curiosity and the CRISPR controversy

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Not that kind of crisper. 

CRISPR is an acronym for a gene editing technique that has been cited as one of the most important biomedical discoveries of our time. Although it is not yet being used to genetically modify human embryos (think designer babies), it is only a matter a time (an initial attempt was made in China). What the acronym stands for is a bit of a science word sandwich (a clever description of complex scientific terms I recently heard listening to TWiEVO). Essentially, CRISPR is a region of DNA in bacteria that works in conjunction with an enzyme, Cas9, that is capable of cutting double-stranded DNA (the DNA comprising your chromosomes) and editing the DNA sequence. The coverage of CRISPR in the popular media has been extensive.

The reason I planned to bring up CRISPR was because of a review article published in the journal Cell on January 14^th. Its relevance here was immediately apparent due to its goal of reviewing 30 years of discoveries that led to the widespread use of CRISPR as the most effective and efficient gene editing system to date. And, unlike most reviews published in high profile peer-reviewed scientific journals, the author included personal narratives for some of the significant players. Originally my intention was to point it out and move on. I was actually going to do it last week when I was on vacation and didn’t have a lot of time to write.

And then there was the ‘Twitter storm’. The author of the Cell paper, Eric Lander, got called out in a huge way. And these were not just a few mumblings here and there, it was by major players in the field of molecular biology. The tweets got attention and eventually led to this and this.  So I took a closer look. There are essentially two labs vying for the intellectual property rights of CRISPR and they are in an ongoing patent dispute. On one side is Jennifer Doudna (UC Berkeley) and Emanuelle Charpentier (Max Planck); on the other is Feng Zhang (Broad Institute of MIT and Harvard - of which Eric Lander is the founding director). Eric Lander is thus being accused of using his status and influence in the middle of a high stakes intellectual property dispute to record a story that will, if carved into history, bring huge benefits to his institution.

The CRISPR dispute highlights several issues in addition to curiosity including the pursuit of discovery, competition, strategy, bioethics, egos, patents, awards, money, and honesty. And, in this instance, there is also potential for issues of gender dynamics to come into play as well (full disclosure, I am a woman). While I may address some of these issues in later blog posts, today I am going to focus on CRISPR, curiosity, the pursuit of discovery, honesty, and who should get credit.

As Eric Lander correctly points out, many of the early discoveries that established the groundwork for CRISPR were not pursued with the intent of developing a groundbreaking gene editing technique. This is also true for the foundational data supporting many discoveries, and one of the things I love most about science. As more and more data accumulated describing how CRISPR worked, its potential for editing genes in organisms other than bacteria became clearer. This type of critical mass occurs often in science because as data accumulate, resolution increases, and suddenly the entire picture of possibilities comes into focus. Often by multiple scientists at the same time. One well-known example of this is the theory of evolution by natural selection. Both Charles Darwin and Alfred Russel Wallace were independently accumulating data and evidence for a theory that would explain the variation they observed as they explored various plants and animals around the world. The coincidence of their ideas is not that surprising as they were both relying on data that had accumulated up until that point in history including fossil discoveries, geological data, and the work of Thomas Malthus, a political economist.

What I find interesting in such situations is how the stories associated with discoveries get woven into our discourse. Even though Darwin and Wallace presented the theory of natural selection simultaneously in 1858, it is Darwin’s name that carries the association. And this is not uncommon, as time moves forward, and stories are told and retold, one name often sticks. For CRISPR, we are at that fork in the road; whose name is going to stick? At present, Doudna and Charpentier have each received a $3 million Breakthrough Prize while Zheng was given rights to the patent. A recent story in The New Yorker on CRISPR profiled Zhang almost exclusively. And then, of course, there is Lander’s Cell review, also featuring Zhang.

The blog, Genotopia, hit the nail on the head when the writer, Nathaniel Comfort, referred to this as “whig history”. Essentially, historical accounts are often generated from a single perspective, and are largely influenced by who recorded the story, how it was portrayed, and how loud their voice was. If the accusations against Lander are true, it is clear why he didn’t address the competition occurring between these two labs in his review (although it is still surprising to me that he could completely breeze by the patent dispute, and Cell would let him get away with it). (To be fair, Doudna and Charpentier published a review in 2014, and while they cited the work coming out of Zhang’s lab, they did not include it on their major timeline of events. And, one could argue it is reasonable that they didn’t address the competitive aspect of their discovery since the review was written by them and would of course be biased.) There is clearly a lot more going on here, and Lander knew about it. Competition occurs, it is not uncommon for two labs to be working on similar things; and if you are going to write a review, especially one with colorful personal narrative, talk about it. That is my goal on this blog. Tell the story. Not the story where we dreamed up a hypothesis, tested it, and made a huge a discovery. The real story. If there is a fight, talk about it. If you have a stake in the game, don’t hide it. If there is an intellectual property dispute and the parties involved can’t talk about it, don’t pretend it’s not happening.

I will leave you with a quote from George Church (Harvard), one of the quieter players in this story, that was published in The New Yorker story: “No single person discovers things anymore……….The whole patent battle is silly. There has been much research. And if anybody should be making a fuss about this I should be making a fuss. But I am not doing that, because I don’t think it matters. They are all nice people. They are all doing important work. It’s a tempest in a teapot.” 

I would say it is multiple egos in a teapot, where the teapot environment is burdened by limited funding dollars fueling competition and battles for credit. Can credit really go to just three people? (Three is the maximum for a Nobel Prize.) And, patents? A topic for another day.