The soul of academic science is being destroyed, one patent at a time.
Nowhere is this more evident than in the acrimonious battle between the University of California and The Broad Institute of Harvard and MIT over who owns the rights to commercialize gene and genome editing systems based on the CRISPR immune system of bacteria. There are a dizzying number of patents involved in this dispute, and many more players staking claims to what has the potential to be billions of dollars in royalties down the road. But the heart of the matter is rather simple.
UC claims it should own broad rights to CRISPR-based gene editing because UC Berkeley’s Jennifer Doudna and colleagues were the first to show how a protein (Cas9) from the bacterium Streptococcus pyogenes could be weaponized to permit the easy editing of DNA. (Full disclosure: I am a professor in Doudna’s department). The Broad counters that they should get the rights to the application of CRISPR-based gene editing in humans and other eukaryotes (which include all animals, fungi and plants – i.e. most of the organisms where there is money to be made) because, they assert, The Broad’s Feng Zhang was the first to demonstrate the use of Cas9 in eukaryotic cells.
Last week a panel of judges of the U.S. Patent Trial and Appeal Board sided with The Broad, finding that the application of CRISPR-based gene editing to humans and other eukaryotes was not an obvious extension of demonstrating the basic utility of the system, and hence constitutes a separate patentable invention.
I encourage you to read the judges’ decision. Far from being a descent into an arcane warren of patent law, as most people seem to expect, this case is very straightforward, resting on the simple question of whether the extension of CRISPR from bacteria and a test tube to human cells would have been expected to work by someone or ordinary skill and experience in the field. I don’t agree with the ruling, but the judges offer a lucid and very accessible account of what was presented to them and how they arrived at their decision.
While on the surface this case seems like a fairly mundane “I invented it first! No I did!” dispute, albeit with unusually large financial stakes, to me it represents something far more important: a battle for the very soul of academic science and the principles upon which it is based.
When I first heard, in 2012, that scientists in the Doudna lab had discovered that the Cas9 protein cuts DNA at a specific point based on instructions in a small piece of RNA, and that they had invented a way to simplify its application, I didn’t give a moment’s thought to patents. Instead I marveled that evolution, through the never ending fight between organisms and the viruses that plague them, had created a protein whose key properties were just what was needed to allow molecular biologist to easily edit the DNA of their favorite organism.
If academic science worked like it should we all would have spent the subsequent five years focused only on figuring out all the cool things we could do with this new toy – and there are a lot of cool things. But where we should have seen nothing but scientific opportunity, many saw dollar signs, and the flurry of CRISPR activity beginning in 2012 has become as much a patent gold rush as a journal of discovery.
The academic quest for patents is no longer the side story. Where once technology licensing staff rushed to secure intellectual property before scientists blab about their work, patents now, in many quarters, dominate the game. Experiments are done to stake out claims, new discoveries are held in secrecy and talks and publication are delayed so as not to interfere with patent claims. This is bad enough. But the most worrying trend has been the willingness of some researchers and research institutions to distort history, demean their colleagues and misrepresent the scientific process to support these efforts.
And while all of academia is complicit, The Broad Institute has taken the game to a new level. In 2015, as the patent fight was heating up, The Broad published a “CRISPR timeline” which defined history as ending with Feng Zhang’s demonstration of CRISPR gene editing in human cells. It also demoted the work from Berkeley to playing second fiddle to the work of Virginijus Siksnys’s group who, conveniently, did not have a competing patent claim.
The Broad set up a website describing their patent claims, which includes the following statement:
In April, 2014, the USPTO granted Patent No. 8,697,359 to Broad Institute, MIT and Dr. Feng Zhang. This Patent (which draws priority from a provisional patent application filed in December 2012) contained successful experiments.
Implying, absurdly, that the Berkeley application did not.
Then there was The Broad Institute Director Eric Lander’s widely derided “Heroes of CRISPR” essay in Cell which further rewrote history. Written under the conceit of giving credit to forgotten scientists, Lander wove a sweeping story of scientists toiling in obscurity until The Broad stepped in an made their work important. Doudna and her close collaborator Emmanuelle Charpentier were once again reduced to bit players in this narrative.
This was all clearly done as part of a public relations strategy to support their patent case, in which the assault on reality continued.
We can agree or disagree whether or not it was obvious that Cas9 would ultimately work in eukaryotic cells. The expert testimony shows that cogent arguments can be made on either side. But The Broad chose not to rely on cogent arguments. They had a trick up their sleeves. They scoured Jennifer Doudna’s public statements about the process of getting CRISPR to work in human cells, and found some where she appeared to be making The Broad’s case for them, which they submitted as evidence for their case and trumpet on their website.
For example, The Broad highlighted Doudna saying she experienced “many frustrations” in getting CRISPR to work in eukaryotic cells. But one can believe that it was obvious that CRISPR would work in eukaryotic cells, and still not expect that it would work the first time someone tried it or that the process would be free or frustration. Because that’s how science works! It is often difficult and frustrating – indeed it almost always is – even when you’re working on something that is obvious. Lander knows this. He was once a scientist. And yet he and The Broad are perfectly happy to misrepresent the scientific process to bolster their legal case.
A second quote featured by The Broad has Doudna saying “it was not known whether such a bacterial system would function in eukaryotic cells.” But this is an absolutely true statement that any good scientist would say even if they believed CRISPR would work in eukaryotic cells. In science something is not known until you demonstrate it. This is what any good scientist should say when they have yet to prove that something is true. By pretending that this is a statement about the patentability of CRISPR in eukaryotic cells, The Broad is once again misrepresenting the scientific process and condemning Doudna for little more than being a careful scientist and speaking honestly about it.
Is this the lesson we really want to learn from CRISPR? That scientists working in fields with commercial potential should never speak honestly about their work and the scientific process? That if they do they will get screwed over by someone unscrupulous who prioritizes winning patents and trains their scientists to behave like clandestine operatives rather than the public servants they really are?
By making the scientific process itself party to their legal case, Lander and The Broad are doing more than just securing victory in court; they are willfully undermining science for personal and institutional gain. If academics – including one of the most prominent academic scientists in the world – are willing to lie to promote their own and their institution’s financial interests, why should anyone believe anything they say? If there’s one thing that’s more dangerous than fake news, it’s fake science.
And it’s not just The Broad. While in this case UC’s defense of their CRISPR intellectual property could rely on a truthful account of its discovery, I have no doubt that they would be willing to resort to unsavory tactics and falsehood to secure victory (see their history of trying to coverup cases of sexual misconduct).
Sadly, there will always be venal and weak people in science – it is, after all, a human endeavor. But we do not need to feed them. As we decry The Broad’s behavior, we have to recognize its source – the transformation of academic science from an engine of discovery into a source of institutional and personal riches. And there is a simple way to reverse this trend: deny academic institutions intellectual property in their research and inventions.
Academic science is, after all, largely funded by the public. By all rights discoveries made on with public funds should belong to the public. And not too long ago they did. But legislation passed in 1980 – the Bayh-Dole Act – gave universities the right to claim patents on inventions made by their researchers on the public dime. Prior to 1980 these patents belonged to the federal government and many languished unused. The logic of Bayh-Dole was that, if they owned patents in their work, universities and other grantees would be incentivized to have their inventions turned into products, thereby benefiting the public.
But this is not how things worked out. Encouraged by a small number of patents that made huge sums, universities developed massive infrastructure to profit from their researchers. Not only do they spend millions on patents, they’ve turned every interaction scientists have with each other into an intellectual property transaction. Everything I get from or send to a colleague at another academic institution involves a complex legal agreement whose purpose is not to promote science but to protect the university’s ability to profit from hypothetical inventions that might arise from scientists doing what we’re supposed to do – share our work with each other.
And the idea that this system promotes the transformation of inventions made with public funding into products is laughable. CRISPR is a perfect case in point. The patent battle between UC and The Broad is likely to last for years. Meanwhile companies interested in actually developing CRISPR into new products are stymied by a combination of a lack of clarity about with whom to negotiate, and universities being difficult negotiating partners.
It would be so much easier if the US government simply placed all work arising from federal dollars into the public domain. We have a robust science and technology industry ready to exploit new ideas, and entrepreneurs and venture capitalists eager to fill in where existing companies are uninterested. Taxpayers would benefit by allowing the market, and not university licensing offices, to decide whose ideas and products make the best use of publicly funded inventions.
And most importantly we all would benefit returning academic science to its roots in basic discovery oriented research. We see with CRISPR the toxic effects of turning academic institutions into money hungry hawkers of intellectual property. Pursuit of patent riches has transformed The Broad Institute, which houses some of the most talented scientists working today, into a prominent purveyor of calumny.
We have to fix this problem now or there will be countless other Jennifer Doudnas slimed by colleagues, their contributions to science attacked not for their validity or importance, but for their impact on some other institutions patent portfolio. The soul of academic science is at stake.