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The
Stem Cell Plot Thickens
August 16, 2001
by
Ramsey Harris, MD
On Thursday August 9, Mr. Bush made a long anticipated (especially
given all the hype his staff created about his hours of ponderous
study) announcement as to whether he would allow the federal
government through the National Institutes of Health (NIH)
to fund research involving human embryo stem cell (ESC) lines.
The issue came under his scrutiny because former President
Clinton had decided that the cell lines did not fall under
a law passed by Congress prohibiting government funding of
research that would harm or destroy embryos. The Department
of Health and Human Services ruled in 1999 that ESCs were
not themselves embryos and therefore the NIH could fund grants
involving their use.
Since that time, the NIH convened a panel to determine whether
each cell line complied with the ethical standards. The NIH
was poised to fund grants when Bush took office. Mr. Bush
had promised not to allow any federal funding of research
involving human embryos. As recently as May 18, in a letter
to the Culture of Life Foundation, he wrote: "I oppose federal
funding for stem cell research that involves destroying living
human embryos. Now suddenly, "involves" differs from "involved",
evidenced by Bush's final decision to allow funding for research
limited to existing cell lines. Mr. Bush is learning to parse,
wiggle and squirm with the best of them. This fence-straddling
extravaganza has been called Clintonesque. So where did it
originate?
Bush had a major dilemma: upset the right-wing pro-lifers
that he made a campaign promise to, or upset the scientific
community, the biotechnology sector and the general public
that overwhelming favors the concept of allowing research
on clumps of cells that will never be human beings. As reported
by Newsweek, Karl Rove had been floating the "existing cell
lines" compromise since around June. After two to three months
of carefully leaked stories about how Bush was wrestling mightily
with the moral and ethical dilemma of ESC funding, even suggesting
that a man with a usual attention span of about 15 minutes
for any given topic, was "obsessed" with learning all about
stem cells, the Bushies felt they had a safe albeit tepid
solution.
Bush met with bioethicists Leon Kass and Daniel Callahan
on July 9 to make sure he got the conservatives' favorite
embryo thinkers on board. The NIH was ordered to find out
how many cell lines existed in early July. They found about
thirty. Bush told them to look again, and within days, they
somehow found thirty more. Not enough for ever, but maybe
enough for a few years, until it isn't Bush's problem anymore.
Of these only ten to twelve have been reported on in scientific
literature, and perhaps another ten have been described at
scientific meetings. You can bet the NIH didn't have time
to test those additional thirty or so cell lines in the few
days Bush gave them to dig him up a more palatable number.
The problem is that thirty to sixty cells lines are only
enough for maybe two to three years. That might give Bush
time to get re-elected before he has to visit the issue again,
but it doesn't address where to go when all the existing cells
have petered out. The first human cell lines were cultivated
in only 1998 and work on their growth characteristics is just
beginning. The ESCs may not be truly immortal. Indeed, of
the existing thirty to sixty cell lines, only a few are stable.
Dr. Doug Melton, a leading researcher in the field, has access
to several cell lines created in Israel, only one of which
is consistently useful. Many have a tendency to differentiate
spontaneously, making them useless for study. Of the six cell
lines owned by Geron, a biotech company that has done the
most work on stem cells, only two are available for distribution,
also because of stability problems.
The promise of ESCs is their ability to differentiate into
all types of cells, and the potential to regenerate organs
or organs functions. Thus they are considered promising avenues
for treatment of diverse diseases from neurodegenerative disorders,
like ALS and Alzheimer's, to organ failure diseases like diabetes.
For example, very early results show that the cells may migrate
to the appropriate parts of the brain, establish synapses
and grow there. But there is also a need for enormous genetic
diversity and cell lines of varying properties on order to
develop treatments for human diseases.
So, perhaps somewhat surprisingly, Mr. Bush agreed that the
research and potential to alleviate human suffering is great.
He thought he had a compromise that would appease his supporters
on the right by refusing to allow any more embryos to be destroyed.
So far this seems acceptable to all but the most intractable
pro-lifers. Scientists generally feel that the funding promised
is woefully inadequate, but are willing to take a few crumbs
rather than the nothing they had feared. But is that all there
is to this decision? With GW, you know you always have to
consider what corporate or personal ally's interest is at
play. In this case, it is as close as his very own head of
Health and Human Services, Tommy Thompson.
This former governor of Wisconsin is known to be a hard-line
abortion foe. He is also, however, a strong supporter of embryonic
stem cell research. Inconsistent? Hypocritical? Perhaps, but
understandable. The University of Wisconsin is one of the
nation's academic leaders in ESC research, and holds the patents
on at least five of the known ESC lines, cultivated by faculty
member, Dr. James Thomson. It is also the home of the Wisconsin
Alumni Research Foundation (WARF). Founded in 1925, the WARF
is a private not-for-profit entity, the oldest and one of
the most successful of all university intellectual property
organizations. Through the management of a large intellectual
property portfolio and the investment of royalties and licensing
fees, WARF has created an endowment that returns on the order
of $20 million annually to UW-Madison for unrestricted use
in research and education. Stem cell lines are one of their
big products.
WARF established the WiCell Research Institute in October
1999 specifically to advance their stem cell research through
their own departments and through the distribution of cell
lines. The institute's only faculty member is Dr. Thomson,
and he currently lists no collaborations. Through WiCell,
one can license five human ESC lines, on which the patents
are listed as "applied for" on the company's website. Academic
researchers may obtain a sample of human cells for $5000.
For-profit labs will pay an unspecified initial and annual
maintenance fee. However if one searches the US Patent Office
online database under "Patent Applications," last updated
August 9, 2001, there are only two applied for patents for
human ESCs listed, neither one of them by Dr. Thomson.
Of the current US approved patents for human embryonic stem
cells lines, two are held by Dr. James Thomson from University
of Wisconsin/Wisconsin Alumni Research Foundation, two by
Dr. Gearhart at Johns Hopkins University, and one by Dr. Hogan
at Vanderbilt University. Dr. Thomson derived his cell lines
from IVF embryos that were donated by the couples to his project.
Dr. Gearhart's cells came from "8-11 week human aborted fetal
material" according to his patent grant. This is where the
corporate interest enters the picture. The Geron Corporation
website lists the patents they hold. They list two patents
by Dr. Thomson, and the two patents of Dr. Gearhart. Thus
Geron Corp. holds the licensing or distribution rights to
probably all of the existing US ESCs.
MSNBC has an editorial by Dr.Glenn McGee from the University
of Pennsylvania Center for Bioethics, who says: "President
Bush's compromise pads the wallet of a few - perhaps only
one or two - companies. A large percentage of the revenue
that will come from federally funded research on existing
stem cell lines will end up paying for these companies' patents
on stem cell research.… Former Governor of Wisconsin Tommy
Thompson, now Secretary of Health and Human Services, helped
to create the most important owner of this research, the University
of Wisconsin Alumni Research Foundation. [Ed-Thompson likely
did not help create WARF which was founded in 1925, but perhaps
he was instrumental in the establishment of WiCell, or the
stem cell division specifically.] WARF… may stand to build
a research empire from the royalties and "reach through agreement"
that ensures that it owns essentially anything created from
its cells. If embryos discarded after IVF had been used, Wisconsin
would have made little from stem cell research. Instead, under
Bush policy, there will be a tariff on any research and it
will be gathered almost exclusively by the home state of one
of his senior cabinet officials." Dr. McGee doesn't mention
the cell lines from Johns Hopkins also licensed by Geron.
Perhaps these are to be excluded from Bush's funding proposal,
since they were derived from aborted fetuses.
On August 13, 2001, WARF filed suit against Geron Corp. WARF
and Geron signed an agreement in 1999 in which Geron had the
rights to the five cell lines and six types of cells that
are derived from them. Remember that stem cells can differentiate
into multiple different cell lineages. This differentiation
in culture depends upon what specific nutrients or cytokines
are added to the culture media. It seems as if they had only
worked out six differentiation pathways or culture conditions
at the time the agreement was signed. An option to add cell
types to the deal expired July 31, and negotiations to extend
it failed, according to WARF. Geron says it still has the
right to add cell types, and that it asked to do so on July
26. WARF wants to stop Geron from working with other companies
to develop additional cell lines.
Clearly, Mr. Thompson's home state institution will benefit
enormously, and perhaps even exclusively, from the $250 million
set aside currently for stem cell research. Especially if
they win the right from Geron to distribute future cell types
derived from Dr. Thomson's five stem cell lines. And now with
their cell lines going out to every NIH grantee, the University
of Wisconsin stands to make a bundle of money too.
So when was Mr. Bush's speech? August 9. After the deadline
for the expiration of licensing agreement between Geron and
WARF/WiCell. Coincidence? Maybe this was one of the reasons
for the timing of the speech. Bush made his decision over
a month ago. Bush apparently always planned to make the announcement
in August, after the Congress recessed, and on his home turf
in Crawford. Early enough in his vacation to make it look
like he was working, but allowing time for the expected furor
to die down before he returned to the heightened scrutiny
of DC. In the meantime he met with the pope as a token gesture
to the Catholics, who mostly support ESC research in the US
anyway.
With the level of orchestration that has gone into this whole
circus from the very beginning, can anyone doubt that Mr.
Thompson kept Mr. Bush informed as to what timing he preferred,
or that WARF and WiCell knew did not know exactly when that
announcement was coming? Was the announcement delayed so that
WARF could allow their deal with Geron to expire? After all,
if they could expect a large influx of government grant money
in the near future, they wouldn't need private funding any
longer. So why give up the rights to distribute and sell future
cell products. What about those pending patents for WiCell,
and when were they applied for? And has anyone bothered to
ask the most basic ethical question of all: is it right to
profit from human cells, especially those derived from donated
embryos intended to help alleviate suffering?
References:
Ramsey's Stem Cell Primer: http://ramsey.dca.net/escprimer.htm
http://www.wisc.edu/warf/
http://www.geron.com
https://www.wicell.org/index2.html
http://www.reuters.com/news_article.jhtml?type=sciencenews&StoryID=158373
http://www.msnbc.com/news/611850.asp
http://www.msnbc.com/news/612806.asp
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