U.S. comes down against gene patents

In a surprising move, the U.S. Justice Department filed a brief last Friday that declared, for the first time, that the U.S. government does not support the patenting of naturally occurring human genes. This new position is contained in a document filed as part of the ongoing legal challenge to the gene patents on the human breast cancer genes, BRCA1 and BRCA2.

As background: a company called Myriad Genetics has held the patents on these two genes since the late 1990s. They sell diagnostic tests that cost nearly $4,000, and if a woman wants to test her own DNA for any mutations in the BRCA genes, they are required to pay for this very expensive test. The gene patents prevent any competitors from offering the same test without paying Myriad a license fee. Earlier this year, the ACLU challenged these patents in federal court, and the initial court ruling, which came as a surprise to many, invalidated the patents. Myriad appealed, and it seems likely this will end up in the Supreme Court before it is finally settled.

I have a scientific interest in this case, having just published a paper that directly challenges gene patents by providing free software that allows anyone to test their own DNA for mutations in the BRCA genes. Our software requires that you first have your genome sequenced, which (of course) is not feasible for most people today, but which I think will be routine in the not-too-distant future.

It seems absurd that, having your own DNA in hand (on a flash drive, perhaps), you wouldn’t be allowed to check your own genes for mutations without first paying a license fee to a company. Actually, under current law you might have to pay hundreds of license fees, because thousands of human genes have already been patented.

The same government that issued these patents has finally woken up to this absurdity. In their amicus brief, the Justice Department wrote:

“the unique chain of chemical base pairs that induces a human cell to express a BRCA protein is not a ‘human-made invention.’ Nor is the fact that particular natural mutations in that unique chain increase a woman’s chance of contracting breast or ovarian cancer. Indeed, the relationship between a naturally occurring nucleotide sequence and the molecule it expresses in a human cell – that is, the relationship between genotype and phenotype – is simply a law of nature. The chemical structure of native human genes is a product of nature, and it is no less a product of nature when that structure is ‘isolated’ from its natural environment than are cotton fibers that have been separated from cotton seeds.”

Rarely have I seen such sensible scientific reasoning from lawyers, and I must say it is very refreshing. Just in case the text quoted above is isn’t clear enough, the brief goes on to point out that “the patent laws do not, however, embrace the products and processes of nature itself.” The reason for the bit about “isolated” DNA is that Myriad’s patents cover DNA that has been “isolated” from the cell, and the Justice Department wanted to make it clear that this distinction should not somehow make the DNA patentable.

The legal implications of my own challenge to the BRCA gene patents were discussed at length at Genomics Law Report, and by Forbes blogger Robert Langreth. It will be interesting to see how this latest filing by the Justice Department changes the picture. The implications go far beyond the BRCA gene patents: if the initial court ruling and the Justice Department’s position hold up, then virtually all gene patents, on human genes and on many other species’ genes, will become invalid.

It’s about time. New genes have been the basis of many exciting discoveries, but they are not inventions. No one should have exclusive rights to a gene that occurs naturally in a human, another animal, a plant, or any other living species.

Personal genetic testing, available soon at your local pharmacy

This past week, Pathway Genomics and Walgreens announced that they would start selling Pathway’s genetic testing kits at 6000 Walgreens stores. I thought this was good news – I, for one, would like to be able to run my own genetic tests. I’d like to know what risks my genes might carry, particularly if there was something I could do to reduce those risks. But what does Pathway’s test tell you, and is it worth it?

Pathway has been selling its testing kits since September, but selling them at a large chain store like Walgreens would undoubtedly reach many more customers. After their joint press release last Tuesday, though, someone at the FDA noticed, and stepped in to ask a few tough questions. In a letter on May 10 (read it here), the FDA told Pathway that they had to get FDA approval for their diagnostic kits, or else explain why they don’t need it. Pathway claims its kit is exempt from FDA approval, but that might be a tricky argument to prove. After the FDA sent its letter, Walgreens announced that it would hold off for now on selling the kits.

Meanwhile, the real question is, what will Pathway’s test tell you about your genes? Some biomedical scientists are saying that the science of genetic testing is too new to offer directly to consumers. They argue that the results of a genetic test are difficult to interpret, and that patients shouldn’t be given this complex information without expert guidance. Stanford University’s Hank Greely, quoted in the Washington Post, said "Information is powerful, but misunderstood information can be powerfully bad." Are doctors just trying to protect their business, or are they right? I decided to take a look.

Pathway promises to tell you about your risk for up to 70 diseases and conditions, if you pay $399 for the full suite of tests. (That's the price if you order directly from Pathway, which you can do right now. The Walgreens price was supposed to be lower.)

For example, if you are a carrier of the cystic fibrosis gene (which is included in the Pathway test), and if your spouse is also a carrier, then as a couple you have a 25% chance of having a child with cystic fibrosis. The genetics of this disease are well understood, and the test for the mutation should be highly reliable. This seems like a good value to me, and I see no reason why people shouldn’t be allowed to know if they’re a carrier for cystic fibrosis; it may be important to their future plans for having children.

For other diseases, though, the Pathway test provides much more ambiguous information. Let’s look at late-onset Alzheimer’s disease, something that almost everyone worries about as they get older. The Pathway site doesn’t specify which gene they test, but there is no known “Alzheimer’s gene.” Research on Alzheimer’s has demonstrated that some genetic mutations are associated with an increased risk, but the picture is far from clear. For example, mutations in the Apolipoprotein E (APOE) gene on chromosome 19 appear to increase the risk for Alzheimer’s after age 60. According to the National Institute on Aging, the e4 (epsilon-4) variant of this gene:

“occurs in about 40 percent of all people who develop late-onset AD and is present in about 25 to 30 percent of the population. People with AD are more likely to have an APOE e4 allele than people who do not develop AD. However, many people with AD do not have an APOE e4 allele.”

Complicated, no? And this is the clearest association between a genetic mutation and Alzheimer’s — a half-dozen other genes are associated with slightly increased risk, and research is ongoing. So should anyone be allowed to test his/her genome for this mutation?

Yes, emphatically yes!

It’s my genome, and I should be able to look at it if I want to. So what if the information is complex? If someone is curious enough to pay for this test, then when they get their results back, perhaps they’ll be motivated to learn more about genetics so that they can understand their own risk. Giving people information about their own genome seems like a great way to educate the public, and to make people more aware of the power of genetic information. Of course there are risks: charlatans might offer to sell bogus treatments for all kinds of genetic conditions, for example. People might misinterpret the results. But that doesn’t mean we shouldn’t allow people to discover more about themselves.

In a very real way, genetic information is no different from other medical facts. We have easy access to our blood pressure numbers, and no one is suggesting that we shouldn’t, despite the fact that interpretation of blood pressure numbers can be complicated. (For example, should you reduce salt intake, or take statins to lower your blood pressure, or change your lifestyle in other ways?)

I hope the FDA allows Pathway to sell its DNA test at Walgreens. Personally, I think the value of the tests they’re offering today is mostly to satisfy curiosity – we don’t have treatments for most of the genetic diseases they can detect, so there's not much you can do about them. Some of the results will be useful to some people, though, and over time we’ll develop new treatments that will make more genetic tests valuable. Now that Pandora’s box is open, we can’t close it again. And we shouldn’t.

10,000 genomes – why?

In the genomics world that I inhabit, a consortium has just published an intriguing proposal to sequence the genomes of 10,000 vertebrate species. It’s described an article in the current Journal of Heredity – unusual in that this is not a research article, but a proposal. Nonetheless, the article is full of interesting facts about what we know (and don’t know) about vertebrate species and how they’re all related. It makes a good read for anyone interested in evolution; for example, how many people know that all vertebrates have a common ancestor who lived about 500-600 million years ago? Perhaps more interesting, evidence is emerging that we all share about 10,000 genes – which means that these 10,000 genes are so useful that their functions have been preserved for 500 million years.

The consortium is led by a number of outstanding scientists, including UCSC’s David Haussler and NIH’s Stephen O’Brien, both of whose work I like and have followed for years. And some aspects of this proposal are terrific: for example, they want to start collecting DNA now from 16,203 vertebrate species. This will make a great specimen collection for future work. (Heck, maybe I’ll even sign on to the project myself.)

But this proposal is more than that: it is also the opening salvo in an effort to raise $50-100 million for the sequencing of these species. The paper was announced with press releases and news articles in both Science and Nature, demonstrating that it is clearly a lobbying effort for new funding. Fair enough – science takes funding, and sometimes you have to build support for new ideas. However, given that two of the three leaders of the consortium are primarily funded by NIH, I can only guess at who they’re expecting to cough up the money. The NIH's human genome funding has been led by NHGRI, which continues to look for new ways to justify maintaining the size of its three enormous sequencing centers (the Broad Institute, Washington University in St. Louis, and Baylor College of Medicine). Now, let me say here that genomes are the bread and butter of my own work, and these centers have done terrific work for the past 10-15 years - and I've often collaborated with them. And I hope they will continue. But it hasn’t escaped my attention that the new NIH Director, Francis Collins, was a key force in building up those centers while he was Director of NHGRI, and we all know that the centers are near and dear to him.

But wait a minute: 10,000 genomes, none of which are human? Exciting idea, sure, but not for NIH. The NIH-led centers are already participating in the 1000 Genomes project, which is attempting to sequence 1000 individuals (at a low-level “draft” quality). If NIH wants to scale up, there are 6 billion more of us available. Admittedly, not everyone wants to have his/her genome sequenced, but plenty of us would be happy to volunteer. Take a look at the Personal Genome Project, which was started by George Church at Harvard, and is trying to sign up 100,000 humans to have their genomes sequenced.

So I’m going to be the skeptic here: if NIH is thinking of throwing its sequencing dollars at 10,000 more genomes, I suggest that it focus on humans rather than a broad collection of other vertebrates. (I know, this should be obvious, right? But sometimes NIH gets distracted.) We still have only scratched the surface of what there is to know about the human genome, and there’s plenty of DNA sequencing to do in the human population. The 10,000 genomes project sounds like a great mission for the National Science Foundation, which has ceded much of large-scale sequencing work to the NIH in the past 10 years, except for plant genomes and some bacteria. In fact, maybe this is a chance for NSF to have its own large-scale sequencing center – I’d be all for that. But I’m not at all convinced that NIH should spend its biomedical research dollars on 10,000 vertebrates. Let’s see how this plays out.