The NY Times is far too worried about 23andMe's genetic test

The New York Times decided to publish an editorial this weekend warning people to "be careful about 23andMe's Health Test." What are they worried about?

Although the NY Times article is accurate, the warning suggests that 23andMe misleading its customers somehow. Is it? I decided to take a look.

 I'm a customer of 23andMe, and I'm also a researcher in genetics and genomics, so I know quite a bit about how their technology works and about what it can reveal. I've looked at 23andMe's latest genetic health reports, and they are remarkably clear and accurate.

Let me illustrate by revealing part of my own genetic test results. First I looked at my results for BRCA1 and BRCA2, the two genes that the NY Times article discusses.

I don't have any of the harmful mutations in the BRCA genes, which 23andMe reports like this:

Notice that they immediately provide the caveat that more than 1,000 other variants in these genes have been linked to cancer risk, and they make it abundantly clear that they didn't test any of those. Here's what the NY Times article said:

"The 23andMe test can miss other possible mutations.... there are more than 1,000 other BRCA mutations that contribute to your breast cancer risk. The 23andMe test doesn’t look for any of them."

A reader of the Times might think, upon reading this, that 23andMe somehow hides this fact. But the Times article's warning is little more than a paraphrase of what 23andMe's website states.

The Times editors also caution that

"Just because you test negative for the few mutations that 23andMe screens for doesn’t mean that you won’t get breast cancer."

Duh. 23andMe explains this as well, and much more, such as:

"This test does not take into account other risk factors for breast, ovarian, prostate, and other cancers, such as personal and family health history." [from 23andMe]

23andMe also provides a wealth of information about the BRCA genes, including links to the scientific papers describing the genes and their link to cancer. I was very impressed by how thorough they are.

The Times editors focused only on the BRCA genes, but 23andMe also tests a handful of others (9, in my case). I looked at the APOE gene report, which has a mutation that has been linked to Alzheimer's disease. The bad variant is called ε4, and fortunately I don't have it.

Once again, the 23andMe site was very clear about what this means, providing a detailed table showing the risks for people with and without the mutation. In my case, they tell me that:

"Studies estimate that, on average, a man of European descent has a 3% chance of developing late-onset Alzheimer's disease by age 75 and an 11% chance by age 85."

Looking at the detailed table, one learns that if you have one copy of APOE ε4 variants, your risk of developing Alzheimer's by age 75 is 4-7%, and if you have 2 APOE ε4 variants–the worst case–then your risk jumps to 28%. The website provide links to 10 scientific papers with far more detail, for those who want to know the basis of these numbers. This is far more than most people will want to know, and I couldn't find any flaws in 23andMe's description of the science.

The Times editorial concludes with this:

"23andMe has said that its health tests can raise awareness about various medical conditions and empower consumers to take charge of their health information. But doctors and geneticists say that the tests are still more parlor trick than medicine."

That last statement is the most egregious misrepresentation by the Times editors. Who are these geneticists who call DNA testing a "parlor trick"? The genetic tests run by 23andMe, which use technology that is run daily at thousands of labs around the world, are nothing of the sort. They are a highly accurate assay that has been repeated millions of times and validated by hundreds of peer-reviewed studies. Usually the NY Times is one of the most thorough and accurate sources in the media, but they really dropped the ball this time.

The fact is, genetics is not fate. Identical twins, who share identical DNA, rarely die of the same causes. Thus even if you knew your genetic risks perfectly, for every mutation in your DNA, you might not find anything to change in your behavior. At most, you might learn that you should get mammograms or colonoscopies slightly more often. It's legitimate to argue that you won't learn anything useful from the 23andMe tests, but you will learn something about genetics.

As far as changing your behavior to reduce health risks, you don't need a sophisticated genetic test for that. Just eat more leafy greens.

[Note: although I'm a customer of 23andMe, I have no financial relationship with the company and I'm neither an advisor to nor an investor in them.]

Massive genetic sharing effort shows power but also shows how little we know

Your genes are not your fate. 

Nonetheless, genes can tell us a lot about our risk for disease, and sometimes they can tell us how to lead healthier lives.

The landscape of the human genome is vast and mostly unexplored. There is far, far more that we don’t know than we do know. This is why it’s so important that as we test people for genetic mutations, we share information as much as possible. Genes have different effects on different people, and a mutation that is harmful in one group might be harmless in another. If we’re ever to fill in all the gaps in our knowledge, we have to pool our resources by sharing data.

This is the goal of ClinGen, a new project described in this week’s New England Journal of Medicine. ClinGen relies on a public database called ClinVar, where researchers, clinical labs, clinicians, and patients can deposit information about genetic variants and their effect on disease. 

What makes this effort so complex is that many disease-causing mutations are quite rare. If two patients share the same disease and the same genetic mutation, and if we’ve never seen that mutation before, can we claim that the mutation cause the disease? Not really: we might have to wait until we’ve seen many more patients before we can have any confidence in the cause-and-effect relationship. This is why sharing data is so important: more data means more power to discriminate between real effects and coincidences.

ClinGen has already shown us that our knowledge has flaws: perhaps 17% of the disease associations that clinicians have reported might be incorrect. More precisely, the NEJM paper reports that out of more than 118,000 mutations that have a clinical affect, almost 13,000 were reported by more than one lab. Of those, 17% were interpreted inconsistently, with some labs calling mutations "pathogenic" while other labs calling them benign.

I disagree with the headline of an AP report headlined “flaws in gene testing,” which reported that 

“The first report from a big public-private project to improve genetic testing reveals it is not as rock solid as many people believe.”

This is a straw man argument: experts in the field don't think genetic testing is “rock solid”, and the 17% rate of disagreement in disease-mutation association is not that surprising. What's more, these conflicts don’t always represent flaws, but rather holes in our knowledge that we just haven’t filled yet. 

Disagreements over the effects of a genetic mutation represent opportunities to clarify and improve our genetic knowledge base. And as the ClinGen authors emphasize, it’s only by sharing our findings that we can discover and correct these flaws. This is why clinicians, scientists, and labs need to adopt a culture of sharing results, as the ClinGen project has emphasized (see their “Wall of Fame” of labs and institutions that have shared data).

All of us have mutations in our DNA; geneticists estimate that each of us carries perhaps 30 new mutations that even our own parents don’t share. The vast majority of these, fortunately, are harmless. Even mutations that do affect our health usually only have a small influence, changing our risk for disease but not actually causing it.

I'd be remiss if I didn't point out that sometimes, your genes are your fate. If you have certain mutations in the CFTR gene, you will have cystic fibrosis, and some mutations in the HTT gene will inevitably cause Huntington’s disease. 

As geneticist Luke Jostins cogently wrote, identical twins usually don’t die from the same thing. So even though genes may influence our fate, we still have control over it. Knowing your genetic risks can be valuable, but we have a lot more to learn about how our genes influence our health.

Should we test all women for breast cancer-causing mutations?

In this week’s Journal of the American Medical Association, famed geneticist Mary-Claire King argues that all women over age 30 should be tested for cancer-causing mutations in the BRCA1 and BRCA2 genes. King, who made the original discovery of the link between BRCA1 and breast cancer, is one of the world’s leading experts on how mutations in these genes cause cancer.

But her proposed new universal testing policy, which fellow Forbes contributor David Shaywitz calls “audacious,” goes far beyond what other experts recommend. Earlier this year, the highly regarded U.S. Preventative Services Task Force (USPSTF) recommended testing BRCA genes only in women with a family history of breast or ovarian cancer. 

Although there’s no question that King is an expert on BRCA gene testing, I think she’s gone much too far with her latest proposal. She has the science right, but she is far too optimistic about how her recommendation would actually play out. The policy might save some lives, but it would also cause a great deal of pain.

First, it’s worth explaining why King thinks universal BRCA testing is a good idea. In her JAMA article, King and colleagues describe a new study they conducted in Ashkenazy Jews that showed, somewhat surprisingly, that 

“50% of families found to harbor BRCA1 or BRCA2 mutations had no history of breast or ovarian cancer that would have triggered clinical attention." 

In other words, under current policy guidelines, 50% of people who have a damaging mutation in one of these genes will not have their genes tested. Many of them will eventually get breast or ovarian cancer—as King explains, women with harmful BRCA1 mutations have a 60% risk of cancer by age 60, and for BRCA2 the risk is 33% by age 60. That’s a very high risk, though it’s important to keep in mind that many women with these mutations will never get cancer.

With modern DNA sequencing technology, any large-scale genetic BRCA testing program is likely to uncover thousands of mutations that have no harmful effects, and thousands more whose effects are simply unknown. (Aside: each BRCA gene spans about 80-90 thousand nucleotides of DNA, and each of those letters can mutate in 4 ways, changing into one of the other 3 bases or just being deleted. This means there are at least 400,000 mutations possible in each gene, not counting larger deletions. A colleague and I published an article in 2010 describing one such BRCA test.) King is clearly aware that such reporting these mutations to patients would only sow confusion, and she recommends that:

“Testing for BRCA1 and BRCA2 should focus solely on unambiguously loss-of-function mutations with definitive effect on cancer risk…. A VUS [variant of unknown significance] can increase confusion and compromise clinical management; for population-based screening, these variants should not be reported.”

Herein lies one of the biggest problems with King’s idea. We don’t have universal agreement on which mutations have no significance, and even if we did, most physicians are not experts on cancer genetics. In our lawsuit-prone medical culture, there exists an unfortunate tendency to over-treat and over-report everything. 

Thus I fear that if we had wider BRCA testing, clinical labs would report all mutations back to physicians (how could they not?), and physicians in turn would report everything to the patients. The result would be that millions of women would be told "you have a mutation in BRCA1, and we don't know what it means." What's a patient supposed to do with that?

The other problem is that the only treatment to prevent breast and ovarian cancer is surgery to remove a woman’s breasts and ovaries. We don’t have a pill you can take, or lifestyle changes you can adopt, that will dramatically reduce your risk of hereditary cancer. But unlike a cancer diagnosis, the discovery of a BRCA mutation does not mean you have cancer. It simply means you have a risk, possibly a high risk, of getting cancer at a young age. We know from decades of research that people are not very good at evaluating risk. We tend to over-estimate the danger of events that seem very dramatic or visible to us, as cancer is to many people. 

By King’s own estimates, widespread BRCA testing would detect cancer-causing mutations in 250,000 to 415,000 women in the U.S. This estimate assumes the test doesn’t have false positives, which it almost certainly would. All of these women would then be faced with an extremely difficult dilemma: should they have both their breasts removed, or live the rest of their lives in fear of breast cancer? 

This dilemma was famously on display last year, when actress Angelina Jolie revealed in a New York Times article that she’d had a double mastectomy, after discovering that she carried high-risk BRCA mutations. Jolie’s mother died from cancer at the age of 56, and she explained in her article that as a result of the surgery, “ I can tell my children that they don’t need to fear they will lose me to breast cancer.”

King’s proposal is audacious, and it’s well worth debating. But without a better treatment option, telling hundreds of thousands of women that they have a high risk of breast and ovarian cancer carries a potentially enormous cost, both physical and emotional, for these women. Rather than putting huge numbers of women under the surgeon’s knife, we should instead double or triple our investments in research on treatments that may eventually make surgery unnecessary. 

A DNA Sequencing Breakthrough for Pregnant Women

DNA sequencing has made its way to the clinic in a dramatic new way: detecting chromosomal defects very early in pregnancy.  We've known for 25 years that traces of fetal DNA can be detected in a pregnant women's blood. But these traces are very small, and until now, we just didn't have the technology to detect an extra copy of a chromosome, where the DNA itself is otherwise normal.

Last week, in a study published in The New England Journal of Medicine, Diana Bianchi and colleagues showed how DNA sequencing can detect an extra copy of a chromosome with remarkable accuracy. This report heralds a new era in prenatal DNA testing.

First, some background: three copies of chromosome 21 causes Down syndrome, a genetic disease that causes intellectual disability and growth delays. Down syndrome is also called trisomy 21, where trisomy = 3 copies of a chromosome instead of the normal 2 copies. Much less common is Edwards syndrome, caused by three copies of chromosome 18. Edwards syndrome, or trisomy 18, has much more severe effects, with the vast majority of pregnancies not making it full term. Having an extra copy of any other chromosome almost always causes an early miscarriage. For many reasons, prospective parents want to know if a fetus carries any of these abnormalities.

The accuracy of the new test is remarkable. Out of 1914 young, healthy pregnant women, there were just 8 pregnancies where the fetus had an extra chromosome, and the test detected all 8. What was most impressive was its low false positive rate: in total, the new DNA-based test had just 9 false positives (for either chromosome 21 or chromosome 18 trisomy).  By contrast, the conventional screening test, which also identified all 8 true cases, produced 80 false positives, nearly 9 times as many as DNA sequencing.

Why does this matter? In most cases, women with a positive result on one of these tests will opt for amniocentesis ("amnio"), an invasive procedure where a doctor inserts a long needle directly into the womb and collects a sample of amniotic fluid. Amnio almost always gives a definitive answer about Down syndrome. With the conventional method, its false positive rate is so high that even with a positive test, over 95% of amnios will be negative, versus 55% with the new DNA sequencing test. Or to put it another way, as Bianci et al. wrote:

"if all women with positive results had .. decided to undergo an invasive procedure, there would have been a relative reduction of 89% in the number of diagnostic invasive procedures."

89% fewer invasive procedures is a huge reduction, not only in costs but in stress for the parents and risk to the baby (because amnio carries a small risk of miscarriage).

With DNA sequencing getting faster and cheaper every year, it might be surprising that we are only now seeing it used to detect trisomy. The difficulty with detecting an extra copy of a chromosome is that the DNA sequence itself is normal. If you sequence the genome, you won't find any mutations that indicate that the fetus has an extra chromosome copy. This is where the remarkable efficiency of next-generation sequencing comes in.

In a matter of hours, modern sequencing machines can sample millions of small fragments of DNA. We can use computational analysis to determine which fragments come from the fetus, and how many came from each chromosome. If any chromosome has three copies, we'll see a 50% increase in DNA from that chromosome. The power of sequencing lies in large numbers: because we can sequence many fragments from each chromosome, a 50% increase is easy to detect.

The method that Bianchi used to detect trisomy was published in 2011 by Amy Sehnert and colleagues from 2011, some of whom are contributors to the new NEJM study. [Side note: they use a software program called Bowtie, developed by my former student Ben Langmead, to do the analysis.] The method is likely to get even better over time, further reducing the false positive rate.

The American College of Obstetricians and Gynecologists has already recommended DNA testing for pregnant women at high risk of fetal aneuploidy (an extra chromosome). To be precise, they recommend that high-risk pregnant women be offered fetal DNA testing as an option, after they get genetic counseling. This new study, which was conducted in a low-risk population, shows that the benefits of prenatal DNA testing should offered to all women.

Federal judges decide that private companies own your DNA

Many scientists cheered last year when a federal judge ruled that human genes couldn't be patented. The case involved Myriad Genetics, which holds the patent rights on two genes, BRCA1 and BRCA2, that are associated with increased risks for breast and ovarian cancer. Thanks to these patents, you can't look these genes in your own body without paying a fee to Myriad. Sounds ridiculous, right? Well, that was the state of gene patents until last May, when judge Robert Sweet ruled that the Myriad's patents were invalid.

But now the courts have reversed themselves again. In a 105-page decision, two federal judges decided that the whole matter comes down to the meaning of the word "isolated." I kid you not.

Judge Sweet's ruling last year was based on the obvious scientific fact that genes are a product of nature, not an invention, and therefore they could not be patented. Patent lawyers were very upset over Sweet's ruling. Why was this controversial? Well, because the U.S. Patent and Trade Office has been granting gene patents for decades. Basically, once the USPTO decided to allow one gene patent, they never looked back, and they've now given out patents for over 4,000 human genes.

But this past week, an appeals court reversed last year's ruling and said yes, Myriad Genetics does indeed own the rights to the BRCA genes. The decision by Judge Alan Lourie reveals an astounding lack of understanding of DNA, genes, and genomes. I guess I shouldn't be surprised, but I had been hopeful that after the earlier ruling throwing out these patents, science and logic would prevail. I guess I should never underestimate the scientific ignorance of judges, though I should add that one of the three judges voted against his colleagues.

What was their contorted reasoning? They decided that "isolated DNA" is not the same as the natural DNA in your body, and that this distinction allows companies to patent it. (The word "isolated" occurs 219 times in the decision.) The judges wrote:

"According to Myriad, isolated DNA does not exist in nature, and isolated DNAs, unlike native DNAs, can be used as primers and probes for diagnosing cancer."

The mind boggles. Following this nugget, Judges Lourie and Moore give us a little mini-lesson in molecular biology:

"Native DNA exists in the body as one of forty-six large, contiguous DNA molecules…. Isolated DNA, in contrast, is a free-standing portion of a native DNA molecule, frequently a single gene…. Accordingly, BRCA1 and BRCA2 in their isolated state are not the same molecules as DNA as it exists in the body."

This is scientific nonsense, but the court bought it. (Over at TechDirt.com, Mike Masnick made the colorful analogy that this is like "arguing that because a severed finger is not attached to a hand, the finger is not naturally occurring, and, thus, is patentable.") Wrote the judges:

"we conclude that the challenged claims are drawn to patentable subject matter because the claims cover molecules that are markedly different—have a distinctive chemical identity and nature—from molecules that exist in nature."

Among other problems, Judges Lourie and Moore don't understand a basic fact of genetics: that genes are "isolated" by our body's own genetic machinery when they are copied into RNA and then translated into proteins. Or perhaps they do understand, but they don't care because they just want an excuse to keep gene patents around. This is what can happen when lawyers (judges) make scientific decisions: they go on for pages and pages about the semantics of a word ("isolated"), and produce a result that is scientifically meaningless.

Judge Bryson makes much more sense in his dissent, writing:

"the question in this case is whether an individual can obtain patent rights to a human gene. From a common-sense point of view, most observers would answer, `Of course not. Patents are for inventions. A human gene is not an invention.' The essence of Myriad’s argument in this case is to say that it has not patented a human gene, but something quite different—an isolated human gene."

So that's two judges (Sweet and Bryson) against human gene patents, and two in favor. This case isn't over yet; last week's ruling by the 3-judge panel will likely be appealed to the full appeals court next. It's hard to predict what they will say. Meanwhile, Myriad charges $4000 to run tests on BRCA1 and BRCA2, as I wrote last year. This means that if a woman wants to test her own DNA for any mutations in the BRCA genes - including mutations that weren't even known when Myriad got the patent - she must pay Myriad merely to look at her own genes.


I'm not a lawyer, but I already see one way around Myriad's patents in this flawed decision. The judge's (and Myriad's) reliance on "isolated BRCA genes" refers to the process of isolating and copying the genes using a laboratory method called RT-PCR, and then sequencing just the isolated bits. Today, though, we can sequence a person's entire genome, without "isolating" any particular genes, for under $5000, and then we can test for mutations in the BRCA genes without ever "isolating" them. In fact, a colleague and I published a paper just last year describing how to do this, and we released a free software package that allows anyone to test their BRCA genes at home on a desktop computer. Genomics Law Report has a detailed legal analysis of what our software means for the Myriad case.

Scientifically, it shouldn't matter how the judges define "isolated" DNA. And as two federal judges have now ruled, genes are not inventions, full stop. What's more, gene patents slow down science by throwing legal barriers in the path of anyone who wants to work on those genes. Finally, I'm amazed at the hubris of companies like Myriad - or anyone else - who claim they "own" a gene. Let's hope the full appeals court will reverse the tortured reasoning of Judges Lourie and Moore, and get the patent lawyers out of the laboratory.

Test your kids' genes for sports ability: hype or reality?

A company called Sports X Factor recently announced that it's selling a genetic test that will reveal your potential to be a sports star. They're marketing it as a way to predict what sports your kid will excel at. Is this real, or just another over-hyped attempt to cash in on parents' aspirations for their children?

Sports X Factor, which sells the test for $180, stated in a press release a few weeks ago that the test

"can make workouts more effective, children’s sports choices more appropriate and trainers’ awareness of potential risk factors more precise. It can even save a life."

Wow, sounds impressive. But is it true?

In some ways, this is nothing new. Another company, Atlas Sports Genetics, started offering a similar test in 2008. They make similar promises, claiming that their test

"Gives parents and coaches early information on their child’s genetic predisposition for success in team or individual speed/power or endurance sports."

Unlike some of the rank pseudoscience I often blog about, this claim actually has some real science behind it. Back in 2003, Kathryn North and colleagues at the University of Sydney published a paper in a leading genetics journal about a gene called ACTN3. They found that mutations in this gene were associated with elite sprinters, both male and female. Superficially, it's easy to take this association and turn it into a "speed gene," but it's not.

The science is much more nuanced. (Isn't it annoying when things aren't so simple?) ACTN3, which affects muscle fibers, has three common genotypes. Let's call them Red, White, and Blue.* Elite-level sprinters are usually Red or White: 92% of male sprinters and 100% of female sprinters in the original study were one of these. In the general population, 30% of people are Red and 52% are White. For elite endurance athletes, there tendency is the opposite: slightly more of them are Blue, but the difference isn't significant.

The advice from Atlas Sports Genetics is a gross over-generalization of the science. Here's how they interpret the test results:

Blue: Predisposition to endurance events

White: Equally suited for both endurance and sprint/power events

Red: Predisposition to sprint/power events

The science simply isn't this clear. The only thing you might say is that Blue genotypes are not likely to be Olympic sprinters. But that's true of 99.999% of us anyway. There's no "predisposition" to particular sports.

The newer test from Sports X Factor looks at 9 genes, not just ACTN3. Although a broader test might sound superior, the genes they test include ApoE4, which is associated with a slightly higher risk of Alzheimer's disease. This raises serious ethical questions. Do you really want your child to know that he/she might be pre-disposed to Alzheimer's? As Hank Greely, a Stanford lawyer and bioethicist, said in the Washington Post, “I think this company is a good advertisement for the need for more regulation of genomic testing,”

I suggest that parents save their money, and instead take a test that I'm offering right here, for free, to determine your child's sports potential. Just follow these two easy steps:

1. Ask your child, "do you want to play soccer?"
2. If the answer is yes, sign your child up for a kids' soccer team.

Wasn't that easy? And it works for almost any sport! Just replace "soccer" by your kid's favorite sport. Oh, and then you have to go to the games. That's the hard part.

*For science geeks only: the genotypes Red, White and Blue are RR, RX, and XX respectively. The mutation is R577X, where the X is mutation that introduces a premature stop codon at position 577 that shortens the ACTN3 protein. RR means that both copies of the protein are full-length. RX means one copy is shortened, and XX means both are. About 18% of the population is XX ("Blue").

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.