Can genes be patented? This spring, the Supreme Court will hear a case that may well decide the question, and the consequences for American biomedicine could be huge.1 Over three years ago, in May 2009, the American Civil Liberties Union (ACLU) and the Public Patent Foundation (PPF) filed a lawsuit in the Federal District Court for the Southern District of New York seeking to overturn the patents on DNA isolated from two human genes.2 Called BRCA1 and BRCA2, the genes significantly increase a woman’s risk of breast and ovarian cancer. The main defendant was the Myriad Genetics Corporation, a biotechnology firm in Utah that controls the patents—and is legally entitled for the life of the patent (now twenty years) to exclude all others from using these genes in breast cancer research, diagnostics, and treatment. Other defendants were the University of Utah Research Foundation, which had come to own the patents, and the United States Patent and Trademark Office (PTO), which had granted them.
The plaintiffs were not the usual parties in patent suits: competitors concerned with their balance sheets. They included medical geneticists, pathologists, and advocates for women’s health, as well as biomedical researchers, genetic counselors, and several women with breast cancer or at risk for it. They were distressed that Myriad’s patents allowed it to exercise such monopolistic control over a biological substance as essential to research, medicine, and patients as DNA implicated in cancer. They contended that BRCA DNA—and by implication all human DNA—should not be eligible for patents as a matter of law and that Myriad’s enforcement of its patents interfered with the progress of science and the delivery of medical services.
The plaintiffs had the support, expressed in friend-of-the-court briefs, of many parties representing the medical profession, biomedical researchers, and patients, all opponents of allowing anyone monopoly rights on human DNA. The Myriad Genetics Corporation, however, had many allies from the biotechnology industry, patent lawyers, and various genomic companies—all of whom said the grant of such rights was needed for their business. In American law, opponents of a public policy cannot ordinarily pursue their objections in the federal courts, including in patent suits, unless the policy causes an injury that gives them standing to sue.3 The plaintiffs contended that they had suffered harms, offering in evidence how Myriad enforced its BRCA patents—in the clinic and the laboratory—to stop others from using the genes to do research on cancer. On November 2, 2009, over the objections of Myriad and the PTO, Judge Robert W. Sweet, the presiding judge, granted all the plaintiffs standing to sue Myriad, holding that, given the gravity of the issue for health and science, they had every right to call Myriad, the PTO, and gene patents to account.
In a sense, the case had originated in 1990, when a geneticist at Berkeley announced that her laboratory had tracked the location of BRCA1 to somewhere on chromosome number 17.4 A transatlantic race then ensued to find the exact position of the gene, and a major competitor was Mark Skolnick, a respected and enterprising geneticist at the University of Utah and a cofounder of Myriad Genetics. Supported by venture capital and both funds and collaborators from the National Institutes of Health, Skolnick and his colleagues won the race in 1994, finding BRCA1 and isolating it from the rest of the DNA and the tangle of protein that form chromosome 17. In 1995, Myriad’s scientists also identified and isolated BRCA2, which resides on chromosome number 13.5
The DNA in the two BRCA genes, like that in other human genes, is a double helical molecule, each side of which is joined, like the rungs of a ladder, by two complementary chemicals called base pairs—adenine, which always links to thymine, and cytosine, which always links to guanine. The order in which the base pairs occur along the helix—that is, their sequence—comprises the genetic code. Myriad sequenced the two genes and found that each is a version of a normal gene that has been corrupted by changes such as mutations and rearrangements that alter the sequence in the DNA.
In 1994, Myriad, omitting its collaborators from the NIH, applied for patents on both the isolated DNA that makes up the BRCA1 gene and also on a set of diagnostic tests to detect its presence. In 1995, it did the same for the isolated DNA of BRCA2. In 1997 and 1998, the PTO awarded a total of seven patents on the two isolated genes, various DNA fragments within them, and the diagnostic tests to find them.
The US patent system rests on ideas of political and moral economy current in the era of the American Revolution.6 Along with many colonists, Thomas Jefferson long opposed the monopolies inherent in copyrights and patents, but James Madison persuaded him of their value as incentives to authors and inventors, so long as they were only temporary. Thus Article I, Section 8, Clause 8 of the US Constitution, now often called the “Progress Clause,” authorizes Congress “to promote the Progress of Science and useful Arts, by securing for limited Times to Authors and Inventors the exclusive Right to their respective Writings and Discoveries.” In the patent law of 1793, Congress defined eligibility partly in language that Jefferson provided and that remains at the heart of the statutory code (USC Title 35, Section 101) for the subject. According to the statute, patents could be obtained for “any new and useful art”—the word was replaced in 1952 by “process”—“machine, manufacture, or composition of matter [Jefferson’s phrase], or any new and useful improvement…[thereof].”
Jefferson’s language emphasized the requirement of newness, or novelty, and bespoke the necessity of an inventive step. It also implied that products made by nature, which were held to belong to everyone, were not to be removed from common possession. Thus products of nature such as the naturally occurring elements in the periodic table or the creatures of the earth, being neither new in the world nor made by man, were taken to be ineligible for patents. So, tacitly, were laws of nature, natural manifestations, abstract ideas, and thought.
During the following two centuries, these exclusions from patent eligibility came to be explicitly articulated in a body of federal court decisions holding, for example, that natural elements taken from the earth, even if they had to be chemically isolated from other substances, did not constitute patentable subject matter under Section 101, if only because they were not new.
Nevertheless, in the 1980s the PTO began issuing patents on DNA—not DNA in the body, which was indisputably a product of nature—but on three different versions of DNA isolated from the body. Scientists call one of them “complementary DNA,” or cDNA. In a gene, only some of the base pairs in the sequence along the double helix are “expressed”—that is, they prompt the production of some of the amino acids that the cells then assemble into the body’s proteins. The rest of a gene’s base pairs—which make a large majority of them—are not expressed. cDNA is constructed of only the expressed base pairs organized in the same order as they occur in the native gene, omitting the rest. The other two patented versions of DNA comprised isolated fragments or the whole of the raw DNA in a gene. Myriad’s patents extended to all three types of DNA extracted from the two BRCA genes.
The PTO did not provide a full legal justification for granting such patents until January 2001, when it issued “Utility Examination Guidelines” to clarify the criteria that patent claims on DNA would have to satisfy.7 There it justified patents on isolated DNA by drawing primarily on two long-standing judicial doctrines. The first was that products of nature can become eligible for patents if—to quote from the Supreme Court’s ruling in 1980 in Diamond v. Chakrabarty, a landmark case that allowed patents on a genetically modified bacterium—they had “markedly different characteristics from any found in nature.”8 The second originated with Judge Learned Hand in Parke-Davis v. H.K. Mulford, a case decided in 1911 that concerned Parke-Davis’s patent on adrenalin, which a chemist had isolated from the body, purified, and produced in concentrated form. In what lawyers term “dicta”—assertions by judges that are neither essential to decisions nor legally binding but that are potentially influential—Hand declared that, having been extracted, purified, and thus made useful, the adrenalin “became for every practical purpose a new thing commercially and therapeutically.” He added, “That was a good ground for a patent.”9
To summarize the reasoning of the PTO: cDNA, which is made by scientists outside the body, differs markedly from the DNA inside it. So does the raw DNA extracted from the body, whether the whole of a gene or a fragment of it: when it is chemically disentangled from its chromosomal housing it becomes a new composition of matter. The PTO holds all three versions eligible for patents in accord with Chakrabarty, and patentable in keeping with Hand’s dicta because, in isolation, they are new and useful commercially, diagnostically, and possibly therapeutically.
The plaintiffs contended before Judge Sweet that the patents should never have been granted on either the DNA or the tests because, according to the patent law (Section 101) and judicial rulings, neither was “patent-eligible.” Myriad’s diagnostic methods boiled down to comparing the base-pair sequence in the DNA taken from a patient with the sequence in a version of the gene that will dispose the person to cancer. The plaintiffs pointed out that the comparison did not require any particular process but only the act of looking at one sequence and seeing whether or not it matched the other. The “claim” (the term refers to the elements in what a patent covers) was therefore to abstract ideas and thought and as such was excluded from patentability.
Whether BRCA DNA could be patented turned primarily on whether any of its three extracted forms in fact were a new composition of matter. The plaintiffs contended that none of them was. The extracted DNA might be useful enough in isolation to meet the criterion of patentability laid down by Learned Hand. But the plaintiffs argued that Hand’s dicta was of dubious merit at the time and that it had in any event been overridden by a series of Supreme Court decisions culminating in the criterion advanced in the Chakrabarty case that, to be patentable, the material in question had to be “markedly different.”
In the plaintiffs’ argument, both the raw DNA and the cDNA forms embodied the same sequences of cancer- disposing base pairs—the same defining genetic information—as did the native genes. The extracted raw DNA differed in material composition only trivially from the native version. It was no more transformed from the natural DNA than was gold upon removal from a stream bed or the yolk after separation from the rest of the egg.
1 Association for Molecular Pathology v. Myriad Genetics Inc. ↩
2 The decision of the District Court and the opinions of the Appeals Court are freely available at dockets.justia.com and www.aclu.org, respectively. All case documents, including briefs and decisions, are available through WestlawNext at store.westlaw.com/westlawnext. ↩
4 The normal human genome contains the sex chromosomes X and Y plus twenty-two pairs of other chromosomes that are numbered in order of their relative size. ↩
5 See Kevin Davies and Michael White, Breakthrough: The Race to Find the Breast Cancer Gene (Wiley, 1996); Shobita Parthasarathy, Building Genetic Medicine: Breast Cancer, Technology, and the Comparative Politics of Health Care ( MIT Press, 2007). ↩
6 See Lewis Hyde, Common as Air: Revolution, Art, and Ownership (Farrar, Straus and Giroux, 2010). ↩
7 US Patent and Trademark Offfice, “Utility Examination Guidelines,” Federal Register, Vol. 66, No. 4 (January 5, 2001), pp. 1092–1099. ↩
8 Diamond v. Chakrabarty, 447 US 303, 100 S. Ct. 2204 (1980), available at supreme.justia.com/cases/federal/us/447/303/case.html. ↩
9 Parke-Davis & Co. v. H.K. Mulford Co., 189 F., 95 (April 28, 1911). See Jon M. Harkness, “Dicta on Adrenalin(e): Myriad Problems with Learned Hand’s Product-of-Nature,” Journal of the Patent and Trademark Office Society, Vol. 93, No. 4 (2011), pp. 363–399. ↩
Association for Molecular Pathology v. Myriad Genetics Inc. ↩
The decision of the District Court and the opinions of the Appeals Court are freely available at dockets.justia.com and www.aclu.org, respectively. All case documents, including briefs and decisions, are available through WestlawNext at store.westlaw.com/westlawnext. ↩
The normal human genome contains the sex chromosomes X and Y plus twenty-two pairs of other chromosomes that are numbered in order of their relative size. ↩
See Kevin Davies and Michael White, Breakthrough: The Race to Find the Breast Cancer Gene (Wiley, 1996); Shobita Parthasarathy, Building Genetic Medicine: Breast Cancer, Technology, and the Comparative Politics of Health Care ( MIT Press, 2007). ↩
See Lewis Hyde, Common as Air: Revolution, Art, and Ownership (Farrar, Straus and Giroux, 2010). ↩
US Patent and Trademark Offfice, “Utility Examination Guidelines,” Federal Register, Vol. 66, No. 4 (January 5, 2001), pp. 1092–1099. ↩
Diamond v. Chakrabarty, 447 US 303, 100 S. Ct. 2204 (1980), available at supreme.justia.com/cases/federal/us/447/303/case.html. ↩
Parke-Davis & Co. v. H.K. Mulford Co., 189 F., 95 (April 28, 1911). See Jon M. Harkness, “Dicta on Adrenalin(e): Myriad Problems with Learned Hand’s Product-of-Nature,” Journal of the Patent and Trademark Office Society, Vol. 93, No. 4 (2011), pp. 363–399. ↩