With the advent of the Human Genome Project, a Pandora's box of ethical, legal, economic, and social issues was irrevocably released. The project, which aims to map the entire human genome by the year 2005, is an enormous international undertaking (7). At the onset, many realized that redundancy and its extraordinary cost could be minimized through international collaboration. With a $3 billion allocation to the DOE (Department of Energy) and NIH (National Institute of Health) towards this project, a database of sequences and gene identifications was established and research poured in from countries around the world such as France, Britain, Switzerland, and Japan.
The extraordinary degree and range of possible medical advances that will come from this database immediately raised questions of intellectual property rights. Every newly sequenced segment of DNA holds a possible clue to a treatment for cancer or heart disease. These benefits to humanity and the associated economic gains to suppliers provide more than enough incentive for researchers to consider protection of their discoveries.
In determining patentability, the U.S. Patent Office evaluates applications by three criterion: novelty, utility, and unobviousness to peers in that field. DNA sequences fall into the "Plant Patent" category of patents, which expire years after application (4).
An important distinction must be made between patenting a human function and gaining ownership of another person. For instance, once a gene is isolated and patented for blond hair, the owner of the patent does not "own" a part of each blond person's genome. Instead, they have the right to prohibit others from developing products or procedures which directly use the gene. Cloning of blond hair genes and subsequent development of a drug which genetically alters hair color would be covered under a patent, while the physical hair of blond people is not.
A final misperception involves the role of publishing in patent applications. Publishing a new discovery does not mean that it is immediately unpatentable, as "no U.S. patent will be granted on an application if the invention was disclosed in a printed publication anywhere in the world more than a year before the filing of the application" (4). Implicit in this law is that if a new discovery is made public information through publication, it can be exploited by "patent-scavengers" for up to one full year.
This issue was brought to the forefront in June of 1991. At the prodding of NIH director Bernadine Healy, J. Craig Venter applied for patents on 347 segments of cDNA. These segments can then be used in screening a DNA library to find if a gene is expressed in a particular kind of cell. As his initial application awaited judgment, Venter applied for more patents, covering the sequences of an additional 2735 gene fragments in February of 1992 (6). Although Venter's applications covered the majority of all genes expressed daily as mRNA, the sequences only accounted for 5% of the human genome. Venter initially requested rights to the proteins that the gene coded for, but later resubmitted his application as he confined his request to only the gene itself (7).
By U.S. Patent Office standards, Venter's application did appear to be novel. He had searched all available databases for matches and the genes, or gene segments, seemed to have never been sequenced before (1). However, unobviousness and utility were much trickier issues. Because Venter did not invent the process which allowed him to sequence cDNA at such a high rate, nor did he create the databases from which he checked his gene fragments, his only innovation was in the combined use of the two resources. Utility was even a greater obstacle, since Venter's genes were 'naked,' and merely expressed DNA of unknown function. He did not know the biological function of the full genes or where they resided along the chromosomes (6). In fact, many of Venter's fragments simply denoted housekeeping genes, such as those that produce and repair organelles within the cell (1).
Although slandered by countless colleagues for patenting a "dumb, repetitive task" that "virtually any monkey" could do (5), Venter did raise the question of when or even whether a gene is patentable. Does the gene's natural expression have to be determined, or are the proteins coded by the DNA adequate? If the proteins are acceptable, how about the mRNA and its cDNA, or the DNA itself, or just the 4 simple bases? If we take this argument to this ridiculous end, the patenting of the periodic table and its elements is called into question. As David Galas, director of NIH's Office of Technology Transfer expressed, "There is no coherent government policy, and we need one ¯ quick ¯ since the sequence is just pouring out" (5).
A refined definition government policy was delineated when Venter's patent applications were rejected by the U.S. Patent Office for insufficient utility. His ESTs, or Expressed Sequence Tags, only serve as a marker of a gene that is expressed in a particular kind of cell (7). That marker is only useful for further research in probing for the gene, and under a 1966 Supreme Court precedent, is not patentable (5). The claimed right to the gene, with no mention as to its function, seemed to establish a "false endpoint" (10) and ensured the rejection of the application (8). Furthermore, the "use of an EST for fishing out the cognate gene from single-stranded DNA is no different from techniques standard in molecular biology since the early 1970s. In patent examiners' language, it was 'obvious'" (8).
With Venter's setback, jockeying for ownership of "naked" gene fragments waned. In November of 1993, the Medical Research Council of Britain decided that it would no longer apply for patents discovered as part of the human genome project (2). "It's just like a land-grab with people saying 'that's mine', which is silly," explained Cambridge geneticist Peter Goodfellow. The council justified earlier patent applications similar to Venter's as simply defensive acts intended to guarantee "a seat at any table where the issue was discussed" (2). With that established, it felt it was time to correct a wrong. The NIH apparently appreciated this gesture and decided not to seek patents on cDNAs in 1994 (3). It appeared to be that peer pressure that was the most effective tool in curbing destructive competition among researchers.
Genes clearly are patentable once they have been isolated and characterized by their expression since the bulk of the work is in isolating the DNA which codes for the protein and discovering how that protein is expressed (6). Since 1980, both private and academic researchers have patented hundreds of complete genes, often claiming broad commercial rights to their potential diagnostic and therapeutic uses. Genes associated with cystic fibrosis, insulin, tissue plasminogen activator, and human growth hormone are a few of those for which patents have either been approved or are pending (7). These patents have already proven productive in stimulating the further development of useful treatments and screening tests.
Although the difference between patenting unidentified DNA segments and determining the expression of an isolated gene is understandable, many private companies such as HGS continued to wishfully apply for patents on partial gene segments (3). To combat this the Human Genome Organization, or HUGO, which is responsible for coordinating efforts to sequence the complete human genome, continues to push for the rejection of applications for patents on unidentified sequences. In a statement in April 1995, they argued that "patent protection of human genes is essential to create necessary incentives for the ongoing development of products without interfering unduly with scientific research. . . . The task of identifying biological functions of a gene is by far the most important step in terms of both its difficulty and its social benefit, therefore it merits the most incentive and protection." It went on to state, "Applying for patent protection on sequences alone ¯ for example on either Expressed Sequence Tags (ESTs), used to identify cDNA clones, or on the cDNAs themselves ¯ without knowing their biological function is like applying for patents on the table of elements" (3).
The definition of what is patentable has become increasingly precise, and patent applications for unidentified DNA sequences are now rare. All genomic patents issued up to 1994 have been classified into 12 groups, nearly all dealing with specific genes or control factors (9). This current system rewards those researchers who isolate specific genes. These genes can then be cloned and the correct form can be inserted into new DNA through recombination as a therapeutic tool. The isolation of a particular gene, such as one associated with a predisposition to a specific disease, is often the last step before development of a treatment and seems an appropriate stage to reward researchers who seek financial reimbursement. Under the protection of a patent there is adequate incentive to develop drugs after the discovery of a gene and the proteins it codes for, and new treatments often surface before the patent wears out. Furthermore, once the patent expires on the gene and/or the treatment, society benefits even more as prices drop and the drug or treatment becomes generic.
In the U.S., which is considered the "most important technological market for major inventions" (9), publication of a valuable unpatented discovery inevitably leads to a patent application within a year from the private sector. Under this system, there is no safeguard to guarantee that those who worked hardest on the discovery are rewarded or that those who contributed nothing to the discovery do not collect windfall profits from successive drug development.
Historically, many have assumed that the government's role is to finance basic research, while private industry reaps the rewards from publicly funded discovery. Despite the fact that "most gene patents have [minimal] cash income value, and many seem unlikely to tap into large commercial markets at all" (10), it is not uncommon for an academic researcher, operating on federal funds, to make a discovery and publish it at no personal profit, and then watch a drug company patent the discovery and develop a multi-million dollar drug. With a valuable patent and subsequent drug development, a drug company can collect license fees, royalties, and profits from production for 17 years after the application. Drug companies point to the millions of dollars they have contributed to basic research, however, this kickback is merely a fraction of their profits.
There are several reasons why many academic researcher decide not to apply for a patent on a potentially valuable discovery. First and foremost, many feel that the spirit of collaboration and anti-competitiveness fostered among peers would be threatened. By decreasing the level of communication, redundancy would compound, and scientific progress would suffer. Secondly, many academic researchers simply do not feel it is their role in the development process to seek large monetary gains. Rather, they focus on the esteem of their peers, their academic freedom in research, and the betterment of science and humanity though their work. For these scientists, the absence of a concretely defined drug or development goals results in a flexible style of research in which many insightful and unexpected discoveries may be made.
While those in the private sector prefer financial rewards from research, those in academia often prefer the intellectual freedom and camaraderie among peers. Patenting a discovery is the researcher's perogative and, in the long run, inconsequential in terms of social benefit. What is paramount is that researchers and drug companies continue their symbiotic relationship in bringing basic research to fruition in the form of new drugs and screening tests.
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Sat Aug 28 00:18:10 GMT-0700 (Pacific Daylight Time) 1999
The beginning of the end