Professor Eric Lander in 2003., following the announcement of the creation of The Eli and Edythe L. Broad Institute of biomedical research. (Josh Reynolds/ AP)

The CRISPR Kerfuffle continues. I feel compelled to update this item with links to the latest news about the dispute over scientific priority in the discovery of this new gene-editing technique. Eric Lander, head of the Broad Institute, wrote a review paper for Cell, “The Heroes of CRISPR,” that incited much dyspepsia in the world of life sciences and particularly rankled a couple of the people who played key roles in this innovation (Jennifer Doudna and George Church — see below).

Some observers are upset that the Cell paper did not disclose that the Broad Institute is in the midst of a huge CRISPR patent fight worth very large sums of money. Lander says he has no personal financial stake in how that patent fight plays out. I should note that every biologist on Earth knows who Lander is and that the Broad has a dog in this CRISPR fight. Still, it would not have been difficult for Cell to include some kind of boilerplate disclosure language.

The more serious accusation is that Lander skewed his historical narrative in a manner that emphasized the role of a Broad-affliated researcher (Feng Zhang) and de-emphasized that of rival scientists, including Doudna.

One can understand, with so much money at stake, not to mention possible Nobel prizes, that interested parties are going to read this Lander article very closely, and that omissions, mistakes, elisions and infelicities will be greeted with great alarm. These alleged errors or distortions are not easily refereed by someone who hasn’t spent a lot of time with the literature.

Lander tried to distribute credit for the CRISPR innovation. Some critics say he didn’t go nearly far enough, and failed to cite the contributions from younger researchers. Still, the casual reader will be struck by how many people were involved with CRISPR. The underlying message is that science is a collaborative process.

Largely lost in the controversy are some very broad lessons that Lander detects in the rise of CRISPR as a revolutionary tool:

  1. Serendipity is crucial to innovation. Breakthroughs “often emerge from completely unpredictable origins.” Like: Some people wanted to improve the flavor of yogurt.
  2. Many CRISPR discoveries emerged from “hypothesis-free” examination of genetic “big data.”
  3. Many CRISPR innovators were quite young, and willing to take chances. Many worked in obscure places and were published in obscure journals after being rejected by more prominent journals. Message: The government agencies that award grants should give the young folks a shot.
  4. Major breakthroughs “are typically ensemble acts, played out over a decade or more, in which the cast becomes part of something greater than what any one of them could do alone.”

Anyone disagree with that?

Now, here are some links to coverage of the dispute.

[WaPo: A social media war just erupted over the biotech innovation of the century]

[WaPo: Control of CRISPR, biotech’s most promising breakthrough, is in dispute]

[MIT Technology Review: A Scientist’s Contested History of CRISPR]

[The Scientist: “Heroes of CRISPR disputed"]

[WaPo: Scientists debate the ethics of an unnerving gene-editing technique]

ORIGINAL BLOG POST:

Said it before but will say it again: There aren’t all that many Eureka! moments in science, legend to the contrary. There is much plodding ahead. There is tedious labor. There are collaborative efforts and incremental advances and minor tweakings of what has previously been established. In science, as in life, you spend a lot of time just grinding the corn.

There is the occasional miraculous epiphany. And there are a few outlier geniuses, such as Einstein, who did their best work alone. But even Einstein had to labor for many years on general relativity, and overcome mistakes, and revise his calculations, and then call in help when the math required a closer.

[General Relativity turns 100.]

Because science is incremental and collaborative, it’s sometimes hard to identify a single person or even a small team of people who deserve credit for a discovery. Although this issue of scientific priority is an old one (ask Darwin and Wallace), it seems more urgent in this era of prize proliferation. The Nobel is the most famous of the prizes, but there are many others, and they come with staggering financial rewards.

At some point soon, some scientists will be honored for the discovery of the revolutionary gene-editing technique called CRISPR. On NPR’s “Diane Rehm Show” on Tuesday, Francis Collins, a doctor, offered a brief summary of the technique’s discovery:

Well, when you go back 30 years, you can see the original discovery of these strange DNA sequences involved quite a number of people who didn’t quite know what they were looking at and that bounced around amongst laboratories, many of them not in the U.S. I think the real advances that have now sort of set the world on fire really only happened about three years ago with two individuals, Jennifer Doudna and Emmanuelle Charpentier, figuring out that this CRISPR Cas system could be programmed to cut any DNA sequence in a test tube if you’ve learned how to set the parameters correctly.

And then, just a year later, Feng Zhang and George Church independently, both in Boston, showed you can do this inside cells, not just in a test tube, including human cells. So a lot of people mentioned those four names when they’re talking about what happened here. But just like in many areas of science, you stand on the shoulders of lots of people.

This was an off-the-cuff response, not a legal brief, and we should note that the discovery of CRISPR is the subject of a furious patent fight, with many millions of dollars at stake and major institutions (Berkeley and the Broad Institute of MIT and Harvard) at loggerheads. But clearly Doudna and Charpentier were the first to the post and Zhang and Church did crucial work to take it to the next step. Setting aside how the lawyers will work that out, let’s look at the Nobel conundrum. The Swedes have a couple of rules: You have to be alive to win the Nobel Prize, and the prize can be awarded to no more than three people for any particular breakthrough.

The “Rule of Three” is obviously problematic when four people are involved in a discovery. Someone here is gonna get hurt.

Consider the Higgs Boson situation, which I wrote about in 2013. If the prohibition on posthumous awards hadn’t been in place, then three people, not two, would have been laureated (word?) for the theoretical work leading to the discovery of the particle. One of the three theorists, Robert Brout, co-wrote with eventual winner Francois Englert the first paper on the mystery particle, back in 1964. But Brout made the terrible mistake of dying before the experimentalists at the CERN laboratory in Geneva confirmed in 2012 what the theorists had predicted. (You might say, “What difference does it make to a dead man?” Such a question implies that the historical record isn’t important — and that reputation, acclaim, renown and intellectual legacy are only for the living.)

In fact, as we noted, six people in 1964 came up with the theories that led to the discovery of the Higgs, and all six have been collectively honored by their fellow physicists for that work. But the Rule of Three required that three living physicists be left out in the cold on Nobel Day.

So you could say this for the Rule of Three: It ain’t very scientific.

Back to the radio show. We talked for an hour about CRISPR and what it means for real people and for the future of the human race.

[Who is smart enough to decide how to improve the human species?]

There was an interesting exchange that many listeners may have missed because the president’s remarks on gun laws preempted the live broadcast in the second half of the show.

JA: Dr. Collins, you mentioned earlier, before the show, that a human being, you know, a human cell that can someday become a human being, is in your view different from the cells of other animals. And I’d be curious just to hear about your own sort of beliefs about the human species and whether or not we should try to enhance the species above and beyond trying to cure diseases.

Collins: Well, that does get us into territory that’s not just reductionist science. It’s also more in the space of philosophy and morality and theology. And are we humans in a circumstance where we could consider ourselves embryonic cells that are ultimately capable of becoming a human being as just any other kind of cell, or is there something special here? I think most people would say there’s something special here, and I would say that, as well. And particularly if we think of ourselves not just as molecular entities but as creatures that have other aspects, including a spiritual nature, by beginning to imagine that we are going to re-engineer ourselves into an entirely new species, there’s something pretty significant to worry about there in terms of what we’ve done as far as our relationships with each other and with God.

Though our theology may diverge, I think Collins is making an important point, one that we’ve discussed many times on this blog: The  big decisions about the future of technology should not be left solely to the technologists, the scientists, the owners of the machines. Just because you can do something doesn’t mean you should go ahead and do it.

Further Reading:

Audio and transcript for this segment of the Diane Rehm Show.

A Harvard professor says he can cure aging, but is that a good idea?

The World We Make: Don’t Leave it to the Engineers

The Resistance Part 1: Meet the digital dissenters.

The Resistance Part 2: The A.I. Anxiety