What happens when a rag-tag band of lawyers and civil liberty activists set out on a Quixotic mission to take on the U.S. government and the biotechnology industry to upend decades of established biotechnology patent law that had fueled unprecedented scientific progress in the fight against cancer? Find out in, The Genome Defense: Inside the Epic Legal Battle to Determine Who Owns Your DNA.
The passage above may seem like a marketing blurb for a new Grisham-esque legal thriller, but in this case the book and the story it tells are real, which in many ways makes for an even more compelling read about the behind-the scenes strategies, machinations, and inter-governmental discord that culminated in the landmark U.S. Supreme Court decision in Association for Molecular Pathology v. Myriad Genetics.
I recently interviewed the author, Professor Jorge Contreras, of the University of Utah School of Law, about his book, the legal and scientific controversies that underpinned this landmark Supreme Court case, and the legal twists and turns that ensued. The following excerpts from that interview have been edited for length and clarity.
Q: Thanks for joining me today Jorge. Your book tells a fascinating and compelling story from a human interest perspective, a scientific perspective, and a legal perspective. It’s a fantastic read, and is written in a way that is easily accessible by almost anyone, not just lawyers and scientists. Congratulations on all the well-deserved accolades you’ve been receiving. Can you start by giving us the brief summary of this story, or the multiple stories that are involved here?
A: Sure, thanks Jim, happy to be here. The story revolves around a set of patents on genes called BRCA, which are highly indicative of elevated risk of breast and ovarian cancer, that were patented by a company that spun out of the University of Utah. And they essentially locked up the use of these genes for diagnostic purposes and charged a fair amount of money to run tests, to tell women whether or not they had an elevated risk of breast or ovarian cancer.
Q: The ability to patent those genes was fairly standard patent practice at the time, right? So set the scene how the situation caught the ACLU’s attention, and how the story began?
A: In the pivotal moment that kicked everything off, a young woman named Tania Simoncelli who had been hired as ACLU’s first ever science director, was meeting with a very senior ACLU lawyer named Chris Hanson, to discuss science-based legal issues that might be of interest to the ACLU, and she offhandedly says, oh, and you know, there’s gene patents, of course. And, he doesn’t believe her. Because she’s not a lawyer, his initial inclination is to think she’s misunderstanding some aspect of the law, which she actually wasn’t. When she sent him articles to show him that this actually had been happening for a couple of decades, he was floored, and realized, yeah, you know, this is something that we ought to pay attention to, something that we ought to do something about. And, this is where he blurts out in her office, “who can we sue?” That’s what gets it all started.
Q: The personal stories you tell of women affected by breast and ovarian cancer are really powerful. How did those women’s experiences play into the litigation itself?
A: One of the reasons the case is so interesting is because it really is about individuals, about people who feel very strongly about and were affected in a very deep and human way by the patents on the BRCA genes. If you have hereditary breast cancer running in your family, and you can’t afford the one test that’s out there to tell you whether you have this mutation, even after you are diagnosed with breast cancer, unless you have this test, you don’t know whether you should also have your ovaries removed because you’ve also got a big chance of getting ovarian cancer. And those are literally life and death decisions that were affected by the abstract legal principles in the case. And I thought it was very interesting that many of the courts, especially the district court, spent pages and pages talking about healthcare, access to medicine and so forth when really those issues aren’t before the courts.
Q: So give me a little bit more of the technical detail; what exactly was patented or was being patented that the ACLU started targeting?
A: There were a number patent claims that were challenged. There were some method claims and various process claims, but, but the ones that were most important and the ones that the Supreme Court eventually ruled on are composition of matter claims. But there is a long standing century and a half old rule in Supreme court jurisprudence under the patent act that you can’t patent products of nature, things that are just find out there in the natural world, even if you’re the first one to discover them. Say I’m an explorer. I go out into the jungle. I find a new mushroom that no one has ever seen before. I rub it on my burn and realize, “Hey, you know, this will cure me. That’s great.” I can possibly patent the use of this mushroom as an anti-burn agent, but I can’t patent the mushroom itself as a composition of matter because I just found it. And that product of nature rule has been around, as I said, for a long time.
Q: So the human genome has been around as long as humans, so how was it even possible to obtain patents on human genes?
A: Various cases over the years have tried to establish where along the spectrum of naturally occurring substance versus something that humans make can be patented because, you know, at root, everything on earth is made from some natural element. At some point if humans change it enough it is “markedly different” from what occurs in nature so that you can get a patent. So where do human genes fall on that spectrum? Is it naturally occurring or is it made by people? Is it clearly inside of your cell or inside of every person’s cells? There are 23 human chromosomes, each of which has several thousand genes which form our genome and are inside of our cells. Those are obviously produced by natural processes. But what if I extract an individual gene out of the chromosome so that it’s free-standing and then I reproduce it, amplify it and make millions of copies of that gene that’s isolated and purified in that way? That doesn’t exist in the human body, right? The chromosome is just this undifferentiated string of tens or hundreds of millions of bases. We don’t know where one gene begins and where it ends. If in the laboratory someone figured it out and effectively snipped out a single gene, now it is something that does not occur in nature. And that argument was made to the patent office starting in the late 1980s to convince them that these isolated and purified genes were in fact new compositions of matter, because they do not exist in the body in that form. So the patent office began to allow patents on them and those genes in their isolated form did get that very broad type of protection like you would with a new material, like rayon or a metallic alloy.
Q: So if it was truly just our genes that were patented, wouldn’t that make each and every one of us patent infringers when we have children, for example?
A: Or, just living our day to day lives, right. Our cells produce like billions of our genes insides of our bodies constantly, to replace dead cells and so forth. And so what ultimately was litigated were patents on a protein sequence that could be encoded by the BRCA genes. Myriad also patented the DNA sequence of the BRCA genes, as well as the number of mutations, and they even patented, at the most aggressive level, any sequence of 15 bases that occur in a row, anywhere in the body. So does that mean that every time we reproduce skin cells, we’re infringing the patent? Well, in theory that’s possible because patents give the patent owner the exclusive right to make use or sell the patented article, but the thing that we’re not doing in our bodies is we’re not reproducing the isolated and purified form of the gene. So I think you’d probably get off the hook and you probably would not infringe.
Q: I would hire you out of academia to defend me, Jorge! So to summarize the path this case took, it starts in federal district court, where the ACLU wins by getting the patents invalidated. Myriad then appeals to the Court of Appeals for the Federal Circuit, which overturns the district court and reinstates the patents. The ACLU seeks review by the Supreme Court, which vacates the Federal Circuit decision and remands to that court for further consideration. But the Federal Circuit again upholds the patents and issues a new opinion that is virtually the same as its original opinion. ACLU again goes to the Supreme Court, which finally invalidated some patents but upheld others.
A: Right. So, you know, in addition to the fascinating scientific and ethical issues that this case brings up, this case also could be used in a law school civil procedure class, as it’s fascinating procedurally, and there are a lot of legal strategy elements to it.
Q: So what were the core positions that each court arrived at along the course of this legal Odyssey?
A: At trial, Judge Sweet in the Southern District of New York basically had the intuition that the gene is inside the body and that outside of the body it’s still the same gene. Like why are we allowing this to be patented?
At the Federal Circuit, the most senior judge on the panel, Judge Lourie, has a PhD. in chemistry and he viewed this question in terms of chemistry, not genetics. To him, if you look at the isolated gene, the isolated gene is just a string of molecules that is extracted from a larger string of molecules from the chromosome. You break it at its two ends and when you do that, you break covalent bonds, and in chemistry, breaking covalent bonds is actually quite important. You create different molecules; We go from hydrogen gas and oxygen to water, right? So it’s important from a chemistry standpoint, breaking those covalent bonds at the beginning and the end of the gene create a different molecule.
At the final merits decision, the Supreme Court basically adopts an argument made by the Solicitor General of the United States that creates a compromise, and says, okay, some of the challenged patent claims are invalid. Claims on the entire DNA sequence as it exists in the human genome, whether it’s isolated or not, it’s still the same gene. So we’re not going to allow patents on it, but we will allow patents on something else, specifically complementary DNA or “CDNA.” To explain, the BRCA gene is about 80,000 bases long, but only about 6,000 of those bases actually code the BRCA protein, and they’re scattered along the 80,000 bases in the gene. We call those introns. We don’t necessarily know if they have biological functions. The 6,000 bases that code the protein, we call exons. If you take out just the exons, and line them up and create something called a complementary cDNA molecule, that’s new, doesn’t exist in the body, and you have something that’s patentable. So the Supreme Court says genomic DNA, the sequence of the 80,000 in the body, is not patentable, but the 6,000, the exons in a CD construct, that is patentable.
Q: The Government was not officially a party in this case after the district court decision, but it still played an active, significant, and controversial role in the outcome. Tell us about that?
A: A decent chunk of the book talks about the inner workings of how the Obama administration intervened in this case in a really unique way. Clearly the patent office liked its patents and was on Myriad’s side. They felt they were following the law and were right and justified in issuing these patents. And they had issued hundreds of them over the years. But that view was not uniformly held within the administration. The National Institutes of Health, for example, or Francis Collins, its director, in particular, had for many years felt that patents on human genes were not necessary to advance science and that they weren’t appropriate.
Q: In the end, the government lawyers essentially took a position against the government agency whose actions were being challenged, right?
A: Right. The Department of Justice is the lawyer for federal agencies in litigation and the Solicitor General of the United States oversees all federal agency litigation. Here, there was significant opposition to the Patent Office’s position from both NIH and other agencies, and from within the White House, including the President’s Office of Science and Technology Policy, the National Economic Council, and other functions and groups within the White House. So the Solicitor General had to get input from all of these different constituencies within the government as to what the government position ought to be, and eventually came out with the GDNA vs CDNA compromise position that was ultimately adopted by the Supreme Court, giving the patent office a little bit of something, but also invalidating most of the challenged patents. Interestingly, the Patent Office lawyers refused to sign the government’s brief and the director of the Patent Office pretty clearly showed his displeasure with what had happened. At the end of the day, the Department of Justice is the agency’s lawyer. And as a lawyer, to take a position that is adverse to that of your client and in favor of the other side in litigation is pretty unprecedented. I don’t know if there’s a way to justify this other than to say that this is how our political system works, for better or worse.
Q: Can you give us a sense of the state of gene patent law, and more broadly speaking, precision medicine patent law, going forward after this case?
A: So as far as access to information about what’s in our DNA, that’s been opened up substantially now that we’re nine years out from the decision, and by today in 2022, most of the patents on isolated human genes, would’ve expired anyway. And, the human genome project, which by 2003 released the basic human genome, that acts as “prior art” blocking anybody trying to patent native state DNA sequences.
That being said, there are still important ramifications of this case, especially as we start to look toward the future of gene editing. So in the lab today with CRISPR and other technologies, we can change the DNA structure within our genomes, but with the Myriad case and other recent court cases you can’t patent a naturally occurring sequence. It’s certainly possible that in the lab, researchers could design genetic variants such as a super COVID resistance gene. If that happens, and the gene doesn’t occur in nature, it could still be patentable. But not if it is identical to sequences that we find in nature. This is problematic to some people, who say that if we create artificially some wonderful genetic sequence, we should be able to patent it. And there have been legislative movements to overturn all the Supreme Court’s jurisprudence on patent eligibility, including another case that in my view has had the biggest impact on precision medicine, a case called Mayo that dealt with method of use patents and came a year before the Myriad decision.
Q: Well maybe that gives us a topic for our next discussion, Jorge! Is there anything else you’d like to mention about the book, or the process you took in writing it?
A: The only thing that I would say in, in closing is that writing this book was a big project for me and it took a lot of time, but I literally am just a messenger here. These are other people’s stories and I really have to thank them for letting me tell their stories, some of which were very personal and meaningful stories. So, you know, I, without them we wouldn’t be having this discussion.
James N. Czaban is an FDA Regulatory and Compliance Partner at Loeb & Loeb LLP in Washington, DC. Recognized as a Global Elite Thought Leader and a “key player in the life sciences sector” by Who’s Who Legal-Life Sciences, Jim has nearly 30 years’ experience in government regulation of pharmaceuticals, biotechnology, and medical devices. His practice maintains a strategic focus on therapeutic product development and approval, compliance and enforcement proceedings, public offerings, M&A, and other transactions for entities regulated by the FDA, FTC, DEA, DOJ, and other federal and state agencies.