Forum Bioethik June 13, 2002


1.       Although controversial, stem cell therapies exhibit potential in
biotechnology markets
2.      Stricter rules for clinical studies sought to protect patients
3.       Human Genome Sequence Has Errors, Scientists Say
4.      Leading Senate opponent of human cloning now willing to accept
two-year moratorium of embryo cloning for research

Public release date: 12-Jun-2002
Contact: Julia Rowell <>
Technical Insights <>

Although controversial, stem cell therapies exhibit potential in
biotechnology markets

Technical Insights genetic technology alert
SAN ANTONIO  June 11, 2002  Stem cells have enormous potential for
repairing damage to the body caused by disease, injury, or aging. When
introduced into an injured area of a patient, a stem cell could survive and
repopulate the region with different types of cells, forming normal tissue.
Stem cells also offer the prospect of treating many inherited diseases
caused by a single, defective gene. Though other treatments are available,
such as gene therapy, the longevity of benefits from stem cell treatment
provides a tantalizing option for researchers.
Heated controversy has arisen over the ethics of using embryonic stem cells,
extracted from either very early embryos or fetuses. The United States has
now limited stem cell use to a relatively small number of existing cell
Stem cells are pluripotent, possessing the ability to differentiate into
other types of cells. However, other stem cells, which are not derived from
embryos and not completely pluripotent, have great potential to
differentiate into cells, redeveloping certain tissues or organs.
Hematopoietic cells, found in the bone marrow and umbilical cord, for
example, can differentiate into all types of blood cells.
In order to make stem cell therapy a reality, it is not only necessary to
have suitable stem cells, but also to know how to direct their
differentiation and formation of new tissues. Scientists have begun to make
new discoveries concerning genes and their protein products that govern
various types of cell differentiation, but additional research is
Stem cell therapies are inherently more complicated than drug treatment,
providing a stumbling block for stem cell therapy in the marketplace.
However, while stem cell therapy remains costly, it will almost certainly
last for several years before the procedure must be repeated. A low annual
cost of $2500 per patient for stem cell therapy products at the manufacturer
s level is an average cost spread over several years.
While stem cells offer the possibility of treating many inherited diseases
caused by a single defective gene, this disease group is composed of a very
large number of different diseases, each one often affecting only a small
number of people. Separate therapies will have to be developed for each one
of them.
Nevertheless, stem cells should be able to compete with replacement therapy
with recombinant proteins to address many of these disorders.
New analysis by Technical Insights, a business unit of Frost & Sullivan ( <> ), featured in Genetic
Technology Alert, highlights nine biotech companies which are developing
innovative stem cell products, providing new avenues to medical
Frost & Sullivan is a global leader in strategic market consulting and
training. Acquired by Frost & Sullivan, Technical Insights is an
international technology research business that produces a variety of
technical news alerts, newsletters, and reports. The ongoing research on
stem cell therapy is covered in Genetic Technology Alert, a Technical
Insights subscription and in Proteomics, a Technical Insights technology
analysis. Analyst interviews are available to the press upon request.
Genetic Technology Alert
Julia Rowell
P: 210-247-3870
F: 210-348-1003
E: <> <>


Trials and errors
Stricter rules for clinical studies sought to protect patients
By Naomi Aoki, Globe Staff, 6/12/2002
Boston Globe
TORONTO - Jesse Gelsinger was 18 when he volunteered to be part of a
clinical trial for gene therapy at the University of Pennsylvania. Within
hours of the treatment, his organs began to fail, and three days later he
was dead. An investigation later revealed that the university and lead
researcher in the trial stood to gain millions from the drug being tested
and had ignored early warning signs.
The 1999 case shocked the public and the research community, and along with
a handful of other highly publicized deaths in clinical trials, it cast
grave doubt on the ability of the existing system to protect patients. As a
result, federal legislators and regulators are considering stricter
regulation of clinical trials. And in a somewhat surprising twist, the
pharmaceutical industry - the chief sponsor of such research - also is
calling for tougher rules.
''Patients are our business,'' Heidi Wagner, head of government affairs for
California biotechnology giant Genentech Inc., said during a panel
discussion this week on protecting people in clinical trials, at the annual
meeting of the Biotechnology Industry Organization here. ''We wouldn't be
anywhere without the patients who volunteer for these trials.''
Biotech and pharmaceutical companies depend on volunteers for clinical
studies of their drugs to prove that they are safe and effective and to
bring the drugs to market. More than 3,000 trials were taking place in
Boston-area hospitals and clinics at any given time last year. If patients
lose faith in the system meant to protect them, industry officials said,
they will shy away from clinical trials. And this is a risk the industry
simply cannot afford to take.
More than 80 percent of biotech and pharmaceutical companies already miss
their deadlines for enrolling patients, in some cases by more than a year.
And every day a trial is delayed costs an estimated $1.3 million in direct
and lost opportunity costs, according to CenterWatch Inc., a Boston
publishing company that focuses on clinical trials.
The stakes only promise to get higher as the pace of scientific research
continues to accelerate. Since 1993, the number of drugs in company
pipelines has doubled. Innovations in technology and the mapping of the
human genome are expected to herald an unprecedented age of discovery,
meaning more drugs, more trials, more competition for study volunteers, and
more money to lose.
''In the past, we've responded when there's been a problem,'' said Dr. Greg
Koski, head of the Office of Human Research Protection, the agency that
oversees all federally funded research. ''We've got to move to a more
proactive system, one that will prevent harm, because that's what will build
the public trust.''
After Jesse Gelsinger's death, the gene therapy study at Penn was shut down.
Federal investigators found that researchers had violated their own protocol
and federal safety rules, ignoring signs seen in earlier patients that the
treatment could be harmful and failing to disclose financial conflicts. Penn
set up a $1.5 million, 13-member Office of Human Research to train, assist,
and monitor researchers. The lead researcher quit in April as head of Penn's
gene-therapy institute, and the FDA has begun a process that could bar him
from human research overseen by the agency.
Though the Gelsinger case is certainly cause for concern, Koski and industry
officials said, such cases remain the exceptions. By and large, they said,
the system does protect patients. Deaths are rare - only about 1 in 10,000
subjects die. But the system has become bogged down in procedural and
bureaucratic complexities that don't necessarily protect study volunteers.
Koski said the system needs to be streamlined; protections must focus on
protecting people in clinical trials rather than the institutions running
them, and on preventing lapses rather than reacting to them.
Informed consent must go beyond getting a person's signature on a form, said
Koski, who prefers the term ''informed participation.'' Study volunteers
need to understand the risks and benefits of the clinical trial. They should
be informed about the study's goals and results from earlier trials, and be
told of any developments as the study progresses.
Koski favors a more centralized system of third-party review. Currently, all
research centers that conduct clinical trials must have institutional review
boards, or IRBs, that oversee a study to ensure it follows standard
protections established for human research. The boards are generally made up
of volunteers from the institution.
The system leads to redundancies, especially in cases where many different
institutions are involved in a single trial, Koski said. Rather than having
IRBs from every institution review the same study, a single IRB could
oversee the entire trial.
He also supports a voluntary accreditation system for IRBs that would
encourage them to go beyond what is legally mandated and strive for a
standard of excellence. And he believes separate boards should be
established to review potential conflicts of interest, monitor trials for
any safety concerns, and watch for any violations of protocol.
Koski's office and industry leaders disagree on relatively few points. One
key point of dissension, however, is in dealing with financial conflicts.
Genentech's Wagner supports full disclosure of all potential conflicts -
financial or otherwise - to IRB members and study volunteers but does not
believe such relationships should automatically disqualify a researcher from
participating in a study. Koski believes there should be a presumption
against a scientist who stands to gain significantly from the success of a
drug being involved in its development.
''No matter how well intended people are, bias creeps in,'' he said.
At the panel discussion Monday, Genentech's Wagner, the sole industry
representative, was the most vocal in support of strong federal legislation.
Companies navigate an increasingly layered system to run clinical trials,
she said. The industry is regulated primarily by the Food and Drug
Administration, while many of the academic researchers with whom the
industry collaborates on trials are regulated by Koski's office. Yet other
laws regulate the privacy of patient information in clinical trials.
Many states also have their own sets of regulations that companies must
meet. And when working with 50 different academic research centers, Wagner
said, companies are often left negotiating the details of informed consent
and study protocols with 50 different IRBs - a task that greatly adds to the
time and complexity of managing clinical trials.
''It's adding burdens and costs to the system that don't necessarily add to
the safety of patients,'' she said.
Wagner said the industry wants one set of rules to extend to all
researchers - regardless of whether they are funded by industry or
government and regardless of the state in which they are conducting
research. She would like to see a move toward a more centralized review
process, encouraging institutions to work with a single independent IRB that
oversees and monitors large, multisite trials.
''Strong federal legislation is the only way to get that kind of unified
system,'' Wagner said, ''because it's the only way to preempt state law.''
Wagner believes that a bill, proposed by US Representatives Diana DeGette,
Democrat of Colorado, and Jim Greenwood, Republican of Pennsylvania, to
extend protections under federal law to all human-research subjects would be
a giant step in the right direction. US Senator Edward M. Kennedy also is
drafting a bill to increase protections for people who volunteer for
clinical trials.
''Right now, there is growing public distrust,'' said Ken Getz, president of
CenterWatch. ''If some of the regulations being considered are passed, it
may be another way for industry and legislators to signal that they are
doing as much as they can.''
Audits of both federally funded and industry-sponsored clinical research
have found that the most common problems are failing to comply with study
protocols, falsifying data, and failing to properly comply with
informed-consent rules. But, Getz said, historically less than 3 percent of
those cases are serious violations that put patients at significant risk.
Nonetheless, Getz said, patients need to feel confident they are being
protected. They need to be treated as partners in the research, rather than
as subjects of study. And critical to that endeavor is to educate people
about the importance of clinical research for medical progress as well as to
be brutally honest about the risks involved.
Although Wagner believes that streamlining clinical trials could reduce
their time and costs, Getz said other measures may increase their cost and
length, driving up prescription drug prices. But he believes the trade-off
is worth it. Better research means better protection for volunteers in
studies, and also for the public at large because the more that is learned
in clinical trials, the better equipped regulators and physicians are to
decide whether to approve or prescribe a drug.
''At the end of the day, what matters most is the protection of patients and
study volunteers,'' Getz said. ''It benefits all of us if research is safer
and has better oversight.''
Naomi Aoki can be reached at <> .
This story ran on page D1 of the Boston Globe on 6/12/2002.




Human Genome Sequence Has Errors, Scientists Say

New York Times
Based on a new genetic map of the human genome, Icelandic scientists say
more than 100 large-scale corrections are needed in a recent draft of the
human genome sequence produced by a public consortium of academic centers in
the United States and abroad.
Corrections are not surprising in a draft that is continually being
improved, but the presence of so many large-scale errors raises the question
of whether the genome will really be finished by its target date next April,
said Dr. Huntington F. Willard, a geneticist at Case Western Reserve
University. Leaders of the Human Genome Project are aiming to declare it
complete then, in conjunction with the 50th anniversary of the publication
of the article by James Watson and Francis Crick on the double helix
structure of DNA.

Dr. Willard, who served last year as president of the American Society of
Human Genetics, said the new map "points up all sorts of errors in the human
genome sequence assembly."
He added, "This isn't surprising to us in the field, who have tried to use
the databases and inevitably find that for the regions we know best, the
assemblies are often wrong, but may be surprising to the public at large."
A spokesman for the National Institutes of Health's human genome office said
that the project had made use of genetic maps to correct the genome sequence
and that because 80 percent of the genome was now finished, "such
misassemblies should be increasingly rare."
The errors were discovered by Decode Genetics, a company based in Reykjavik,
Iceland, that is hunting for the genetic roots of common diseases by using
special qualities of the Icelandic population.
Needing an accurate genome sequence for its gene-hunting program, Decode
created a so-called recombination map of the human genome. The map, which
tracks how sections of two parents' chromosomes are exchanged, or
recombined, in the chromosome bequeathed to a child, yields the correct
order of the sections on the chromosome. The company said it would make all
the map's genomic data, though without the patients' names, available to
The Decode map indicates that numerous large sections of DNA were in the
wrong order or flipped head-to-tail in the December 2000 version of the
consortium's draft. The April 2001 version corrected some errors but
introduced others. The August 2001 version, the latest analyzed, was a "real
improvement," the Decode scientists say, but still contained 104 large-scale
errors, according to their recombination map.
The authors of the Decode article, posted yesterday on the Web edition of
Nature Genetics, include the company's chief statistical geneticist, Dr.
Augustine Kong, and its founder, Dr. Kari Stefansson.
Dr. David Haussler, a computer scientist at the University of California at
Santa Cruz, who is overseeing the assembly of data from the consortium's DNA
sequencing centers, said he had used two genetic maps to help put the DNA
sections in the right order. But these maps, known as the Genethon and
Marshfield maps, suffered from small sample size and lacked good resolution.
"So I am not surprised that with substantially more accurate genetic map
data some further corrections to the assembly are suggested," he said.
Dr. James L. Weber, a geneticist at the Marshfield Medical Research
Foundation in Marshfield, Wis., said Decode had found nothing to correct in
the sequence of chromosomes 20, 21 and 22. These chromosomes, the three
smallest, have been finished, showing that chromosome sequence can be
tackled without a fine resolution genetic map. The new map from Decode "will
certainly help the sequencers finish their chromosomes," he said.
Celera Genomics, a company that raced the public consortium to produce a
first rough draft of the human genome, is not attempting to produce a
complete version.
Having large sections of DNA in the wrong place or orientation probably
makes little difference to biologists searching for genes with a particular
sequence of DNA letters. But it throws off the statistics of gene-hunters
like Decode Genetics who are trying to map a disease-causing gene to a
particular section of the genome.
A spokesman for the National Institutes of Health office, which pays for the
human project, said, "We are on track to complete the final and highly
accurate version of the human genome sequence in April 2003."
But Dr. Willard said the draft human genome sequence, though
"extraordinarily useful," was a long way from complete. Referring to leaders
of the rival efforts to sequence the human genome, he said: "As much as
Francis Collins and Craig Venter and others like to call the sequence
complete, it is still sketchy in places and likely to remain so for some
time. To call it complete, as will happen next April to match the 50th
anniversary of the Watson-Crick paper, is a bit of a sham."


Leading Senate opponent of human cloning now willing to accept two-year
moratorium of embryo cloning for research
Wed Jun 12, 6:01 AM ET
By DAVID ESPO, AP Special Correspondent
WASHINGTON - Short on votes, a leading Senate opponent of human embryo
cloning for medical research is scaling back a proposal to ban the
Republican Sen. Sam Brownback told fellow party members on Tuesday he would
advance a two-year moratorium rather than a permanent ban, according to
several Republican lawmakers who attended the session. Senate debate on the
issue could begin as early as this week.
Brownback's office declined to comment on the reports, relayed by Senate
Republican leader Trent Lott, Sen. Arlen Specter and others.
"He stated he needed to go to a lesser standard" in hopes of gaining
support, Specter said.
Ironically, Brownback relayed his intentions as President George W. Bush (
eorge%20W.%20Bush%22&c=&n=20&yn=c&c=news&cs=nw>  - web sites
ailyNews/manual/*> )
was reaffirming his opposition to human embryo cloning in a speech by
satellite to the Southern Baptist Convention in St. Louis.
"We believe that a life is a creation, not a commodity, and that our
children are gifts to be loved and protected, not products to be designed
and manufactured by human cloning," the president said.
The issue has sparked intense debate, with advocates on one side arguing
that cloned human embryos qualify as human life, not to be destroyed even
for promising medical research on cures for diseases such as Alzheimer's and
It was unclear whether any proposal  the one supported by Brownback or an
alternative that would allow medical research  would gain the 60 votes
needed to overcome possible filibusters.
Democratic Sen. Edward M. Kennedy, an advocate of cloning for medical
research, issued a statement critical of even a moratorium:
"A moratorium of a year or two may not seem like much to you and me, but it
could mean the difference between life and death for a patient with
Parkinson's disease ( news
%20disease%22&c=&n=20&yn=c&c=news&cs=nw>  - web sites
disease> ), diabetes, cancer or many other serious disorders."

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