There’s been a lot of talk about crowdsourcing lately. Everything from criminal investigations, to the tax code, to ski resorts have been crowdsourced or considered for crowdsourcing. And now medicine has thrown its hat in this trendy ring. KQED’s “Future of You” recently reported on a company called CrowdMed that wants to be the “Wikipedia of medicine.” (Due to space constraints, this blog post will not engage the important question of whether Wikipedia itself, is, in fact, the Wikipedia of medicine.)
In 2010, Congress enacted the Biologics Price Competition and Innovation Act (BPCIA) as part of the Affordable Care Act. BPCIA is, in a broad sense, intended to be the analog of the Hatch-Waxman Act for biologic drugs. Hatch-Waxman provides a pathway for Food and Drug Administration (FDA) approval for small-molecule generic drugs. Vastly simplified, the Hatch-Waxman process comes down to this: if a follow-on (i.e., generic) manufacturer can make an identical copy of the branded drug molecule, it can obtain FDA approval to market the drug without the clinical trials that the drug’s originator had to go through to prove that the drug is safe and effective. This saves costs for the generic manufacturer and, once the generic goes on the market, lowers prices for consumers. Under Hatch-Waxman, a follow-on manufacturer’s act of filing a so-called Abbreviated New Drug Application is an act of patent infringement, and so the originator can try to keep generic drugs off the market using patent law. The Food, Drug, and Cosmetics Act also provides periods of market and data exclusivities even for originator drugs that are not covered by patents. But once those periods end and the generic manufacturer can prove chemical identity to the brand, the generic drug is good to go on the market as far as the FDA is concerned—and the only barrier left is the brand’s potential patent infringement claims.
For those of you who may have an interest in the intersection of Law, Policy, and Neuroscience, we are now looking for our next SPINS (Stanford Program in Neuroscience and Society) fellow. See the call for applications here.
Asilomar is one of my favorite places in the world. It is just on the west side of the northern end of the Monterey peninsula in Central California, between the towns of Pacific Grove and Monterey to the east and Pebble Beach to the south. Although it is used as a geographical designation for that part of the peninsula, the name comes from a conference center created by the Young Women’s Christian Association (the YWCA), which sits on and behind sand dunes, just across the road from the surf and tide pools of the Pacific.
The following history is taken largely from the history page at the Asilomar Conference Center’s web site: http://www.visitasilomar.com/history/asilomar-the-complete-story.aspx. From 1900 the YWCA held annual meetings of its Pacific Coast Field Committee and a Western Regional Conference at a hotel in Santa Cruz, California. That hotel burned down in 1912, leading the committee decided to build its own site.
The very long post I put up yesterday about the call for a moratorium on germline genome modification in humans made me think about Asilomar and its parallels. I know that STS (Science, Technology, and Society or Science and Technology Studies) scholars have long debated the value of the “first” Asilomar, the Asilomar Conference on Recombinant DNA held in February 1975, and its lessons for other efforts. I have not looked into any of that research for this post, but instead am putting up my very lightly researched thoughts. I conclude that, at this point, there have been at least two “Asilomars” with several other contenders for the label and two other topics possibly ripe for one.
On Thursday, March 19, 2015 Science published (on-line) a Policy Forum entitled A Prudent Path Forward for Genomic Engineering and Germline Gene Modification. The piece had 18 authors, including David Baltimore, Paul Berg, Alta Charo, George Church, George Daley, Jennifer Doudna, Ed Penhoet, Keith Yamamoto, and (as, with Alta, one of only two non-scientists and definitely as one of the lesser lights) me. The Policy Forum recommended that steps be taken to “strongly discourage…any attempts at germline genome modification for clinical application in humans, while societal, environmental, and ethical implications of such activity are discussed among scientific and governmental organizations.”
A bit more than forty years earlier, on Monday morning, February 27, 1975, David Baltimore opened the famous Asilomar conference on recombinant DNA. That conference had been called after a letter in Science from the leaders in the field called for a moratorium on recombinant DNA research until important safety issues could be worked out. The three and a half days of the Asilomar meeting produced safety guidelines which led the group to lift their (totally informal and non-binding) moratorium – and ultimately led the NIH Recombinant Activities Committee; to federal (and foreign) biosafety regulations; in some tellings the wildly successful application of recombinant DNA techniques to research and medicine; and, undoubtedly, the most famous story in modern scientific self-regulation. (An excellent, non-speculative, memoir of the Asilomar meeting by George Frederickson, head of the Institute of Medicine at the time of Asilomar and director of NIH a few months later, can be found here.)
Our own Hank Greely has co-authored an article, published yesterday in Science, discussing the opportunities and challenges presented by genome engineering technologies. Krista Conger, writing for SCOPE, the Stanford Medical School’s blog, discusses the article in a recent post. Read Krista’s post here.
It’s almost spring break here at Stanford, and in that vein, I thought I’d talk about a topic that is likely to be on at least a few spring breakers’ minds: marijuana.* Last week, a bipartisan trio – Senators Booker, Gillibrand, and Paul – proposed the Compassionate Access, Research Expansion, and Respect States (CARERS) Act, which has been described as the “first ever” Senate bill to “legalize” medical marijuana.
It is a tautology to say that our political views affect our attitudes toward various societal issues. If I knew in advance whether you were a conservative or a liberal, for example, I could probably predict with better-than-chance accuracy your views on climate change, teaching evolution in public schools, or genetically modified foods.
But did you know that our political leanings can also alter our perceptions of reality?
This may seem surprising, but it’s true. A growing body of research shows that our political beliefs can influence not only the way our brains interpret and remember scientific information, but even our subjective perceptions of our physical environments.
In mid-February, the USDA approved the first genetically engineered (GE) apples. These apples will be marketed as Arctic® apples, and have been modified to stall browning after cutting or bruising. In an interesting Q&A sheet, the USDA explained its approval process. It is required to approve (technically, to “deregulate”) a crop once sufficient evidence shows that the crop meets pest safety standards set by the USDA Animal and Plant Health Inspection Service (APHIS)—the crop must be unlikely to be a pest to other agricultural crops or plants. The Arctic® Apple passed these pest tests conducted in both Washington and New York states, which combine produce almost 70% of all apples grown in the United States.
The FDA is also involved. Although it considers deregulated biotech crops similar to their conventional counterparts, it provides a voluntary consultation process to help ensure food safety. The biotech company, Okanagan Specialty Fruits, is apparently still waiting for the FDA’s approval through this voluntary review process.
There has been, and will continue to be, controversy surrounding these apples. Characteristic of the larger food genetic engineering debate, the USDA stated that the majority of public comments received, “did not raise any specific disagreement with APHIS’ analysis of the pest risk of this GE apple. Rather, they expressed general opposition to GE organisms or GE apples.” The company has conceded that many stores might be hesitant to stock GE apples for fear of customer backlash. And other apple growers oppose the new technology, citing concerns that customers will associate all apples as GE apples (although in the age of organic, I’m skeptical about this complaint).
Despite these fears, concerns, and doubts, I’m optimistic that GE apples could be good for both consumers and for reframing the GE debate.
(1) The Technology
When a normal apple is cut or sliced, the enzyme polyphenol oxidase (PPO) is produced and is responsible for the immediate apple-enzymatic browning. But this pathway can be silenced when copies of low-PPO genes from other apples are inserted. This modification silences the normal PPO gene. The modified Arctic® Apples end up producing only 10% of PPO amounts compared to traditional apples, which is not enough to cause browning. PPO does not affect other apple pathways and Arctic® Apples will still undergo normal rotting.
For some opponents to GE technology, could this type of engineering be an acceptable form of GE? There might be less fear about crossbreeding or “Frankenfruits” or fear that these apples are “unnatural,” since they still only contain apple genes. There could be less confusion about what is being added to the fruits since it is a relatively easy process, and gene, to explain. Even without genetic modification, consumers could imagine a similar mutation happening naturally after years of DNA replication, and then continued through selective breeding.
(2) The Public Health
Apples are healthy. Kids (generally) like apples. Kids (generally) like apple slices even more. Cheaper, more appetizing, and easier to package fruit could help transform cafeteria lunches and reduce cafeteria waste. And apples that don’t turn brown as quickly or as often meet all those criteria.
Additionally, as with Golden Rice, the public understands that we need nutritional solutions both in developing and developed settings. These apples provide another example of biotechnology that could help with obesity and poverty. It is inherently easier to support something that is healthy, compared to something like corn that is used in high fructose corn syrup or even the GE potato (which might be the next approved new GE crop).
(3) The Small Company
Monsanto didn’t create this! Okanagan Specialty Fruits is just a small company, without a reputation for profit seeking or pesticide advocating products. As cynical as this sounds, it is great that a smaller biotechnology company created this apple—not just for public perception, but also for opening the field of genetic possibilities to smaller companies. Biotechnology doesn’t always have to be associated with Big Agriculture!
There are still many challenges regarding public acceptance of GE fruits before Arctic® Apples go mainstream. McDonalds and Gerber both announced that they had no plans to sell or use Arctic® Apples. But I do hope that products like these will help further meaningful and informed conversations about what types of technology we are willing to accept in our foods.
For more information about the company, the products, and what these apples are all about, visit Okanagan Specialty Fruits.
Malia McPherson is a 2L at Stanford Law School
The American Quarter Horse is a breed that excels at sprinting over short distances—Quarter Horse races may range from 220 to 870 yards. It is the most popular breed in the United States, and the American Quarter Horse Association (AQHA), headquartered in Amarillo, TX, is the largest horse breed registry in the world. Because of the interest in this breed, Quarter Horses have become the subject of commercial efforts at reproductive cloning. One company, Viagen, has produced over 150 cloned foals. The cloning is achieved via somatic cell nuclear transfer (SCNT), the technique that famously created Dolly the Sheep. As some readers may be aware, Dolly was the focus of In re Roslin Institute (Edinburgh), 750 F.3d 1333 (2014), an important patentable subject matter eligibility case decided by the Federal Circuit last May.
While Roslin dealt with animal cloning and patent law, a recent Fifth Circuit case, Abraham & Veneklasen Joint Venture v. American Quarter Horse Association, No. 13-11043, 2015 WL 178989 (Jan. 14, 2015) (Fifth Circuit Opinion), addresses antitrust law issues raised by animal clones. AQHA registry is essential for the owners of Quarter Horses to have profitable horse breeding businesses. According to the Fifth Circuit, “[w]ithout access to AQHA’s breed registry, . . . the cloned horses cannot participate in the lucrative racing, breeding or horse shows.” Id. at *1. AQHA registers horses born from in vitro fertilization and artificial insemination techniques, but it does not allow the registration of clones. Interestingly, the Jockey Club, which is the breed registry for Thoroughbred horses in the United States, Canada, and Puerto Rico, does not allow registration of horses produced by any assisted or artificial reproduction techniques. In contrast, cloned polo ponies are allowed to compete in events alongside their natural-born counterparts. So AQHA is somewhere in between.
On Tuesday, the Supreme Court declined to review a California court’s decision that a plaintiff could sue generic drug companies on certain failure-to-warn claims. If you’ve been following the Supreme Court’s drug-labeling-preemption decisions over the last 5 or 6 years, you might find this news a little surprising at first glance. After all, as I explained in a blog post about a year ago, state failure-to-warn claims are generally preempted by federal law for generic drugs. But, once you dig into the facts of the California case – Teva Pharmaceuticals v. Superior Court – the outcome isn’t all that surprising, and it highlights some of the nuances of when state failure-to-warn-claims are, and are not, preempted in the generic drug context.
So what happened in this case?
In this edition, we discuss sunscreen regulations, fetal DNA testing patents, intermittent fasting, and Ebola.
If you’re a regular listener to the CLB podcast, you’ll hear me, in our next episode (coming soon!) discussing the latest neuroscience research on intermittent energy restriction (IER). IER, as the name implies, involves intermittently restricting energy intake, or calories. You can do this in several ways. In one method you severely restrict calories (think 400-500 total intake per day) two to three days a week; in another you confine your food intake to an 8-hour period every day; and in yet another you fast once a week for a 24- to 36-hour period.
Sound intriguing? Difficult? Impossible? Read on . . .
An article published last month on Law360 (behind paywall) discusses recent developments in the law of patent eligibility, which is enforced through Section 101 of title 35. We have covered patent eligibility issues on this blog before in connection with diagnostic patents and patents on isolated DNA, and these posts (and others) have a great deal of helpful background information on the applicable law. By way of a brief recap, Section 101 limits patent eligibility to processes, machines, manufactures, and compositions of matter. The courts have held, however, that even if a patent claim nominally falls into one of these categories, the claim is not patent eligible if it is directed to a law of nature, a product of nature, or an abstract idea. The courts have recently explained that, to survive a patent eligibility challenge, the claim must be directed to an inventive application of a law of nature or abstract idea. And if the material is alleged to be a product of nature, it must be markedly different from the natural counterpart.
The authors of the article, Professor Bernard Chao of University of Denver Sturm School of Law and Lane Womack of Kilpatrick Townsend & Stockton LLP, briefly survey the landscape of Section 101 case law and go on to discuss a few patent applications that the U.S. Patent and Trademark Office (PTO) recently rejected on patent eligibility grounds. Although the highest-profile patents are those that have been the subject of court cases, Chao and Womack—though based on an “admittedly unscientific and small sample”—show how the law works on the ground. The authors focus on rejections of composition of matter claims under the product of nature doctrine. In particular, they document a PTO rejection of claims to isolated human monoclonal antibodies that “neutralize a HIV-1 virus in vitro” because these antibodies are not markedly different from antibodies amplified from patient B-cells. The authors also discuss a patentable subject matter rejection of claims to compositions that include peptides for interfering with replication of cancer.
Watching Your Spouse Die on a Television Reality Show: De-Identification as a Myth, in Death and Life
Much biomedical research relies on the idea of “de-identification.” The Common Rule, the federal regulation on human subjects research, applies, as a general matter, if the researchers make some kind of intervention with the research subject or if they use “identifiable private information” about the research subject. But the “Private information must be individually identifiable (i.e., the identity of the subject is or may readily be ascertained by the investigator or associated with the information) in order for obtaining the information to constitute research involving human subjects.”
If the private information was not collected by the researcher (it comes from someone’s medical record or was collected as part of someone else’s research) and the research subject’s identity is not known to and cannot “readily be ascertained” by the researcher, it doesn’t count. No consent is required, no IRB review is required – it isn’t “human subjects research.”
And why should it be? If no one knows it is you, you cannot be hurt, or so the argument goes.
On January 2, the New York Times published an extraordinary article entitled Dying in the E.R., and on TV Without His Family’s Consent by Charles Ornstein, a reporter for ProPublica. It recounted how Anita Chanko, a 75-year-old widow, watching an ABC reality television show, NYMed, suddenly realized that she was watching her husband’s death in the emergency room. More than a year earlier, the 83-year-old man had been hit by a garbage truck while crossing the street and had died in the NewYork-Presbyterian hospital. The televised version blurred his face, but not the face of the surgeon, the description of the accident, or the sound of her late husband’s voice, asking “Does my wife know I’m here?”
Yesterday, Bloomberg reported that drugmakers are working with third-party companies to link pharmacy records with online accounts, to tailor drug ads to a person’s particular needs. In other words, if you buy drug X at the pharmacy – the example drug trotted out in the Bloomberg piece is Viagra – a drugmaker will know you bought drug X, and will tailor online ads accordingly (buy more of drug X! buy drug Y, which treats the same condition as drug X! etc). The links between pharmacy records and online accounts, called “matchbacks,” are made without names changing hands, meaning drugmakers don’t know the names of the patients that they are targeting with particular ads. But, nevertheless, a number of quotes in the article raise privacy concerns. And when I tweeted this story, my spouse’s immediate response was “creepy.”
If you missed our October 13th conference on how the United States should regulate genetic testing, you can now watch video of the conference. It was a fascinating day, with speakers from industry, government, professional associations, genetic counseling, and academia contributing their perspectives. Check it out here!