The Fight for CRISPR Is Exposing the Dark Side of the Business of Science

Note: This story has been appended with a correction on Feb. 12, 2016, at bottom.

After the United States Patent and Trademark Office (USPTO) declared that an interference proceeding would take place in order to settle claims between the University of California and the Broad Institute of MIT, the internet exploded.

The two elite institutions are fighting for billions in potential profits from CRISPR gene editing technology while also perfectly illustrate the deep, systemic problems that emerge when science — fundamentally, a method of intellectual exploration — creates something of extreme economic value. CRISPR (clustered regularly-interspaced short palindromic repeats), is a powerful gene editing technique that gives scientists an enormous amount of control to modify the genome of an organism. The University of California requested the interference proceeding after the USPTO granted a patent to the Broad Institute. The request was made because the UC’s own Jennifer Doudna had not only published pertinent ideas on this topic previously, but had also filed for her own patent. Because the University of California made the request, the burden is on the Broad Institute to demonstrate that it invented the technique, and therefore, has the right to claim the technology.

Since 2013, the United States has been on a “first to file” patent system, meaning whoever files the application first gets the patent (assuming they actually invented the thing and did not steal it). Doudna’s patent application was filed one day before the U.S. made the switch to this system, however, meaning that the case will be heard under the previous system of “first to invent.” This means that a rigorous undertaking will have to be carried out to establish who had the “complete” idea first. The Broad will have to demonstrate both the idea and the “reduction to practice” (making it actually work, either by physically demonstrating it or publishing a written description). This process can rely on published data, but also on lab notebooks, email correspondences, even personal notes.

This will be a grueling fight, with fortunes and fame on the line, and the competing institutions are leaning in. Immediately after the USPTO announcement, Eric Lander, head of the Broad Institute, published an article called “The Heroes of CRISPR” that highlighted the history of CRISPR. Or rather, the “history” of CRISPR.

Other scientists and commentators blasted Lander’s piece as a biased attempt to manipulate the public record to support Zhang. One response accused Lander of attempting to write women out of the field, reminiscent of the way Rosalind Franklin was excluded from credit for her work in elucidating the structure of DNA. Doudna herself even stated that Lander’s article was factually incorrect. The most egregious offense committed by the article, as most saw it, was that there was no conflict-of-interest statement to make clear Lander’s association with the Broad and its dispute in the matter.

One of the more outspoken critics of Lander’s article, Michael Eisen, also at UC Berkeley with Doudna, responded by writing “The Villains of CRISPR” on his own blog. In it, Eisen dissects many aspects of Lander’s article and effectively calls it out as science propaganda by a man abusing his position of power. Eisen makes a great case, but also declares that he would prefer a system in which no one patents any scientific discovery.

Not only do I think this is unlikely, I think we’re in for more Eric Landers.

Eisen, I believe, is saying that it’s not in the spirit of true science to try to patent discoveries — that the sort of person who tries to capitalize on discovery seems to have prioritized business opportunities above discovery itself.

If science were conducted in a world of infinite resources, I would be inclined to agree with Eisen. But he is a member of an elite group of scientists that have very large budgets that come largely from the Howard Hughes Medical Institute (HHMI), one of the three largest biomedical philanthropic organizations in the world (as of 2012, HHMI had 13 Nobel Laureates on its payroll and assets in excess of $18 billion). Though Eisen is an outstanding scientist and certainly deserves generous, stable funding, I can’t help but wonder if his position has lessened his sensitivity to the instability most scientists face.

Lab budgets like Eisen’s were made possible by Howard Hughes himself, the billionaire tycoon. Hughes, incidentally, got his start after inheriting a massive fortune from his father, who had built a lucrative business around a patent for a drill bit. So while I am certainly sensitive to (and even genuinely appreciate) Eisen’s desire to keep patents out of scientific discovery, it strikes me as pollyanna. While Eisen may be right that patents don’t help to make the technology widely accessible, they do help to make the technology available in the first place. (I should also disclose here that I serve as a technical expert for Rocky Mountain Patent, so I am not unbiased myself.)

It may not be a perfect arrangement, but neither is academia. NIH funding (e.g., NINDS) trends are moving away from blue skies, basic research, and towards translational projects. Universities appear more than happy to support a trend in developing ideas that can be licensed. And, as it turns out, academic science is oversaturated with scientists competing for limited resources, a well-known situation among scientists that appears to be getting much worse. All of this appears to be driving a linearity in thinking toward conservative, goal-directed projects that have a higher chance of getting funding. But, like Albert Einstein said, “If we knew what we were doing, it wouldn’t be called research.” Proposing things that we already know will probably work doest tell us much. It’s blinkered thinking, and doesn’t maximize the value of taxpayer-funded science.

In an ideal world, resources would not be so fiercely fought over and new technologies could be shared freely. But our current system is likely to endure, as there doesn’t appear to be any large-scale resolutions coming in the near future. As the next generation of students and graduates is forced to prioritize career over research interest, those individuals most skilled at networking and self-promotion — talents that are independent of scientific acumen — will excel.

While academia invests resources into grooming schmoozy researchers and enriching for alpha scientists, the (often very highly skilled) individuals leaving this system have to be going somewhere, and the private sector seems to be largely reaping the benefits. The career path in academia is well-defined and leaves little room for variation. Conversely, a career in the private sector is fairly wide open, and requires one to chart her own course. If your interest is in lateral thinking, this decision seems easy. And patenting, incidentally, is the bedrock of the private industry.

Academia was once regarded as the only place where “blue skies” research occurs, the kind without a clearly defined (or marketable) end. But competition there has become so fierce that even many academics are prioritizing careerist thinking before scientific thinking. They must find ways to creatively promote, monetize, or otherwise exploit their contributions. As a result, we’re incentivizing brazen self promoters. Jeffrey M. Drazen, an extremely highly regarded physician scientist, recently tried to call any scientist who uses data not generated by themselves a “data parasite,” in an ostensible attempt to establish data ownership. Incidentally, this is the exact opposite of how science is actually carried out (else we call the Theories of Relativity parasitic). Drazen was brutally called out.

While I am wont to give Lander the benefit of the doubt, I am forced to admit that this certainly reads like a deliberate attempt to leverage his position in order to manipulate the system, and I have yet to hear a response from him to convince me otherwise — but time will tell. If true, though, it is unsettling. That he can justify an action like this — not only to himself but also outwardly — points to a victor of dollars over knowledge. As the leader of an extremely prestigious institute and a major role model in science, this is indeed pernicious, and may foretell the way that the business of academic science is conducted in years to come.

Perhaps this points to the trouble with holding any highly regarded post. The more prestigious the job, the more it seems to attract the wrong sort of person — or to cultivate the wrong attitude in an otherwise good person. We primates certainly seem to be starting to abuse an otherwise outstanding system of discovery and understanding. If only scientists were regarded as deadbeats! Maybe then they wouldn’t attract power-hungry careerists.

This all may come down not to the allure of industry so much as the failure of academia to provide the spirit of thoughtful openness. One way or another, though, I’m confident we’ll find a solution. The human spirit of discovery is powerful and such an enormous source of satisfaction for so many of us. Whether that solution involves an intact academic structure as we know it remains to be seen.

Story update Feb. 12, 2016: The following sentence has been removed from the original article: “Despite Doudna having generally been recognized for her contribution to the work (in particular by a 2015 Breakthrough Prize), and despite having applied for a patent first, Zhang applied for fast-track approval, and was therefore awarded the patent first.” As the Broad Institute has pointed out, Feng Zhang shared a Gabbay Award with Doudna in 2014. Because the reference to the Breakthrough Prize was mentioned as a means to indicate her claim as an inventor, this has been removed, as it is not relevant. Wording of this sentence in the original article suggested that the fast-track status of Zheng’s application was the definitive reason that the Broad was awarded the patent before the University of California was. The Broad Institute, however, contends that the USPTO made the decision to grant a patent to Zhang. et al. because its application more definitively demonstrates “reduction to practice,” which challenges this assertion. This section has been adjusted to be less suggestive.

Additionally, the original article inferred that Dr. Lander had failed to disclose his professional interests to Cell in his article, “The Heroes of CRISPR.” The Broad Institute points out that Lander indeed disclosed his professional interests, but it is the policy of Cell Press to publish only personal conflicts of interest. The paragraph has been modified accordingly.