By Daniella Goldberg
A new era of experimentation on the basic cells of human life appears to
be making science fiction into truth. Community and governments are
sitting up and asking: why are scientists fooling around with human
stem cells?
Every morning before breakfast, Scott
would jab himself in the leg with an
insulin injection. Twenty minutes after
his cereal and tea, he would prick his
finger to check his blood glucose levels
were OK. Often they were not.
"I had to do five injections a day and up
to eight blood sugar tests," he says. "It's
not easy."
Scott, 15, had been performing this daily ritual since he was first diagnosed
with type I diabetes — the kind that starts in childhood — at age 3. He now
uses an insulin pump to control his medication, but he is still at risk of
developing complications such as blindness, kidney failure, and nerve
damage as he gets older.
A better treatment for type I diabetes is just one of the hopes for stem cell
therapy. Parkinson's disease, Alzhiemer's, blindness, heart disease, and
even the aging process are other candidates. All are human frailties that may
be helped by replacing old, diseased organs or tissues with healthy new
ones. That's what stem cell technology aims to do.
Human stem cells
Stem cells are a type of cell that can be
transformed into virtually any of the
200 kinds of cell in the human body.
This means that in theory at least, they
can be 'grown to order' to help people
suffering from degenerative diseases. In
practical terms, there are two big
challenges: persuading the stem cells to
develop into exactly the kind of cell you
want, and persuading the body to
accept them. It's not easy, but progress
has been rapid since the first human
stem cell line was created just three
years ago.
While the science has flourished, so has
the controversy surrounding it.
When an egg meets a sperm, in a dish or
inside a woman's uterus, an embryo cell
forms. The single cell grows and divides.
Within 5 or 6 days there are up to 120
cells. They form into a ball called the
blastocyst. Each cell is pluripotent,
capable of developing into any cell type in
the human body such as heart, skin or
hair. (Pic courtesy Liz Sanders, Women's Specialty
The first big problem with stem cells is
where to get them. Everyone has stem
cells — they exist in the bone marrow,
for example, where new blood cells are Center, Jackson, Mississippi, USA)
constantly regenerating — but in adults
and children, these are already partly specialised. Many researchers doubt
that they are truly capable of developing into any kind of cell.
Scientifically more promising, but ethically more problematic, are stem cells
derived from human embryos. Most of the stem cells now being used in
research were originally sourced either from leftover IVF embryos or from
aborted foetuses. In the case of IVF procedures, a five-day-old embryo —
called a blastocyst — is implanted into a woman's uterus, and hopefully, nine
months later, a baby is born. Any extra embryos are usually kept in case of
miscarriage, or for a future pregnancy, but they are not always required.
To create human embryonic stem cells for research, some of the blastocyst's
cells are isolated, harvested and allowed to grow in a separate dish. To turn
them into long-lasting stem cell lines, the cells are fed special growth factors.
The embryo is destroyed in the process.
It's a bioethical minefield. But many scientists believe it's worth it. Professor
Bernie Tuch, Director of the Pancreas Transplant Unit at Prince of Wales
Hospital in Sydney, Australia, is using human embryonic stem cells to try and
find a cure for diabetes patients like Scott. He turned to stem cells after
another, equally controversial plan — to transplant pancreatic tissue into
humans from a pig — was put on hold.
"We are searching for a way to replace the insulin-producing cells that are
missing in type I diabetes patients," says Professor Tuch. Their ultimate aim
is to reverse the disease, eliminating the need for insulin injections and
preventing the complications that often affect people later in life.
Tuch believes the promises of stem cell therapy are still a long way off. But
molecular geneticist Dr Leon McQuade, senior research officer in the
hospital's stem cell team, is optimistic.
"It's very exciting," says McQuade, who
for months has been nurturing tiny
mouse embryo cells, persuading them
to mature into the insulin-producing
cells that are missing in a type I
diabetes patient. "We now know that we
can produce insulin cells from
embryonic stem cells," he says, and
very soon, he will be developing his
own techniques to grow human
embryonic stem cells into a purified
source of insulin-producing pancreatic beta cells in the lab.
At the Technion in Haifa, Israel, Dr Karl Skorecki's team has already
managed to turn human embryonic stem cells into insulin-producing cells.
"We've been working on the project for only a year," he says, and already, his
team is trialing the insulin cells in diabetic mice. "It's been successful so far",
he says, although the studies are not complete. The trick will be applying
stem cell therapy to humans without using immuno-suppressive drugs. In
their experiments, genetically immuno-suppressed mice are used to avoid
tissue rejection in, but humans, unlike laboratory mice, are not genetically
altered for the purpose of transplants, and are therefore likely to reject any
tissue that is not their own.
Tissue rejection is a huge problem facing all transplant patients. Immunosuppressive drugs have serious side effects, including kidney failure and an
increased risk of cancer. Professor Tuch believes that delivering stem cells in
tiny capsules may overcome tissue rejection, and is investigating this
approach in his laboratory.
Cloning for therapy
Another approach to overcoming the problem of tissue rejection is to be
'transplanted' with cells containing your own genetic material. But this
involves the most contentious of all stem cell therapies — therapeutic cloning.
This is how it would work for diabetes.
A doctor takes a sample of skin cells from the patient and isolates their DNA. Next, a donor
egg cell, emptied of its own genetic contents, is injected with the DNA from the patient. The
embryo is nurtured to grow and divide into a blastocyst. Some blastocyst cells are
harvested and coaxed with growth factors to mature into insulin-producing cells. Finally,
millions of insulin-producing cells are injected back into the patient. In an ideal world, the
patient's diabetes is temporarily 'reversed', with no side effects. (Pic: adapted from Stem Cells: A
Primer, US National Institutes of Health
'Therapeutic cloning' was the intention stated by the US company, Advanced
Cell Technology, when it announced in November 2001 that it had created a
cloned human embryo. This was a preliminary development — the longestsurviving embryo reached only the six-cell stage, and no stem cells were
harvested. But the development was significant because it was done by
transferring the nucleus of an adult cell into an egg cell which had had its own
nucleus removed. Called 'somatic cell nuclear transfer', this is the same
technique that was used to create Dolly the sheep.
Skorecki is planning to use the same nuclear transfer technique, but in a
different way. It involves the combination of two of the most debated issues,
genetic engineering and cloning. He believes that therapeutic cloning from
each patient's own cells would be too costly and not practical. "We genetically
modify the cloned adult cells [from other cell lines] so that they interfere with
the cell's mechanism of tissue rejection," he says. Ideally, these cloned
insulin-producing cells will not be rejected by any patient.
Human embryonic stem cells have been successfully turned into insulinproducing cells, blood cells and nerve cells. But even if the problem of tissue
rejection is overcome, the big question, says Leon McQuade, is whether the
transplanted cells will continue to function once inside a patient's body. For
diabetes, though, he says: "Even if they need to be replenished once a year,
it's a better option than injecting insulin on a day to day basis".
At Melbourne's Monash University, Professor Alan Trounson's team was the
first in the world to create mature nerve cells from human embryonic stem
cells. That team has just announced that they have successfully transplanted
nerve cells into the brain of newborn mice. The cells seemed to function like
normal brain cells, meaning such an approach shows real promise for treating
neurodegenerative diseases like Parkinson's.
Setting the rules
But scientific challenges aside, the big social question for stem cell research
is what conditions should be applied. For many religious and right-to-life
groups, destroying an embryo for research is destroying a potential life, and
politicians worldwide have been forced to develop regulations for this
burgeoning new science.
THE POLITICS of EMBRYO STEM CELL RESEARCH
January 2001 British Houses of Commons and Lords bans human
reproductive cloning but votes in favour of wide-ranging research
on stem cells, including creation of cloned embryos for therapeutic
cloning.
August 2001 US House of Representatives bans all governmentfunded human cloning research, including creation of a cloned
human embryo for therapeutic purposes.
September 2001 Australian House of Representatives committee
recommends a ban on human reproductive cloning but votes in
favour of wide-ranging research on stem cells, although with a
three-year moratorium on the creation of cloned human embryos
for therapeutic use.
In August 2001, US President George Bush announced that Federal funding
could be used for stem cell research, but only for research using existing cell
lines as at 9pm on August 9. This meant excess IVF embryos, purpose-made
embryos, and aborted foetuses could no longer be used to create new cell
lines, at least not in publicly-funded research programs. (The human cloning
research by Advanced Cell Technology had private funding.)
In Britain, the decision was more liberal. In January 2001 the Parliament
voted to fund the entire range of stem cell research, including therapeutic
cloning. Reproductive cloning, which intends to 'grow' a cloned cell into a new
individual, was banned, and the ban was made more explicit in November
2001 in legislation banning embryo clones from being implanted into wombs.
In Australia, a House of Representatives report into the issue in September
2001 gave the green light to a range of stem cell research but recommended
a three-year moratorium on therapeutic cloning, and argued that the current
framework for setting ethical guidelines for such research was inadequate.
Federal, state and territory governments have agreed to establish a national
regulatory approach by June 2002.
We've been chewing over stem cells for two hours, and Dr McQuade's hands
are starting to shake. Like Scott, he was diagnosed with type I diabetes when
he was three years old. He joined the stem cell team at the hospital recently,
opting for the healthier lifestyle of regular hours instead of the long stints at
the lab bench required in pure medical research.
"When I saw this job advertised in the newspaper, I had to apply," he says.
For a molecular geneticist living with diabetes, there couldn't be a more
rewarding job. It's sweet serendipity.
Further information
Human cloning controversy - News in Science 27/11/2001
Stem cell research okay - with better regulation - News in Science 21/9/2001
House of Representatives report: Human cloning: scientific, ethical and
regulatory aspects of human cloning and stem cell research - 17/9/2001
Biotechnology Australia - Commonwealth Government
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