Questions persist about informed consent, patents,
and licenses
http://www.the-scientist.com/yr2001/sep/agres_p8_010917.html
The Scientist 15[18]:8, Sep. 17,
2001
Federal funding for research involving
human embryonic stem cells (ESCs) is moving closer to reality as the Bush
administration rushes to finalize a public registry of approved cell line
providers. In late August, the National Institutes of Health announced
10 organizations that it said had developed 64 stem cell lines that meet
all the criteria for federal funding (see table). Nevertheless, some licensing
and patent issues need to be resolved and new and potentially complicating
questions are emerging about the standards of donor consent used by the
stem cell providers outside the United States.
During the three weeks after President
George W. Bush announced limited federal funding for human ESC research
Aug. 9, NIH officials held virtually nonstop discussions, in person and
by telephone, with the 10 potential stem cell line suppliers. To be eligible
for federal funding, Bush said ESC lines had to be derived with informed
consent of donors, from excess embryos created solely for reproductive
purposes, without any financial inducements to the donors, and had been
created prior to the time of his announcement.
Many scientists have been skeptical
over the quality of the cells, especially following reports that up to
half of the 64 lines may not be developed sufficiently for research. During
a Sept. 5 Senate hearing, Health and Human Services Secretary Tommy Thompson
acknowledged that some of these lines "are in the earliest stages of development,"
but he stressed their usefulness can only be determined through actual
research. The NIH had reported earlier that all the cells were said by
their suppliers to be "viable, show characteristic stem cell morphology,
can be maintained frozen, as well as in culture, and have undergone at
least several population doublings." The Senate is holding three hearings
this month to examine the adequacy of the approved cell lines and other
research-related issues (see News Notes).
Consent Dilemma
Concerning donor consent, Lana Skirboll,
NIH associate director for science policy, told reporters after Bush's
Aug. 9 announcement that officials had received copies of the forms for
each of the cell lines. "They are reasonable informed consent," she said.
"The [criterion] is, as stated by the president, that there was an informed
consent for the donation for research purposes." However, in a later published
interview, she admitted, "we didn't analyze the informed-consent forms."
The institutions providing the forms, she said, "were held to whatever
standard was in place for the country, the hospital, or the facility they
were working in."1
This could create problems for universities
and research facilities, says Mark Frankel, director of the scientific
freedom, responsibility, and law program at the American Association for
the Advancement of Science (AAAS). Institutions receiving federal funds
for human subjects research typically must adhere to the "Common Rule"
of the Department of Health and Human Services, which stipulates strict
guidelines for informed consent. While human ESC research does not fall
directly into this category, the ethics committees at universities and
research institutions potentially could find themselves at odds if they
embrace divergent standards. "We don't know what the consent process was
for cell lines in Singapore or anywhere else," Frankel says. "That may
end up being as important a qualifier as whether the cell lines are genetically
diverse, viable, and useful."
In an Aug. 17 statement questioning
Bush's stem cell policy, AAAS noted: "We need to know how many of the existing
cell lines have been derived in a manner that would meet or exceed the
ethical standards that the American public expects will be associated with
such research. Too often we have learned that procedures used in other
parts of the world in research with human subjects do not measure up to
the ethical standards that we embrace in this country."
Leon Kass, the chairman of Bush's
proposed new President's Council on Bioethics, declined to discuss whether
that panel would have input into the ethics of the donor consent guidelines,
pending the group's formal establishment later this year. However, the
White House expects the council to deal with broad bioethical issues and
Kass previously has stated it will not oversee the government grant-making
process.
Aside from Kass, no other council
members have been named. A senior White House official said the panel will
consist of "really talented people" who will not necessarily be charged
with coming up with consensus recommendations. "Sometimes, striving for
consensus recommendations tends to water down the recommendations," the
senior official said, adding that the country can benefit "from a divergence
of opinions when they exist."
The Legalities
Scientists remain worried that licensing
and patent issues might restrict the boundaries and usefulness of their
research. This is because WARF, a non-profit technology licensing entity
affiliated with the University of Wisconsin, holds a broad U.S. patent
on ESC derivation and the cells themselves. WARF officials have promised
to grant research rights broadly and economically, but they have also licensed
important commercial development rights to Geron Corp., the Menlo Park,
Calif. biotech company that helped fund pioneering work by James Thomson
and his lab at the University of Wisconsin in 1998.
Less than one week after Bush's announcement,
WARF filed a lawsuit against Geron seeking to block the latter's attempt
to exercise an option to commercially license 12 more cell types. WARF
spokesman Andy Cohn said the action was "absolutely coincidental" in timing
and both sides are attempting to negotiate an out-of-court resolution to
the matter.
WARF has granted Geron exclusive
commercialization rights to six cell lineages (hepatocytes, myocytes, neural
cells, pancreatic islet cells, hematopoietic cells, and osteoblasts) from
five WARF cell types, meaning that any therapy independently derived for
these tissues might require commercial collaboration with Geron. WARF licenses
its stem cells to researchers through the WiCell Research Institute Inc.
and charges $5,000 for a Material Transfer Agreement (MTA) per human stem
cell line. "Our goal here is to get these cells to as many researchers
who are interested in doing good research," Cohn says.
WiCell and NIH officials reached
agreement in early September on terms for licensing five cell lines for
NIH's intramural scientists. The agreement allows NIH scientists to publish
their research findings and permits the institute to own the intellectual
property rights from the research. WiCell said it would extend these same
terms to other nonprofit institutions. "This agreement will help us make
these cells readily available to qualified scientists in government and
universities where the science can be openly advanced and the technology
brought to fruition as quickly as possible," said Carl Gulbrandsen, WARF's
managing director.
"Whoever makes a discovery [with
a WARF research license] is free to patent that discovery," Cohn says.
"They can publish that discovery and we don't get in the way of that. If
they then wanted to commercialize that, they would contact us and we would
determine if it fits within our patent, determine if it's within Geron's
rights or our rights. They would negotiate a commercial agreement with
either one of us," he says.
BresaGen stated it would make its
four stem cell lines available to researchers with no upfront cost provided
the company receives the right of first refusal for any resulting discovery
having commercial potential. This kind of relationship between researchers
and developers is fairly common.
In reality, all these licensing issues
are fairly straightforward. "I don't think there's anything here that's
unusual, aside from the visibility and the fact that it's gotten to the
presidential level as a matter of public policy," says Q. Todd Dickinson,
former commissioner of the U.S. Patent and Trademark Office and now an
attorney with Howrey Simon Arnold & White in Washington, D.C. "I've
seen much more complex licensing schemes than this. It can look kind of
complex, but this is pretty simple stuff. It's a pretty garden-variety
kind of licensing program."
Ted Agres (tagres@usa.net) is a freelance
writer based in Washington, D.C.
1. C. Connolly et al, "Viability
of stem cell plan doubted," Washington Post, Aug. 20, 2001, page A1.
© Copyright 2001, The Scientist,
Inc
By Ted Agres