Science in the Triangle

Dan Vorhaus

Dan Vorhaus is a lawyer with Robinson Bradshaw and Hinson in Charlotte, N.C. where a portion of his practice comprises the growing field of personal genomics law. Given the interest in personal genomics in the Triangle, I thought I’d create an expanded version of the short question-and-answer interview I did with him for an up-coming issue of the Sci-Tech section in the Charlotte Observer and the Raleigh News and Observer (be on the lookout for that next Monday in print and online), and post it here. Vorhaus also authors the Genomics Law Report, a blog about the legal side of personal genomics, and he will be giving testimony to the Food and Drug Administration in the near future as the agency attempts to sort out particulars of how it plans to regulate genomic diagnostic testing.

How did you become interested in concentrating on personal genomics as an area of the law?
I have a master’s in bioethics; I did that degree before I went to law school. So as I started thinking about the areas of law and policy that were most interesting to me, that was clearly one of them. And it seemed like there was a tremendous opportunity for a field that is developing and emerging and creating all sorts of new and exciting legal issues. And it’s something that I’ve always had an interest in the underlying science and technology, and I was fortunate enough in law school to start working with some real pioneers in the field, specifically George Church in the personal genome field. Everything sort of built from there. Now, it’s how I make my living, it’s my career. And I love it. It’s something new and fascinating every single day and I can’t get enough of it.

It sounds like the bioethics degree had a big influence on you.
It did, although I already had this interest before, that was what caused me to pursue the bioethics degree. And I knew I was going to law school. I kind of applied those two things simultaneously. So, they have kind of worked together simultaneously. And I decided kind of early on that I was more interested in pursuing the law than some of the pure policy or philosophy or ethical issues behind a lot of these technologies. I think there is a real need… One thing you find with the law is that new areas tend to lag in new areas of technology and new areas of social development. And that is certainly true in the areas of personal genomics, personalized medicine, there is a long way for the law to go to catch up to where science and technology already are. And they continue to press on ahead. And the law continues to play catch up. So it seems that there is a real opportunity to be involved in helping to lay the legal framework for what I think will be important and meaningful technologies and services in people lives for years and decades to come.

That formalizes what I had suspected, with some of the things I’ve read about the Myriad ruling and the FDA announcing its intent to regulate direct-to-consumer genomic testing, it does seem that these formal regulations and policies are lagging behind the business practices.
That’s right. Both the examples you gave, the Myriad litigation — and really, the state of biotechnology patents more broadly – and the FDA and Congress’s involvement in genetic testing, especially consumer genetic testing, both of those are areas where there is a lot of uncertainty right now whether the law today is doing as good a job as it could be as far as protecting individuals and enabling commerce, and really striking the right balance between allowing the science and the technology to press forward while making sure that we have the right protections in place for people using these technologies. That is always going to be a tension in this area, I don’t ever foresee that dissipating; but that does not mean that we should work any less hard to get that balance as close as we can as quickly as we can.

You’ve posted about the Myriad gene patent litigation, in which a federal judge invalidated patents that Myriad held for human genes, BRCA-1 and BRCA-2, which are used to test for the likelihood of developing breast cancer. What was the most unusual thing about this ruling, because it seems to have caused quite a splash?
You’re right, it does cause a splash, but I would say the splash that it caused is probably greater than its legal significance, at least for right now. It’s important to keep in mind that this was a district court ruling, so without getting to much into the weeds, there is a long way to go with this litigation before it gets to the point where it will really impact the commercial landscape, before it really impacts what people feel comfortable doing in laboratories – whether it is research laboratories or commercial laboratories – it needs to .. It’s already been appealed to the federal circuit, which is the federal appeals court that hears patent cases. And it’s quite possible that from there it will go to the Supreme Court, and we’re talking at least another year. Perhaps two. Maybe even three more years before we get a final resolution in this case. The reason I think it garnered so much attention is because it really struck a nerve – and going back to this idea of law not always keeping up with where science is – it really struck a nerve when people heard that there were companies out there that held patents on human genes. And we are talking about isolated human genes, genes outside the body, no one owns you, but it is the case that some companies have patents on genes, and they have the ability if they want – and Myriad has done this because of the way patents work – they grant the patent holders monopoly rights, they have the ability to keep other people from doing tests to analyze those genes, to sequence those genes, to ask what does this mean, in the case of BRCA, for the susceptibility of a woman’s or a man’s, risk of getting breast cancer. And I think that struck a nerve with a lot of people.

It’s not the only sort of development with this area… [Other reports] have gone to the Secretary of Health and Human Services that looked at these issues and looked at the gene patent landscape and said this is a problem, this is impeding our ability to do the type of diagnostic or clinical work that we need to do, to advance the state of science and technology. There is another supreme court case that will likely come out on Monday, that also may be significant as far as the extent of biotech patents, in terms of how far they can reach. And it all goes back to this question of trying to strike the right balance. In the case of patents, we’re trying to strike the right balance of information disclosure and getting these technologies out there and allowing people to benefit from them, and preserving the commercial incentive to investments. That is how our legal system works, we build up this body of law over years and decades – in this case, patenting of human genes which reaches back to a 1980s Supreme Court case, probably even further, and it built up incrementally. And science does not work that way, it moves much faster. It was only 10 years ago that we published the first draft of the human genome sequence, and now, 10 years later, we are routinely sequencing whole genomes, let alone individual genes. And so, again, it’s that pace of technological innovation and scientific advancement that is much faster than we have the ability to move in the legal realm. So that causes a conflict in cases like Myriad where now everyone has to sit down and ask, do we have the right balance here? Should genes be patentable? Is this where we want to be? I think there is plenty of debate about that. It may be something that litigation solves, or maybe Congress steps in, or maybe there are people out there working on industry private solutions to work things out without having to wait on the courts to solve it.

One thing that confused me about this, is the idea of patenting human genes. In the case of Myriad, one of the things I was wondering was why do they have to patent a human gene? Why can’t they just patent their test? That seems like a more level playing field.
You’re right, that would be a more level playing field, and I think the simple answer is that if you are going to invest a lot of money into developing a test and researching an association between a gene a certain disease, and then figuring out the corresponding test, you may not want a level playing field. You may want to do all the testing, and that is what Myriad does. I should mention, there are other companies out there that have patents on human genes, and they have a patent that allows them to have exclusive rights to practice that patent. So, to conduct a test, or even to examine the gene, if the patent is one the gene itself; but they license out that patent or set of patents. Myriad, for example, I think has several dozen patents with almost two hundred claims, so we’re not talking about one or two patents, they have a whole suite of patents, that protects this business they’ve built around diagnostic testing for breast cancer, but there are other companies out there that have similar patents that do license them out to other people, and they say, here you can use this technology, you can use this gene that we’ve patented, there is going to be some sort of commercial terms with that, you’ll pay us some sort of royalty, or some kind of fee based on tests that you do, but you can get in the game too and essentially provide the same sort of service that we are providing.

Or, Myriad is a good example. They did not actually patent this themselves, they licensed this from the University of Utah. And so it is interesting because one of the reasons why Myriad was swept up in this litigation is because there are thousands of genes that are patented, Myriad only has patents on a handful, but the reason they became a target in this litigation is partly due t otheir practice of not licensing out their IP, their intellectual property, and not giving people a chance to conduct or to develop competing gene tests. But that is the prerogative of a patent-holder. You have the right to exclude everybody else from practicing your patented invention. You can wave that right, in the form of a license, out to other people, if you want, but you don’t have to. So that is why there is this big question over what should be patentable. The technical discussion centers around section 101 of the Patent Act which defines what is patentable subject matter. And the question is, are genes patentable subject matter, or are they what is considered to be a product of nature?

Is it that things in the natural world can’t be patented?
Well, it doesn’t specifically say that in the Patent Act, but that is the way it has developed in the case law over time. The 1980 case that I referred to earlier … said that what is patentable is anything under the sun made by man. And there is this products of nature doctrine, and it says, well the Supreme Court says, that something that is a product of nature can’t be patented. And then the question is, what is a product of nature? And Myriad argues, in this case, that this is not a product of nature because you are taking genes, which occur naturally in the body, and you are separating them out, you are isolating them, you are doing things to them technically that make them no longer products of nature. And in the technical sense, that is correct because genes do not naturally occur in laboratories. But what Judge Sweet ruled is that what is fundamentally important in these genes, what really makes them significant, is the information that they carry. And that is the same whether you are talking about a BRCA gene in your body, in my body, or in Myriad’s laboratory. The information content is the same, and that is what is significant, so they are products of nature and they can not be patented. Whether that ruling stands up, remains to be seen. There is quite a good chance that it won’t.

That’s an interesting interpretation.
And it’s one that people share. I think it resonates quite strongly with people at a gut level. But again, there are limits to how that can be implemented by law in courts. Congress of course has the ability to change the law. As has happened in many, many cases, if Congress does not like a law they have the ability to go out and change the law.

The Food and Drug Administration is constricting regulations for direct-to-consumer genetic testing services offered by companies that scan a person’s genome and offer analysis for health risks or ancestry. What are the FDA’s specific concerns?
It’s interesting… since the whole Walgreens-Pathways thing blew up about five or six weeks ago now, they went after five or six companies. They’ve taken a step back and said, you know, we think we need to regulate all genetic testing. It’s important to remember that most genetic testing is not what is known as DTC [direct to consumer] or commercial or consumer genetic testing. Most of it occurs in a clinical context, done in clinical laboratories, and that is the vast majority of genetic testing on the market right now. Now, the concerns they raise about taking a risk-based approach to regulation, and specifically they are concerned about the safety and efficacy of these tests. So, making sure that the tests are accurate, making sure that – accurate in the sense that when you test for X, you actually get X – that’s what’s called analytical validity.

And then also what is known as clinical validity, which is making sure that the association or the link reported by the tests so that if you do have X, that means you have an increased risk of getting breast cancer, is actually a valid one. And in an area of science that is so new and so changing, that is something that can be difficult to show. Or it may be controversial. So there is a lot of recorded genetic associations that require confirmation, maybe they need more traditional studies to confirm the results, and some studies that have disproved associations, so that is a concern too.

Then there is a third problem which is what is known as clinical utility which is that even if you measure the association correctly and it does mean what you say it does, so you have X, you’ve actually measured X accurately and it does mean that you have an increased risk of disease Y, then clinical utility asks, Can I do anything with this? Can I take this to my doctor and can he start me on a new medication, or tell me that if I lose 15 pounds, then I can prevent myself from developing condition Y. That’s the clinical utility prong, and there is a lot of disagreement there about whether that is something the FDA should really be concerned with, or if that is something that should be left up to individuals. And there are varying definitions as to what constituted clinical utility. Alzheimers is a good example. There aren’t many drugs on the market right now that can be used to reverse the effects of Alzheimers, or be used as a preventative measure for preventing Alzhiemers.

But there are a lot of lifestyle changes that have some evidence that they might help. And there are lot of people that argue that for me, clinical utility means just knowing. If I want to know, then I should be able to know because then I can engage in family planning. I might decide to take an earlier retirement. I might do other things differently. There is going to be a big public meeting July 19 and 20 in DC where I will be at the FDA to talk about some of these issue and give them feedback as they start writing regulations. And of course, in addition to the FDA, the House of Representatives, Congressman Waxman’s committee, have gotten involved with writing letters and they appear to be gearing up to hold hearings and maybe do something in this area. I heard recently that Senator Hatch has a bill out that would address genetic tests and specifically create a new division within the FDA to address those. There is another bill on the House side, I think,… that would also wade into this area. So there are a number of different pathways on the table right now for how the regulation of genetic tests may develop. It’s a bit of a scramble right now.

Even though you said that direct-to consumer genomic tests are a small slice of the genomic testing pie, what legal concerns do consumers need to be aware of when using personal genomic testing?
Well, it is a small… let me back up by saying that consumer genetic testing is a small slice of the overall genetic testing pie, but diagnostics — and that includes an increasingly large percentage of what we think about when we talk about personalized health care – and there are some people that believe that within the not-to-distant future, it’s going to be diagnostics riving therapeutics, so drugs and pharmaceuticals, and not the other way around. Right now, you’ve got these big diagnostic companies, and you’ve got big pharmaceutical companies, but that may flip. We are really looking at, I think, a shift coming down the road. There are some questions associated with consumer tests. A lot of the issues are similar to just the issues associated with learning about genetic information in any context. You want to know that you understand… what information you will find out, if it will be useful to you.

There have always been concerns about somebody else getting ahold of that information and somebody else using that against you. That’s one reason we passed the information non-discrimination act in 2008, to prevent employers and health insurers from using that information. But, that doesn’t mean that other people can not potentially get access to that information and use it against you. That could be your friends, or your co-workers or your family workers.

One thing you hear happening is non-paternity as a result of genetic testing, so you go get tested and your father gets tested and you find out, wait a second, our DNA doesn’t match. I think it’s something like a 10 percent non-paternity rate in this country, which is pretty high compared to what the known rate of non-paternity is. So there is a lot of those cases out there that I think are probably unknown to the family. So you can find out information that might be upsetting to you, or that might be surprising to you. You can also find out information that might be very useful, or interesting to you. That is a balance that everybody needs to sort of strike for themselves and think carefully about. So there are privacy concerns, discrimination concerns. The accuracy of the information… you have to be prepared that it’s not always accurate. There is clinical genetic testing and consumer genetic testing.

Have you tested your genome?
I have. I’ve had myself genotyped by 23AndMe, which is one of the companies that is in the middle of all this. Probably one of the most prominent companies. I paid for it myself. I did not want a conflict of interest because they have gien away a number of reduced cost or low-cost kits and I did not want to have any conflict there. And I think that is all I’ll say about that, because I’m going to be talking publicly about that in the not-too-distant future.