More MS news articles for Sep 2001

Stem Cells: Steady Momentum Toward Funding

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
By Ted Agres

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.
 

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