Introduction to Biotechnology
Max Roehr - Scientia difficilis sed fructuosa.
Biotechnology comprises a wide range of disciplines – from classical biotechnology to the socalled new biotechnologies.
Classical biotechnology is usually defined as “the utilization of the chemical potentioa of
cells (in most cases of microbial origin) or enzymes thereof for the industrial production of a
great variety of useful substances“.
With the “new biotechnologies“ the situation is somewhat more complex: if defined as the
production and industrial utilization of genetically engineered cells, this will be according to
the description given above. Frequently, however, the term biotechnology has merely been
used to describe the methodology of genetic engineering and similar techniques. (e.g., US
Congress, Office of Technology Assessment, 1984.)
What is Biotechnology?
Pamela Peters, from Biotechnology: A Guide To Genetic Engineering. Wm. C. Brown Publishers, Inc., 1993.
Biotechnology in one form or another has flourished since
prehistoric times. When the first human beings realized that they
could plant their own crops and breed their own animals, they
learned to use biotechnology. The discovery that fruit juices
fermented into wine, or that milk could be converted into cheese
or yogurt, or that beer could be made by fermenting solutions of
malt and hops began the study of biotechnology. When the first
bakers found that they could make a soft, spongy bread rather than
a firm, thin cracker, they were acting as fledgling
biotechnologists. The first animal breeders, realizing that different
physical traits could be either magnified or lost by mating
appropriate pairs of animals, engaged in the manipulations of
biotechnology.
What then is biotechnology? The term brings to mind many
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different things. Some think of developing new types of animals. Others dream of almost
unlimited sources of human therapeutic drugs. Still others envision the possibility of growing
crops that are more nutritious and naturally pest-resistant to feed a rapidly growing world
population. This question elicits almost as many first-thought responses as there are people to
whom the question can be posed.
In its purest form, the term "biotechnology" refers to the use of living organisms or their
products to modify human health and the human environment. Prehistoric biotechnologists
did this as they used yeast cells to raise bread dough and to ferment alcoholic beverages, and
bacterial cells to make cheeses and yogurts and as they bred their strong, productive animals
to make even stronger and more productive offspring.
Throughout human history, we have learned a great deal about the
different organisms that our ancestors used so effectively. The
marked increase in our understanding of these organisms and their
cell products gains us the ability to control the many functions of
various cells and organisms. Using the techniques of gene splicing
and recombinant DNA technology, we can now actually combine
the genetic elements of two or more living cells. Functioning
lengths of DNA can be taken from one organism and placed into
the cells of another organism. As a result, for example, we can cause bacterial cells to produce
human molecules. Cows can produce more milk for the same amount of feed. And we can
synthesize therapeutic molecules that have never before existed.
Where Did Biotechnology Begin?
"Biotechnology At Work" and "Biotechnology in Perspective," Washington, D.C.: Biotechnology Industry
Organization, 1989, 1990.
With the Basics
Certain practices that we would now classify as applications of biotechnology have been in use since
man's earliest days. Nearly 10,000 years ago, our ancestors were producing wine, beer, and bread by
using fermentation, a natural process in which the biological activity of one-celled organisms plays a
critical role.
In fermentation, microorganisms such as bacteria, yeasts, and
molds are mixed with ingredients that provide them with food. As
they digest this food, the organisms produce two critical byproducts, carbon dioxide gas and alcohol.
In beer making, yeast cells break down starch and sugar (present in
cereal grains) to form alcohol; the froth, or head, of the beer results
from the carbon dioxide gas that the cells produce. In simple terms, the living cells rearrange
chemical elements to form new products that they need to live and reproduce. By happy
coincidence, in the process of doing so they help make a popular beverage.
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Bread baking is also dependent on the action of yeast cells. The bread dough contains
nutrients that these cells digest for their own sustenance. The digestion process generates
alcohol (which contributes to that wonderful aroma of baking bread) and carbon dioxide gas
(which makes the dough rise and forms the honeycomb texture of the baked loaf).
Discovery of the fermentation process allowed early peoples to produce foods by allowing
live organisms to act on other ingredients. But our ancestors also found that, by manipulating
the conditions under which the fermentation took place, they could improve both the quality
and the yield of the ingredients themselves.
Crop Improvement
Although plant science is a relatively modern discipline, its fundamental techniques have been
applied throughout human history. When early man went through the crucial transition from
nomadic hunter to settled farmer, cultivated crops became vital for survival. These primitive
farmers, although ignorant of the natural principles at work, found that they could increase the
yield and improve the taste of crops by selecting seeds from particularly desirable plants.
Farmers long ago noted that they could improve each succeeding year's harvest by using seed
from only the best plants of the current crop. Plants that, for example, gave the highest yield,
stayed the healthiest during periods of drought or disease, or were easiest to harvest tended to
produce future generations with these same characteristics. Through several years of careful
seed selection, farmers could maintain and strengthen such desirable traits.
The possibilities for improving plants expanded as a result of Gregor Mendel's investigations
in the mid-1860s of hereditary traits in peas. Once the genetic basis of heredity was
understood, the benefits of cross-breeding, or hybridization, became apparent: plants with
different desirable traits could be used to cultivate a later generation that combined these
characteristics.
An understanding of the scientific principles behind fermentation and crop improvement
practices has come only in the last hundred years. But the early, crude techniques, even
without the benefit of sophisticated laboratories and automated equipment, were a true
practice of biotechnology guiding natural processes to improve man's physical and economic
well-being.
Harnessing Microbes for Health
Every student of chemistry knows the shape of a Buchner funnel, but they may be unaware
that the distinguished German scientist it was named after made the vital discovery (in 1897)
that enzymes extracted from yeast are effective in converting sugar into alcohol. Major
outbreaks of disease in overcrowded industrial cities led eventually to the introduction, in the
early years of the present century, of large-scale sewage purification systems based on
microbial activity. By this time it had proved possible to generate certain key industrial
chemicals (glycerol, acetone, and butanol) using bacteria.
Another major beneficial legacy of early 20th century biotechnology was the discovery by
Alexander Fleming (in 1928) of penicillin, an antibiotic derived from the mold Penicillium.
Large-scale production of penicillin was achieved in the 1940s. However, the revolution in
understanding the chemical basis of cell function that stemmed from the post-war emergence
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of molecular biology was still to come. It was this exciting phase of bioscience that led to the
recent explosive development of biotechnology.
Overview and Brief History
Ann Murphy and Judy Perrella. Woodrow Wilson Foundation Biology Institute. "A Further Look at
Biotechnology." Princeton, NJ: The Woodrow Wilson National Fellowship Foundation, 1993.
Biotechnology seems to be leading a sudden new biological revolution. It has brought us to
the brink of a world of "engineered" products that are based in the natural world rather than
on chemical and industrial processes.
Biotechnology has been described as "Janus-faced." This implies that there are two
sides. On one, techniques allow DNA to be manipulated to move genes from one
organism to another. On the other, it involves relatively new technologies whose
consequences are untested and should be met with caution. The term
"biotechnology" was coined in 1919 by Karl Ereky, an Hungarian engineer. At that time, the
term meant all the lines of work by which products are produced from raw materials with the
aid of living organisms. Ereky envisioned a biochemical age similar to the stone and iron
ages.
A common misconception among teachers is the thought that biotechnology
includes only DNA and genetic engineering. To keep students abreast of current
knowledge, teachers sometimes have emphasized the techniques of DNA science as
the "end-and-all" of biotechnology. This trend has also led to a misunderstanding in
the general population. Biotechnology is NOT new. Man has been manipulating living things
to solve problems and improve his way of life for millennia. Early agriculture concentrated on
producing food. Plants and animals were selectively bred, and microorganisms were used to
make food items such as beverages, cheese, and bread.
The late eighteenth century and the beginning of the nineteenth
century saw the advent of vaccinations, crop rotation involving
leguminous crops, and animal drawn machinery. The end of the
nineteenth century was a milestone of biology. Microorganisms
were discovered, Mendel's work on genetics was accomplished,
and institutes for investigating fermentation and other microbial
processes were established by Koch, Pasteur, and Lister.
Biotechnology at the beginning of the twentieth century began to bring industry and
agriculture together. During World War I, fermentation processes were developed that
produced acetone from starch and paint solvents for the rapidly growing automobile industry.
Work in the 1930s was geared toward using surplus agricultural products to supply industry
instead of imports or petrochemicals. The advent of World War II brought the manufacture of
penicillin. The biotechnical focus moved to pharmaceuticals. The "cold war" years were
dominated by work with microorganisms in preparation for biological warfare, as well as
antibiotics and fermentation processes.
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Biotechnology is currently being used in many areas including agriculture, bioremediation,
food processing, and energy production. DNA fingerprinting is becoming a common practice
in forensics. Similar techniques were used recently to identify the bones of the last Czar of
Russia and several members of his family. Production of insulin and other medicines is
accomplished through cloning of vectors that now carry the chosen gene. Immunoassays are
used not only in medicine for drug level and pregnancy testing, but also by farmers to aid in
detection of unsafe levels of pesticides, herbicides, and toxins on crops and in animal
products. These assays also provide rapid field tests for industrial chemicals in ground water,
sediment, and soil. In agriculture, genetic engineering is being used to produce plants that are
resistant to insects, weeds, and plant diseases.
A current agricultural controversy involves the tomato. A recent article in the New Yorker
magazine compared the discovery of the edible tomato that came about by early
biotechnology with the new "Flavr-Savr" tomato brought about through modern techniques.
In the very near future, you will be given the opportunity to bite into the Flavr-Savr tomato,
the first food created by the use of recombinant DNA technology ever to go on sale.
What will you think as you raise the tomato to your mouth? Will you hesitate? This moment
may be for you as it was for Robert Gibbon Johnson in 1820 on the steps of the courthouse in
Salem, New Jersey. Prior to this moment, the tomato was widely believed to be poisonous. As
a large crowd watched, Johnson consumed two tomatoes and changed forever the humantomato relationship. Since that time, man has sought to produce the supermarket tomato with
that "backyard flavor." Americans also want that tomato available year-round.
New biotechnological techniques have permitted scientists to manipulate desired traits. Prior
to the advancement of the methods of recombinant DNA, scientists were limited to the
techniques of their time - cross-pollination, selective breeding, pesticides, and herbicides.
Today's biotechnology has its "roots" in chemistry, physics, and biology . The explosion in
techniques has resulted in three major branches of biotechnology: genetic engineering,
diagnostic techniques, and cell/tissue techniques.
Helping Heal Mother Nature with Her Own
Remedies
Leona Fitzmaurice and Karen Bankston, "Helping heal mother nature with her own remedies: Environmental
biotechnology is alive and well in Wisconsin." BioIssues Vol. 5, No. 4. Madison, WI: University of Wisconsin
Biotechnology Center, 1994.
At first glance, environmental biotechnology may seem the newest
branch of an emerging science. Compared with agricultural and
medical biotechnology, environmental research and
biotechnological applications are relatively recent. In reality,
however, humankind has been using Mother Nature's own remedies
for thousands of years to preserve the environment and heal damage
done to it.
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Biotechnology can be defined as the use of living organisms to make a product or drive a
process. One of the earliest examples of environmental biotechnology is composting, the
process whereby bacteria, fungi, and other organisms break down organic matter and return
nutrients to the soil. The practice of composting originated nearly simultaneously with
agriculture, i.e., during the period when humankind turned from hunting and gathering food to
tilling fields and growing crops. Thus, environmental biotechnology and agricultural
biotechnology developed during the same time continuum.
Why, then, do we still tend to think of environmental biotechnology as something new? After
all, the human impact on the environment is as old as our kind: We leave our imprint as we
clear the land for homes and farming; harvest fuels, minerals, and other natural resources;
manufacture finished goods from raw materials; and travel from one place to another. As a
nation and as a world, we have become increasingly aware of the consequences of fouling our
planet.
Rachel Carson's book, "Silent Spring," shocked society awake to the destructive power of
pesticides entering the food chain. Her warning echoed a long history of similar concerns
expressed by environmentalists and conservationist's, including Wisconsin's Aldo Leopold,
the great American naturalist and wildlife biologist, who promoted conservation and the
creation of wilderness areas in the 1930s and '40s.
Remediation, prevention, and risk assessment are all disciplines that have grown from the
seminal work of Carson, Leopold, and other naturalists. For example, the scientific
understanding of the effects of such pollutants as DDT and polychlorinated biphenyls (PCBs)
began with studies of wild bird populations and eggshell thinning in the '60s and early '70s.
And integrated pest management has been around for about 15 years.
What is new is modern environmental biotechnology - and its newness is a natural result of
the advent in the 1970s of recombinant DNA technologies and genetic engineering.
Environmental biotechnology and modern biotechnology have been interwoven ever since.
For example, one of the landmarks in modern biotechnology occurred in 1980 when the U.S.
Supreme Court allowed the award of a patent to Ananda Chakrabarty for a genetically
modified bacterium capable of breaking down crude oil. Chakrabarty's bacterium was
designed in 1972; since that date, thousands of useful microbes have been isolated.
Challenges being addressed by modern environmental biotechnology range from the search
for microbes that will reduce acid rain by removing sulfur from power plant coal to the
biological production of biodegradable plastics. As society struggles with the dilemma of
protecting the environment while simultaneously promoting economic development,
environmental biotechnology is playing a key role in attaining a healthy balance between
what are often competing interests.
Taking a Global Perspective
The earth has been affected by pollutants for thousands of years. Pollutants enter the
environment and are broken down by naturally occurring organisms and events. This global
process has been working less and less well as a direct result of the increased production of
pollutants by human activity. Humans can take steps to heal this process.
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From a historical perspective, environmental biotechnology can be characterized by three
phases:
1. growing societal awareness of the damage being suffered by the environment as it was
exposed to increased pollution and the nearly frantic attempts to clean up the mess (remedial
actions including treatment and bioremediation),
2. increasingly sophisticated approaches to assess environmental damage (monitoring and risk
assessment), and
3. conscious and deliberate attempts to reduce significantly the entry of pollutants into the
environment (prevention).
This history is paralleled in our everyday experience of recycling household waste. First we
recycled nothing and read about overflowing landfills. Then we recycled newspapers and a
few other items while purchasing products manufactured from recycled paper - and still read
about overflowing landfills. Now we recycle numerous items - and read manufacturer's labels
touting the reduced environmental impact of the packaging materials they use.
Rio Declaration On Environment and
Development
The United Nations Conference on Environment and Development,
Having met at Rio de Janeiro from 3 to 14 June 1992,
Reaffirming the Declaration of the United Nations Conference on the Human Environment,
adopted at Stockholm on 16 June 1972, and seeking to build upon it,
With the goal of establishing a new and equitable global partnership through the creation of
new levels of cooperation among States, key sectors of societies and people,
Working towards international agreements which respect the interests of all and protect the
integrity of the global environmental and developmental system,
Recognizing the integral and interdependent nature of the Earth, our home,
Proclaims that:
Principle 1
Human beings are at the center of concerns for sustainable development. They are entitled to a
healthy and productive life in harmony with nature.
Principle 2
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States have, in accordance with the Charter of the United Nations and the principles of
international law, the sovereign right to exploit their own resources pursuant to their own
environmental and developmental policies, and the responsibility to ensure that activities
within their jurisdiction or control do not cause damage to the environment of other States or
of areas beyond the limits of national jurisdiction.
Principle 3
The right to development must be fulfilled so as to equitably meet developmental and
environmental needs of present and future generations.
Principle 4
In order to achieve sustainable development, environmental protection shall constitute an
integral part of the development process and cannot be considered in isolation from it.
Principle 5
All States and all people shall cooperate in the essential task of eradicating poverty as an
indispensable requirement for sustainable development, in order to decrease the disparities in
standards of living and better meet the needs of the majority of the people of the world.
Principle 6
The special situation and needs of developing countries, particularly the least developed and
those most environmentally vulnerable, shall be given special priority. International actions in
the field of environment and development should also address the interests and needs of all
countries.
Principle 7
States shall cooperate in a spirit of global partnership to conserve, protect and restore the
health and integrity of the Earth's ecosystem. In view of the different contributions to global
environmental degradation, States have common but differentiated responsibilities. The
developed countries acknowledge the responsibility that they bear in the international pursuit
of sustainable development in view of the pressures their societies place on the global
environment and of the technologies and financial resources they command.
Principle 8
To achieve sustainable development and a higher quality of life for all people, States should
reduce and eliminate unsustainable patterns of production and consumption and promote
appropriate demographic policies.
Principle 9
States should cooperate to strengthen endogenous capacity-building for sustainable
development by improving scientific understanding through exchanges of scientific and
technological knowledge, and by enhancing the development, adaptation, diffusion and
transfer of technologies, including new and innovative technologies.
Principle 10
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Environmental issues are best handled with the participation of all concerned citizens, at the
relevant level. At the national level, each individual shall have appropriate access to
information concerning the environment that is held by public authorities, including
information on hazardous materials and activities in their communities, and the opportunity to
participate in decision-making processes. States shall facilitate and encourage public
awareness and participation by making information widely available. Effective access to
judicial and administrative proceedings, including redress and remedy, shall be provided.
Principle 11
States shall enact effective environmental legislation. Environmental standards, management
objectives and priorities should reflect the environmental and developmental context to which
they apply. Standards applied by some countries may be inappropriate and of unwarranted
economic and social cost to other countries, in particular developing countries.
Principle 12
States should cooperate to promote a supportive and open international economic system that
would lead to economic growth and sustainable development in all countries, to better address
the problems of environmental degradation. Trade policy measures for environmental
purposes should not constitute a means of arbitrary or unjustifiable discrimination or a
disguised restriction on international trade. Unilateral actions to deal with environmental
challenges outside the jurisdiction of the importing country should be avoided. Environmental
measures addressing transboundary or global environmental problems should, as far as
possible, be based on an international consensus.
Principle 13
States shall develop national law regarding liability and compensation for the victims of
pollution and other environmental damage. States shall also cooperate in an expeditious and
more determined manner to develop further international law regarding liability and
compensation for adverse effects of environmental damage caused by activities within their
jurisdiction or control to areas beyond their jurisdiction.
Principle 14
States should effectively cooperate to discourage or prevent the relocation and transfer to other
States of any activities and substances that cause severe environmental degradation or are
found to be harmful to human health.
Principle 15
In order to protect the environment, the precautionary approach shall be widely applied by
States according to their capabilities. Where there are threats of serious or irreversible damage,
lack of full scientific certainty shall not be used as a reason for postponing cost-effective
measures to prevent environmental degradation.
Principle 16
National authorities should endeavor to promote the internalization of environmental costs and
the use of economic instruments, taking into account the approach that the polluter should, in
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principle, bear the cost of pollution, with due regard to the public interest and without
distorting international trade and investment.
Principle 17
Environmental impact assessment, as a national instrument, shall be undertaken for proposed
activities that are likely to have a significant adverse impact on the environment and are
subject to a decision of a competent national authority.
Principle 18
States shall immediately notify other States of any natural disasters or other emergencies that
are likely to produce sudden harmful effects on the environment of those States. Every effort
shall be made by the international community to help States so afflicted.
Principle 19
States shall provide prior and timely notification and relevant information to potentially
affected States on activities that may have a significant adverse transboundary environmental
effect and shall consult with those States at an early stage and in good faith.
Principle 20
Women have a vital role in environmental management and development. Their full
participation is therefore essential to achieve sustainable development.
Principle 21
The creativity, ideals and courage of the youth of the world should be mobilized to forge a
global partnership in order to achieve sustainable development and ensure a better future for
all.
Principle 22
Indigenous people and their communities and other local communities have a vital role in
environmental management and development because of their knowledge and traditional
practices. States should recognize and duly support their identity, culture and interests and
enable their effective participation in the achievement of sustainable development.
Principle 23
The environment and natural resources of people under oppression, domination and
occupation shall be protected.
Principle 24
Warfare is inherently destructive of sustainable development. States shall therefore respect
international law providing protection for the environment in times of armed conflict and
cooperate in its further development, as necessary.
Principle 25
Peace, development and environmental protection are interdependent and indivisible.
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Principle 26
States shall resolve all their environmental disputes peacefully and by appropriate means in
accordance with the Charter of the United Nations.
Principle 27
States and people shall cooperate in good faith and in a spirit of partnership in the fulfillment
of the principles embodied in this Declaration and in the further development of international
law in the field of sustainable development.
Biotechnology Industry Review
Biotechnology Industry Organization (BIO). Washington, D.C.
Agricultural and Chemical Industries
The bio-revolution resulting from advances in molecular biosciences and
biotechnology has already outstripped the advances of the "Green Revolution." In the
early 1960s, the pioneering studies of Nobel prize winner Norman Borlaug, using
cross-breeding techniques based on classical genetics, offered for the first time a
weapon against hunger in the countries of Latin America, Asia, and Africa. As a
direct result of the comprehensive studies of Borlaug and his contemporaries, new
wheat hybrids began to transform the harvests of India and China, although they had a
relatively minor influence on agriculture in more temperate climates. There is little
doubt that genetic manipulation will open more new doors in this field, and will
dramatically alter farming worldwide.
It does not require a crystal ball to imagine the potential of the immediate
biotechnological future. From the advances in recent years, it is possible to
extrapolate to a number of likely developments based on research now in
progress. In the plant world, the 1978 development of the "pomato," a
laboratory-generated combination of two members of the Solanaceae family
(the potato and the tomato), was a significant advance. The Flavr Savr tomato
was reviewed by the FDA in the spring of 1994 and found to be as safe as
conventionally produced tomatoes. This is the first time the FDA has
evaluated a whole food produced by biotechnology.
Exciting prospects are likely to result from industrial-scale plant tissue culture. This may soon
obviate the need for rearing whole plants in order to generate valuable commodities such as
dyes, flavorings, drugs, and chemicals. Cloning techniques could prove to be the way to
tackle some of the acute problems of reforesting in semi-desert areas. Seedlings grown from
the cells of mature trees could greatly speed up the process. In the summer of 1987, a Belgian
team introduced into crop plants a group of genes encoding for insect resistance and
resistance to widely used herbicides. This combination of advantageous genes could bring
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about a new era in plant protection. The crop can be treated safely with more effective doses
of weed killer, and it is also engineered to be less susceptible to insect damage.
Dairy farming is also benefiting from advances in biotechnology. Bovine somatotropin
(growth hormone) will enhance milk yields, with no increase in feed costs. Embryo
duplication methods mean that cows will bear more calves than in the past, and embryo
transfer techniques are enabling cattle of indifferent quality to rear good quality stock, a
potentially important development for nations with less advanced agriculture. Genetic
manipulation of other stock, such as sheep and pigs, appears to be feasible, and work is in
progress on new growth factors for poultry.
The outcome of this intense activity will be improvements in the texture, quality, variety, and
availability of traditional farm products, as well as the emergence of newly engineered food
sources. Such bioengineered super-foods will be welcomed, and will offer new varieties, and
hence find new markets in the quality-conscious advanced countries. Despite the enormous
potential gains, the economic consequences of possible overproduction in certain areas must
also be faced. It will be essential for those concerned with making agricultural policies to
keep abreast of the pace of modern biotechnology. Short-term benefits to the consumer of
lower agricultural prices must be weighed against a long-term assessment of the impact of
new discoveries on the farming industry.
Medicine
In the medical field, considerable efforts will be devoted to the development of vaccines for killer
diseases such as AIDS. Monoclonal antibodies will be used to boost the body's defenses and guide
anti-cancer drugs to their target sites. This technology may also help to rid the human and animal
world of a range of parasitic diseases by producing specific antibodies to particular parasites.
Synthesis of drugs, hormones, and animal health products, together with drug-delivery mechanisms,
are all advancing rapidly. Enzyme replacement and gene replacement therapy are other areas where
progress is anticipated. The next decade will see significant advances in medicine, agriculture, and
animal health directly attributable to biotechnology.
Mining and Waste Management
The impact of the new technology will not, however, be confined to bio-based industries. Genetically
engineered microbes may become more widely used to extract oil from the ground and valuable metals
from factory wastes. In short, the lives of every one of us will be influenced by biotechnology.
Growth potential for worldwide biotechnological markets by the year 2000:
Market sector
$ (In millions)
Energy
15,392
Foods
11,912
Chemicals
9,936
Health care (pharmaceuticals)
Agriculture
Metal recovery
8,544
8,048
4,304
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Pollution control
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The Future Of Genetic Research
Harold Schmeck
Pines, Maya, ed. "Blazing the Genetic Trail." Bethesda, MD: Howard Hughes Medical Institute, 1991.
The eminent British molecular biologist Sydney Brenner once got a hearty laugh from his
audience by describing how some future graduate student will define a mouse: "ATC, GCC,
AAG, GGT, GTA, ATA. . . ." But every year the idea of defining an organism by the
sequence of its DNA bases seems a little less farfetched.
In the sharpest image ever obtained of the DNA double helix (above,right) DNA is magnified approximately 25
million times with the aid of a scanning tunneling microscope, a powerful tool invented in the early 1980s. The
turns and grooves of the DNA segment shown in this image closely match those of a corresponding computergraphics model (above, left).
Victor McKusick, of The Johns Hopkins University School of Medicine, notes that scientists'
growing ability to read and write in the language of the genes has already explained some of
the once-mysterious basic concepts of genetics. The difference between dominant and
recessive traits as causes of genetic disease used to be just an abstraction based on a great deal
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of observation. If a genetic defect expressed itself only in patients who inherited the trait from
both parents, it was called recessive; both copies of the gene coding for the trait were
presumably defective, resulting in disease. If the trait was dominant, on the other hand, it
meant that one defective copy of the gene was sufficient to spell disaster.
But why should some disorders require two mistakes, while others resulted from only one?
Molecular biology has given a concrete and remarkably simple explanation.
"It now appears that these two categories [recessive and dominant] correspond pretty closely
to the two fundamental categories of proteins: enzymatic and structural," McKusick said in a
recent review of genetics research. Recessive disorders tend to result from failures in genes
that code for enzymes, the biological catalysts that do much of the body's chemical work. A
person who has inherited the defective gene from only one parent often goes disease-free
because the normal gene inherited from the other parent produces enough of the enzyme to
serve the body's needs. The disorder appears only when the person inherits the same defect
from both parents and therefore lacks any working copy of the normal gene.
If the genetic defect affects structural proteins, however, for example, collagen, a key
component of connective tissues and bones, one copy of the faulty gene is usually enough to
cause disease. It is easy to see why. A four-engine airplane can still fly even if one of its
engines fails, as long as the other engines provide enough power, but a single faulty strut that
makes a wing fall off will cause the plane to crash.
The reason some genetic disorders are relatively common while most are
extremely rare has also proved to be almost ridiculously obvious. The
bigger the gene, the greater the chance that something will go wrong with
part of it. In many cases, it seems as simple as that.
Sometimes rather subtle differences in the defects of a single gene can
make a profound difference in a patient's fate, as Louis Kunkel of the
HHMI unit at Harvard University learned after he and his team
discovered the gene for Duchenne muscular dystrophy (DMD) in 1986. Major flaws in that
huge gene result in the presently incurable DMD, a muscle-wasting disease that leaves young
boys wheelchair-bound by age 12 and generally kills them by age 20, because the muscles
that control breathing fail. By contrast, lesser defects in that same gene produce a much more
benign disease, Becker's muscular dystrophy.
A year after discovering this gene, the team identified the protein it codes for - a previously
unknown protein, now named dystrophin, which occurs in muscles in such small amounts that
it would never have been found by ordinary means. Dystrophin plays a key role in muscle
cells and may be involved in many other muscle diseases. Researchers are now analyzing how
dystrophin functions, what other proteins it interacts with, and whether it might be replaced to
interrupt the course of disease.
Experts see many more insights such as these in the future, as research in molecular genetics
opens some of the "black boxes" of biology.
"I think we are going to have an explosion of understanding," says David Valle, of the HHMI
unit at The Johns Hopkins University. For example, the causes of mental disorders certainly
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include environmental factors, but biological psychiatrists believe the genes are whispering an
important message, if only it can be heard.
Genetic research will illuminate many disorders of single organs, such as the eye, teeth, skin,
and cochlea (the hearing apparatus of the ear), Valle believes. The deafness of about twothirds of patients with serious hearing problems has a genetic basis, he says. Molecular
biologists can find genes that are expressed only in the cochlea and therefore are probably
important in hearing. Once such genes have been identified, several strategies exist for
determining their functions and suggesting treatments.
Valle's current research focuses on a rare genetic disorder of the eye, gyrate atrophy, which
leads to blindness through degeneration of the retina. The basic fault is an enzyme defect that
causes an abnormal buildup of the amino acid ornithine. Surprisingly, some 35 different
mutations in a single gene are able to produce the disease. The excess ornithine is found
almost everywhere in the body - blood, urine, tears, spinal fluid, but the serious ill-effects are
limited almost entirely to the retina. As yet, nobody knows why.
Understanding the genetic cause of the disease has led to a medical treatment that seems
effective: severely restricting the patient's diet to bring the ornithine levels down to nearly
normal. Recently, the scientists have compared the effects of this treatment on children in
whom it was started early and on siblings who did not receive it until an older age. The
studies confirm that the dietary restriction minimizes damage to the retina, Valle reports. But
the diet is only a stopgap solution.
Geneticists are searching for more effective remedies, including possible treatment for the
gene defect itself.
"One of the really exciting things about modern molecular genetics is that we now have
opportunities to make animal models of these diseases and to study what happens at the tissue
level in a direct way," Valle says. "That is one of the big things that is going to be happening
in the next decade or so.
Philip Sharp, director of the Center for Cancer Research at MIT, divides the benefits of
genetics research into two categories: those that generate knowledge and those that generate
treatment. He sees animal models as extremely important to both. Deliberately produced
genetic diseases in animals will have pathologies like those of human diseases. "We will learn
how to recognize them, treat them, and analyze them in animals," he says. "That is going to be
the forefront of biomedical science, in one area of it at least."
In addition, many aspects of human development will be clarified by work with mice, flies,
and worms, he says. Scientists have discovered that genes which are developmentally active
in both Drosophila, the fruit fly, and C. elegans, the nematode worm, have direct counterparts
in mammals, although the functions of these genes in humans are not yet entirely clear.
When genes of species that separated from each other many millions of years ago show so
much similarity, there is every reason to believe they are related. Many molecular biologists
have noticed that nature is quite frugal in preserving devices that have proved biologically
effective. As an example, Valle points out that the human enzyme ornithine delta
aminotransferase, which is defective in gyrate atrophy, is 54 percent identical to the
comparable enzyme that functions in yeast.
15
"I think one of the real themes of biology is that Mother Nature uses things over and over
again once she figures out how to solve a problem," Valle says.
This concept offers scientists a great opportunity, says Eric Lander of the Whitehead Institute.
He thinks there is hope of compiling, eventually, a complete thesaurus of protein parts that
function in Earth's myriad species. "That would be spectacular," Lander says. "If we had the
thesaurus of all the moving parts, then we would understand life in a remarkable way."
Gene mapping and cloning are key to the assembly of the thesaurus, and progress in these
areas is clearly accelerating. However most of the 50,000 to 100,000 human genes remain
totally unknown, and there is still a long way to go.
To date, most of the progress in understanding the genetics of human disease has involved
relatively rare conditions, such as cystic fibrosis or Duchenne muscular dystrophy, which are
caused by errors in single genes. But science is also stalking the genes that contribute to heart
disease, cancer, diabetes, and mental illness - the big killers and cripplers of mankind.
It may soon be possible to tell some people that they have certain genetic predispositions to a
specific major illness and suggest that they tailor their lifestyles accordingly. Similarly, the
use of drugs to treat some of the important diseases could be tailored to the genetically varied
needs of patients, with benefits for them and for the health care system in general: "Different
strokes for different strokes," as one scientist put it.
On the other hand, some scientists fear that people might be stigmatized or become
uninsurable because of genetic traits, such as carrier states, that don't in themselves have any
appreciable effect on health.
Genetic research is advancing steadily, often rapidly, on many fronts. It has long been known
that some disorders affect males, others affect females primarily, while still others may appear
in either sex. But a few years ago researchers discovered that, even in some of the latter
disorders the gravity and sometimes even the nature of disease may depend on which parent
provided the faulty gene. This phenomenon is called imprinting. Although it has been
detected only in rare human conditions, imprinting is a subject of intense study as researchers
look for other examples.
Other scientists have forsaken the genes that reside in cell nuclei and are finding new clues to
disease in the genes of what are probably our oldest and most entrenched "parasites" - the
mitochondria - tiny, energy-generating organs inside every cell. Mitochondria are thought to
be the descendants of ancient bacteria that not only found a home in animal cells, but also
adapted so thoroughly that they became indispensable functional parts of those cells. We
inherit mitochondria only from our mothers; sperm leave their mitochondria behind when
they enter the egg. Flaws in mitochondrial genes have been found to lead to certain types of
blindness and epilepsy and may also contribute to some degenerative disorders, such as
dementia, which are associated with aging.
"Mitochondrial DNA gives us a whole new way to think about genetic transmission of
diseases," says Douglas Wallace of Emory University, a specialist in those vital intracellular
power stations.
16
In even more fundamental ways, discoveries in genetics have led to novel strategies for
treating disease. Decades ago, scientists learned that DNA is mainly the archive of genetic
information. Its orders are translated into action by segments of ribonucleic acid (RNA),
which serve as the working blueprints for all proteins. Today, chemists are beginning to create
valuable new drugs by fabricating "anti-sense" segments of RNA, whose sequence is the
exact opposite of an unwanted sequence, to combine with certain existing strands of RNA and
thus block the action of specific genes.
The bottom line in any kind of biomedical research lies in the realm of treatment and
prevention. The ultimate step in that direction is gene therapy - the deliberate transplantation
of genes to treat or even prevent human disease. Many geneticists dismiss gene therapy as a
distant prospect, but others disagree. "We are going to have gene therapy," Philip Sharp says.
"We are probably going to have it soon."
Gene therapy was actually tried in 1970 and again in 1980 without success, but the knowledge
and techniques were primitive by today's standards. The first attempt in what might be called
the modern era of gene therapy began in September 1990 at the National Institutes of Health
(NIH), when doctors treated a 4-year-old girl. The child suffered from a grave immune
deficiency because she lacked the enzyme adenosine deaminase. The doctors took her own
white blood cells, altered them by adding the gene for the missing enzyme and transplanted
the altered cells back into her.
Next on the NIH agenda was a substantially different strategy introducing a cancer-fighting
substance, tumor necrosis factor, into the genetic repertoire of melanoma patients' own
cancer-fighting white blood cells. Ultimately the same approach may be applied to other types
of cancer.
Philip Sharp suggests one possibility that might be tried as soon as techniques are sufficiently
refined. Instead of treating an AIDS patient for the rest of his or her life with a drug to protect
the immune system against the HIV virus, doctors might use gene transplants to render the
patient's immune system permanently resistant to the virus.
W. French Anderson of the NIH, one of the architects of the new attempts at gene therapy,
sees a bright future. By the early years of the next century, he predicts, gene therapy will have
become a highly sophisticated drug delivery system. Doctors will give the patient one, or
perhaps several, transplants of his or her own cells that have been genetically engineered to
manufacture a drug. In many cases this might replace the conventional practice of injecting
drugs at regular intervals. How far in the future is this new application of genetic medicine?
Five to ten years for the essential techniques, he estimates, somewhat longer to achieve a high
degree of sophistication.
The first gene therapy attempts at NIH used the patient's white blood cells as the target for
gene insertion. In the future, scientists hope to perfect techniques for using bone marrow cells.
Several research centers are making progress in animal experiments using liver cells and
endothelial cells, such as those that line blood vessels, to deliver valuable genes to the tissues
where they would be useful. Another strategy that would have seemed sheer fantasy a few
years ago is being discussed by serious scientists today. That is the idea of using inhalant
spray to deliver copies of a good gene to airway tissues of cystic fibrosis patients.
17
The transplantation and manipulation of genes in other species has already proved valuable in
genetics research and will probably play an even larger role in the future.
Mario Capecchi and his team at the University of Utah have recently used the method of gene
manipulation known as homologous recombination to discover the function of a mouse gene.
The gene first attracted notice because it produced breast cancer in the animals when it
became activated abnormally. By developing mice in which that gene, and only that gene, had
been knocked out, the scientists showed that the gene's normal function is crucial to the
development of two regions of the animals' brain: the midbrain and cerebellum. The discovery
opens an important door to studies of brain development and brain function.
To use homologous recombination, scientists must be able to identify and grow embryonic
stem (ES) cells, the unspecialized precursors of all other cells in an organism. In Capecchi's
mouse experiments, ES cells are modified to alter the specific gene under study and then
implanted in a very early mouse embryo and used to breed animals that have the desired trait
or flaw. Some experts consider this technique among the most exciting recent advances in
genetics research.
But the excitement in genetics is general and pervasive. "Having been part of genetics
research for 30 years, I find it almost stupefying that it is every bit as exciting and maybe even
more so than it has seemed in the past," says Leon Rosenberg, dean of the Yale University
School of Medicine. "I continue to be dazzled by the pace and surprise of new information in
the field."
Studies of microbes, plants, animals, and many normal human beings are all contributing to
the explosion of new knowledge. In recent years, molecular genetics has given important
insights into the origin of life and its evolution, the emergence of humans, and our intimate
relatedness to every other species on Earth. We can expect many more advances as geneticists
continue to explore the wonder of life.
The Human Genome Project
National Center for Human Genome Research, National Institutes of Health. "New Tools for Tomorrow's Health
Research." Bethesda, MD: Department of Health and Human Services, 1992.
Since the beginning of time, people have yearned to explore the unknown, chart where they
have been, and contemplate what they have found. The maps we make of
these treks enable the next explorers to push ever farther the boundaries
of our knowledge - about the earth, the sea, the sky, and indeed,
ourselves. On a new quest to chart the innermost reaches of the human
cell, scientists have now set out on biology's most important mapping
expedition: the Human Genome Project. Its mission is to identify the full
set of genetic instructions contained inside our cells and to read the
complete text written in the language of the hereditary chemical DNA
18
(deoxyribonucleic acid). As part of this international project, biologists, chemists, engineers,
computer scientists, mathematicians, and other scientists will work together to plot out several
types of biological maps that will enable researchers to find their way through the labyrinth of
molecules that define the physical traits of a human being.
Packed tightly into nearly every one of the several trillion body cells is a complete copy of the
human "genome" - all the genes that make up the master blueprint for building a man or
woman. One hundred thousand or so genes sequestered inside the nucleus of each cell are
parceled among the 46 sausage-shaped genetic structures known as chromosomes.
New maps developed through the Human Genome Project will enable researchers to pinpoint
specific genes on our chromosomes. The most detailed map will allow scientists to decipher
the genetic instructions encoded in the estimated 3 billion base pairs of nucleotide bases that
make up human DNA. Analysis of this information, likely to continue throughout much of the
21st century, will revolutionize our understanding of how genes control the functions of the
human body. This knowledge will provide new strategies to diagnose, treat, and possibly
prevent human diseases. It will help explain the mysteries of embryonic development and
give us important insights into our evolutionary past.
The development of gene-splicing techniques over the past 20 years has given scientists
remarkable opportunities to understand the molecular basis of how a cell functions, not only
in disease, but in everyday activities as well. Using these techniques, scientists have mapped
out the genetic molecules, or genes, that control many life processes in common
microorganisms. Continued improvement of these biotechniques has allowed researchers to
begin to develop maps of human chromosomes, which contain many more times the amount
of genetic information than those of microorganisms. Though still somewhat crude, these
maps have led to the discovery of some important genes.
By the mid-1980s, rapid advances in chromosome mapping and other DNA techniques led
many scientists to consider mapping all 46 chromosomes in the very large human genome.
Detailed, standardized maps of all human chromosomes and knowledge about the nucleotide
sequence of human DNA will enable scientists to find and study the genes involved in human
diseases much more efficiently and rapidly than has ever been possible. This new effort - the
Human Genome Project - is expected to take 15 years to complete and consists of two major
components. The first - creating maps of the 23 pairs of chromosomes - should be completed
in the first 5 to 10 years. The second component - sequencing the DNA contained in all the
chromosomes - will probably require the full 15 years.
Although DNA sequencing technology has advanced rapidly over the past few years, it is still
too slow and costly to use for sequencing even the amount of DNA contained in a single
human chromosome. So while some genome project scientists are developing chromosome
maps, others will be working to improve the efficiency and lower the cost of sequencing
technology. Large-scale sequencing of the human genome will not begin until those new
machines have been invented.
Why do the Human Genome Project?
Most inherited diseases are rare, but taken together, the more than 3,000 disorders known to result
from single altered genes rob millions of healthy and productive lives. Today, little can be done to
treat, let alone cure, most of these diseases. But having a gene in hand allows scientists to study its
structure and characterize the molecular alterations, or mutations, that result in disease. Progress in
19
understanding the causes of cancer, for example, has taken a leap forward by the recent discovery of
cancer genes. The goal of the Human Genome Project is to provide scientists with powerful new tools
to help them clear the research hurdles that now keep them from understanding the molecular essence
of other tragic and devastating illnesses, such as schizophrenia, alcoholism, Alzheimer's disease, and
manic depression.
Gene mutations probably play a role in many of today's most common diseases, such as heart
disease, diabetes, immune system disorders, and birth defects. These diseases are believed to
result from complex interactions between genes and environmental factors. When genes for
diseases have been identified, scientists can study how specific environmental factors, such as
food, drugs, or pollutants interact with those genes.
Once a gene is located on a chromosome and its DNA sequence worked out, scientists can
then determine which protein the gene is responsible for making and find out what it does in
the body. This is the first step in understanding the mechanism of a genetic disease and
eventually conquering it. One day, it may be possible to treat genetic diseases by correcting
errors in the gene itself, replacing its abnormal protein with a normal one, or by switching the
faulty gene off.
Finally, Human Genome Project research will help solve one of the greatest mysteries of life:
How does one fertilized egg "know" to give rise to so many different specialized cells, such as
those making up muscles, brain, heart, eyes, skin, blood, and so on? For a human being or any
organism to develop normally, a specific gene or sets of genes must be switched on in the
right place in the body at exactly the right moment in development. Information generated by
the Human Genome Project will shed light on how this intimate dance of gene activity is
choreographed into the wide variety of organs and tissues that make up a human being.
Ethical Issues of the Human Genome
Project
"Mapping and Sequencing the Human Genome: Science, Ethics, and Public Policy." Developed by BSCS, in
collaboration with the American Medical Association, under the U.S. Department of Energy Grant #DE-FG0291ER61147.
Critics express several concerns about the Human Genome Project
(HGP), and most involve the extent of the project or its funding.
Original proposals for the project emphasized sequencing the entire
human genome. This goal, however, is controversial because of the
high cost and because many critics believe that sequencing a huge
amount of noncoding DNA should have low priority in a time of
limited funds for research. On the other hand, most individuals
involved in the project agree that detailed genetic and physical maps
would be extremely useful. Therefore, mapping of the genome now is
the primary goal, with complete sequencing to follow only if the cost
becomes reasonable.
20
Only about 5 percent of the genome contains sequences that are coding regions, and some
biologists still maintain there is little point in sequencing the other 95 percent. Because
biologists already know that several regulatory signals are in noncoding regions of DNA, a
compromise has been reached. A few pilot sequencing projects are focusing on sequencing
certain coding regions that are most likely to contain information valuable to the medical and
biological communities.
A major criticism of the HGP is similar to that raised against other mega-science projects such
as the space station or the superconducting supercollider: The high cost is not justified. This
big science vs. little science argument maintains that funding such large-scale projects takes
scarce resources from researchers who may study certain areas of particular interest more
efficiently. Conversely, others argue that coordination of the HGP is a more efficient way to
conduct research in human genetics because it minimizes duplication of effort.
Some critics suggest that the ability to diagnose a genetic disorder before any treatment is
available does more harm than good because it creates anxiety and frustration. Indeed,
geneticists have isolated several disease-causing gene mutations and have studied them in
great detail without developing a treatment. For example, the mutation in the beta-globin gene
that results in sickle cell disease was identified in 1956, but there is no treatment as yet.
Scientists eventually may develop successful therapies, but until they do, this criticism is
significant.
Even in the absence of new treatments, however, the HGP may make diagnosis possible
before the onset of symptoms and, thus, make management of the disorder more effective. In
addition, improved preconceptual analysis of the parents' genotypes can provide couples with
a broader range of options for family planning.
Some critics of the HGP maintain that social and political mechanisms to regulate the ultimate
outcomes are insufficient. Because of the genetic variation between individuals, there never
will be one definitive human sequence. The lack of a definitive sequence creates uncertainty
about the appropriate definition of "normal," which in turn makes the discussion of public
policy issues difficult. Questions about controlling the manipulation of human genetic
materials concerns these critics, as does the idea that simply because these scientists are able
to do this science, they ought to. These critics point to the development of atomic weapons
and argue that the science that led to their development caused far more problems than it
resolved.
Few religious groups in the United States formally have addressed the specific ethical and
public policy issues raised by the HGP, although there is active interdenominational
discussion of issues related to human genetics in general. Public policy debates are enriched
considerably by input from these various groups.
Research Update - Animals and Animal
Health
21
J. Glenn Songer, Ph.D., University of Arizona
"NBIAP News Report." U.S. Department of Agriculture (June 1994)
The National Animal Genome Research Program (NAGRP), recently approved as a USDA
regional research project, has as a general goal the determination of the genetic makeup of
various economically important domestic animals. Specific objectives of the program are (1)
to improve our understanding of the structure and organization of specific genes, (2) to
identify and characterize genes controlling important metabolic processes (such as growth,
aspects of reproduction, and milk production), and (3) to assign these genes to specific
locations on chromosomes, so that they can be more easily manipulated in breeding programs
designed to enhance expression of specific traits.
Integral to the process of genome mapping is the detection and characterization of "markers."
Markers are sequences of DNA with unusual patterns or characteristics that are easily
recognized, and the position of specific genes can be determined by ascertaining the location
of the gene relative to a marker. Some have variable number tandem repeats; microsatellite
markers are repeats of a simple DNA sequence (such as CACACACA, where C and A are the
bases cytosine and adenine, respectively). Other markers may be identified on the basis of
conformational differences.
Responsibility for the various domestic species has been spread out over the geographic
regions of the U.S., each supervised by an administrative advisor. The Animal Genome
Technical Committee involves 51 scientists at 27 locations, and the industries for which these
studies are relevant have been actively supportive of the program.
Committees representing the major animal groups (swine, sheep, cattle, and poultry) are
developing computer databases similar to that available for mice. These will serve as banks
for genomic data representing the entire array of genes of a particular animal. The data will
provide a basis for comparative studies among animals, to facilitate correlations between
genes and their functions, and also to determine the relative positions of genes in the DNA
sequence.
The committee responsible for swine genome research has made significant progress in
development of a genetic linkage map, with 400 markers already identified. The immediate
goals for this committee include continuing to develop a genetic linkage map and to produce
swine cells that can grow independently in a laboratory setting to allow for constant
availability. The swine database, USPIGBASE, is already available for use.
Several genetic linkage maps for cattle have been produced, and these cover approximately
90% of the bovine genome. The U.S.-developed map contains 313 markers, and several
hundred cattle microsatellite markers have been identified in the past year. The "international"
map has 201 areas of genetic diversity and is the result of an international collaboration
involving ten laboratories in seven countries. A major goal for the immediate future is to
develop a consensus linkage map, combining information from all independent maps now
available, and to subsequently develop a database from this information.
The committee directing the mapping of the poultry genome is striving to develop a
consensus genetic linkage map of chickens, with many easily identified markers, and to
22
extend this map to other poultry of economic importance. Further, this map will be used to
identify genes responsible for specific traits, to work with industries to develop effective
applications for this knowledge, and to enhance progress in all of these areas through the
sharing of information via a database. Recent efforts have seen the number of known markers
increase to 230, and efforts to produce a consensus linkage map have begun, using several
maps now available.
Researchers in the sheep genome project have been successful in developing genetic linkage
maps containing several hundred markers, and work on a consensus genetic linkage map is
underway.
Animal genetics and gene mapping have received major support through the National
Research Initiative Competitive Grants Program (NRICGP) of the USDA. One primary
objective of the NRICGP is to increase our understanding of the structure, organization,
function, expression, and regulation of genes. Further knowledge in these areas will help to
maintain genetic diversity, improve animal productivity and efficiency, locate economically
important production traits (including size, reproductive vigor, and genetic diseases), and
finally to provide methods for utilizing this information to select for desired characteristics in
animals.
A Short History of Mapping
Reading The Human Blueprint
Beverly Mertz
Pines, Maya, ed. "Blazing a Genetic Trail." Bethesda, MD: Howard Hughes Medical Institute, 1991.
"All human disease is genetic in origin," Nobel laureate Paul Berg of Stanford University told
a cancer symposium a few years ago. Berg was exaggerating only slightly. It has become
increasingly evident that virtually all human afflictions, from cancer to psychological
disorders and susceptibility to infection, are rooted in our genes. "What we need to do now is
find those genes," claims James Watson, who shared a Nobel Prize for deciphering the
structure of DNA and who now directs the National Center for Human Genome Research at
the National Institutes of Health.
The necessary guide will be a map fixing each of the
estimated 50,000 to 100,000 human genes to its
correct location on the chromosomes. "Like the
system of interstate highways spanning our country,
the map of the human genome will be completed
stretch by stretch," Watson says. He expects that this
map, the goal of the federally funded Human
Genome Project, will provide the key to
understanding the nearly 4,000 known genetic
disorders and the countless diseases whose origin
23
may be due in part to genetic malfunctions, as well as the astonishing variety of normal
human traits.
Such a map has been on the wish lists of molecular explorers for years. Without it, nailing the
culprits responsible for genetic diseases requires not only hard work, ingenuity, and
determination, but more than a little luck. Although researchers were aided by luck when they
found the general location of the gene for Huntington's disease (HD) on chromosome 4 in
1983, for instance, since that time they have spent eight years painstakingly slogging through
the target area at the tip of the chromosome and still have no gene in sight.
Yet single-gene diseases such as HD are relatively easy targets. Disorders that seem to be
caused by the interplay of several genes, hypertension, atherosclerosis, and most forms of
cancer and mental illness, are much more difficult to track down. Having a map of the entire
human genome will make it theoretically possible to identify every gene that contributes to
them.
A gene map can also lead researchers to new frontiers in drug development. Once all the
genes are identified and their bases are sequenced, it will be possible to produce virtually any
human protein-valuable natural pharmaceuticals, such as tissue plasminogen activator,
interferon, and erythropoietin - as well as new molecules designed specifically to block
disease-producing proteins.
The NIH gene-mapping project officially began in October, 1990. But the
map of the human genome has been in the making for a good part of the
century. It started in 1911, when the gene responsible for red-green color
blindness was assigned to the X chromosome following the observation
that this disorder was passed on to sons by mothers who saw colors
normally. Some other disorders that affect only males were likewise
mapped to the X chromosome on the theory that females, who have two X
chromosomes, were protected from these disorders by a normal copy of
the gene on their second X chromosome unlike males, who have one X
and one Y chromosome.
The other 22 pairs of chromosomes remained virtually uncharted until the late 1960s. Then
biologists fused human and mouse cells to create uneasy hybrid cells that cast off human
chromosomes until only one or a few remained. Any recognizable human proteins in these
hybrid cells thus had to be produced by genes located on the remaining human chromosomes.
This strategy allowed scientists to assign about 100 genes to specific chromosomes.
Map-making really took off in the early 1970s, when geneticists discovered characteristic
light and dark stripes or bands across each chromosome after it was stained with a chemical.
These bands, which fluoresced under ultraviolet light, provided the chromosomal equivalent
of latitudes. They made it easier to identify individual human chromosomes in hybrid cells
and served as rough landmarks on the chromosomes, leading to the assignment of some 1,000
genes to specific chromosomes.
Around the same time, recombinant DNA technology began to revolutionize biology by
allowing researchers to snip out pieces of DNA and splice them into bacteria, where they
could be grown, or cloned, in large quantities. This led to two new mapping strategies. In one,
in situ hybridization, scientists stop the division of human cells in such a way that each
24
chromosome is clearly visible under a light microscope. Then they use probes to find the
location of any DNA fragment on these chromosomes. Originally these probes were
radioactively labeled, but chemically-tagged probes that can be made to fluoresce have been
found to yield far more accurate and rapid results.
The other strategy is to use DNA variations as markers on the human genome, as proposed by
Botstein, White, Skolnick, and Davis in 1980. This has resulted in a flood of new markers and
an explosion in the knowledge of genes' chromosomal whereabouts. The number of genes
mapped grew from 579 in 1981 to 1,879 in 1991. Gene mappers, who used to meet to
coordinate their findings every year or so, now update the map every day via electronic
databases.
Meanwhile, scientists learned to sequence the genes they isolated. This became possible in the
mid-1970s when Frederick Sanger at Cambridge University and Walter Gilbert and Allan
Maxam at Harvard University developed efficient new methods for determining the order of
bases in a strand of DNA. Automated high-speed sequencing by machine followed in the
1980s. Now, once a new gene has been identified, it is immediately sequenced to understand
the nature of the protein it codes for and to identify mutations that are related to disease.
Sequencing the entire genome, however, means sequencing at least 3 billion base pairs of
DNA - a chromosome of each type, or half the total number of chromosomes in a human cell.
This remains a daunting project.
Generally the most interesting or accessible genes have been located first, creating a disparity
among chromosomal maps. While the map of the X chromosome appears to be as densely
populated as the New York coast, for instance, chromosome 18 looks as lonesome as central
South Dakota.
The Human Genome Project should even out the map by sending explorers into chromosomal
terra incognito. "The project really isn't doing anything new. What it's doing is creating order
and accountability," says geneticist Eric Lander of the Whitehead Institute.
This orderly process is expected to produce a genetic linkage map in which the positions of
genes for specific traits and diseases are superimposed on a grid of evenly spaced markers
along the chromosomes. The project's five-year goal is to cover the entire genome with 1,500
genetic markers placed at equal intervals. Scientists will be able to determine any gene's
location relative to these markers.
In addition, the project will create a physical map that shows actual distances along the
chromosomes in terms of base pairs.
The physical map probably will be constructed of long overlapping stretches of DNA cloned
in yeast and known as yeast artificial chromosomes (YACs). Developed in 1987 by Maynard
Olson, now an HHMI investigator at Washington University in St. Louis, YACs make it
possible to clone and store very large DNA segments - much larger than those that can be
cloned in bacteria. The technique has reduced the number of DNA pieces that need to be
placed in the right order from about 100,000 to 10,000. Recently, Olson assembled a YAC
library of the entire genome and distributed it for the use of gene mappers.
25
At least two approaches have been developed to unite the genetic linkage map and the
physical map so that a researcher can easily move back and forth between the two. One is to
dot both maps with a new kind of marker known as sequence-tagged sites, or STSs - long
sequences of DNA that generally occur only once in the whole human genome and can be
used as common reference points. The other approach is to plot the position of existing
genetic markers onto the physical map by means of in situ hybridization.
Meanwhile, new strategies promise to speed up sequencing significantly. Some researchers
have reported that it may not be necessary to sequence every base but to sequence certain
pivotal regions of DNA and fill in the blanks later. Moreover, automated sequencing and
computer software designed specifically for genome analysis are already reducing sequencing
time. As the pace of mapping and sequencing quickens, so does the pace of data collection.
The Genome Data Base, developed by The Johns Hopkins University in collaboration with
HHMI, integrates various kinds of mapping and sequencing data, as well as the constantly
evolving genetic linkage map. The Paris-based Centre d'Etude du Polymorphisme Humain
collates data from laboratories around the world to develop a series of consensus maps for
each chromosome. Another international body, the Human Genome Organisation, is starting
to coordinate gene-mapping efforts in 42 nations.
The Genome Project has often been criticized as the intrusion of "Big Science" on the
traditionally "small science" of biology. However, "everyone's beginning to realize this isn't at
all like putting up a space station or erecting a supercolliding superconductor," says Glen
Evans of the Salk Institute in La Jolla, California. "We're not going to undertake large-scale
sequencing until new technology makes it cheap to do," explains James Watson.
If a map of the genome and sets of overlapping clones had been available when researchers
set out to find the cystic fibrosis gene, their task would have taken only a fraction of the time
and cost, points out Thomas Caskey, of the HHMI unit at the Baylor College of Medicine.
"The investigators wouldn't have had to clone region after region looking for the gene," he
says. "They could have just reached into the freezer and pulled out two markers flanking it.
The same would be true for many other diseases. And remember, once we make this map, we
will never have to do it again."
What Can We Expect from the Human
Genome Project?
"Mapping and Sequencing the Human Genome: Science, Ethics, and Public Policy."
Developed by BSCS, in collaboration with the American Medical Association, under the
U.S. Department of Energy Grant #DE-FG02-91ER61147.
Diagnosis and Prediction of Disorders
Geneticists cloned genes responsible for genetic disorders even before the
organization of the Human Genome Project (HGP). In the last few years, wellpublicized successes included the cloning of genes responsible for Duchenne
26
muscular dystrophy (DMD), retinoblastoma, cystic fibrosis, and neurofibromatosis. If other such
disease-related genes are isolated, biologists can learn about the structure of the gene's corresponding
protein and the pathology of the disorder. This knowledge could lead to better medical management of
the resulting disorders.
Several techniques to detect gene mutations allow immediate and accurate diagnosis in
individuals with some symptoms. For example, before geneticists cloned the DMD gene, the
confirmation of a diagnosis required expensive and uncomfortable tests, and the tests were
inadequate to detect carriers. Now, with only a blood sample, geneticists can detect most
mutations associated with DMD very rapidly. DNA-based tests clarify the diagnosis quickly
and enable geneticists to detect carriers within the same family.
The probability of erroneous results from a genetic test is small, but not zero; false-positive or
false-negative results can occur because of technical abnormalities or human error such as the
mislabeling of samples. In addition, some tests such as that for cystic fibrosis cannot detect all
of the mutations associated with the disorder. The use of genetic tests to detect carriers, for
prenatal diagnosis and for presymptomatic diagnosis, has created ethical and public policy
issues.
Genome information can indicate the future likelihood of some diseases. For example, if the
gene responsible for Huntington's disease is present, it is a near certainty that symptoms
eventually will occur, although geneticists cannot accurately predict the time of onset.
Genome information also helps geneticists predict which individuals have an increased
susceptibility to disorders such as heart disease, cancer, or diabetes, which result from
complex interactions between genes and the environment. There is no guarantee that
symptoms will occur, but the risk is greater for individuals with specific genotypes than for
the general population.
Insight into Basic Biology
Information generated by the HGP may shed light on several interesting biological questions. The
discovery of new genes is an obvious benefit, as is the determination of their functions. The
organization of genes within the genome is another area of investigation in biology. Is it important,
for example, for genes to reside on a particular chromosome, or in a particular order, or both?
When biologists compare the human genome with the genomes of other organisms, they may
gain some insight into molecular evolution, including human evolution. Comparisons of
human and mouse DNA sequences will help identify genes that are unique to one or more
complex organisms, and comparisons of DNA sequences from humans and fruit flies or
nematodes may help identify genes essential for all multicellular organisms. Comparisons of
human and yeast DNA sequences may help identify genes related to functions essential for all
eukaryotic cells.
Development of New Technologies
The HGP has catalyzed enormous advances in the development of technology, and it will continue to
do so. One of the biggest challenges of the HGP is finding faster ways to sequence DNA. A yet
unproved idea uses a DNA "chip." The chip is not a piece of electronic equipment, but an array of
short pieces of DNA, each with a known sequence, arranged on a substrate. When a solution
containing DNA with an unknown sequence is applied to the substrate, some of it reacts with the
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short DNA whose sequence is known. The signal indicates to which unknown sequence the known
sequence hybridized. This yields a pattern that a computer can use to determine the sequence of
bases.
By one estimate, the HGP ultimately will provide 10 million times more data about each
individual than is available at the chromosome level, and researchers are developing computer
hardware and software necessary to manipulate the huge quantity of data. One important
addition is the Genome Data Base, located in Baltimore, which incorporates data from human
genetic maps as they accumulate. Several other data bases around the world accumulate
sequence data from a variety of organisms.
Researchers have made great progress in developing automated machines and robotic work
stations to perform repetitive procedures. These machines are particularly useful in large-scale
sequencing operations, and computers can read the results of a sequencing experiment and
load the data directly into a data base. Although automation accelerates the procedure and
reduces the opportunity for human error, human involvement is still necessary.
Limits and Opportunities
Determination of the entire DNA sequence contained in the human genome will not answer the
question: What is a human? Geneticists will not be able to look at a person's DNA sequence and
predict everything about the appearance and characteristics of that person. Even if geneticists can
identify segments of DNA as genes, the vast majority of the genes they discover still will have
unknown functions. In addition, many human traits such as body stature and intelligence result from
multiple genes, and the exact number of genes that might contribute to such a trait is not obvious,
nor are the ways in which those genes interact. An individual's genetic make-up greatly contributes
to the type of person he or she is, but environmental variables such as diet, education, climate,
family values, and access to health care also play a considerable role in determining an individual's
characteristics.
Even in single-gene disorders, there usually is considerable variation in the expression of the
gene. This variability may result from different mutations in the same gene, environmental
effects, interactions with other genetic features, or any combination of these factors. Thus,
even when geneticists discover a disease-related gene in an individual, they cannot always
predict the exact course of the disorder.
Although it may appear that our genes are relatively stable, the human genome changes
continually because of errors in DNA replication. Genes responsible for genetic disorders may
be inherited from one or both parents, or they may arise from new mutations because of errors
in the replication of an individual's DNA. It is unlikely, therefore, that a geneticist could
absolutely exclude the possibility of a genetic disorder by examining an individual's genome.
New mutations are more likely in X-linked and autosomal dominant disorders than in
recessive disorders.
There are certain areas of human genetics in which researchers expect to expand their current
knowledge. Two such areas are the regulation of gene expression and the role of the vast
majority of DNA that has not yet been assigned a function - the inappropriately named "junk"
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DNA. Research published early in 1992 demonstrated that an intron, which is thought to be a
noncoding region of DNA, plays a role in the function of transfer RNA, which is critical to
protein synthesis. Additional research likely will reveal other functions for such junk DNA.
Geneticists already have made one surprising observation from their increased knowledge of
the human genome - a phenomenon called imprinting. Imprinting describes a molecular signal
that indicates whether one allele of a pair was inherited from the mother or the father.
Apparently, in some cases it is not sufficient merely to have two copies of a gene. Rather,
each copy must be inherited from a different parent.
Imprinting is implicated for example, in Prader-Willi syndrome and Angelman syndrome.
Individuals with either of these disorders are mentally impaired. Infants with Prader-Willi
syndrome usually are small at birth and may experience respiratory and feeding problems.
They become obese as young children, their skin is sensitive to light, and their hands and feet
are small. Children with Angelman syndrome have an abnormal puppet-like gait and sudden
outbursts of inappropriate laughter. These two dissimilar disorders apparently result from a
disruption of the same region on chromosome 15, but in Prader-Willi syndrome, the mutation
is inherited from the father, whereas in Angelman syndrome, the mutation is from the
maternal side.
In addition to expanding our knowledge of genetics, the HGP also will provide a number of
new job opportunities in biotechnology, health care, computing and information storage, and
ethics and public policy. Discussions of ethics and public policy will require input from
individuals trained in disciplines such as philosophy, theology, law medicine, science,
sociology, and public policy.
Whose Genome is It, Anyway?
National Center for Human Genome Research, National Institutes of Health. "New Tools for Tomorrow's Health
Research." Bethesda, MD: Department of Health and Human Services, 1992.
A quick glance around any public gathering will attest to the
physical diversity of the human population. In most groups of
people, some will be tall, others hefty; some will have brown
eyes, and others blue. Physical attributes such as height,
complexion, and hair and eye color are largely determined by
genes - packets of the genetic material DNA, which makes up
chromosomes in the human cell.
As scientists begin to map and analyze the molecular details
of the complete set of human genes, whose will it be? In
many ways, describing the anatomy of the human genome
will be similar to studying the human heart, for example, or
the human brain. While there are small differences from
person to person in the size and shape of these organs, most of the key characteristics are the
same. Although human beings are distinct from one another, they are really very similar in
most biologically important respects. That's what makes us human. So the map of the human
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genome can really be based on information collected from many different people. And most
of the information in that map will pertain to everyone.
The tiny differences between any two people rest in only 2 to 10 million (out of the 3 billion
total) nucleotide bases, an amount that computes to about 1 percent or less of their total DNA.
Because these small differences vary from person to person, it doesn't matter whose genome it
is. For some studies, the differences will be the focus of interest. In other cases, it will be the
similarities. Researchers at Baylor College of Medicine were given the assignment of
mapping the sex chromosome X and chromosome 17. They collected DNA from patients who
came into the clinic for genetic testing. Each sample is from a different and unrelated person.
The cell culture collection contains a number of different human genomes.
Eventually, scientists will "map", or establish distinctive genetic
landmarks, from one end of a chromosome to the other and add that
information to the genetic map of the entire human genome. This
complete map will become the "reference" to which researchers will
compare DNA taken from a variety of people, as scientists look for
disease genes and other important genetic regions located on
chromosomes. A particular region on a chromosome, for example,
may be found to contain information about height. Although the
genetic content of that specific site may change slightly from person
to person, the location of the site will be the same in each person's
genome.
Because studying the entire six-foot stretch of human DNA is a huge project, scientists are
tackling the genome one chromosome at a time. Even then, analyzing the information in just
one chromosome is an enormous task for a single research group, so many scientists are
studying only portions of a chromosome at a time. Even then, analyzing the information in
just one chromosome is an enormous task for a single research group, so many scientists are
studying only portions of a chromosome. The complete map for a single chromosome will
then be derived from samples collected from several unrelated people by researchers in many
different laboratories.
For several decades, geneticists searching for disease genes have studied human cells
maintained in the laboratory. These cells originally came from people who have an inherited
disease, from their healthy relatives who are carriers, or from other unrelated healthy people.
But because human cells do not ordinarily survive long under laboratory conditions, scientists
have had to invent ways to keep the cells alive long enough to perform detailed studies of
DNA inside the cells.
Since almost all cells in the body contain the same genetic information, nearly any type of cell
can be used as a source of DNA. A type of white blood cell called a lymphocyte is commonly
used because it is easy to obtain from a blood sample. To get the cells to last longer in the
laboratory, scientists infect lymphocytes in the test tube with a common virus known as EBV.
This virus, the cause of mononucleosis, interrupts the cell's normal life cycle so it literally
doesn't know when to die. Cells "immortalized" by EBV then grow and divide indefinitely in
laboratory cultures, providing researchers with unlimited amounts of human DNA for genome
studies.
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In most labs, the donors of these pieces of biology's greatest puzzle will never be known.
They are the genetic equivalent, according to one researcher, of the unknown soldier.
A Worldwide Effort
The Human Genome Project Around the World
National Center for Human Genome Research, National Institutes of Health. "New Tools for Tomorrow's Health
Research." Bethesda, MD: Department of Health and Human Services, 1992.
The six-foot thread of DNA inside each human cell might be thought of as
the thread unifying all of mankind. Because information about the human
genome will be applicable to the entire human race, not only the National
Institutes of Health (NIH), but also other U.S. agencies and indeed
programs in other countries will fund and carry out the goals of the genome
project.
In the U.S., institutions currently supporting genome programs include the
NIH, the Department of Energy (DOE), the Department of Agriculture
(USDA), the National Science Foundation (NSF), and the privately funded
Howard Hughes Medical Institute (HHMI).
The DOE has established a human genome program to expand its ability to investigate the
effects of radiation and energy-related chemicals on human genetic material. The major
objectives of their program are the development of resources, including expanded sets of
overlapping DNA fragments and new chromosome mapping and DNA sequencing
technologies. Database management systems, including automated techniques for entering
DNA sequences into databases, and computer systems for analyzing genome data, are also the
focus of DOE efforts.
The NIH has established a formal Memorandum of Understanding with DOE, which lays out
guidelines for interactions between the two agencies. The NIH's National Center for Human
Genome Research (NCHGR) and DOE staff meet regularly, and a subcommittee of both DOE
and NCHGR advisors meet to develop complementary research plans.
The USDA has begun to map and sequence the genomes of a number of plants important to
agriculture and forestry. Already genetic linkage maps are being constructed for corn,
tomatoes, wheat, potatoes, cotton, alfalfa, and grapes. Genes that control or influence flavor,
yield, drought tolerance, or insect resistance for certain plants have been mapped.
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The NSF has a special interest in developing hardware and software tools, providing
instrumentation and facilities for genetic research, supporting basic genetics research
(primarily on nonhuman organisms), and developing biological databases. In collaboration
with the NCHGR and other agencies, the NSF has also launched a project to map and
sequence the genome of the plant Arabidopsis thaliana, a relatively simple plant in the
mustard family used widely in studies of plant genetics.
The Howard Hughes Medical Institute, a private, non-profit organization, currently funds
several resources important to the Human Genome Project. These include a database at the
Center for the Study of Human Polymorphisms (CEPH) in Paris, which contains genetic
linkage information on a large number of multi-generation families.
Internationally, NCHGR is collaborating with the Human Genome Organization (HUGO).
Established in 1988, HUGO is an international consortium of molecular biologists organized
to ensure that the genome project is coordinated internationally and that the information
gleaned by project researchers will be freely accessible to scientists worldwide. HUGO will
promote international cooperation and negotiate overlapping interests.
Other countries involved in human genome research include the United Kingdom, France,
Germany, Japan, Italy, Russia, Canada, and Israel. France's CEPH is a centerpiece for
researchers developing genetic linkage and physical maps of the human genome. The
Japanese are focusing efforts on developing automated technology for DNA sequencing,
identifying E. coli, rice, a yeast chromosome, and Arabidopsis as models to sequence during
technology development.
Issues and Bioethics
Issues focuses on scientific breakthroughs that have propelled
biotechnololgy at a dizzying pace into the 21st century. Evolving in
tandem with biotech innovations, ethics looks at complex decisions that
affect a few individuals or an entire social group or society.
Table of Contents
Bioethics
Issues
Overview
Environmental
Management
Animal Genome Gene Therapy
Social Practices &
Policies
Bioethics & You
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Projects
Plant Genome
Projects
Issues
Overview
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Biotechnology Industry Review - overview of the biotechnology
industry from dairy farming to waste management
The Future Of Genetic Research - 1991 report looks at the perils and
problems of gene manipulation
Animal Genome Projects
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Introduction - The Human Genome Project - the "why's" of identifying
our genetic instructions
Ethical Issues of the Human Genome Project - high costs limit
sequencing efforts to non-coding regions with complete sequencing
to follow
Research Update - Animals and Animal Health - efforts to determine
the genetic makeup of domestic animals
A Short History of Mapping - the grand plan to map the human
genome
What Can We Expect from the Human Genome Project? - the "what's
to be gained" from sequencing human genes
Whose Genome is It, Anyway?
A Worldwide Effort - sequencing human genetic code involves many
countries
Plant Genome Projects
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Are Bioengineered Foods Safe? from the FDA Consumer Magazine,
January-February 2000
Who Controls and Who Will Benefit from Plant Genomics? "The 2000
Genome Seminar: Genomic Revolution in the Fields: Facing the Needs
of the New Millennium" AAAS Annual Meeting
Environmental Management
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Why It Matters - Humans are superconsumers of the environment
and there are economic, aesthetic and ethical reasons for concern
Helping Mother Nature Heal with Her Own Remedies Rio Declaration On Environment and Development - 27 principles
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directing an equitable global partnership for managing the
environment
Gene Therapy
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Gene Therapy - An Overview - dealing with genetic diseases
amenable to treatment in the future
Bioethics
Social Practices and Policies: Connecting You to Society
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An Approach to Teaching Ethical Decision Making in Medicine and
Life Sciences - a conversation with Ernle Young, Ph.D. about how
clinicians and others make complex decisions when people are ill
Biotechnology's Impact on Society - the risks of biotechnology to
society: cost-benefit ratios
Challenges to Public Policy - talk given by Donald Kennedy, Ph.D
about regulating biotechnology.
Culture Clash - Most collaborations between industry and academia
are positive: companies get research done, and academics get
funding. But when results are unexpectedly negative, things can get
messy.
Democratizing Technology - government efforts to "politicize"
technology through competiveness
DNA on the Witness Stand Eric S. Lander, DPhil. The issues concerning
the use of genetic evidence in civil and criminal court cases from
Winding Your Way Through DNA Symposium
Epistemology of Science - ways of knowing the truth: role of science
in decision making
The Genetic Revolution: Ethical Issues - Ernle Young, Ph.D. comments
on gene testing, genetic therapies, eugenics and enhancement
Genetic Testing - Health Care Issues - an interview with Neil Holzman,
Ph.D. regarding genetic testing and Constitutional issues
Musings On Cattle Cloning - Tom Zinnen, Ph.D. comments on the
promise and problems of cloning domestic animals
NIH Publishes Revised Guidelines for Research Involving Recombinant
DNA Molecules - 1994 guidelines and brief historical perspective for
development
Scientist Returns Research Grant to Show Concern about Dangers of
Genetically Engineered Organisms - 1994 John Fagan, Ph.D. returns
grant money to NIH because of concerns about genetic manipulation
of plants and animals
Talking and Teaching Biotech - Tom Zinnen, Ph.D comments on how
to educate the general public about biotechnology
To Regulate or Not to Regulate - Henry Miller, Ph.D. says that
regulatory red tape is strangling progress in biotechnology and calls
for a government overhaul of relevant agency policies
Risky Business: Issues in Teaching about Safety and Regulation - Tom
Zinnen, Ph.D. argues for improving public understanding of
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biotechnology products to correct misconceptions
Some Questions and Answers about BGH/BST - bovine growth
hormone: safe and sane?
Wholesome, Holistic and Holy: Controversies over Biotechnology and
Food - overview of the controversies around food consumption and
genetic manipulation of food sources
Bioethics and You: Issues of Individual Decision Making
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Genetic Testing in a Clinical Setting - perspectives of a genetic
counselor dealing with real cases in a clinical setting
Promise and Perils of Biotechnology: Genetic Testing (teacher
resources & student activities)
Teaching Bioethics - incorporating bioethics information into biology
curricula
Why Teach Bioethics in the Classroom - theoretical discussion of
ethical principles and practical suggestions for classroom use
The Gene Connection™ Second Annual Bioethics Symposium and
Workshop presented by the San Mateo County Biotechnology
Education Partnership, features discussions and case studies on ethical
and social issues arising from genetic testing, gene therapy, genetic
enhancement, cloning, and genetic counseling.
Issues and Ethics Index
About Biotech Index
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