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28th November 2002

1. Experts wary of human clone claims
2. Delhi's rich adopt gender selection of the poor
3. Time for a New Pair of Genes?
4. Protein therapies spark scrutiny
5. GM Stem-Cell Patent Jumps Through EPO Hoop
6. DNA patterns produce ultimate personalised gift
7. Nordic genes for would-be moms

Experts wary of human clone claims
November 27, 2002

ROME, Italy -- Experts have greeted with scepticism the claims by an Italian
doctor that a woman was 33 weeks' pregnant with a cloned baby boy.

Dr Severino Antinori has claimed without proof in the past that several
women are carrying cloned babies -- for example in March, 2001 saying he
would produce a human clone in 18 months. There has been no evidence yet
this has happened.

The doctor who clones Dolly the sheep, Professor Ian Wilmut of the Roslin
Institute in Edinburgh, Scotland, said people should be "extremely
sceptical" of Antinori's claims.

Wilmut said Antinori had said he had cloned large number of pigs and even
primates, but no one had seen them and no scientific paper had been

Michael Le Page, biomedical news editor of New Scientist magazine, told CNN
it was very difficult to know what to believe when Antinori had become known
for making bold comments.

"If anyone has cloned a human baby I would be surprised if they would make
an immediate announcement," he said.

Le Page said cloning was illegal in some countries, like the UK, so if a
cloned baby was announced and a year later was found to be retarded in some
way the doctors involved would look "a bit silly."

Dr Sandy Thomas, director of Britain's Nuffield Council on Bioethics which
examines ethical issues arising from developments in medicine, told CNN: "In
the absence of any evidence it's impossible to judge whether it is going to
happen or not."

But Dr Thomas if a child was to be born she said she had a number of
concerns. First, if it were born in a country where there was no regulation
its would show the need for regulation in that country.

"Second, our experts tell us we don't know enough about cloning to apply the
technique to humans. It goes against normal development and there are likely
to be a high rate of deformities."

John Kilner, president of the U.S. think tank the Center for Bioethics and
Human Dignity, said: "While there are well-founded reasons to be sceptical
of Dr. Antinori's claim that a woman is due to give birth to a clone soon,
he reminds us that there are those who would continue this dangerous,
unethical quest.

"Such experiments subject human beings produced through cloning to a high
risk of death and deformity. The best way to ensure that cloning is not
pursued is to pass a comprehensive ban on human cloning.

"The United States should do this as soon as possible and continue to press
the case for a comprehensive ban treaty in the United Nations.

"Regardless of the health and well-being of the clone upon birth, all
nations should affirm the child's human rights. The risk of doing nothing is

Antinori told a news conference in Rome on Tuesday that a woman was 33
weeks' -- more than eight months' -- pregnant with a cloned baby boy and
that the child was developing in an "absolutely healthy" way.

In April, Antinori claimed that he knew of three pregnancies -- then in the
ninth, seventh and sixth weeks of development -- involving cloned babies. He
said on Tuesday that the oldest of these was about to be born.

However, according to his statement in April, the longest pregnancy would
have passed nine months in mid-November. Antinori would not explain the
discrepancy on Tuesday.

He also refused to specify if he had any role in the alleged clonings. He
did say that he would not be involved in the delivery of the baby, but that
he had given a "cultural and scientific contribution" to a consortium of
scientists involved in the pregnancies. He refused to identify the
scientists. Other groups are claiming to be working on cloning a human.

Antinori refused to identify the woman who was to give birth in January or
give her nationality. When asked where she was going to give birth he said
only "countries where this is permitted." Cloning has been declared illegal
in many countries.

Antinori, who runs a private fertility clinic in Rome, gained attention in
the 1990s when he used donor eggs and hormones to help post-menopausal women
to have children.

Experts have repeatedly dismissed Antiniori's claims and say they doubt that
he is capable of achieving a cloned pregnancy.


Delhi's rich adopt gender selection of the poor
November 27, 2002

by Catherine Philp

WHEN Bhanvi Kumri found out that the child she was carrying was a girl, she
burst into tears. "I wanted to get rid of it," she said. Her first child had
been a girl and when she became pregnant a second time, she prayed that it
would be a boy. "A girl is OK, but a boy is a necessity in India."

In the end she had the baby, but she and her wealthy politician husband
vowed that next time they would not leave it to chance. Four months ago, in
a swanky Bombay fertility clinic, she underwent in vitro fertilisation to
weed out female embryos and implant two males, the future heirs to her
husband's business.

Aniruddha Malpani, who treated Bhanvi, is an unapologetic crusader for what
he calls "family balancing" although he admits he has yet to treat a patient
seeking to have a girl. "People used to kill baby girls," Dr Malpani argues.
"This technology means they don't have to do that anymore."

Prakash Kakodkar, a gynaecologist in Bombay who admits to carrying out
sexselective abortions long after they were outlawed, goes further, arguing
that it is women who benefit through sex selection. "If a woman isn't able
to produce a male, she's badly treated and you want to help her," Dr
Kakodkar said. "Girl children are also very badly treated if they are not

India's preference for male children is nothing new and the history of
female infanticide in rural villages is long and brutal, with girl babies
smothered, drowned or simply abandoned by poor families desperate to have a

The bias is deep-rooted, born of traditions such as dowry-giving, the loss
of daughters to their husbands' families after marriage and the belief that
only a son can light his parents' funeral pyre.

Now, however, officials are detecting an alarming new trend: the spread of
the gender imbalance up the social scale, assisted by new technology
available to the increasing number of Indians with money to burn. The fear
is that the most influential classes are setting the trend for practices
contributing to a dramatic sex imbalance that could throw up all manner of
social ills in years to come.

The ratio of girls to boys in India has been on a steady slide throughout
the past century, but when census officials compiled the results of their
latest survey, they were met with a rude surprise. The most pronounced drop
in the number of girls under the age of six was no longer in rural areas but
in the cities. And not just any neighbourhoods, but in the wealthiest
enclaves, where the educated elite live.

In the past decade, the number of girls under six in Delhi has slipped from
945 per 1,000 boys to 865. Yet areas that include some of the most exclusive
neighbourhoods showed as few as 796 girls.

"We were shocked by the results," Suman Prashar, a senior census official,
said. But the conclusions were not hard to draw. "These are the areas
best-equipped with medical technology and these wealthy, educated people are
misusing it to ensure they don't have girls."

The preimplantation genetic determination method used by Bhanvi is legal, at
present, but the method most couples use to guarantee a male heir is not. At
"kitty parties" - social gatherings in the leafy enclaves of south Delhi -
wealthy housewives swap names of medical practioners willing to break the
law to perform ultrasound sex testing and sex-selective abortions.

A recent crackdown has made doctors more cautious, but has also had the
effect of driving prices up.

A prominent sign outside the Chopra ultrasound clinic in Delhi's smart
Jorbagh suburb proclaims that no sex testing is done there, but that does
not stop the flood of inquiries from the city's ladies-who-lunch.

"One excuse they'll give is that their husband is going to London on
business and he wants to know whether to buy blue or pink clothes," Avnish
Chopra, a doctor, said. "They may be educated, but they have the same
cultural mindset as villagers who abandon their babies in rice fields to

Already villages in Haryana and Punjab, the traditional bastions of female
infanticide, are suffering the consequences of two decades of systematic
eradication of females, with young men forced to buy in brides from
elsewhere or even share a wife with their brothers. Sexual violence is also
on the rise amid frustrated single men. It may only be a matter of time
until upscale society is struck by its own set of consequences.

"We'll feel it in about 20 years' time when these children come to marry,"
Promilla Kapur, a sociologist, said. "The rigidity of the caste system may
have to melt, but it will do nothing to improve the situation of women
because the problem springs from the fact they are undervalued."

The saddest thing, campaigners say, is that it is educated women themselves
who are helping to perpetuate the old attitudes. "What are they saying about
themselves if they are so desperate for sons?" Ms Prashar asked in
exasperation. "And when it's the influential classes that are doing this,
it's extremely worrying. What hope is there for the rest?" Happily pregnant
with her male twins, Bhanvi was unrepentant about her own contribution to
India's gender time bomb. "Whatever is available, one buys," she shrugged.
"If you want a boy, you buy a boy."

And as the Indian middle class swells year by year, more and more are
queueing to do so.


Time for a New Pair of Genes?
November 27, 2002,1282,56608-2,00.html

By Kristen Philipkoski

Families who share a history of heart disease or breast cancer would likely
jump at the chance to erase that hereditary trait.

Today that's still a fantasy, but advances in genetic research could lead to
that possibility by altering genes in utero.

Bioethicists say changing the DNA of future generations in order to correct
genetic diseases raises serious ethical questions, and the National
Institutes of Health has funded a study to evaluate when, if at all,
hereditary genetic changes might be appropriate.

Some critics are surprised the NIH would fund even the evaluation of such

"I think it's a matter of real concern that people are now paving the way to
do germ line genetic engineering," said Stuart Newman, a member of the
Council for Responsible Genetics and a cell biologist at New York Medical

"They might be simply asking, 'Well, what are the pros and cons?' But to me
it's like saying 'What are the pros and cons of torture?'" he said.

Newman believes that changing the genes of an embryo flies in the face of
the Nuremberg Code, which states that before performing human experiments
it's necessary to get the patient's consent. Of course, since the patient in
this case is an embryo, that isn't possible.

But it gets even more complicated when you consider that such procedures
don't just affect the embryo in question, but future generations as well.
Genes inserted into an embryo (or egg or sperm cells) would be incorporated
into sex cells, which would then proliferate the changes across generations.

Since inherited changes would be achieved specifically through embryonic or
sex cell changes, Newman sees no potential for developing a safe and
effective protocol with patient consent.

Others argue that the consent issue is a non-starter, since physicians
already perform other kinds of surgeries before birth. In such cases,
parents must give consent for their children.

"If you can modify gametes (egg or sperm cells) so as to prevent serious and
very disabling genetic diseases, then the risks involved in attempting germ
line (hereditary) change would be worth doing," said Art Caplan, director of
the Center for Bioethics at the University of Pennsylvania. "That is our
rationale now for in utero surgery, amniocentesis, and neonatal
interventions -- to try and prevent harm from a variety of genetic

Caplan believes that if techniques that prevent disabling inherited diseases
become viable, caregivers are obligated to use them.

Rebecca Dresser, professor of law and ethics in medicine at the Washington
University in St. Louis, Missouri, is leading the NIH-funded study. She
proposed the study partly because discussion of the ethics involved in these
procedures had fallen off the radar in recent years.

The Recombinant DNA Advisory Committee, the arm of the NIH that reviews all
studies that combine DNA molecules of different origins, refuses to review
such protocols.

Most likely the stall in discussions happened because scientists would first
need to perfect gene therapy before they could consider using it on an
embryo or gamete. Advances in gene therapy have lagged in recent years.

If nothing else, the slow progression of scientific breakthroughs in this
area gives ethicists more time to ponder the implications of changing future
generations of genes.

"With human inheritable interventions, we have the chance to think and plan
ahead, to give direction to this technology through rigorous analysis and
dialogue," the American Academy for the Advancement of Science researchers
say in their introduction of a paper on inherited genetic changes.

Some critics worry that changing embryos or gametes genetically could lead
to "designer babies." Most ethicists agree that the procedure would not be
worth the risk for adding, say, the Michael Jordan gene for athletic

"(The argument) really (centers around) what are the potential benefits and
potential harms, and do the potential benefits justify exposing this to be
child or hoped for child to risk," Dresser said.

Researchers are able to change genetic inheritance in animals -- transgenic
animals are now quite common. But the techniques for creating them are
imprecise. It sometimes takes several generations to breed change, and lots
of the animals die.

No one is arguing that these procedures should be used on humans, but other
new technologies might be safer and more effective, such as gene therapy or,
further in the future, artificial chromosome replacement.

When researchers discovered that there are likely only about 30,000, not
100,000, human genes as they had once thought, they also realized that each
gene does a lot more work than they previously realized. In turn, that means
therapies that alter with genes could have any number of unintended effects.

"You'd have to have some sort of safe technique where you change a (DNA)
sequence and you don't disrupt other things effected by that sequence,"
Dresser said.

Dresser's study, which began in April, is a two-year project. By the end,
she and her colleagues on the project (who include pediatricians, a genetic
counselor, a science policy expert, several former RAC members and a patient
advocate) will submit two papers, one scientific and one for a general
audience, on what they believe are the most important ethical considerations
in terms of changing the genes of future generations.

Protein therapies spark scrutiny: Researchers weigh potential risk of immune

27 November, 2002

By Naomi Aoki

It's the worst fear of every drug maker - when a drug that has been on the
market for more than a decade and has brought in billions in revenue
suddenly begins causing a potentially deadly condition in the very patients
it is meant to help.

For Johnson & Johnson, it has become a reality. Earlier this year,
researchers published evidence that its anemia drug Eprex, a genetically
engineered version of the human protein erythropoietin, was causing the
body's natural defenses to go haywire and attack its own red-blood cells,
leaving a small but growing number of patients severely anemic and facing a
lifetime of transfusions to survive.

The story of Eprex, a drug that has freed millions of patients with cancer
and kidney disease from their reliance on blood transfusions, has sent
chills through the biotechnology industry. The issue brings into bold relief
how dangerous immune responses to their drugs can be and how poorly
understood they remain. Engineered versions of human proteins
likeerythropoietin, insulin, and growth hormone are the cornerstone of

But Eprex illustrates how horribly awry things can go when the body reacts
to these drugs as if they were a germ, triggering an immune attack not only
on the drug itself but also on the body's own version of that protein. Now,
researchers and regulators are questioning whether similar defenses
triggered by other protein therapies could prove dangerous.

Eprex is a worst-case scenario. But already, there is growing controversy
about whether antibodies triggered by certain multiple-sclerosis drugs could
render patients immune to the entire class of therapies, including
Cambridge-based Biogen Inc.'s top-selling Avonex.

''No doctor in his right mind wants to immunize a quarter of his patients to
an entire group of therapies,'' said Dr. Tim Vartanian, an assistant
professor of neurology and neuroscience at Harvard Medical School.

The biotech industry's top players - from Biogen to California-based Amgen
Inc. to New Jersey-based Johnson & Johnson - have devoted an increasing
amount of resources to understanding and preventing the immune reactions.
Regulators have begun to demand more information on immune reactions when
considering drugs for approval and monitoring those already on the market.
And as researchers and regulators struggle to balance the benefits of these
drugs against their potential risks, the burden on companies developing
protein-based drugs promises to grow.

''We're walking a fine line,'' said Dr. Amy Rosenberg, director of the
division of therapeutic proteins at the Food and Drug Administration's
Center for Biologics Evaluation & Research. ''We don't want to inhibit drug
development. We want to get good drugs out there for the public. But we want
them to be safe. They have to be safe.''

Researchers have long known that protein therapies could trigger the body's
natural defenses. Recognizing subtle differences even in drugs genetically
engineered to be identical to substances found in the body, the immune
system sometimes produces neutralizing antibodies to fend off what it views
as foreign invaders. But the effect of the antibodies has varied among
drugs. And in many cases, the science remains unclear.

For years, the antibodies have been suspected of reducing or eliminating a
drug's potency over time. But until recently, researchers have not
considered them a potential safety concern. Because the mission of the
immune system is to protect the body, scientists reasoned that it would not
turn on itself. They simply didn't believe neutralizing antibodies to a
genetically engineered version of a human protein would cause the body to
attack its own version of that protein.

Then, in 1998, an experimental drug being developed by Amgen, the world's
largest biotech company, did just that. The drug, an engineered version of
the human protein, known as MGDF and which spurs the production of
platelets, was hailed as a potential blockbuster. But after three years of
testing in more than 1,000 people, researchers noticed that some patients
mounted an immune attack on their own platelet-producing cells, leaving them
vulnerable to excessive bleeding. Amgen dropped the drug.

''It was stunning,'' said Dr. Burt Adelman, executive vice president of
research and development at Cambridge-based Biogen. ''The conventional
wisdom had been that this was a theoretical risk. This was Amgen; these were
excellent scientists; and nobody saw it coming. If you're in my business,
it's really unnerving.''

Less than a year later, French physician and researcher Dr. Nicole
Casadevall began seeing a similar phenomenon in patients taking Eprex, which
is only sold outside the United States. The immune attack on the native form
of erythropoietin was devastating because there is no backup systems within
the body when the protein fails to do its job.

Until then, cases of red cell aplasia caused by erythropoietin products had
been extremely rare. In the decade before, only two cases were linked to
Eprex and two to Epogen, a version of erythropoietin sold in the United
States by Amgen. As of July, the number of suspected cases of red cell
aplasia caused by Eprex had grown to 160, and answers remained elusive. J&J
believes the problems are linked to manufacturing changes made shortly
before the problems began. The company continues to sell the drug.

Per Peterson, J&J's head of research and development, said the problem
affects the entire industry. When erythropoietin and other protein therapies
first reached the market, they were breakthroughs in treating devastating
diseases. When the choice was either to treat a patient or not, Peterson
said, the formation of neutralizing antibodies in response to therapy was a
theoretical concern. But as more drugs have come to market, he said, the
issue becomes more significant.

''As always in medicine, it comes down to a question of risk vs. benefit,''
Peterson said. ''If 20 percent of your patients are dying each year from
renal disease and you see one out of 10,000 patients who no longer responds
to erythropoietin, you go back to transfusing that patient and worry about
the others who are dying. As a practical matter, it can't be a top priority.
It is only in the last few years, now that you have a choice of drugs that
you can ask, `Is one safer than the other?'''

The question is the subject of much debate in multiple sclerosis. Since
1993, three drugs that are variations of the human protein beta interferon
have reached the US market. The drugs are more similar than they are
different. But Avonex has the lowest rate of neutralizing antibody
formation - 5 percent compared to more than 20 percent for its competitors,
Serono's Rebif and Berlex's Betaseron.

The failure of MGDF marked the beginning of a shift in the FDA's attitude
toward immune responses in reviewing the safety of drugs, said Rosenberg of
the FDA. That shift has only been cemented by the recent experience in
Europe with Eprex. The agency is asking for more information on antibody
responses before allowing protein therapies to be tested in people,
especially in cases where the drugs could interfere with the action of
native proteins that serve a critical function in the body.

It is also asking for more information from the earliest stages of human
testing rather than waiting for the data to be generated in larger,
later-stage trials. Rosenberg said the FDA is also struggling with questions
of how to evaluate manufacturing changes to already approved drugs. As
highlighted by the Eprex case, she said, even minor changes can produce
major differences in the safety and effectiveness of drugs.

But the issue is not always clear cut. Animal studies suggested that MGDF
could cause the devastating immune response later seen in people, triggering
more stringent scrutiny of such data. In most cases, however, immune
responses seen in animals do not accurately predict how people will respond.
Existing lab tests don't always forecast how manufacturing changes will
affect a drug's potential to trigger an immune response.

''This all points to the fact that no matter how much we know in biology,
there's a lot we don't know,'' said Biogen's Adelman. ''And it comes back to
bite us at some of the most inopportune moments - when people's lives are on
the line.''


GM Stem-Cell Patent Jumps Through EPO Hoop

26 November, 2002
World Markets Analysis

A patent covering genetically-modified embryonic stem cells, also known as
the 'Edinburgh' patent after one of the research locations, has recently
been  approved by the oral proceedings of the Opposition Division   of the
European Patent Office (EPO), albeit with  modifications. The patent, which
refers to a method of  using genetic engineering to isolate stem cells to
derive pure stem- cell cultures, originally covered embryonic stem cells and
was therefore challenged by the governments of
Germany, Italy and the Netherlands, as well as the non-governmental
organisation (NGO) Greenpeace. According to the European Patent Convention,
human embryos cannot be patented for industrial and commercial purposes,
which, however, does not include embryonic stem cells and human germ lines,
although still referring to modified human and animal stem cells.


DNA patterns produce ultimate personalised gift

27 November, 2002

by Andy Coghlan

Items bearing colourful patterns based on the recipient's own genetic
fingerprint are being touted as the ultimate personalised gift.

The patterns are not based on regions of DNA that could reveal a person's
genetic secrets Neil Sullivan, CEO of Complement Genomics in Sunderland,
England, conceived the idea as a sideline to his company's main business.
This includes collecting DNA for pharmaceuticals companies and paternity

Using a kit provided by the company, customers swab the inside of the lucky
recipient's mouth to collect some cells. They then send the swabs back with
a description of the kind of gift they want. Sullivan's team then extracts
DNA from the cells and analyses it to provide the basis for a pattern.

The patterns, which have so far been applied to necklaces, rugs and
glassware, resemble the DNA bar codes seen in genetic fingerprints taken for
paternity testing or forensic examination. These patterns correspond to DNA
sequences called short tandem repeats, that are unique to each individual.

To demonstrate the technique, Sullivan's team produced a necklace that used
gemstones to represent the bands in a genetic fingerprint, with slugs of
silver in between, representing the distances between each band.

"It's an exclusive gift based on a unique gene profile," said Sullivan at
the International Biotech Conference in London last week. "It's a one-off
that can never be replicated." He uses a pool of 10 local artists to create
the different objects, which the company call DesigNAgifts.

Sullivan stresses that the DNA never belongs to the company and is taken in
accordance with international legal standards. It is not entered into any
databases and is destroyed after three months.

He adds that the patterns are not detailed enough to be used for paternity
testing and avoids regions of DNA that could reveal a person's genetic



Nordic genes for would-be moms

Friday, November 22, 2002
Seattle Post-Intelligencer Reporter

By Carol Smith

Scandinavian Cryobank, one of the largest sperm banks in the world, has
opened a distribution branch in Seattle, site of its first U.S. operation,
for the bulk import of sperm samples from Norway, Sweden and Denmark.

 "Seattle was an obvious choice because of the Scandinavian background of
the population here," said Peter Bower, director of Seattle operations, who
is half-Danish himself and chose Seattle because he had lived here

Also, until the cryobank opened its doors last November, Seattle had not had
a freestanding, commercial sperm bank.

Swedish Medical Center operates a non-profit local sperm bank as part of its
reproductive technology laboratories.

Before the arrival of Scandinavian Cryobank, women who didn't want to use a
local bank would usually request sperm from California, which is home to
several large commercial banks, said Mary Forster, director of the Swedish

Swedish has had several patients use Scandinavian sperm, both since it has
been available locally, and prior to that by having it shipped from Denmark.

Now patients increasingly use the Internet to order sperm, she said.

The sperm bank sells directly to female patients, but only if they are
clients of a fertility clinic, or have a doctor's permission.

The bank won't sell to a woman who is not being cared for by a doctor who
approves of the procedure, Bower said. The sperm is shipped all over the

The market for donor sperm is worth between $50 million and $100 million a
year, according to Scandinavian Cryobank.

Although having a sperm bank devoted to one ethnicity is unusual, patients

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