09-08-2001

Science & Technology: An Interesting Disinterest in Cloning

In times past, the public image of a scientist was that of a lone genius,
working tirelessly in his laboratory to unlock nature's secrets for the
common good. But a vastly larger enterprise subsumes the modern scientist.
Today, each scientist's prospects depend on the work of other scientists
in related fields, and on the vast industrial enterprises that have the
capital, the large testing laboratories, and the worldwide production
facilities needed to get medical discoveries into the marketplace.


These interrelationships are reflected in the National Academy of
Sciences, a private, nonprofit group that seeks to give "independent
advice on matters of science, technology, and medicine" to
government. In June, the NAS set up a panel of experts to advise policy
makers about human cloning. The panel members are all top-flight
scientists-but many are also company directors, patent holders, research
managers, association executives, and applicants for government research
grants. They are all, to retool an old phrase, part of the
"scientific-industrial complex."


But these parallel roles-scientist, shareholder, manager, patent-owner,
association president-can create conflicts of interest, or at least an
appearance of conflicts of interest, that are impossible to avoid and
difficult to manage. The standard defense offered by scientists is that
they fully disclose all of their various financial and research interests
so that observers can gauge possible bias, as well as ensure that
contending camps are fully represented on scientific panels.


These rules of full disclosure, meant to achieve openness and scientific
balance, certainly apply to the NAS panel on cloning. The 11-member panel
was established to explain all types of human and animal cloning, to
assess the safety of carrying a cloned human through pregnancy and birth,
and to consider whether there should be a moratorium on work aimed at
cloning a human for birth.


In that context, how full is full disclosure? How extensively should
scientists disclose all their present and past links to studies, and to
companies that may have a present or future interest in the research at
issue?


Given the cloning panel's mandate, the members clearly have no conflicts
of interest, says E. William Colglazier, spokesman and executive officer
at the NAS and National Research Council. The members have no ties to
companies that are seeking to birth a cloned human nor to those who use
cloned human embryos to obtain stem cells, he said. "We are looking
at current ties, not the future or speculation ... [so] no member of the
panel had what we call a conflict of interest," he said. This point
was echoed by panel member Gerald Rubin, a vice president of biomedical
research at the Howard Hughes Medical Institute. "I still own stock
[in biotech companies].... But none of those companies are involved
directly in any of these areas of cloning, or stem-cell research," he
said. "To me, that means I don't have any obvious conflict of
interest."


Rubin's point is well taken. No U.S. company has announced plans to clone
a person for birth, so it is unlikely any of the NAS panel members have a
direct conflict of interest.


However, cloning is a continuum, with birth-cloning just the most
advanced, and controversial, step. According to a paper released in August
by the NAS, the scientific term cloning covers many processes, including
the replication of tissues that are not embryos and stop far short of a
living human-things such as a single cell, a molecule, an organ, or a
complete plant or animal.


And cloning already is so prevalent in biotech-much of which is funded by
grants from the National Institutes of Health-that "90 percent of the
NIH grantees do some sort of cloning," said Rubin, in an interview
with National Journal. And much of this cloning is noncontroversial-the
cloning of plants and animals, for example, or the cloning of individual
human "somatic," or bodily, cells, such as skin, brain, or hair
cells.


But on July 31, the House voted, by 265-162, to ban the creation of cloned
human embryos for any purpose, whether for birth, or for creating
embryonic stem cells for subsequent transplantation into patients, or for
research. These three basic types of human cloning, despite their
different purposes, are intertwined because all three involve the same
initial technological step-cloning a human embryo.


The future of stem-cell research is tied to cloning because some
scientists say that a patient's immune system may reject stem-cell
therapies unless the stem cells come from that patient's own cloned
embryo. Indeed, this may be stem cells' "killer app"-computer
jargon for a fantastic application of some technology that leads to
commercial success-said R. Alta Charo, a bioethicist from the University
of Wisconsin (Madison), who testified at the NAS panel's single public
meeting, on August 7.


Cloning is also tied to another central research direction of modern
biology: genomics, the effort to understand how genes work. Genes are the
basic instructions for life and are found in everything from weeds to
humans. Scientists want to understand how each of a human's 30,000-plus
genes works, and how they all work in concert with each other. One common
method of studying genes is to transplant a single human gene into
hundreds or thousands of "models" for a controlled experiment,
much as one would test out a new tire on many types of cars. In biology,
these models are usually either fruit flies or mice. For example, a human
gene suspected of causing schizophrenia can be inserted into mice, after
which the mice can be studied for clues to the cause and cure of the
disease.


But medicines can't be sold until they're proven safe, so scientists also
want to experiment on human embryos. Cloning can theoretically provide a
source of identical, quality-controlled human embryo "models."
Indeed, large numbers of embryos are important to ensure accuracy,
scientists say.


This use of human cloning for general research and genomics is more
important than cloning for birth or to obtain stem cells, Dr. Irving
Weissman, the chairman of the NAS panel, said on August 7. "To me,
that's the most important issue about research cloning, because it will
provide the best and the brightest [scientists] the possibility of
studying, in a test tube, the developmental potential of cells," he
said.


But the cloning of humans, even of embryos just a few days old in a test
tube, may not be politically viable. The House's vote is one indicator of
that opposition. And the Senate may join the House in passing a bill
banning all forms of human cloning this fall. President Bush has promised
to sign such a bill.


NAS panel members are only too aware of this political environment. During
their August 7 public meeting, panel member Patricia Donahoe urged her
colleagues to take a stand, and quickly, before the Senate votes. "I
would also say that we as a panel must come out with a statement very
soon, so that it is not obsolete."


Clearly, panel members would prefer that Congress ban only birth-cloning.
But what they don't say, at least in their disclosures, is how extensive
their various business and research interests are, and how these interests
might be tied to future research that depends on cloned embryos.


For example, Weissman and several other members of the panel own part of,
or help manage, companies that hope to gain from genomics and stem-cell
science. Much of that future scientific endeavor could be helped by, or
even dependent on, the cells obtained from cloned human embryos.


The potential rewards for such scientific entrepreneurship can be great;
Weissman was one of three co-founders of SyStemix Inc., which was sold to
pharmaceutical giant Novartis A.G. in 1991 for $392 million. Weissman now
heads a second company, StemCells Inc., which is trying to commercialize
therapies based on stem cells found in adults. StemCells Inc. is not
performing research on embryonic stem cells taken from human clones. But
Weissman has repeatedly said that research on adult stem cells will gain
from research on embryo stem cells. And he said at the August 7 meeting
that the cloning of ill patients to get diseased embryo stem cells would
provide a "wonderful opportunity" for disease researchers.
"I believe that human embryonic stem-cell research is vital for the
health of science ... academic medical science, and for the developing of
the next round of biotech [businesses]," he told National
Journal.


The panel also includes David Galas, a vice president at the Keck Graduate
Institute in California, who also has an extensive background in the
genomics and biotech business. Galas founded and headed Darwin Molecular
Corp., later renamed Chiroscience R&D Inc. He is still the chief
scientific adviser to Chiroscience. And Galas belongs to the board of Blue
Heron Biotechnology, a genomics company in Bothell, Wash. Panel member
Gerald Rubin, meanwhile, helped found a successful gene research firm,
Exelixis Inc.


Several panel members are also research managers, responsible for helping
other scientists develop their research, much of which will be tied to
cloning over the next decade. Rubin oversees research by 350 scientists at
71 institutions, while serving as vice president of biomedical research at
the Howard Hughes Medical Institute.


Other panel members are linked to professional associations that are part
of a larger coalition called the Federation of American Societies for
Experimental Biology, which is actively trying to prevent a ban on all
types of cloning. Panel member Brigid Hogan, for example, served until
July 22 as president of the Society for Developmental Biology, which is a
member of the FASEB coalition. FASEB lobbied for federal funding of
research on stem cells taken from human embryos. The society was
instrumental in pushing the federation to advocate a ban on only
birth-cloning. Panel members Robert Jaffe and Judith Hall are also
officers in two additional societies that are affiliates of FASEB. Another
NAS official overseeing the study, Maxine Singer, serves on the public
policy panel of the American Society for Cell Biology, which also
advocates a birth-only cloning ban. Singer is director of Perlegen
Sciences Inc., a genomics company.


If President Bush were to sign a bill that outlaws federal funding for all
cloning, NIH would see its funds for cloning-dependent research into stem
cells or genomics severely limited. Research would be greatly affected,
partly because so many researchers are reliant on NIH funding. For
example, five of the panel's members-Donahoe, Hogan, Jaffe, Weissman, and
Edward McCabe-have received a total of 258 NIH grants since 1990.


Many of the ties that the NAS panel members have to companies,
professional institutions, and NIH funds were absent from their short
biographies posted at the NAS Web site.


For example, Galas cited his past ties to Chiroscience and Darwin
Molecular, but he did not mention his affiliation with Blue Heron. At the
NAS site (www.nationalacademies.org), there is no mention of Exelixis,
founded by Rubin. Hogan, Hall, and Jaffe did not cite their roles in the
professional societies, nor did they cite their links to FASEB.


Panel members are required to submit a full disclosure form, said
Colglazier, of NAS. But "it is up to our discretion to decide what we
put in the bios" released by the NAS, he said. Panel members, at
their first meeting, do explain themselves to each other, disclosing any
related work, Colglazier said.


Several of the panel members denied any conflict of interest, or said that
it is manageable by proper disclosure. Moreover, said Rubin, all panel
members have some link to industry and to sources of funds. "There
are no people who are scientifically competent ... who don't have company
connections or NIH funding. Money has to come from
somewhere."


But when the panel's final report is released, said Colglazier, "we
are going to look again at [NAS-provided biographies] to explain to the
reader where these people are coming from."


Neil Munro

National Journal