Gene Patenting Is On The Rise, But Scientists Are Unimpressed

Buoyed by enabling legislation and scientific advances, institutions are aggressively shopping their faculties' `blue-sky' investigations. In just the past year, patents on the genes implicated in obesity, breast cancer, and other disorders have generated headlines in newspapers across the United States. In several of these cases, scientists have turned their patented discoveries into lucrative commercial deals worth several times their funding from other sources--crucial money in light of proposed cuts in the federal government's support for biomedical research. And behind the patents attracting attention in the popular press are an ever-rising number of gene patent applications and awards, according to scientists, patent officials, technology transfer managers, and others. Despite this increased activity, however, scientists insist that the pursuit of a patentable discovery has not become a driving factor in their research strategies. The patent stories in the newspapers are the rare exceptions rather than the rule, they say, and not the stuff upon which to build a well-run laboratory. Instead, they maintain, competitive research leading to publications and steady grant support remains the key to a secure future in basic science, as has been the case for many decades. Fundamental curiosity continues to be the primary motivation for most research, investigators contend, rather than financial reward. Nonetheless, one of these inventions, when licensed to a company for development, can lead--albeit infrequently--to substantial royalty income for researchers, their labs, and their institutions. In February, associate professor Jeffrey Friedman, a Howard Hughes Medical Institute (HHMI) investigator who is head of the laboratory of molecular genetics at Rockefeller University, and his colleagues landed a major windfall. The biotechnology firm Amgen Inc. of Thousand Oaks, Calif., agreed to a $20 million initial fee--one third of which goes to the scientists personally, with equal parts also going to the university and to HHMI--for the exclusive rights to develop their discovery of a human gene thought to regulate obesity (Y.Y. Zhang et al., Nature, 372:425-32, 1994). Subsequent payments are expected to exceed the initial fee over time. "We were interested in the intrinsic scientific value of what we were doing," Friedman reports. "That it turned out to have pecuniary rewards was just never relevant. "We were interested in the way behaviors were regulated and the possibility that there could be molecular bases for behaviors. One of the easier behaviors to think about is feeding behavior, and we had spent some time working on a neuropeptide that had been suggested to affect food intake. When we became somewhat disillusioned about its possibilities, we began turning our attention to this mouse strain that we worked with, which led to our discovery. The motivations were purely basic science." Some scientists point out, however, that substantial research support can be extracted from the corporate world's interest in a patent--or even the possibility of a patent. Geneticist Mark Skolnick of the University of Utah and privately held Myriad Genetics Inc., Salt Lake City, for example, was able to translate the commercial possibilities of identifying the gene linked to some inherited forms of breast cancer into $14 million in support for the quest from Myriad and Eli Lilly and Co. of Indianapolis. The research effort, with $4.6 million in additional support from the National Institutes of Health, narrowly beat a number of hard-charging competitors to net the BRCA1 gene last year (Y. Miki et al., Science, 266:66-71, 1994). Commercial rights to the patent are retained by Myriad, Eli Lilly, and a Lilly subsidiary, Hybritech Inc. in San Diego. Some researchers use patents to ensure a role for themselves and their laboratories in a company's efforts to create products from their discoveries. This tactic allows them to generate ongoing support for their work and to influence the direction of development. "Patents are a way to get industry involved in academic research," says Gary A. Weisman, an associate professor of biochemistry at the University of Missouri, who shares in the patented discovery of the gene for a human airway receptor protein, a purinoceptor, that may prove useful in treating cystic fibrosis (C.E. Parr et al., Proceedings of the National Academy of Sciences, 91:3275-79, 1994). "And that's becoming more critical as federal funding shrinks. "But I'm not necessarily interested in what percent of sales I'll get or how much money my university will get from a company. I would rather talk to them about how they're going to develop an invention, whether they need help developing it, and whether my lab can get some research support from them." Patent officials, university technology managers, and other patent experts agree that the number of gene patents being awarded has grown in recent years. However, because patents on genetic discoveries are categorized under many different, sometimes overlapping classes and subclasses by the United States Patent and Trademark Office (PTO), this belief is difficult to quantify with specific data. "We don't collect it," says Elizabeth Weimar, a biotechnology practice specialist at PTO, of exact gene patent figures. Many gene patents--those involving DNA or RNA--are classified under Class 536, one of the organic compounds classes, Weimar notes. These are then subdivided according to the type of molecule the genetic sequence codes for: enzymes, polypeptides, hormones, interferons, immunoglobulins, and so on. "Then there's a section for the noncoding genes, the part of the genome that regulates protein expression, but doesn't itself produce a protein. "But there has been quite a bit of expansion in the actual number of [gene] patents that have been issued in the 1993 to 1995 time frame, mainly because some cloning techniques have been developed that have made it much easier to isolate the gene from the chromosome. And the development of the PCR [polymerase chain reaction] technique for amplification has certainly been a major component of why there is more completed research in this area now." Joyce Brinton, director of Harvard University's office for technology and trademark licensing, agrees that, while reliable patent information does not exist in this area, greater numbers of gene patents are being awarded each year. "It's the growth in the science," says Brinton, who is also president of the Association of University Technology Managers (AUTM), Norwalk, Conn., which does not track gene patents. "The sequencing of the genome began some years ago at a relatively slow pace and has moved forward, gradually gaining momentum. There's more and more knowledge, and as more genes are identified there are increases in the numbers of patent applications being filed related to them." Pressure several years ago on PTO to increase the number of patent examiners in this area resulted in new hires and has contributed to the rise in gene patents being awarded, according to Gregory Aharonian, a patent-search consultant and publisher of the free Internet Patent News Service (http://sunsite.unc.edu/patents/intropat.html), Belmont, Mass. Aharonian says that many gene patents fall under PTO's Class 935, genetic engineering, and notes that the annual numbers for this class--which includes other types of patents in addition to gene patents, per se--jumped sharply several years ago and have remained high since then. As the number of gene patents continues to rise, many scientists and others keep a watchful eye on the work of J. Craig Venter, president of The Institute for Genomic Research (TIGR), Gaithersburg, Md. (F. Hoke, The Scientist, Dec. 12, 1994, page 1). In the past few years, TIGR has assembled a database of about 150,000 expressed sequence tags (ESTs)--partial sequences of cDNA obtained from various tissues--and is currently attempting to patent these, thus controlling their future commercial uses. NIH attempted to patent ESTs when Venter was an intramural researcher there, a move that was widely criticized by scientists because no basic biological knowledge accompanied the partial sequences. Some investigators charged that such patents, if allowed, would have foreclosed much future research, because even curiosity-driven scientists would not want to invest their efforts in work whose results might be controlled by TIGR. Venter, however, has countered that placing the partial sequences in the public domain would render the full genes unpatentable, thus removing the incentive for companies to develop them into useful products, such as drugs. After an initial rejection of the patent filings, NIH chose not to pursue appeals, leaving the question open. Venter's patent filings for a number of ESTs remain "under review," according to PTO's Weimar. If patents are granted, TIGR and its licensees, Human Genome Sciences of Rockville, Md., and SmithKline Beecham of Philadelphia, might gain commercial leverage over large portions of the human genome. For most scientists, an economic return on laboratory investigations akin to Jeffrey Friedman's is highly unlikely. The greatest majority of discoveries published are never patented, patents often go unlicensed, and those licensed almost never produce the kind of income upon which secure laboratory support can be based, scientists note. A much more reliable approach to capitalizing on research findings, they say, is the time-honored rewards system linked to being the first to publish a major discovery. Publication of important results often leads to additional grant support, career promotions, invitations to speak at important gatherings, and many other benefits that accompany a boost in scientific status. And it is in this area that competition among scientists is sharpest, researchers contend, rather than for patents. More than financial rewards, researchers want to be credited with discoveries. "Most scientists work on a credit economy and not a money economy," says David Botstein, chairman of the genetics department at Stanford University. Botstein, who was vice president for science at Genentech Inc., South San Francisco, Calif., from 1987 to 1990, shares in a number of genetic technology patents, including one for second-generation activase t-PA, a potential post-heart-attack treatment, developed while he was at the biotech firm. The technology for which he may be best known, however--the genetic markers known as restriction fragment-length polymorphisms (RFLPs)--was never patented. Other researchers agree that the competition to publish scientific results first is central to their research approach. The decision to pursue a patent, on the other hand, is "almost an afterthought," according to Mark Keating, an associate professor of human genetics at the University of Utah and an HHMI investigator. Keating recently discovered two genes responsible for long QT syndrome, a genetic flaw in the heart's ion channels that can lead to sudden death from arrhythmia in otherwise healthy individuals (M.E. Curran et al., Cell, 80[5]:795-803, 1995; Q. Wang et al., Cell, 80[5]:805-11, 1995). "Patenting is not anywhere near top priority on my list of things to do," Keating says. Only late in his laboratory team's scientific process, after a manuscript has been prepared for submission, but before it is sent, do "we call up the technology transfer office and tell them that we might have something patentable. It's not an important part of my life. My science is not driven by wanting to get patent applications. "Nobody goes into science because they think they're going to get rich. Some patents are world-beaters, but most don't amount to a hill of beans." "As scientists within a university setting, we don't really expect to benefit financially," Weisman says. "Now, in the back of our minds, of course, we hope to avoid a situation where someone uses our discovery to develop a drug, for example, and then profits by that, and we see nothing in return." Botstein contends that patents not only protect a scientist's self-interest, but also actually promote the dissemination of research findings. Without patents the only way inventors--including scientists--could protect the commercial value of their ideas would be to keep them secret. One of the primary purposes of patents, he says, has been to reduce the economic motivation for excessive trade secrecy, thought to have a deleterious effect on progress. So, patents benefit the public--rather than only the inventors--by allowing inventors to retain control over their ideas while also publishing them freely, stimulating further development and exchange. "When Jefferson, Franklin, and those guys put the patent law into the Constitution, their intent was to allow inventors to publish without losing their potential remuneration," Botstein asserts. "The law was intended, explicitly, as a compromise between the [inventor's] rights and [the public's need for] publication, the alternative being thought of then--and still is now--more secrecy. In some nontrivial sense, patents have got to be good, because secrecy is bad." What secrecy does exist, he says, has as much to do with the "credit economy" as it does with patents. "In a well-run circumstance, the amount that you have to keep quiet before publication and the amount that you have to keep quiet before patenting are essentially the same." Constrained federal research funding in an increasingly competitive atmosphere has put pressure on laboratory scientists to be creative in finding funding. Scientists say, however, that while royalties from gene patents may be a partial solution to the problem for a few researchers, top-notch basic science remains the heart of the solution for most. In the 1950s and 1960s, Keating points out, half to two-thirds of all NIH grant proposals were funded. Now, in many areas, something closer to a tenth receive money, he says. "That's pretty severe competition," he says. "That competition means that you need to try to stand out in a crowd. And the way you stand out in a crowd is by publishing first, making discoveries."

Gene Patenting Is On The Rise, But Scientists Are Unimpressed

Interested in reading more?

Become a Member of