Molecular Medicine Israel

Life Science Controversies of 2016

This year, the developers of CRISPR gene-editing technology argued over patent rights, a researcher fought to unmask anonymous PubPeer commenters, US regulators considered “three-parent” babies, and troubles continued for Theranos.

Two ongoing disputes brought The Scientist to the courtroom to listen in on the proceedings this year. The first is a defamation suit that former Wayne State University researcher Fazlul Sarkar brought against anonymous commenters on the post-publication peer review website PubPeer. Sarkar asked the court to reveal the identities of the individuals who had accused him of image manipulation, a claim he disputes but which allegedly cost him a job. The second is a heated patent battle over the intellectual property rights for CRISPR-Cas9 gene-editing technology, which holds great medical and industrial promise.

Meanwhile, the controversial assisted reproductive technique known as mitochondrial replacement therapy (MRT), which creates an embryo using DNA from three individuals, made great strides, resulting in the first successful births and an international a debate around the procedure, which is banned in the U.S.

Sarkar saga

As 2016 dawned, former Wayne State University pathologist Fazlul Sarkar vowed to continue his legal fight against anonymous commenters on post-publication peer review website PubPeer as tech industry and scientific bigwigs weighed in on the case. In January, former National Cancer Institute Director Harold Varmus, former Science Editor in Chief Bruce Alberts, and tech titans Google and Twitter filed amicus briefssupporting PubPeer and the anonymity of commenters after a Michigan judge ordered the identities of one of those commenters revealed to Sarkar’s legal team and PubPeer appealed the decision.

In October, The Scientist attended that hearing, held  in the Michigan Court of Appeals in Detroit, and learned a couple of things: that PubPeer had made efforts to stop collecting anonymous commenters’ IP addresses so they could avoid similar legal proceedings in the future, and that Wayne State had conducted an internal investigation into Sarkar’s alleged misconduct in 2015. The Scientist obtained a copy of the university’s investigation report, which concluded that Sarkar fostered a culture of research misconduct over several years in his lab and was guilty of manipulating research images, as some anonymous PubPeer commenters had claimed.

American Civil Liberties Union lawyers representing the PubPeer commenters then successfully entered The Scientist’s reporting on the investigation into the appellate court record but subsequently failed to have the whole report entered into the record after they obtained it themselves.

But despite this minor setback, the anonymity of the PubPeer commenters remained intact after the court of appeals ruled that the commenters’ identities were protected under the First Amendment.

The next twists this legal drama may take are unclear, but earlier this month, Sarkar’s lawyer, Nicholas Roumel, told The Scientist that he and the pathologist had not yet determined whether they would appeal the decision to the Michigan Supreme Court or pursue some other course of action. “I have no idea what we’ll do next,” Roumel said at the time.

CRISPR patent dispute

Who should own the intellectual property for the use of CRISPR—a natural bacterial immune pathway—in eukaryotic systems? Should it be the Broad Institute of MIT and Harvard, which was awarded the first CRISPR patent in April 2014 based on the Feng Zhang’s work in human and mouse cells? Or should it be the University of California, Berkeley, where Jennifer Doudna and colleagues were first to file a provisional patent application for the use of CRISPR to edit genes, describing their work in prokaryotic cells and in vitro? (Or, as the court could well decide, should it be some combination of the two?)

The key to deciding who owns this lucrative technology—in a battle that came to a head this month as both sides presented their cases in front of a panel of US Patent Trial and Appeal Board judges—comes down to a single question: Was it obvious to use CRISPR in eukaryotes after Doudna and colleagues identified the components of the pathway (in other words, could CRISPR be used by a “person of ordinary skill in the art” of genome engineering to edit eukaryotic genomes with a “reasonable expectation of success”), or did that application require additional innovation?

The Broad Institute, which was awarded the first patent for CRISPR technology in April 2014, maintained that Zhang’s innovation was key to making the pathway work in eukaryotes. UC Berkeley, which filed for a patent interference, argued that it was obvious, and that Doudna and colleagues’ earlier work and patent application regarding the use of CRISPR in vitro and in prokaryotes should garner the valuable IP. And Rockefeller University’s Luciano Marraffini also stakes a claim for the technology.

See “<a href=" .view/articleNo/42595/title/Who-Owns-CRISPR-/” target=”_blank”>Who Owns CRISPR?”

See “Who Owns CRISPR, Cont’d

Catherine Coombes, a senior patent attorney with HGF Limited in the U.K., noted in an opinion piece that researchers within and beyond the field should take note of these ongoing disputes and make sure to take the proper precautions to avoid such trouble over IP ownership in their own work.

“Three-parent” babies

This year saw the first baby born as a result of MRT, also known as “three-parent” in vitro fertilization (IVF). The technique earned this nickname because embryos produced through MRT carry the mitochondria (and thus mitochondrial DNA, or mtDNA) of a donor egg, and nuclear DNA from an egg carrying mtDNA defects and from a sperm. In April, a couple from Jordan had a son following MRT performed at a clinic in Mexico by U.S.-based scientists.

MRT holds great promise for allowing women with mitochondrial disorders to have healthy children, and researchers continue to improve the technique. One recent advance aims to reduce the risk of transferring defective mitochondria along with the nucleus into the donor egg. Other works are revealing the potential importance of matching donor and carrier egg mtDNA haplotypes.

Meanwhile, regulators grapple with how to oversee this new technology. MRT is currently banned in the U.S., but last week (December 16), Britain’s Human Fertilisation and Embryology Authority greenlighted the procedure (clinics will have to get permission on a case-by-case basis). As MRT undergoes more testing in the lab and the clinic, it’s likely that the technique will continue to be a consideration for regulatory agencies around the world.

“MRT will probably emerge as an effective method to enable women with mitochondrial disease to have healthy children, among other possible medical benefits, and should not be banned because of presumed social or ethical complexities,” John Loike and Nancy Reame of the Columbia University College of Physicians and Surgeons write in an opinion article appearing in The Scientist’s January issue. “Given its potential for permanent alterations of DNA, this technology should not be viewed as equivalent to classical organ donation but rather treated with precautions in line with other germline interventions, such as egg or sperm donation, for which regulatory practices are already in place. Using these as a framework, governments and the scientific community should invest time and money into making MRT widely available to patients.”

More trouble at Theranos

In July, following a handful of federal investigations, including a criminal probe, Theranos founder and CEO Elizabeth Holmes was banned from running labs for two years. In August, Holmes gave a presentation at the American Association for Clinical Chemistry, in which—rather than addressing her firm’s existing technologies and issues—she presented the idea behind a new device, dubbed “miniLab.” The audience was not impressed. Nevertheless, Theranos announced in October that the company was turning its focus from blood testing to research. “We will return our undivided attention to our miniLab platform,” Holmes wrote in a letter to stakeholders.

The move signified “perhaps the most significant retreat for a company that had once been valued at $9 billion, higher than any other venture-backed private company in health care,” STAT News reported at the time. That same month, The Wall Street Journal—which in 2015 broke the story of shoddy results at the startup—reported on the experiences of patients who said they were misled by Theranos blood test results. Investors later said they had also been misled by the company. Meanwhile, Walgreens is suing Theranos for $140 million, alleging breach of contract.

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