||June 13, 2002
1. Although controversial, stem
cell therapies exhibit potential in
2. Stricter rules for clinical studies
sought to protect patients
3. Human Genome Sequence Has Errors,
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 <http://www.ti.frost.com/>
Although controversial, stem cell therapies exhibit potential in
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
repopulate the region with different types of cells, forming normal
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
extracted from either very early embryos or fetuses. The United States
now limited stem cell use to a relatively small number of existing
Stem cells are pluripotent, possessing the ability to differentiate
other types of cells. However, other stem cells, which are not derived
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
have suitable stem cells, but also to know how to direct their
differentiation and formation of new tissues. Scientists have begun
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
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
large number of different diseases, each one often affecting only a
number of people. Separate therapies will have to be developed for
Nevertheless, stem cells should be able to compete with replacement
with recombinant proteins to address many of these disorders.
New analysis by Technical Insights, a business unit of Frost &
http://www.ti.frost.com <http://www.ti.frost.com/> ), featured in
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
training. Acquired by Frost & Sullivan, Technical Insights is an
international technology research business that produces a variety
technical news alerts, newsletters, and reports. The ongoing research
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
E: firstname.lastname@example.org <mailto:email@example.com>
Trials and errors
Stricter rules for clinical studies sought to protect patients
By Naomi Aoki, Globe Staff, 6/12/2002
TORONTO - Jesse Gelsinger was 18 when he volunteered to be part of
clinical trial for gene therapy at the University of Pennsylvania.
hours of the treatment, his organs began to fail, and three days later
was dead. An investigation later revealed that the university and lead
researcher in the trial stood to gain millions from the drug being
and had ignored early warning signs.
The 1999 case shocked the public and the research community, and along
a handful of other highly publicized deaths in clinical trials, it
grave doubt on the ability of the existing system to protect patients.
result, federal legislators and regulators are considering stricter
regulation of clinical trials. And in a somewhat surprising twist,
pharmaceutical industry - the chief sponsor of such research - also
calling for tougher rules.
''Patients are our business,'' Heidi Wagner, head of government affairs
California biotechnology giant Genentech Inc., said during a panel
discussion this week on protecting people in clinical trials, at the
meeting of the Biotechnology Industry Organization here. ''We wouldn't
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
bring the drugs to market. More than 3,000 trials were taking place
Boston-area hospitals and clinics at any given time last year. If patients
lose faith in the system meant to protect them, industry officials
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
their deadlines for enrolling patients, in some cases by more than
And every day a trial is delayed costs an estimated $1.3 million in
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
human genome are expected to herald an unprecedented age of discovery,
meaning more drugs, more trials, more competition for study volunteers,
more money to lose.
''In the past, we've responded when there's been a problem,'' said
Koski, head of the Office of Human Research Protection, the agency
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
the public trust.''
After Jesse Gelsinger's death, the gene therapy study at Penn was shut
Federal investigators found that researchers had violated their own
and federal safety rules, ignoring signs seen in earlier patients that
treatment could be harmful and failing to disclose financial conflicts.
set up a $1.5 million, 13-member Office of Human Research to train,
and monitor researchers. The lead researcher quit in April as head
gene-therapy institute, and the FDA has begun a process that could
from human research overseen by the agency.
Though the Gelsinger case is certainly cause for concern, Koski and
officials said, such cases remain the exceptions. By and large, they
the system does protect patients. Deaths are rare - only about 1 in
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
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,
Koski, who prefers the term ''informed participation.'' Study volunteers
need to understand the risks and benefits of the clinical trial. They
be informed about the study's goals and results from earlier trials,
told of any developments as the study progresses.
Koski favors a more centralized system of third-party review. Currently,
research centers that conduct clinical trials must have institutional
boards, or IRBs, that oversee a study to ensure it follows standard
protections established for human research. The boards are generally
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
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
standard of excellence. And he believes separate boards should be
established to review potential conflicts of interest, monitor trials
any safety concerns, and watch for any violations of protocol.
Koski's office and industry leaders disagree on relatively few points.
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
believe such relationships should automatically disqualify a researcher
participating in a study. Koski believes there should be a presumption
against a scientist who stands to gain significantly from the success
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
laws regulate the privacy of patient information in clinical trials.
Many states also have their own sets of regulations that companies
meet. And when working with 50 different academic research centers,
said, companies are often left negotiating the details of informed
and study protocols with 50 different IRBs - a task that greatly adds
time and complexity of managing clinical trials.
''It's adding burdens and costs to the system that don't necessarily
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
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
Wagner believes that a bill, proposed by US Representatives Diana DeGette,
Democrat of Colorado, and Jim Greenwood, Republican of Pennsylvania,
extend protections under federal law to all human-research subjects
a giant step in the right direction. US Senator Edward M. Kennedy also
drafting a bill to increase protections for people who volunteer for
''Right now, there is growing public distrust,'' said Ken Getz, president
CenterWatch. ''If some of the regulations being considered are passed,
may be another way for industry and legislators to signal that they
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
protocols, falsifying data, and failing to properly comply with
informed-consent rules. But, Getz said, historically less than 3 percent
those cases are serious violations that put patients at significant
Nonetheless, Getz said, patients need to feel confident they are being
protected. They need to be treated as partners in the research, rather
as subjects of study. And critical to that endeavor is to educate people
about the importance of clinical research for medical progress as well
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
length, driving up prescription drug prices. But he believes the trade-off
is worth it. Better research means better protection for volunteers
studies, and also for the public at large because the more that is
in clinical trials, the better equipped regulators and physicians are
decide whether to approve or prescribe a drug.
''At the end of the day, what matters most is the protection of patients
study volunteers,'' Getz said. ''It benefits all of us if research
and has better oversight.''
Naomi Aoki can be reached at firstname.lastname@example.org <mailto:%email@example.com>
This story ran on page D1 of the Boston Globe on 6/12/2002.
Human Genome Sequence Has Errors, Scientists Say
New York Times
By NICHOLAS WADE
Based on a new genetic map of the human genome, Icelandic scientists
more than 100 large-scale corrections are needed in a recent draft
human genome sequence produced by a public consortium of academic centers
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
of whether the genome will really be finished by its target date next
said Dr. Huntington F. Willard, a geneticist at Case Western Reserve
University. Leaders of the Human Genome Project are aiming to declare
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
Human Genetics, said the new map "points up all sorts of errors in
genome sequence assembly."
He added, "This isn't surprising to us in the field, who have tried
the databases and inevitably find that for the regions we know best,
assemblies are often wrong, but may be surprising to the public at
A spokesman for the National Institutes of Health's human genome office
that the project had made use of genetic maps to correct the genome
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
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,
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
the map's genomic data, though without the patients' names, available
The Decode map indicates that numerous large sections of DNA were in
wrong order or flipped head-to-tail in the December 2000 version of
consortium's draft. The April 2001 version corrected some errors but
introduced others. The August 2001 version, the latest analyzed, was
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
Nature Genetics, include the company's chief statistical geneticist,
Augustine Kong, and its founder, Dr. Kari Stefansson.
Dr. David Haussler, a computer scientist at the University of California
Santa Cruz, who is overseeing the assembly of data from the consortium's
sequencing centers, said he had used two genetic maps to help put the
sections in the right order. But these maps, known as the Genethon
Marshfield maps, suffered from small sample size and lacked good resolution.
"So I am not surprised that with substantially more accurate genetic
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
the sequence of chromosomes 20, 21 and 22. These chromosomes, the three
smallest, have been finished, showing that chromosome sequence can
tackled without a fine resolution genetic map. The new map from Decode
certainly help the sequencers finish their chromosomes," he said.
Celera Genomics, a company that raced the public consortium to produce
first rough draft of the human genome, is not attempting to produce
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
particular section of the genome.
A spokesman for the National Institutes of Health office, which pays
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
of the rival efforts to sequence the human genome, he said: "As much
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
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
advance a two-year moratorium rather than a permanent ban, according
several Republican lawmakers who attended the session. Senate debate
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.
- web sites
was reaffirming his opposition to human embryo cloning in a speech
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
for promising medical research on cures for diseases such as Alzheimer's
It was unclear whether any proposal the one supported by Brownback
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,
could mean the difference between life and death for a patient with
Parkinson's disease ( news
- web sites
disease> ), diabetes, cancer or many other serious disorders."