Pitfalls of Genetic Patenting Confound Consumers, Industry by Gina Shaw Who owns your genes? You do, of course. But itís a bit more complicated than that. As the human genome has been sequenced, some 8,000 U.S. patents have already been granted to the laboratories and organizations that originally isolated them. Intellectual property law in the United States (and in many other countries) allows for the patenting of isolated genes and gene sequences removed from their natural state. Patenting products from nature is nothing newóLouis Pasteur patented purified yeast back in 1873. Although clarified rules issued by the U.S. Patent and Trademark Office in 2001 require patenters to prove that their ìinventionî (the isolated gene or gene sequence) has specific, credible and substantial useótheoretically preventing scientists from patenting huge chunks of isolated genes before they even know what the genes in question might doóthe patent gold rush continues. And under whatís known as a ìreach-throughî clause, genetic patents give the patent holder control ofóand royalties fromóany future use of the patented genetic sequence. This includes genetic tests for many inherited diseases. In the late 1990s, several Florida families were startled to discover that after they had put in years of exhaustive effort putting together a registry of children suffering from Canavan disease (a rare and fatal genetic disorder similar to Tay-Sachs), the hospital they were working with had patented the gene they discovered using those childrenís blood and tissue samples, as well as the genetic tests that went with it. Instead of offering to make the prenatal and ìcarrierî genetic tests for Canavan disease available the general public, as the test for Tay-Sachs is, the hospital holding the patent refused to allow anyone to conduct Canavan testing without paying a license fee. The parents sued. Filed in October 2000, Greenberg v. Miami Childrenís Hospital, et al. is still making its way through the Florida courts. In the lawsuit, according to the Canavan Foundation, ìThe Canavan families and organizations primarily seek injunctive relief to prevent Miami Childrenís Hospital from restricting access to prenatal and carrier testing for Canavan disease and from impeding research on finding a cure or therapies for Canavan disease through enforcement of its patent.î Genetic patents donít always mean exclusive licensure. The patent covering the most common form of the cystic fibrosis (CF) gene, originally isolated by the Human Genome Projectís Dr. Francis Collins, is broadly licensed by the University of Michigan to anyone who performs CF testing. The Tay-Sachs test is similarly licensed. But under the current system, decisions whether or not that kind of public access is granted rest solely with the patent holder. The battle over ìwho owns the book of genesî isnít isolated to the United States. Four patents related to testing for an iron-overload disease called hemochromatosis are currently pending before the European patent office, and American biotechnology giant Myriad Genetics is locked in combat with the French Gustave Roussy and Curie Institutes over breast cancer testing. In November, Myriad inked a deal with Australian biotech company Genetic Technologies, granting it exclusive Australia-New Zealand rights to test for mutations in BRCA1 and the other breast cancer gene, BRCA2, along with several other genes. By late 2000, according to research conducted by the British newspaper The Guardian, ìPharmaceutical companies, biotech firms of all sizes, government institutes and universities [had] filed patents on a staggering 127,000 human genes or partial human gene sequences.î Locking Down Research? Opponents of gene patenting argued early on in the game that such patents would stifle scientific research, limiting it to the labs that held the patents or those that could afford high licensing fees. Evidence is accumulating that these concerns may have been well founded. At a November conference on biotechnology and intellectual property rights held in Australia, Stanford researcher Dr. Mildred Cho reported that gene patents have already served to limit the availability of testing for such genes as those implicated in breast cancer (BRCA1 and BRCA2) and Alzheimerís disease (apoE). Two years ago, Cho and a colleague, bioethicist Dr. Jon F. Merz of the University of Pennsylvania, reported in the journal Nature on a survey they had conducted on genetic patenting. At the time of the survey, 14 of a sample of 27 disease gene patents had been licensed, and ìall licenses were exclusive,î Merz told a House Judiciary subcommittee. ìPatents covering the diagnosis of various neurological diseases including Charcot-Marie-Tooth disease, spinocerebellar ataxia and apolipoprotein E in Alzheimerís disease have all been exclusively licensed to Athena Diagnostics. The first patent on the breast and ovarian cancer geneóBRCA1ówas exclusively licensed to Myriad Genetics,î he reported. In research set for publication in Nature this month, Cho, Merz and colleagues report that hemochromatosis-testing restrictions illustrate ìthe pitfalls of patents.î ìWe have found that U.S. laboratories have refrained from offering clinical testing services for hemochromatosis because of the patents,î Cho wrote. ìA lot of clinical study is needed to validate and extend the early discovery of a disease gene such as that for hemochromatosis, so our results give us reason to fear that limiting clinical testing will inhibit further discovery as well as the understanding that emerges naturally from broad medical adoption.î Cho and Merz werenít surprised to find the chilling of hemochromatosis testing after patents were filed. The pattern mirrored continuing patent-related problems with earlier genetic tests. ìIn a pilot survey of a convenience sample of 74 laboratory physicians Ö [we] found that 25 percent reported abandoning a clinical test that they had developed, and 48 percent reported that they had not developed a clinical test because of patents,î Merz told the House subcommittee. ìRespondents also reported paying royalties for using patented technology ranging from 9 percent for polymerase chain reaction to 75 percent for the human chorionic gonadotropin patent, which covers but a small part of the maternal serum triple test,î Merz added. The average license fee for one-time use of a test now runs a steep $2,000, noted Cho. Okay, so itís costing researchers a lot of money to run genetic tests they donít own the patents to, but what does that mean to the average person? Potentially quite a lot, say some experts. First, thereís the fact that when a test for a patented gene costs a lot of money to license, those costs are frequently passed down to the consumer. If, say, you have a family history of breast cancer and would like to get tested for the BRCA1 and BRCA2 mutations, those tests donít come cheap. Until the license agreement was signed in Australia, public hospitals there offered the test for freeóa situation thatís expected to change quickly post-license. But letís not forget that patents exist for a reason: to encourage, not stifle, scientific discovery. Patents provide an incentive for companies to engage in costly research that they might ignore altogether if they couldnít expect a return on their investment. Genetic patents are essential for medical progress, argue the large biotechnology companies as well as the small startups that sponsor a large chunk of the research that now seeks to take genetic information and transform it into actual treatments and therapeutics. ìBecause biotech companies depend on private investments, patents are among the first and most important benchmarks of progress in developing a new biotechnology product,î said the Biotechnology Industry Organization, which represents many of these companies. ìPatents offer limited protection against commercial use of a companyís invention by a competitor. In biotechnology, patents are critical to raising capital to fund the research and development of products.î An Ongoing Debate Leaders in the medical and scientific community continue to grapple with the practical and ethical implications of genetic patenting. The highly respected Center for Bioethics at the University of Pennsylvania, along with the Geraldine R. Dodge Foundation, sponsored the symposium ìWho Owns Life?î and published a follow-up book with the same title. In December 2002, Academic Medicine, the journal of the Association of American Medical Colleges (AAMC), which represents U.S. medical schools and teaching hospitals, devoted a whole issue to the topic, featuring contributions both supporting and critical of genetic patenting. In that issue, Dr. David Korn, former dean at the Stanford University School of Medicine and AAMC senior vice president of biomedical and health sciences research, argues that current patent law just isní t equipped to deal with the complexities of the genome. ìAt the heart of the matter is the patent systemís treatment of human gene sequences as simply ëchemical compositions of matter,í concerning which both patent law and practice are well settled,î said Korn. ìBut it can be argued that genetic sequences are not properly managed by this approach because in fact their biological and medical importance rests far more in the wealth of information they contain than in simply describing their structure,î he added. ìThe depth, complexity and physiological ramifications of that information are not obvious from the simple description of the sequence, but can only be determined by future experimentation. This fundamental fact is not dealt with adequately in current patent law or practice.î But itís unlikely that the Patent and Trademark Office will reverse the thousands of gene-related patents it has already granted, and the laboratories, companies and universities that have obtained those patents say they are necessary to protect the years of exhaustive work and millions (or billions) of dollars theyíve invested into isolating the genes. So the focus now in the scientific community turns to another question: How can, and how should, genetic patents be used and enforced to protect the investment of the people who did the initial, often costly research, while at the same time not stifling science or pricing necessary tests out of the reach of the people who need them? Some scientists argue for a broad-based ìdiagnosticî exemption to genetic patents, while others suggest a carve-out of infringement liability for researchers. Last May, then-Rep. Lynn Rivers (D-Mich.) introduced the Genomic Research and Diagnostic Accessibility Act of 2002, which would have revised federal patent law to include both exemptions. It proposed allowing scientists to use patented genetic sequence information for noncommercial research and physicians to perform genetic diagnostic and other testing without infringing on a gene patent. (The bill was referred to committee, but its status in a new Congress, with its original sponsor no longer in the House, is uncertain.) Such exemptions might sound like a good ideaóafter all, who wants to put the brakes on research or hold diagnostic tests hostage? But these seemingly simple solutions might not be so simple, argue Rebecca Eisenberg and Richard Nelson, professors of law at the University of Michigan Law School and Columbia University, respectively. ì[It] is difficult to define the proper scope of such an exemption when there is no clear line between the commercial and research spheres. Should researchers in academic and commercial laboratories be treated similarly? Should patents on research tools that have no significant market outside the research community be subject to a research exemption that effectively eviscerates their commercial value,î Eisenberg and Nelson asked in the special genetics issue of Academic Medicine. They continued, ìThe Human Genome Project offers numerous examples of patented research tools that were marketed to both academic and commercial researchers to the great benefit of the research community. Such tools might never have been developed without patents, making the ultimate impact on research of such a change in the law difficult to predict. On the other hand, many important research tools have come out of government-funded university research, and their invention arguably did not require patent protection.î Another option might be a legislative or regulatory solution designed to stop patent-holders from charging unreasonably high rates for research or diagnostic test licensingóprotecting their right to receive compensation for their work and investment of resources, but preventing them from going too far. ìToo many parties have the possibility, at least, to obtain too many patents that affect the ability of scientists and others to do research, and the monopoly power obtained by the patentee is absolute,î said San Diego attorney Kate Murashige, another contributor to the debate in Academic Medicine. She suggests a way around such absolute patent power that is permissible under U.S. trade law: ìCompulsory licensing is permitted in certain defined circumstances, and there is much to be said for applying such provisions to research tools. Perhaps this is the most direct way to counter the problem that a patentee can essentially prevent research from taking place by simply refusing to license or demanding too much in return for a license to research tools. The developer of the research tool would certainly be compensated for the contribution to science, but not at a prohibitive rate.î Confused yet? Youíre not alone. The gene-patenting debate continues to challenge scientists, governments and ethicists around the world. Is it possible to find a solution that protects everyoneópatent-holders, researchers, physicians, patients and science itself? Stay tunedóthe answers may be just as complex as the debate. Gina Shaw is the medical writer for The Washington Diplomat.