The question has been debated for years but not addressed directly by the U.S. Supreme Court—until this week. It came up for consideration on 15 April thanks to a coalition of clinicians, researchers, and legal activists who have waged a 4-year legal campaign to invalidate one company's patents on the genes BRCA1 and BRCA2, used in diagnostic tests to estimate cancer risk. The challengers argue that human genes are "products of nature"—not inventions—and so cannot be patented. The defendant, Myriad Genetics of Salt Lake City, argues that its patents are valid because they describe genes not as they occur in nature but as they exist after they have been "isolated" from tissue.
The oral argument in the case—Association for Molecular Pathology v. Myriad Genetics Inc.—took the court deep into the territory of molecular biologists. For more than an hour, the justices quizzed the competing sides about exons, introns, and cDNAs, proposing several different metaphors in an effort to squeeze the complex biology into a manageable legal mold. At the end, it was clear that many of the justices did not seem to like the idea of patenting human genes. But they struggled to find a way to distinguish between what might be called artificial genes (patentable) and "natural" genes (not patentable). The decision, expected later this year and from which there is no appeal, could have an impact on hundreds of companies and thousands of researchers.
The first justices to attack the question with a metaphor were Samuel Alito and Ruth Bader Ginsburg. They compared Myriad's patented genes to a molecule taken from an imaginary tree deep in the Amazon. Alito proposed that the leaves of this tree contained a molecule with "tremendous medicinal purposes. … Let's say it treats breast cancer." Questioning the lead attorney for the challengers, Christopher Hansen of the American Civil Liberties Union, Alito wanted to know whether a drug made from these leaves would be considered a product of nature and for that reason unpatentable. Hansen replied: "If we simply pick the leaf off the tree and swallow it, … I think it is not patentable." Hansen suggested, however, that an inventor might instead get patents on a process for extracting a molecule from the leaves and giving it a new function as medicine.
Alito said that he considered Hansen's response to be an important concession, because, "Isolated DNA has a very different function from the DNA as it exists in nature. And although the chemical composition may not be different, … it certainly is in a different form." Hansen said that he disagreed with this interpretation.
Justice Elena Kagan challenged Hansen to explain what economic incentive would be left, if human gene patents were ruled out, for any company to do "what Myriad did" -- develop a genetic test for cancer risk. This "takes a lot of work and takes a lot of investment," Kagan said. "Why shouldn't we worry that Myriad or companies like it will just say, well, you know, we're not going to do this work anymore?" Hansen responded: "We know that would not have happened in this case. … There were other labs doing BRCA testing and Myriad shut all that testing down." He added that the "whole point" of the argument is that "when you lock up a product of nature, it prevents industry from innovating and making new discoveries."
Justice Antonin Scalia then pounced, charging that Hansen had not answer the question about incentives: "Why would a company incur massive investment if it cannot patent?" Hansen said: "I think scientists look for things for a whole variety of reasons, sometimes because they're curious about the world." Kagan said that she had "hoped" for a different answer—such as that there were other patents that could make the investment worthwhile. Justice Anthony Kennedy noted that he, too, had expected to hear that other kinds of patents—on an industrial process, for example—would provide the incentive. Kennedy said: "I just don't think we can decide the case on the ground, oh, don't worry about investment, it'll come."
Hansen agreed with several justices who suggested that it's not the isolation of the gene, but the use of the gene that's inventive and suitable for patenting. "That's the whole point, isn't it?" asked Justice Sonia Sotomayor. Hansen replied: "That's exactly correct."
The justices then focused on the question of whether isolated DNA—from which sequences that don't code for proteins (introns) are removed—is a human invention or a product of nature. Myriad claims that the isolated DNA of BRCA1 and BRCA2 are its own inventions. (An isolated DNA may also be contained in a "complementary DNA," or cDNA, with an identical sequence, a useful format for laboratory work.) Kennedy said that when he first looked at the case, "I thought that maybe the cDNA was kind of an economy-class gene" but then realized that it wasn't; he seemed confused. Sotomayor suggested that the whole gene without the introns "is just not found in nature." Hansen argued that while cDNAs are a modified form of DNA, the process used by Myriad to create them involves "letting nature manipulate" the sequence, "not the scientist manipulating" it. Scalia confessed, "You've really lost me when you say that it's nature that does the alteration rather than the scientist."
Midway through the proceedings, the spokesperson for the Obama administration, Solicitor General Donald Verrilli, rose to present the government's view. He said that isolated DNA should not be patentable "because it is simply native DNA extracted from the body." In contrast, he added, cDNA should be patentable: "cDNA is an artificial creation in the laboratory that doesn't correspond to anything in your body," Verrilli argued. The problem in his view appears to be in the wording of Myriad's patent claim.
Soon, the court sought aid in another metaphor—baking cookies. When Myriad's attorney, Gregory Castanias, rose to speak, Sotomayor said, "I can bake a chocolate chip cookie using natural ingredients … and if I combust those in some new way I can get a patent on that. But I can't imagine getting a patent simply on the basic items of salt, flour, and eggs simply because I've created a new use or product from those ingredients." Castanias argued that the combination of materials in the Myriad invention was original. But he ran into a series of objections from Sotomayor based on the cookie recipe. Stymied, he said: "That's the problem with using the really simplistic analogies, with all due respect."
Castanias, seemingly in retreat, then decided to resort to a simple metaphor himself. "A baseball bat doesn't exist until it's isolated from a tree," he said. "But that's still a product of human invention, to decide where to begin the bat and where to end the bat." Justice Stephen Breyer challenged him, noting that briefs filed by scientists described how BRCA genes are isolated by a natural process in the body that clips away introns, unlike the making of a baseball bat. He demanded to know whether this view of the science was correct. Castanias disagreed.
Chief Justice John Roberts also weighed in on the baseball bat, saying that it is "quite different" from an isolated gene. As Roberts read the scientific briefs, he said, "you don't have to invent the particular segment" of DNA that Myriad patented. "You just have to cut it off." Castanias disagreed, describing some of the research that went into creating a cDNA version of the BRCA genes in the lab. Roberts remained skeptical: "I still don't understand … in what sense it's different than just snipping along the line."
Before adjourning, the justices explored the possibility of a compromise decision. Sotomayor, for example, asked Hansen: "Is there some value to us striking down isolated DNA and upholding the cDNA?" Hansen said that although this was not exactly what his side was seeking, it would help. He argued that it would prevent companies like Myriad from getting patents that can be used to block research by others "on a part of the human body."
The court will deliberate on all this and is expected to render a decision by 30 June.