Forum Bioethik |
INFO/ Human Genetics Alert
December 20, 2001
Contents
1. THIRD GENETIC CHAPTER
PUBLISHED
2. GENE THERAPY MAY
HELP RESTORE HAIR AFTER CHEMO
3. FEARS OF HUMAN
CLONING
4. A THICK LINE BETWEEN
THEORY AND THERAPY, AS SHOWN WITH MICE
1.
Thursday, 20 December, 2001, 05:20 GMT
THIRD GENETIC CHAPTER PUBLISHED
The tips of chromosome 20 are visible stained red (Molecular
Cytogenetics,
Wellcome Trust Sanger Institute)
By BBC News Online's Helen Briggs
Another chapter in the human book of life has been published.
Scientists have deciphered the complete genetic instructions
of a third
chromosome, one of the 24 bundles of DNA that carry our
genetic material.
The latest to be finished, chromosome 20, is the largest
so far.
The discovery could shed light on why some people are
more likely to develop
common diseases such as diabetes, obesity or eczema because
of their genes.
It could also give an insight into variant Creutzfeldt-Jakob
disease (vCJD),
the human form of mad cow disease. The gene that appears
to make some people
more susceptible to contracting vCJD is found on chromosome
20.
Disease 'quest'
The work is part of the ongoing Human Genome Project,
an international
effort to sequence (read) the genetic make-up of humans.
One third of the work was carried out in the UK at the
Wellcome Trust Sanger
Institute near Cambridge.
Dr Mike Dexter, Director of the Wellcome Trust, said:
"This is one more
completed chapter of our genomic anatomy textbook - medical
research will be
using this information for decades to come in its quest
to tackle our common
diseases.
"Once again, we are seeing the fruits of the two key
commitments of the
Human Genome Project: to make the sequence freely available
and to produce a
quality finished sequence."
'Gold standard'
The first draft of the entire human genome, the instructions
needed to make
a human being, was unveiled in the spring.
The work was carried out by two groups, the publicly
funded International
Human Genome Sequencing Consortium, and a private US
company, Celera
Genomics.
Scientists are now trying to fill in some of the gaps
in the data to come up
with a "gold standard".
Two human chromosomes have already been completed to
this standard. The
sequence of chromosome 22 was revealed two years ago.
This was followed, in
May 2000, by chromosome 21.
The completion of chromosome 20 is significant for a
number of reasons:
It is the largest chromosome to be finished so far. Nearly
60 million
genetic "letters" have been sequenced and there are only
four gaps
It is also the first chromosome to be sequenced that
has a typical structure
of long and short arms
More than 720 genes have been found. They include the
genes that underpin
multi-factorial diseases such as diabetes, obesity and
childhood eczema
Intriguingly, some people (37%) have an extra chunk of
DNA in chromosome 20
and could have an extra copy of a specific gene of unknown
function.
Dr Panos Deloukas, leader of the project at the Sanger
Institute, said the
discovery was another important step towards understanding
the link between
genes and diseases.
"The next step is to start understanding the functions
of the genes," Dr
Deloukas told BBC News Online.
"The sequence, the genes and the variations between people
in the population
is the tool to start dissecting complex common diseases
like diabetes,
obesity and eczema."
The chromosome 20 results are published in full in the
journal Nature.
Other related stories
Chromosome Veers Off Genome Map
<http://www.wired.com/news/medtech/0,1286,49263,00.html>
http://www.wired.com/news/medtech/0,1286,49263,00.html
Contents
*************
2.
Tuesday December 18 5:52 PM ET
GENE THERAPY MAY HELP RESTORE HAIR AFTER CHEMO
By Merritt McKinney
NEW YORK (Reuters Health) - An experimental form of gene
therapy holds
promise for speeding the regrowth of hair after chemotherapy,
new research
suggests.
By boosting levels of a gene called ``sonic hedgehog,''
or Shh, New York
researchers saw signs of the growth of new hair in mice
treated with
chemotherapy.
The gene ``seems to be the master switch for making the
hair follicle
grow,'' the study's lead author, Dr. Ronald G. Crystal
at the Weill Medical
College of Cornell University in New York, told Reuters
Health in an
interview.
About 85% of people who undergo chemotherapy to treat
cancer lose at least
some of their hair. Hair usually takes 3 to 6 months
to grow back after
treatment, but it fails to return in a small group of
cancer patients.
The problem of hair loss may seem insignificant in the
face of a cancer
diagnosis, but hair loss can be devastating, according
to Crystal, since it
is a visible sign of a disease that is otherwise hidden.
He noted that
several studies have shown that chemotherapy-induced
hair loss can have ``a
real psychological impact.''
Crystal explained that chemotherapy does not destroy
hair-producing
follicles, but it does damage them temporarily.
``The hair follicles are still there,'' he said. ``They
just get beat up a
little.''
Crystal and his colleagues have been working to develop
a way to use Shh to
speed hair growth after chemotherapy. This gene is involved
in the formation
of several organs, including the brain, heart, lung,
gut, skin and skeleton,
but it also seems to be involved in getting hair follicles
to grow.
Crystal's team used a harmless virus to deliver extra
amounts of Shh to mice
with chemotherapy-induced hair loss.
The gene therapy appeared to work, stimulating hair follicles
around the
injection site, the researchers report in the December
19th issue of the
Journal of the National Cancer Institute.
In a group of 7-week-old mice that received the treatment,
researchers
observed that the hair follicles around the site of the
injection entered
the growth phase of development sooner than hair follicles
in animals that
did not receive the boost of Shh. In mice that received
gene therapy, but
not in untreated mice, skin around the injection site
darkened, which is a
sign that hair is growing.
Gene therapy also achieved similar results in younger
mice, Crystal and his
colleagues report. The growth of hair follicles was accelerated
in nearly
all of a group of 3-week-old mice, but in none of the
mice that received the
virus without the sonic hedgehog gene or no treatment
at all.
The therapy gives hair follicles a ``genetic boost to
get them growing
again,'' Crystal said.
The next step, the New York researcher said, is to consider
whether to test
the therapy in human clinical trials. According to Crystal,
``there's a good
chance'' that such trials could begin within a few years.
SOURCE: Journal of the National Cancer Institute 2001;93:1858-1864.
Contents
*************
3.
FEARS OF HUMAN CLONING
One News
Fear that humans could be cloned in New Zealand is prompting
an urgent law
change.
The government is rushing through legislation to ban
human cloning, the
genetic engineering of human babies and putting animal
material into humans.
The changes are being tacked on to legislation being
debated by parliament
on Thursday.
But the Greens say that this may not be enough to prevent
genetically
engineered humans being developed in New Zealand.
Italian doctor Severino Antinori and rival doctors, say
they are close to
cloning a human child.
"There is always the possibility, I heard him say he
(Antinori) was looking
for a beautiful country to clone children in, people
said it could be New
Zealand, we don't have any legislation to stop him at
the moment, so this is
stop gap legislation," said Labour List MP Dianne Yates.
Yates says the law is being rushed through but will expire
in two years to
allow for more consultation.
The new law will ban putting animal parts into human
beings. It also outlaws
genetically engineering human babies and covers cloning.
But the law does allow a minister to authorise an exemption,
and that is
what has got the Greens worried.
"I'm appalled at the idea that the Minister is acting
alone without any
public process of submissions or hearings could give
consent to genetically
engineered human babies," said Jeanette Fitzsimons Greens,
co-leader.
But scientist Professor Bob Elliot is angry for other
reasons, the Health
Ministry has turned down his application to put pig cells
in diabetics as a
possible cure.
Elliot says the new law is an attempt to head off his
legal challenge.
"In New Zealand we have this incredible backward move
banning what is going
to be a very very valuable technique," Elliot says.
Officials will meet with he Greens on Thursday in a bid
to win their
support.
Published on Dec 19, 2001
Contents
*************
4.
December 18, 2001
New York Times
A THICK LINE BETWEEN THEORY AND THERAPY, AS SHOWN WITH
MICE
By GINA KOLATA
Dr. Brigid Hogan has never worked with human embryonic
stem cells her
expertise is with mouse cells. But patients with virtually
every sort of
chronic disease have found her, and they plead for help.
"I even hear from patients whose fathers have lung cancer,"
said Dr. Hogan,
a professor at Vanderbilt University School of Medicine.
"They have a whole
slew of problems they think can be treated. They think
stem cells are going
to cure their loved ones of everything."
If it ever happens, it will not happen soon, scientists
say. In fact,
although they worked with mouse embryonic stem cells
for 20 years and made
some progress, researchers have not yet used these cells
to cure a single
mouse of a disease.
Scientists say the theory behind stem cells is correct:
the cells, in
principle, can become any specialized cell of the body.
But between theory
and therapy lie a host of research obstacles. Though
not often discussed in
public forums, the obstacles are so serious that scientists
say they foresee
years, if not decades, of concerted work on basic science
before they can
even think of trying to treat a patient.
Yet as excitement over stem cell research built over
the summer, and surged
again with recent reports of experiments with human cloning,
scientists and
doctors became deluged with calls from desperate patients
who saw salvation
around the corner. Somehow this research has come to
be seen as the great
hope for medical science. How, scientists ask, did expectations
grow so
quickly?
Though some say the news media overplayed the issue,
some scientists say the
problem lies within themselves. The crucial questions
involve basic
research, the sort supported by federal funds and conducted
in universities.
But with calls by some politicians to ban the work, and
to bar any use of
tax money to pay for it, scientists say they feel obliged
to stress how
important the research is. And, some say, they now fear
they may have
promised too much.
"We're being forced into taking extreme positions by
the whole need to try
and convince people of the need to go ahead," Dr. Hogan
said.
Dr. Gail Martin, a mouse stem cell researcher at the
University of
California at San Francisco, said: "The expectations
have been raised a
little higher than perhaps is appropriate. It became
politicized and tied up
in the abortion debate." But, as the exaggerations and
talk of revolutionary
treatments continued, few made concerted efforts to set
the record straight.
And some small biotechnology companies continued to promise
quick cures.
One problem is simply to find a way to get stem cells
to grow into the types
of cells that are needed, and not a mixture of cells.
Scientists know this is a thorny problem, but their views
were not widely
heard when the public and politicians seemed to assume
that it was easy to
grow any tissue type desired from embryonic stem cells.
In fact, no one has
been able to do this even with mouse cells.
Using stem cells to cure diabetes, for example, would
mean converting them
to islet cells, specialized cells of the pancreas that
secrete insulin. And
then the new islet cells would have to be protected from
the underlying
disease process that caused the diabetes in the first
place. The science is
not even close.
"Do we know how to make islet cells? No. Do we know how
to make kidney
cells? No," said Dr. Shirley M. Tilghman, a mouse molecular
geneticist, who
is the president of Princeton. "You can go on and on,"
she said.
"In the early days there was a cottage industry of trying
to get them to do
different things," Dr. Tilghman said. But the stem cells
would never become
just one type of cell, developing instead into mixtures
of specialized cell
types.
Few outside the field realize the difficulty of working
with stem cells, Dr.
Martin and others said. When mouse stem cells grow in
the laboratory, she
said, some of them spontaneously change, with chunks
of genetic material
moving from place to place on chromosomes. She said that
if such changes
gave cells even a 5 percent growth advantage in the laboratory,
the altered
cells completely took over the stem cell population within
three
generations. And if such cells were put into patients,
they could cause
cancer.
Even if all the other problems with stem cells are solved,
researchers will
face another problem. The body's immune system will see
the new cells as
foreign tissue and reject them. The only sure way to
prevent this is to take
powerful immune suppression drugs for a lifetime, trading
insulin
injections, for example, for immune suppression.
The problem would be avoided if the stem cells were derived
from an embryo
that was a clone of the patient the stem cells of such
an embryo would be
genetically identical to the patient's cells. But cloning
has its own
problems. Not only do many politicians and religious
leaders find it
ethically abhorrent to create a clone and then destroy
it as an embryo to
extract its stem cells, but no one has yet come near
getting the process to
work.
One company, Advanced Cell Technology, recently announced
its first attempts
to create human embryos by cloning. The company failed
its embryos never
grew or developed anywhere near a point where they would
contain stem cells.
That normally occurs after about five days, when the
embryo becomes a sphere
with a ball of stem cells inside. Most of the company's
embryos died without
dividing even once, although one made it to an amorphous
clump of six cells.
In animals where cloning has succeeded, it remains very
inefficient, often
requiring 100 or more eggs to get a single viable clone.
Finally, researchers must get replacement cells derived
from stem cells to
integrate into the body's complex machinery and fill
in the blanks left by
diseased or dying cells. That task may pose its own problems,
as scientists
found when they tried to supply fetal brain cells to
patients with
Parkinson's disease. In some patients, the fetal cells
apparently grew too
well. They pumped out too much of the brain chemicals,
and there was no way
to remove the cells or turn them off.
But these cautionary findings were seldom mentioned when
advocacy groups for
patients with various disease took up the cause, even
though researchers
expressed little optimism for cures any time soon, if
ever. The task of
getting stem cells to develop into specialized nerve
cells and then getting
those cells to repair the damage in the disease is well
beyond today's
science, experts say.
"I have no idea how someone expects that you will inject
neuroblasts and
they will run all over the brain and replace your sick
and dying neurons in
Alzheimer's disease," said Dr. Davor Solter, a mouse
stem cell researcher
who directs the Max Planck Institute in Germany.
Dr. Martin, who is a co-discoverer of mouse embryonic
stem cells and the one
who named them, added, "There are a gazillion issues."
That is not to say that the issues will never be resolved.
Dr. Steen
Willadsen, a Danish scientist and a cloning pioneer who
saw the impossible
happen in his field, said demand for stem cell therapies
was so great that
scientists would make it happen, sooner or later.
But Dr. Martin and others say they worry about the short
term, concerned by
how the public will react when it becomes clear that
stem cells are not an
immediate answer for suffering patients. She and others
say they are bracing
themselves for a backlash when treatments fail to materialize.
"There's almost certainly going to be a backlash," said
Dr. James A.
Thomson, the University of Wisconsin scientist who first
isolated human
embryonic stem cells. "These are novel, unproven therapies.
I believe there
is tremendous promise, but it's going to take years to
develop therapies."
He said, however, that the media, not scientists, were
at fault for the
exaggerated promises.
"I blame the press," Dr. Thomson said. "It is very compelling
to be able to
make new body parts. It captures the imagination."
But Dr. Inder Verma, a gene therapy researcher at the
Salk Institute in San
Diego, said scientists set off the frenzy with their
own hyperbole. And, he
said, he has seen this sort of process unfold once before,
with disastrous
consequences.
Gene therapy, Dr. Verma said, had the same sort of promise
attached to it
two decades ago. In that field, too, scientists predicted
too much too soon.
When gene therapy failed, many turned against it. Stem
cell therapy is
heading in the same directions, Dr. Verma said, and some
scientists are
beginning to worry.
"We started it," Dr. Verma said, speaking of the debate.
Now, he said, "we
withdraw from it because we realize it is going out of
control."
Yet, he said, this time, with abortion politics entwined
in the story, the
public backlash may be far worse than it was with gene
therapy.
"In five years, if it doesn't work out, people will turn
to us and say, `You
divided the nation,' " Dr. Verma said.
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