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Applied Biotechnology, Ethics, Fertility, Genetics, Medicine and Society, Parenting

Medical practice, patents, and “custom children”: A look at the future of reproductive medicine

Medical practice, patents, and "custom children": A look at the future of reproductive medicine

black and white baby

Recently, 23andMe, the direct-to-consumer genetic diagnostic company, announced it had been issued a patent for a system of applying genetic testing – and, consequently, genetic screening – to egg and sperm banks. (Full disclosure: I am a 23andMe consumer.) In brief, 23andMe’s system involves receiving information from would-be parents about which traits they’d like their children to possess, and then determining which egg or sperm donations would be the best genetic fit to create those children. While egg and sperm banks currently allow would-be parents to sort through the traits of egg and sperm donors – such as race, height, athleticism, and even SAT scores – 23andMe’s patent envisions applying statistics to the genetic profiles of both donors and recipients to create something of a “custom child.”

To be clear, 23andMe’s patent is just that: a patent. There’s no indication that 23andMe has put its system into implementation or even made a serious business attempt to do so. Nonetheless, others have discussed the ethics behind 23andMe’s system, the propriety of the patent, and 23andMe’s ultimate plans with its intellectual property. But one question I’m particularly intrigued by is: Assuming 23andMe’s vision comes to pass – one easily within our technological if not cultural grasp – what will the future of reproductive medicine look like?

First, it would be a tremendous boon to the medical care of those “custom children,” as it would likely eliminate many common gene variants responsible for disease. These range from simple, single-gene diseases, such as Marfan syndrome, spinal muscular atrophy, and Huntington’s disease, to complex multi-gene diseases, such as breast and ovarian cancer, for which certain gene variants play a significantly large etiological role. And, as is demonstrated by the list above, these diseases need not be limited to the traditional fatal-in-childhood diseases, such as Tay-Sachs or Niemann-Pick syndrome, that are currently screened for. Rather, as is the case with Huntington’s disease, which only afflicts its sufferers in mid-life, the method could quash those genetic variants that cause disease through all stages of life.

Second, the robustness of the technology behind the 23andMe patent may spur demand for  in vitro fertilization. Few couples capable of conceiving without technological intervention undergo IVF today. But some of that is ultimately a matter of choice: that there are few benefits to be had through IVF relative to natural conception. The possibilities for customization described in the 23andMe patent – choosing a child possessing hundreds of hand-picked traits, from curly hair down to caffeine metabolism – may, at least for some, change that calculus. The potential for customization drives demand in other enterprises – smartphones, cheeseburgers, insurance policies, even house paint. It’s culturally naïve to think it will have no effect on reproductive technology.

And lastly, I suppose it also means that reproductive medicine will increasingly come within the ambit of patent law. Since its inception in the 1970s, IVF has largely been free of the destructive and costly patent litigation seen in other industries, such as smartphones. If 23andMe’s patent is indicative of a future norm, reproductive medicine may very well operate in a world controlled by licensing agreements and cowered by threats of litigation. Whether one is entitled to a particular genetic screening method may have little to do with the quality of the institution – as it generally does now – but more with whether an institution has agreed to pay the appropriate royalties. At least this aspect of reproductive medicine is not so futuristic: The current set of patent infringement lawsuits among Verinata, Sequenom, Natera, and Ariosa has held up much non-invasive, prenatal screening for Down’s syndrome.

These issues are both fascinating and complex, and the larger concerns raised by the system described in the 23andMe patent only touch a small fraction of the ethical and practical quandaries involved. For a discussion of the remainder, Stanford’s own Hank Greely, JD, will attempt to address them in his upcoming book, “The End of Sex“. Let us at least hope that that institution’s end is not because of patents.

Jake Sherkow, JD, is a fellow at Stanford Law School’s Center for Law and the Biosciences. His current research focuses on the intersection of patent law, biotechnology, and agency regulation.

Previously: Whole-genome fetal sequencing recognized as one of the year’s “10 Breakthrough Technologies”Stanford bioethicists discuss pros, cons of biotech patents, The end of sex? Maybe not just yet, New techniques to diagnose disease in a fetus, and Sex without babies, and vice versa: Stanford panel explores issues surrounding reproductive technologies
Photo by Lisa Williams

Cancer, Genetics, Medicine and Society, Science, Science Policy

A closer look at Supreme Court’s decision on gene patenting

A closer look at Supreme Court's decision on gene patenting

As previously discussed here and elsewhere, the Supreme Court today issued its opinion in the gene patenting case Association for Molecular Pathology vs. Myriad Genetics, Inc. In a unanimous decision (.pdf) authored by Justice Thomas, the Court declared that isolated genomic DNA was not eligible for patent protection, but that cDNA – “cloned” or “complementary DNA” – could be patented. This was largely the outcome some predicted after oral argument. And while the actual business and research effects of the decision remain to be seen, this does bring to a close the longstanding practice of patenting isolated portions of the human genome in its native state.

This likely brings to a close Myriad Genetics’ saga of aggressively enforcing its patents directed to BRCA1 and BRCA2 testing

The Court’s decision was relatively simple. It began with a largely accurate, and lengthy, recitation of the molecular biology behind transcription and translation. This factored significantly into the Court’s discussion of the differences between isolated genomic DNA and cDNA, particularly the absence of introns from cDNA molecules. It then assessed the patents’ claims at issue, which were generally directed to “an isolated DNA” of varying lengths and sequences. The opinion noted that, “Myriad’s patents would, if valid, give it the exclusive right to isolate an individual’s BRCA1 and BRCA2 genes… by breaking the covalent bonds that connect the DNA to the rest of the individual’s genome.” And the Court concluded its opinion by declaring that claims directed to molecules of isolated genomic DNA, themselves, were unpatentable “products of nature” because Myriad did not “alter any of the genetic information encoded in the BRCA1 and BRCA2 genes,” nor did the isolated genomic DNA possess “markedly different characteristics from any found in nature.”

The Court rejected Myriad’s claim that it created a new chemical entity because, in isolating the genes from their surrounding chromosomes, Myriad necessarily cleaved the chemical bonds of the chromosomes’ phosphate backbones. This was irrelevant because “Myriad’s claims are simply not expressed in terms of chemical composition, nor do they rely in any way on the chemical changes that result from the isolation of a particular section of DNA.”

As for Myriad’s cDNA claims, however, the Court – in a single, short paragraph – declared them eligible for patent protection because the “non-coding regions have been removed,” thus creating a new molecule not found in nature. Interestingly, the Court recognized the possibility of retrovirii potentially creating identical DNA transcripts to the cDNAs at issue, but dismissed this concern in a footnote: “The possibility that an unusual and rare phenomenon might randomly create a molecule similar to one created synthetically through human ingenuity does not render a composition of matter nonpatentable.”

Bizarrely, Justice Scalia joined the Court’s opinion in its entirety except for its preliminary scientific discussion. In a separate concurrence, Justice Scalia wrote: “I am unable to affirm those details on my own knowledge or even my own belief.” Typically, Justice Scalia does not qualify the factual portions of opinions he joins, even where they involve science. And notably, in the Court’s recent decision in Maryland v. King involving the constitutionality of warrantless DNA tests for arrestees, Justice Scalia’s dissent is replete with the factual differences between DNA and fingerprint testing.

This likely brings to a close Myriad Genetics’ saga of aggressively enforcing its patents directed to BRCA1 and BRCA2 testing. Myriad will continue to offer its BRACAnalysis product, which, because of its trade secret mutational database, is likely still the most robust BRCA test on the market. And competitors will be able to enter the BRCA testing market and make use of Myriad’s methods, although they will have to do so without the benefit of certain cDNA molecules or Myriad’s clinical data.

But the decision leaves a number of legal questions unanswered: What about other patents directed to “isolated and purified” natural products? Are cDNAs nonetheless obvious, and therefore unpatentable for that reason? And, considering the Court’s mention of retrovirii, how “unusual and rare” must a “natural phenomena” be to still be patent eligible if synthetically created? These are issues that the lower courts are likely to struggle with going forward, and issues that may, one day, be back in the hands of the Supreme Court.

Jake Sherkow, JD, is a fellow at Stanford Law School’s Center for Law and the Biosciences. His current research focuses on the intersection of patent law, biotechnology, and agency regulation.

Previously: Supreme Court rules on Myriad’s “gene patenting” case and Are genes patentable? A summary of the Supreme Court case

Genetics, In the News, Medicine and Society, Science, Science Policy

Are genes patentable? A summary of the Supreme Court case

Are genes patentable? A summary of the Supreme Court case

As you likely heard, the Supreme Court heard oral arguments yesterday in a case that’s of interest to many biomedical researchers. That case, widely known as the “gene patenting case,” has a single question presented: “Are human genes patentable?” It may irk some researchers and clinicians that the answer isn’t a straightforward “no.” But the issues are surprisingly complex: How does one define a “gene,” and a “human” vs. a “synthetic” one at that? What about primers, probes, and cDNA? And what does one mean by “patentable”?

First, a brief lay of the legal landscape. Typically, an inventor cannot patent a “product of nature.” But ever since a 1911 appellate decision (.pdf), a natural product can be patented if it’s “isolated and purified” from its surrounding environment. Thus, the chemical compound adrenaline was itself patented because it was isolated and purified from adrenal glands. Shockingly, the Supreme Court has never directly reviewed this isolated and purified doctrine, even after 102 years.

This all raises the question of whether human genes should be allowed to be patented as a matter of policy, if not law.

And so, on this basis, isolated human genes have long been patented. In 1994, researchers at the University of Utah finally located and sequenced (.pdf) the BRCA-1 and BRCA-2 genes, variants of which put women at astonishingly high risk for early onset breast and ovarian cancer. Those researchers obtained patents on both the isolated sequences and cDNA variants of those, and assigned them to Myriad Genetics, a diagnostic testing company.

Arguments at the Supreme Court - and the justices themselves – grappled with the distinctions between isolated genomic DNA and cDNA. Lower court opinions had made a significant case out of the fact that because the covalent bonds of isolated genomic DNA were cleaved from the surrounding chromosome, an isolated gene was, in fact, a new chemical entity. Similarly, several justices suggested that because cDNA was not found in nature, it too, was patentable – even if it was simply the product of reverse transcribing an mRNA sequence. (For a further breakdown on the oral arguments themselves, see Stanford’s Center for Law and the Biosciences’ oral argument recap.)

But it seems that at least five justices – and thus, a majority – believe that patents on isolated DNA are not eligible for patent protection. They don’t seem to buy the argument that simple covalent cleavage renders something a new chemical entity. The Court and lawyers deployed various analogies to make this point: gold from ore, a piece of wood from a tree, a liver from a patient, etc. It seems less clear, however, whether a majority will similarly rule cDNA to be patent ineligible.

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