therapeutic cloning, which
produces stem cells that may be used to improve human health. This chapter focuses on
cloning genes and reproductive cloning and the following chapter describes therapeutic cloning
and stem cell research.
Just as GenBank is an online public repository of the human genome sequence, the Clone
Registry database is a sort of "public library." Used by genome sequencing centers to record
which clones have been selected for sequencing, which sequencing efforts are currently under
way, and which are finished and represented by sequence entries in GenBank, the Clone
Registry may be freely accessed by scientists worldwide. To effectively coordinate all of this
information, a standardized system of naming clones is essential. The nomenclature used is
shown in Figure 8.3: Standardized clone names.
Cloning Genes
Molecular cloning is performed to enable researchers to have many copies of genetic material
available in the laboratory for the purpose of experimentation. Cloned genes allow researchers
to examine encoded proteins and are used to sequence DNA. Gene cloning also allows
researchers to isolate and experiment on the genes of an organism. This is particularly
important in terms of human research; in instances where direct experimentation on humans
might be dangerous or unethical, experimentation on cloned genes is often practical and
feasible.
Cloned genes are also used to produce pharmaceutical drugs, insulin (a pancreatic hormone
that regulates blood glucose levels), clotting factors, human growth hormone, and industrial
enzymes. Before the widespread use of molecular cloning, these proteins were difficult and
expensive to manufacture. For example, before the development of recombinant DNA
technology, insulin used by people with diabetes was extracted and purified from cow and pig
pancreases. Because the amino acid sequences of insulin from cows and pigs are slightly
different from those in human insulin, some patients experienced adverse immune reactions to
the nonhuman "foreign insulin." The recombinant human version of insulin is identical to
human insulin so it does not produce an immune reaction.
Figure 8.4: Cloning DNA in plasmids shows how a gene is cloned. First, a DNA fragment
containing the gene being studied is isolated from chromosomal DNA using restriction enzymes.
It is joined with a plasmid (a small ring of DNA found in many bacteria that can carry foreign
DNA) that has been cut with the same restriction enzymes. When the fragment of
chromosomal DNA is joined with its cloning vector (cloning vectors, such as plasmids and yeast
artificial chromosomes, introduce foreign DNA into host cells), it is called a recombinant DNA
molecule. Once it has entered into the host cell, the recombinant DNA can be reproduced along
with the host cell DNA.
Another molecular cloning technique that is simpler and less expensive than the recombinant
cloning method is the polymerase chain reaction (PCR). PCR has also been dubbed "molecular
photocopying" because it amplifies DNA without the use of a plasmid. Figure 6.5: Polymerase
chain reaction (PCR) shows how PCR is used to generate a virtually unlimited number of copies
of a piece of DNA.
A collection of clones of chromosomal and vector DNA (a small piece of DNA containing
regulatory and coding sequences of interest) is called a library. These libraries of clones
containing partly overlapping regions are constructed to show that two particular clones are
next to one another in the genome. Figure 8.5: Construction of an overlapping clone library
shows how, by dividing the inserts into smaller fragments and determining which clones share
the same DNA sequences, clone libraries are constructed.
Organismal or Reproductive Cloning
Another way to describe and classify cloning is by its purpose. Organismal or reproductive
cloning is a technology used to produce a genetically identical organism—an animal with the
same nuclear DNA as an existing animal.
The reproductive cloning technology used to create animals is called somatic cell nuclear
transfer (SCNT). In SCNT scientists transfer genetic material from the nucleus of a donor adult
cell to an enucleated egg (an egg from which the nucleus has been removed). This eliminates
the need for fertilization of an egg by a sperm. The reconstructed egg containing the DNA from
a donor cell is treated with chemicals or electric current to stimulate cell division. Once the
cloned embryo reaches a suitable stage, it is transferred to the uterus of a surrogate (female
host), where it continues to grow and develop until birth. Figure 8.6: Reproductive cloning
shows the entire SCNT process that culminates in the transfer of the embryo into the surrogate
mother and ultimately the birth of a cloned animal.
Organisms or animals generated using SCNT are not perfect or identical clones of the donor
organism or "parent" animal. The clone's nuclear DNA is identical to the donor's, but some of
the clone's genetic materials come from the mitochondria in the cytoplasm of the enucleated
egg. Mitochondria, the organelles that serve as energy sources for the cell, contain their own
short segments of DNA called mtDNA. Acquired mutations in the mtDNA contribute to
differences between clones and their donors and are believed to influence the aging process.
Dolly the Sheep Paves the Way for Other Cloned Animals
In 1952 scientists transferred a cell from a frog embryo into an unfertilized egg, which then
developed into a tadpole. This process became the prototype for cloning. Ever since, scientists
have been cloning animals. During the 1980s the first mammals were also cloned from
embryonic cells. In 1996 cloning became headline news when, after more than 250 failed
attempts, Ian Wilmut (1944-) and his colleagues at the Roslin Institute in Edinburgh, Scotland,
announced they had successfully cloned a sheep, which they named Dolly. Dolly was the first
mammal cloned from the cell of an adult animal, and since then researchers have used cells
from adult animals and various modifications of nuclear transfer technology to clone a range of
animals, including a gaur, sheep, goats, cows, horses, mules, oxen, deer, mice, rats, pigs, cats,
dogs, and rabbits.
To create Dolly, the Roslin Institute researchers transplanted a nucleus from a mammary gland
cell of a Finn Dorsett sheep into the enucleated egg of a Scottish blackface ewe and used
electricity to stimulate cell division. The newly formed cell divided and was placed in the uterus
of a blackface ewe to gestate. Born several months later, Dolly was a true clone—genetically
identical to the Finn Dorsett mammary cells and not to the blackface ewe, which served as her
surrogate mother. Her birth revolutionized the world's understanding of molecular biology,
ignited worldwide discussion about the morality of generating new life through cloning,
prompted legislation in dozens of countries, and launched an ongoing political debate in
Congress.
Dolly was the object of intense media and public fascination. She proved to be a basically
healthy clone and produced six lambs of her own through normal sexual means. Before her
death by lethal injection in February 2003, Dolly had been suffering from lung cancer and
arthritis. An autopsy (postmortem examination) of Dolly revealed that, other than her cancer
and arthritis, which are common diseases in sheep, she was anatomically like other sheep.
In February 1997 Don Paul Wolf (1939-) and his colleagues at the Oregon Regional Primate
Center in Beaverton successfully cloned two rhesus monkeys using laboratory techniques that
had previously produced frogs, cows, and mice. It was the first time that researchers used a
nuclear transplant to generate monkeys. The monkeys were created using different donor
blastocysts (early-stage embryos), so they were not clones of one another—each monkey was a
clone of the original blastocyst that had developed from a fertilized egg. Neither of the cloned
monkeys survived past the embryonic stage.
An important distinction between the process that created Dolly and the one that produced the
monkeys was that unspecialized embryonic cells were used to create the monkeys, whereas a
specialized adult cell was used to create Dolly. The Oregon experiment was followed closely in
the scientific and lay communities because, in terms of evolutionary biology and genetics,
primates are closely related to humans.
In 2000 the Oregon researchers succeeded when one of four embryos that were created by
splitting a blastocyst four ways and implanting the pieces into surrogate mothers survived. The
survivor was named Tetra, from the Greek prefix for the number four. Researchers and the
public speculated that if monkeys could be cloned, it might become feasible to clone humans.
In May 2001 BresaGen Limited, an Australian biotechnology firm, announced the birth of that
country's first cloned pig. The pig was cloned from cells that had been frozen in liquid nitrogen
for more than two years, and the company employed technology that was different from the
process used to clone Dolly the sheep. The most immediate benefit of this new technology was
to improve livestock—cloning enables breeders to take some animals with superior genetics
and rapidly produce more. Biomedical scientists were especially attentive to this research
because of its potential for xenotransplantation (the use of animal organs for transplantation
into humans). Pig organs that have been genetically modified so that they will not be rejected
by the human immune system could prove to be a boon to medical transplantation.
That same year the first cat was cloned, and the following year rabbits were successfully
cloned. In January 2003 researchers at Texas A&M University reported that cloned pigs
behaved normally—as expected for a litter of pigs—but were not identical to the animals from
which they were cloned in terms of food preferences, temperament, and how they spent their
time. The researchers explained the variation as arising from the environment and epigenetic
(not involving DNA sequence change) factors, causing the DNA to line up differently in the
clones. Epigenetic activity is defined as any gene-regulating action that does not involve
changes to the DNA code and that persists through one or more generations, and it may explain
why abnormalities such as fetal death occur more frequently in cloned species.
In May 2003 a cloned mule (the first successful clone of any member of the horse family) was
born in Idaho. The clone was not just any mule, but the brother of the world's second-fastest
racing mule. Named Idaho Gem, the cloned mule was created by researchers at the University
of Idaho and Utah State University. The researchers attributed their success to changes in the
culture medium they used to nurture the eggs and embryos.
In August 2003 scientists at the Laboratory of Reproductive Technology in Cremona, Italy, were
the first to clone a horse. Cesare Galli et al. describe their cloning technique in "Pregnancy: A
Cloned Horse Born to Its Dam Twin" (Nature, vol. 424, no. 6949, August 7, 2003).
The mule was cloned from cells that were extracted from a mule fetus, whereas the cloned
horse's DNA came from her adult mother's skin cells. There were other differences as well. The
University of Idaho and Utah State University researchers harvested fertile eggs from mares,
removed the nucleus of each egg, and inserted DNA from cells of a mule fetus. The
reconstructed eggs were then surgically implanted into the wombs of female horses. In
contrast, Galli et al. harvested hundreds of eggs from mare carcasses, cultured the eggs,
removed their DNA, and replaced it with DNA taken from either adult male or female horse skin
cells.
In May 2004 the first bull was cloned from a previously cloned bull in a process known as serial
somatic cell cloning or recloning. Before the bull, the only other successful recloning efforts
involved mice. Chikara Kubota, X. Cindy Tian, and Xiangzhong Yang describe their cloning
technique in "Serial Bull Cloning by Somatic Cell Nuclear Transfer" (Nature Biotechnology, vol.
22, no. 6, June 2004). Their effort was also cited in the Guinness Book of World Records as the
largest clone in the world.
At the close of 2004 a South Korean research team reported cloning macaque monkey
embryos, which would be used as a source of stem cells. Conservationists then focused
research efforts on cloning rare and endangered species. In April 2005 Texas A&M University
announced the first successfully cloned foal in the United States. That same month scientists at
Seoul National University cloned a dog they named Snuppy. In May 2005 Embrapa, a Brazilian
agricultural research corporation, reported the creation of two cloned calves from a Junquiera
cow, which is an endangered species. In 2006 ferrets were cloned using somatic cell nuclear
transfer.
In 2009 the first camel was cloned in Dubai, United Arab Emirates. In 2010 researchers in Spain
reported cloning the first fighting bull. By the close of 2010, over 20 animal species had been
successfully cloned using nuclear transfer and surrogate mothers, the same technique that was
used to produce Dolly the sheep.
Cloning Endangered Species
Reproductive cloning technology may also be used to repopulate endangered species such as
the African bongo antelope, the Sumatran tiger, and the giant panda, or animals that reproduce
poorly in zoos or are difficult to breed. In January 2001 scientists at Advanced Cell Technology
(ACT), a biotechnology company in Massachusetts, announced the birth of the first clone of an
endangered animal, a baby bull gaur (a large wild ox from India and Southeast Asia). The gaur
was cloned using the nuclei of frozen skin cells taken from an adult male gaur that had died
eight years earlier. The skin cell nuclei were joined with enucleated cow eggs, one of which was
implanted into a surrogate cow. The cloned gaur died from an infection within days of its birth.
That same year scientists in Italy successfully cloned an endangered wild sheep. Cloning an
endangered animal is different from cloning a more common animal because cloned animals
need surrogate mothers to be carried to term. Furthermore, the transfer of embryos is risky,
and researchers are reluctant to put an endangered animal through the rigors of surrogate
motherhood, so they opt to use nonendangered domesticated animals whenever possible.
Cloning extinct animals is even more challenging than cloning living animals because the egg
and the surrogate mother used to create and harbor the cloned embryo are not the same
species as the clone. Furthermore, for most already extinct animal species such as the woolly
mammoth (Mammuthus primigenius) or the smilodon (Smilodon populator), there is
insufficient intact cellular and genetic material from which to generate clones. In the future,
carefully preserving intact cellular material of imperiled species may allow for their
preservation and propagation.
In 2003 ACT announced the birth of a healthy clone of a Javan banteng (an endangered
cattlelike animal native to Asian jungles). The clone was created from a single skin cell that was
taken from another banteng before it died in 1980. The skin cell was kept frozen until it was
used to create the clone. The banteng embryo gestated in a standard beef cow in Iowa.
Born in April 2003, the cloned banteng developed normally, growing its characteristic horns and
reaching an adult weight of about 1,800 pounds (816 kg). The banteng lived at the San Diego
Zoo until it died in April 2010 at the age of seven, less than half of the anticipated lifespan of a
uncloned banteng. Hunting and habitat destruction have reduced the number of banteng,
which once lived in large numbers in the bamboo forests of Asia, by more than 75% from 1983
to 2003. In "Ecological-Economic Models of Sustainable Harvest for an Endangered but Exotic
Megaherbivore in Northern Australia" (Natural Resource Modeling, vol. 20, no. 1, March 2007),
Corey J. A. Bradshaw and Barry W. Brook of Charles Darwin University report that in 2007 a
population of between 8,000 and 10,000 banteng lived on an isolated peninsula in northern
Australia.
In August 2005 the Audubon Nature Institute in New Orleans, Louisiana, reported that two
unrelated endangered African wildcat clones had given birth to eight babies. These births
confirmed that clones of wild animals can breed naturally, which is vitally important for
protecting endangered animals on the brink of extinction.
Rob Waters describes in "Animal Cloning: The Next Phase" (Bloomberg BusinessWeek, June 10,
2010) the Frozen Zoo, a laboratory repository of frozen skin cells and DNA from about 800
species that are housed at the San Diego Zoo's Institute for Conservation Research. Even
though the lab was established in 1972, the technology necessary to use the cells to clone
animals was still under development in 2010. In June 2010 tissue from the Frozen Zoo was used
to create stem cells of an endangered African monkey and the stem cells successfully
developed into brain cells, giving rise to the hope that in the not-too-distant future it will be
possible to clone endangered animals and save them from extinction.
Despite this progress, ethicists caution that there are moral considerations around the issue of
animal cloning. Several cloned animals, including two endangered cattle and the banteng, died
prematurely. Furthermore, ethicists question whether the risks (deformed and short-lived
animals) outweigh the benefits if just a few endangered animals that ultimately live in zoos are
created using cloning. According to Waters, Autumn M. Fiester of the University of
Pennsylvania observed, "There has been a lot of suffering with these early deaths and
malformations."
Reproductive Human Cloning
In December 2002 a religious sect known as the Raelians made news when their private
biotechnology firm, Clonaid, announced that it had successfully delivered the world's first
cloned baby. The announcement, which could not be independently verified or substantiated,
generated unprecedented media coverage and was condemned in the scientific and lay
communities. At least some of the media frenzy resulted from the beliefs of the Raelians—
namely, the sect contends that humans were created by extraterrestrial beings.
Clonaid's announcement, which ultimately was viewed as a hoax, brought attention to the fact
that several laboratories around the world had embarked on clandestine efforts to clone a
human embryo. For example, in 2002 Panayiotis Zavos (1944-), a U.S. fertility specialist, claimed
to be collaborating with about two dozen international researchers to produce human clones.
Another doctor focusing on fertility issues, Severino Antinori (1945-), attracted media attention
when he maintained that hundreds of infertile couples in Italy and thousands in the United
States had already enrolled in his human cloning initiative. As of January 2011, neither these
researchers nor anyone else had offered proof of successful reproductive human cloning.
Moral and Ethical Objections to Human Cloning
The difficulty and low success rate of much animal reproductive cloning (an average of just one
or two viable offspring result from every 100 attempts) and the as-yet-incomplete
understanding of reproductive cloning have prompted many scientists to deem it unethical to
attempt to clone humans. Many attempts to clone mammals have failed, and about one-third
of clones born alive suffer from anatomical, physiological, or developmental abnormalities that
are often debilitating. Some cloned animals have died prematurely from infections and other
complications at rates higher than conventionally bred animals, and some researchers
anticipate comparable outcomes from human cloning. Furthermore, scientists cannot yet
describe or characterize how cloning influences intellectual and emotional development. Even
though the attributes of intelligence, temperament, and personality may not be as important
for cattle or other primates, they are vital for humans. Without considering the myriad
religious, social, and other ethical concerns, the presence of so many unanswered questions
about the science of reproductive cloning has prompted many scientists to consider any
attempts to clone humans as scientifically irresponsible, unacceptably risky, and morally
unallowable.
People who oppose human cloning are as varied as the interests and institutions they support.
Religious leaders, scientists, politicians, philosophers, and ethicists argue against the morality
and acceptability of human cloning. Nearly all objections hinge, to various degrees, on the
definition of human life, beliefs about its sanctity, and the potentially adverse consequences for
families and society as a whole.
In an effort to stimulate consideration of and debate about this critical issue, the President's
Council on Bioethics examined the principal moral and ethical objections to human cloning in
Human Cloning and Human Dignity: An Ethical Inquiry (July 2002,
http://bioethics.georgetown.edu/pcbe/reports/cloningreport/pcbe_cloning_report.pdf). The
council's report distinguished between therapeutic and reproductive cloning and outlined key
concerns by trying to respond to many as yet unresolved questions about the ethics, morality,
and societal consequences of human cloning.
The council determined that the key moral and ethical objections to therapeutic cloning
(cloning for biological research) center on the moral status of developing human life.
Therapeutic cloning involves the deliberate production, use, and destruction of cloned human
embryos. One objection to therapeutic cloning is that cloned embryos produced for research
are no different from those that could be used in attempts to create cloned children. Another
argument that has been made is that the ends do not justify the means—that research on any
human embryo is morally unacceptable, even if this research promises cures for many dreaded
diseases. Finally, there are concerns that acceptance of therapeutic cloning will lead society
down a slippery slope to reproductive cloning, a prospect that is almost universally viewed as
unethical and morally unacceptable.
The unacceptability of human reproductive cloning stems from the fact that it challenges the
basic nature of human procreation by redefining having children as a form of manufacturing.
Human embryos and children may then be viewed as products and commodities rather than as
sacred and unique human beings. Furthermore, reproductive cloning might substantially
change fundamental issues of human identity and individuality, and allowing parents
unprecedented genetic control of their offspring may significantly alter family relationships
across generations.
The council concluded that "the right to decide 'whether to bear or beget a child' does not
include a right to have a child by whatever means. Nor can this right be said to imply a
corollary—the right to decide what kind of child one is going to have. ... Our society's
commitment to freedom and parental authority by no means implies that all innovative
procedures and practices should be allowed or accepted, no matter how bizarre or dangerous."
Nearly universal opposition to human cloning persisted in 2011. According to the Center for
Genetics and Society, in "About Reproductive Cloning" (2011,
http://www.geneticsandsociety.org/section.php?id=16), even though some researchers now
believe that it may be possible to safely clone humans, many more researchers remain
unconvinced. Other compelling arguments against human cloning focus on the psychological
health of cloned children and the concern that if human reproductive cloning was permitted, it
would also usher in the use of genetic manipulation techniques that could markedly alter the
fabric of society and even change the definition of human life.
Cloning of a human. By: Choi, Charles Q., Scientific American, 00368733, Jun2010, Vol. 302,
Issue 6
Ever since the birth of Dolly the sheep in 1996, human cloning for reproductive purposes has
seemed inevitable. Notwithstanding past dubious claims of such an achievement--including one
by a company backed by a UFO cult-- no human clones have been made, other than those born
naturally as identical twins. Despite success with other mammals, the process has proved much
more difficult in humans--which may strike some people as comforting and others as
disappointing.
Scientists generate clones by replacing the nucleus of an egg cell with that from another
individual. They have cloned human embryos, but none has yet successfully grown past the
early stage where they are solid balls of cells known as morulas--the act of transferring the
nucleus may disrupt the ability of chromosomes to align properly during cell division.
"Whenever you clone a new species, there's a learning curve, and with humans it's a serious
challenge getting enough good-quality egg cells to learn with," says Robert Lanza of Advanced
Cell Technology in Worcester, Mass., who made headlines in 2001 for first cloning human
embryos. Especially tricky steps include discovering the correct timing and mix of chemicals to
properly reprogram the cell.
Even with practiced efforts, some 25 percent of cloned animals have overt problems, Lanza
notes--minor slips during reprogramming, culturing or handling of the embryos can lead to
developmental errors. Attempting to clone a human would be so risky, Lanza says, it "would be
like sending a baby up into space in a rocket that has a 50-50 chance of blowing up."
Ethical issues would persist even assuming foolproof techniques. For instance, could people be
cloned without their knowledge or consent? On the other hand, a clone might lead a fuller life,
because it "really gets to learn" from the original, says molecular technologist George M.
Church of Harvard Medical School. "Say, if I learned at 25 I had a terrific ear for music but never
got music lessons, I could tell my twin to try it at 5."
The possibility of human cloning may not be restricted to Homo sapiens, either. Scientists may
soon completely sequence the Neandertal genome. Although DNA is damaged during
fossilization, an excellent fossil could yield enough molecules to generate a cloneable genome,
Church suggests. Bringing a cloned extinct species to term in a modern species is even more
challenging than normal cloning, considering that such factors as the womb environment and
gestation period might be mismatched. The only clone so far of an extinct animal--the bucardo,
a variety of ibex that died off in 2000--expired immediately after birth because of lung defects.
In the U.S., not all states have banned human reproductive cloning. The United Nations has
adopted a nonbinding ban. If human cloning happens, it will "occur in a less restrictive area of
the world--probably by some wealthy eccentric individual," Lanza conjectures. Will we recoil in
horror or grow to accept cloning as we have in vitro fertilization? Certainly developing new
ways to create life will force us to think about the responsibilities of wielding such immense
scientific power.
Clone Wars
January 1, 2013 Popular Science Edition: US EDITION
Section: Headlines
Page: 30
Author: Luke Mitchell
Susannah F. Locke Volume 282, Issue 01
Music piracy? Who cares. Wait until people start copying iPhones
L AST JANUARY
, the Swedish BitTorrent tracker Pirate Bay quietly introduced a new category, called Physibles,
to its inventory. “We believe that things like three-dimensional printers, scanners, and such are
just the first step,” one of the site's managers wrote at the time. “We believe that in the nearby
future you will print your spare parts for your vehicles. You will download your sneakers within
20 years.”
That's probably an understatement. MakerBot's $2,199 Replicator 2, which prints small objects
from drips of melted bioplastic filament, is generating headlines today. But far sharper home
stereolithographic printers, which selectively cure liquid photopolymer resins with lasers, are
on the way; Formlabs is set to begin delivery on its $2,299 Form 1 in February. And that's just
the start. The next generation of consumer 3-D printers will be able to generate complex parts
of variable elasticity and conductivity, and from far more than plastic or resin. A commercial
“bioprinter” from Organovo can already shape human cells into usable tissue, and a Columbia,
Missouri, start-up called Modern Meadow is working on a device that prints edible meat. A
team at the University of Glasgow has even found a way to print custom chemical compounds,
opening the way to home pill-printers. In September, meanwhile, Autodesk released a free
iPhone app, 123D Catch, that scans objects on the fly. And, as CT scanning gets cheaper, you'll
be able to map the interior as well. Forget sneakers. We're gaining the ability to copy anything:
a leaked iPhone 7, a life-saving medicine, a deadly virus.
Digital rights management for 3-D printers is just the beginning.
Which means the Physibles section at Pirate Bay, among other places, is about to become the
site of some important battles. In October, Intellectual Ventures, a company run by Nathan
Myhrvold, former CTO of Microsoft, patented a scheme “to control object production rights”
that would require every 3-D printer to validate every file in a print queue against a database of
authorized items. No validation, no copy. The system likely won't catch on—Apple ditched
clunky digital rights management on iTunes years ago—but it's just the beginning. The
intellectual property battles of the last two decades will seem trivial in comparison to the
coming war over who, in the most literal sense, controls the means of production.
“Cyberspace, left to itself, will not fulfill the promise of freedom. Left to itself, cyberspace will
become a perfect tool of control
.” —Lawrence Lessig, from Code 2.0: And Other Laws of Cyberspace