Picturing DNA
Chapter 4:
Who Owns Your Genes? Patents and the Biotech Marketplace

Introduction

Chapter 1

Chapter 2

Chapter 3

Chapter 5

Chapter 6

Chapter 7

Epilogue

John Moore, a patient with hairy-cell leukemia, entered the University of California at Los Angeles Medical Center, a state-owned hospital, in 1980. As part of the treatment, his physician removed Moore's spleen. His leukemia went into remission, but during the next few years the cancer specialists at UCLA continued to take samples of his blood, skin, bone marrow and sperm. Eventually, Moore grew suspicious that these tissues were being used for something other than his personal care and sought legal advice. He was more than a little surprised, however, to discover in 1984 that his cell line had been patented; what had been inside his body had become patent number 4,438,032.

How the particular tissue from a particular person wound up in the U.S. Patent Office is a story of the interconnection between two-hundred-year-old patent law and contemporary economic interests. The U.S. Constitution promises to promote "the progress of science and the useful arts by securing for limited times to authors and inventors the exclusive right to their. . . discoveries." This right to ownership was given statutory expression in 1793 by Thomas Jefferson, who defined as patentable "any new and useful art, machine, manufacture, or composition of matter, or any new or useful improvement thereof." The only change to this wording was the substitution of "process" for "art" in 1952 when Congress overhauled U.S. patent law.

No matter how imaginative American inventors and businessmen may have been in the eighteenth and nineteenth centuries, none of them tried to patent a living organism. The only exception was made for a Frenchman: Louis Pasteur developed a purified yeast, for which the U.S. Patent Office granted him patent 141,072 in 1873.

There was an important case, however, in 1889, when a would-be inventor tried to patent a fiber found in pine needles. Although not a living organism, a fiber is product of nature. The Patent Office rejected the claim on this ground, noting that the composition of a tree in the forest "was not a patentable invention. . . any more than to find a new gem or jewel in the earth would entitle the discoverer to patent all gems which should be subsequently found." Moreover, the office stated, it would be "unreasonable and impossible" to allow patents upon the trees of the forest and the plants of the earth. Processes devised to extract something found in nature could be patented, but objects discovered during a search cannot be. This reasoning would reverberate in the patent wars a hundred years later.

The issue was dormant until agricultural interests, which had lobbied Congress throughout the 1920s, secured an act that allowed patenting of new varieties of plants. The Plant Patent Act of 1930 protected new versions of asexually reproducing plants like vines and roses. Forty years later, sex got into the act. In 1970, agricultural interests secured an act that protected new varieties of sexually reproducing plants. The patenting of tiny animals would be the next giant leap for the interests of animal husbandry and biomedicine.

The breakthrough case began in 1972, when Ananda Chakrabarty, a biochemist on the research staff of General Electric, decided to resume work on a bacterium he had investigated when he was a visiting postgraduate student from India at the University of Illinois. At GE he transformed the bacterium Pseudomonas by altering its DNA so that it ate oil and could be put to work combating oil spills. His explanation for his work was disarmingly candid: "I simply shuffled genes, changing bacteria that already existed." The result of this process is called recombinant DNA. GE decided to patent this bug, and when the Patent Office dismissed the application, GE appealed the decision.

During the decade in which Chakrabarty's case moved through the courts, the issue of recombinant DNA and its ramifications in agriculture and animal husbandry awakened advocates and opponents all over the world. In 1980, the Supreme Court ruled that whether the invention was alive or dead was irrelevant: the bacterium was not a product of nature, but a product of Chakrabarty's research and hence deserved a patent. GE secured the patent, and the biotech industry, then in its infancy, had a go-ahead signal. The decision scotched the presumption that Congress ever intended to limit patents to inanimate inventions.

When marine biologists in Washington state tried to patent a new kind of infertile pacific oyster in 1984, the Patent Office, while rejecting that particular patent, agreed for the first time that higher organisms could be patented. But the office suggested that higher organisms did not include human beings. In 1988, Harvard University received the first patent on a transgenic animal, a mouse with a human-cancer gene.

Biologists had long been interested in exploring the human genome, seeking out genes for heritable conditions like Huntington's disease and cystic fibrosis. Their relatively slow effort to find and sequence human genes moved to the fast track in 1980s with the development of computerized gene machines that could automatically sequence genetic material.

Soon, gene maps seemed to appear almost daily from the various laboratories contributing to the Human Genome Project. The laboratories' progress stimulated a gold rush in the biotech world and triggered several momentous changes in the patenting process. Congress passed new laws permitting publicly funded researchers to claim patent rights. Researchers at the National Institutes of Health or in federally aided university laboratories who mapped a vital gene sequence while supported by public monies could now patent their findings and receive a royalty from any company using the genes to make a diagnostic test or therapy. The cost of those royalty payments would, of course, be passed on to consumers, but defenders of the patenting process argue that without patent protection it is unlikely they would have been developed at all. For example AZT, the anti-HIV drug developed and tested with funds from the National Cancer Institute, was marketed at great expensive by Burroughs Wellcome, the pharmaceutical company that had purchased the patent right from the institute.

What a pharmaceutical company will get in return for its investment in gene patents is not altogether decided, but with the completion of the Human Genome Project, this issue has become urgent. The patents on genes do not include ways the gene can be manipulated for medical use. The patents only claim proprietary rights to genes, or perhaps fragments of genes, which the patentee has identified and isolated for future development. The value of this kind of claim is still being disputed. In the past, the test for the viability of a patent was that the "invention" had to be both non-obvious and useful. The new, and disputed, interpretation of the law gives the patent to those who have located the gene but have not yet identified a specific way to use it. Rebecca Eisenberg, a law professor at the University of Michigan, explains: "The utility requirement is rarely invoked in practice, perhaps because few people go to the trouble and expense of seeking patents on useless inventionsÖIt is the as-yet-undiscovered utility of the sequences, rather than the uses that are disclosed in the patent application, that makes NIH's [publicly supported scientists] claims worth fighting for."

Fortunes have been made by participating scientists, many of whom do not disclose their financial interest in the discoveries they publish. The gold-rush mentality of the race to patent human genes has changed the way biologists work. A 1996 Tufts University study of 789 biomedical articles by Massachusetts academics found that 34 percent of the authors had a financial stake in the research, although they did not reveal that fact in their articles. The potential bonanza has skewed the scientific process by delaying publication, limiting the amount of data shared, and suppressing the publication of negative data.

Those opposed to the patenting of human genes include religious spokesmen like the president of the Christian Life Commission of the Southern Baptist Convention, who told The New York Times that "the patenting of human genetic material attempts to wrest ownership from God and commodifies human biological materials and, potentially, human beings themselves." Among the strange bedfellows on the same side of the argument are lawyers who offer evidence that too many of these patents have deterred innovation in biomedicine. In 1998, a pair of patent lawyers stated in Science magazine that "A proliferation of intellectual property rights upstream may be stifling lifesaving innovations further downstream in the course of research and product development." In other words, because there are just too many interests to pay off, researchers are stymied before they begin.

In January 2000, President Bill Clinton and British Prime Minister Tony Blair applauded the commitment by government scientists "to release raw fundamental information about the human DNA sequence and its variants rapidly into the public domain." Princeton biologist Lee Silver challenged their statement, arguing that there is discord between American biotech companies that are mining the genome and publicly funded scientists in both countries, and it is not about ethics, but about profits and control. He believes that the companies that find the raw data are entitled to sell it, and traces the emotional reaction against these companies to the fact that the information they are selling is not about inanimate objects like computers or automobiles, but about human genetic information. Silver and the people who agree with him believe that the profits potentially available to genetic-engineering companies could well stimulate the production of new medical products that will enhance and lengthen all of our lives.

Europeans have taken a strong stand on the problem. In 1998, the European Parliament approved the patenting of genes but with specific ethical constraints on what can be patented. It prohibits patents on human parts, embryos and the products of human cloning. It also prohibits patents on animals if what they suffer by being modified exceeds the benefits that the modification would yield.

Q & A with Dr. Eric Lander

Q: Do you know the story of John Moore?

Lander: That was the Cell line case.

Q: Right. Do you think that he should have had a certain right to some of the proceeds of the development of his cell line?

Lander: It's a question of contract law. I didn't read the contract.

Q: There was no contract.

Lander: Well, then, it's a question of whether there was an implied contract by law. To me, this is a business question. Somebody supplies his cell line to somebody else for something, and it's a matter of public policy. However confused the case must have been for Moore, you're really not asking me about what Moore should have had-you're really asking what the policy should be in the future.

Q. Moore had tissue samples taken at UCLA, he had hairy-cell leukemia, and they took out his spleen. And then they kept asking him for four years to come back and keep giving different types of samples, like sperm and blood. After a few years, he began to wonder what they were using these for, and that's when he investigated and found out. They never told him.

Lander: Oh, so it's unethical, isn't it?

Q: It certainly does sound that way.

Lander: Well, unethical. But legally, I think the Moore case is probably not the thing you want to reason from. You want to say, "Going forward, should patients be reasonably asked to give up their right or not give up their right?" Of course they should. I suspect that almost everybody, after the Moore case, has been putting in the informed consent. You don't want to do experiments on anybody without them saying OK.

The history of patent law reflects the history of economic development. Plants, pigs and now certain human body parts are fair game, when there is a market. What Silver and others who argue for unrestrained patenting and exploitation of human genes do not acknowledge is that many people find a qualitative difference between their own genome and the genes that make up soybeans, bacteria and cows. If one is a believer, then it's a given that while God undoubtedly made pine trees and bacteria, which humans have been manipulating for years, He created humankind in His own image, and this is not subject to change.

In a sense, it was this belief that his body was God-given, and therefore entirely his own, that made John Moore question the way UCLA had invaded his integrity when he discovered that his doctor had sold rights to his cell line to two companies, one in Boston and one in Switzerland, for a total of $18 million. Moore had never consented to this sale and, indeed, had been ignorant of the matter until the constant demand for more blood and tissue aroused his suspicions. He sued his doctors for malpractice and property theft.

UCLA responded that Moore had waived interest in his body parts, including cells from his diseased spleen, when he signed a general consent form giving the pathology department the right to dispose of the tissue that was removed for testing. In response, Moore's lawyer argued that he should have been informed of his physician's plans. She claimed that since organ-donation laws give patients control over what is to be done with their bodies after they die, it seems logical that patients should have control before they die as well. UCLA, a defendant in the case, argued that even if Moore's tissue was his property, UCLA, as a government institution, was entitled to take the tissue under the doctrine of eminent domain. The doctrine permits the state to appropriate property for the greater good, but it is usually invoked when the state needs to seize real estate for highway construction or other public works. And the owner of real property is usually compensated at a fair market price. By citing the plaintiff's own body tissue as the same kind of property as a

sheep ranch or a suburban backyard, UCLA was advancing a new interpretation of the law. By that logic, could an individual be obliged to forfeit a kidney or a hand if the government decides someone else could use it more profitably?

Moore's case is not the only instance in which an individual's cell line, or DNA, has been taken or donated to a laboratory for research and then patented, with the researchers occasionally reaping huge profits. Families with hereditary diseases often offer their help in finding treatments by creating databases from volunteers in the diseased community. Some have been disheartened to find that their contributions did not prevent the researchers from charging them and their families for the tests developed from their contributions. One family in Massachusetts, which has two children with a rare genetic disease, formed a company and after finding two thousand people with the condition, asked researchers to sign a contract giving the company rights to share in the profits from any gene patent that might arise. Not surprisingly, this act has led to distress in the research world.

The California Supreme Court agreed with UCLA when it decreed in 1990 that while doctors ought to inform patients of their plans before surgery, Moore had no claim on the enormous profits his doctors had spun from selling his tissue. The court's argument was based on economics: giving Moore a claim would destroy the financial incentive for biotech companies to invest in research. But Moore and his supporters remain outraged by the decision. He continues to say that his body was "harvested" against his will. If this case stands as precedent, does this mean that as whole human beings, we are really worth less than the sum of our parts? Of course, this puts researchers in an awkward position. They cannot very well appear outraged at patient demands for a piece of the pie when they themselves have patents on half a dozen pies. In the long run, it is not a good idea for patients to feel cheated, embittered and betrayed, because if they do, it will become difficult, if not impossible, to continue to do research with human volunteers.

Q & A with Dr. Eric Lander

Q: How do you feel about patenting genes in general?

Lander: In general I'm supportive of the patent system. I'm supportive of the idea that society grants inventors a monopoly for a limited period of time as an incentive for creating inventions and making them available to the public. Now the question is, "What constitutes an invention for which society should be giving such a monopoly?" I don't think being in the midst of sequence stuff about which you know nothing constitutes an invention of any significant substance. And therefore, this should not be the subject of patent rights.

Q: This is still now in the patent office, right?

Lander: Well, the patent office is struggling with the following questions: If you have an utterly random sequence about which you know nothing, are you entitled to a patent? And I think they've now said "no" as a guideline. The next question is: Suppose you have a sequence where you haven't done any experiments but you've run it through the computer. And the computer says, using an utterly standard program, it's a kinase, or it's a phosphatase, or something like that. Should you be able to get a patent? I think this answer also is no. But the patent office thinks the answer is yes. The third category is [when] you've done experiments on something and you've biologically proven what it does. In that case, I have no problem granting a patent. And the patent office has no problem. So the point is that the disagreement has now shifted from random sequence, which is no longer patentable, I believe, to random sequence where you have a computer hint. I think the computer hint doesn't qualify as significantly substantial.

Q: All right. We're going to jump to another area.

Lander: We're all over the map on this. This is great!

Q: That's true. Do you think it's going to become normal procedure for people to scan their own embryos, obviously in vitro, to see if there is a problem such as cystic fibrosis or Tay Sachs?

Lander: Scanning embryos in vitro meaning in vitro fertilization?

Q: Yes. Let's say they have six embryos.

Lander: They choose which to re-implant. Allow me to predict that the old way of making babies will still continue to be the popular one.

Q: I think that a lot of people really have a great deal of confidence in their own genes.

Lander: You can also do prenatal diagnostics. So an amniocentesis is going to be able to pick up a lot of these problems.

Q: Oh, sure. Well, then there are the people who want only a boy or only a girl.

Lander: I think people who want only a boy or only a girl so much, that in this country there will be a lot of abortions over that. There will always be frivolous cases. But for the most part, my guess is people will use amniocentesis, and if the kid is going to have some severe problems, they will abort.

Q: That's kind of the negative situation. What if people want to select a child who's going to have say, a gene for musical talent?

Lander: The problem is that if you're going to do it not by in vitro fertilization but by in vivo fertilization, then the only way to do the positive eugenics is by aborting the slightly less smart, slightly less athletically inclined kids. And I don't think... I don't know. Do you think most couples are going to abort because the kid isn't quite as smart as he might be, even if we can predict that?

Q: I don't know.

Lander: I doubt it.

Moore had lost possession of the right to tissue removed from his body; he had not lost the right to his DNA. There were no patents for human DNA until the early 1980s, when recombinant DNA was used to make a form of human insulin. While not cheaper than the beef- and pork-derived insulin diabetics had been using for fifty years, this engineered insulin did not produce allergic reactions in the 10 percent of diabetics who had trouble with animal-derived insulin. Since then, recombinant DNA has been used to produce, patent and sell other kinds of artificial human hormones. But these are not anyone's personal genes.

If a stranger can patent the DNA from another person's tissue, can an entire person be patented as well? When Dolly the cloned sheep burst into the world's consciousness, the cloning of mammals became palpably real. The U.S. Patent Office acted promptly, disavowing the possibility of patenting a whole human being. But patents for the sequences of newly discovered human genes are being sought in increasing numbers. The argument in the Moore case, that patenting human biological material is good for business, is now being used by large pharmaceutical companies. They apply for patents by the thousands, based on their sequencing of the human genome, even though they can only give an educated guess as to the function of the genes they are patenting.

Meanwhile, the question remains: who should own access to the information that the completion of the Human Genome project will make available?

In February 2000, as the map of the human genome reached completion, the Presidents of the Royal Society of London and the National Academy of Science in the United States issued a joint statement. Noting the rush of private companies to file patents on human genes by virtue of identifying fragments using high-powered sequencing machines, these spokesmen for science said that such efforts did not serve society well. They stressed that "the human genome itself must be freely available to all mankind."

American patent law and the laws of the European Community differ in several ways, but there is an important area of mutual concern. American patent law is narrowly limited to economic considerations. But the Patent Office does adhere to the Thirteenth Amendment to the Constitution, which, in abolishing slavery, forbade ownership of the body of any human being. The European Parliament held in 1998 that biotechnology patents must safeguard the dignity and integrity of the person and prohibits patents on human parts,

human embryos and the products of human cloning. The benefit of this new avenue of human knowledge promises many advantages, but to how many people, and at what cost, is still undetermined.

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Picturing DNA by Bettyann Holtzmann Kevles & Marilyn Nissenson
Copyright © 2000 Bettyann Holtzmann Kevles & Marilyn Nissenson
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