Striking the Balance
Brave New World of Human Gene Sequencing Finds Porous Policy Guidelines to Its Liking
"If somebody uses this gene . . . after the patent has been issued . . . we'd be entitled not just to damages, but to double and triple damages."
-- William Haseltine, Los Angeles Times, February 28, 2000
"There is no patent. Could you patent the sun?"
-- Jonas Salk, See It Now, April 12, 1955
"Public Policy Minefield"
"If somebody uses this gene in a drug discovery program after the patent has been issued . . . and does it for commercial purposes, they have infringed the patent." Should a company bring a drug to market after infringing a patent, "we'd be entitled not just to damages, but to double and triple damages."--William Haseltine, former AIDS researcher and Chairman and CEO of Human Genome Sciences, Los Angeles Times, February 28, 2000.
Haseltine was talking about CCR5, the gene for the second receptor HIV needs (after docking to the CD4 molecule) to penetrate human cells. The company stumbled upon the CCR5 gene during its mass sequencing of the human genome. They applied for and later received a patent on the gene sequence covering its use as a receptor and potential receptor antagonist. Meanwhile, most of the researchers who actually established CCR5's role in HIV infection were left out in the cold. In fact, if any of them have ideas about developing drugs that target this protein or gene for therapeutic use, they'll have to deal with Haseltine and Human Genome Sciences. Gregg Gonsalves reports.
The case of the CCR5 gene brings up thorny issues in biomedical ethics, intellectual property rights, and patent law. Who owns the human genome? The first gene patents were granted on sequences that code for known human proteins with clear physiological or therapeutic effects. Later, in the early 1990s, the National Institutes of Health, under the leadership of Bernadine Healy, applied for thousands of patents on little snippets of DNA called expressed tag sequences (ESTs) without any knowledge of their function. These patents were withdrawn after an outcry by the scientific community, but industry quickly stepped in and began applying for millions of patents on ESTs. Craig Venter, the NIH researcher who developed EST technology, then entered the private sector, forming Celera Inc., and joined Haseltine and Human Genome Sciences in a now dissolved gene-hunting and database-searching partnership.
The more radical view on gene patents decries any commercialization of the human genome whatsoever, maintaining that genes and their mutations are naturally occurring substances that should not be patented. Jonas Salk, when asked years ago in an interview with Edward R. Murrow about who owned the rights to the polio vaccine, replied, "Well, the people, I would say. There is no patent. Could you patent the sun?" Those who oppose any patents on DNA would extend Dr. Salk's proposition to the human genome.
The United States Patent and Trademark Office has granted a few patents on ESTs, but recently has begun to reevaluate the wisdom of its EST-based gene-patenting policy. Recent statements from U.S. Patent Office Director of Biotechnology, John Doll, has indicated that patents on genetic material will need to demonstrate "some substantial, real world utility" before they can be approved. Currently, most EST patents are sitting in limbo.
Unfortunately, information that establishes this "real world utility" may be curiously general. It can result from a database search that simply identifies a gene or gene fragment as part of a larger family of known genes. The National Institutes of Health objects to this drift in U.S. Patent Office (USPTO) policy, saying it doesn't go far enough. Former NIH director Harold Varmus and current National Human Genome Research Institute director Francis Collins recently wrote the Patent Office asking for more stringent standards that would demand elucidation of a gene's specific physiological function before granting a patent.
From TAG's perspective, the NIH's position makes more sense than the USPTO's or that of the DNA sequencing industry. While TAG has its disagreements with the NIH, here we find common ground. Allowing patents on ESTs with only a vague, accompanying theoretical function, based on database findings rather than pathophysiological research, favors companies that have invested their resources in the simply mechanical task of churning out potentially active DNA sequences. This will create monopolies on the human genome that could impede research on AIDS and other diseases, especially the development of new therapies.
We don't need a new Microsoft for the biological software of human genes. We have already heard of researchers foregoing critical experiments on CCR5 inhibition rather than risk conflict with Human Genome Sciences' alleged patent rights. What other havoc are companies like Human Genome Sciences and Celera going to wreak on drug discovery research in the future? If the U.S. Patent Office doesn't change its standards and require established physiologic functions before granting gene patents, Congress should change the relevant patent law or find other ways to protect researchers and small companies from these genetic robber barons. We should reward those who invest their time and resources in the difficult scientific work of figuring out the function of human genes and proteins. And we should protect those who use this knowledge to develop new ways to diagnose, treat and cure disease.
There are additional difficulties in this emerging world of patented genetic information, with fragmented and overlapping intellectual property rights having the greatest potential to stymie drug development efforts. Rather than rush to judgment on gene patenting, the Patent Office, Congress and other relevant institutions need to consider a wide range of issues before crafting regulation and legislation in this area. The stance of those who would ban gene patenting altogether may seem attractive in light of anticipated difficulties in negotiating this public policy minefield, but in the end reflects a flawed utopian view. If incentives for the commercialization of products derived from genetic research are removed, the development of a new generation of treatments, including treatments for HIV, will certainly be slowed. It will be a challenge for policymakers and researchers to strike the proper balance that maximizes incentives for competition in the interest of public health.