There are some scientific technologies that rapidly become ubiquitious and indispensible, and they become the engine that drives tremendous amounts of research, win Nobel prizes, and are eventually taken for granted. Polymerase chain reaction (PCR) is one example: PCR is routine in molecular biology now, but I remember when PCR machines were magical objects of reverence, and you were cutting edge when you used one. No more; I actually tell my senior students presenting their final thesis presentation that they don’t have to explain what PCR is anymore, everyone knows what it is and how it works and what it is used for.
The new technology of today that is going to be showered with awards and money and accolades and become totally ubiquitous is CRISPR/Cas. This technique exploits the molecular biology of a prokaryotic adaptive immune system to target gene sequences in living cells and swap in a different sequence — it’s a mechanism for going into a cell and editing its genome selectively. This is huge. It has gigantic implications — people are already fretting over the ethical use of a way to modify people’s genes, even before it has been applied in any practical way. I’m not exaggerating when I say that this is going to be the universal tool for experimental molecular biology for the next several decades, possibly indefinitely.
So there’s a lot at stake. There are reputations to be won and patents to reap colossal profits and a Nobel for someone is practically guaranteed. The question is, who?
This is real science. It can’t be traced to one obsessed genius slaving away in a dark basement lab, suddenly shouting “Eureka!” and producing the answer. It’s a long, gradual development with multiple players in many countries all around the world, putting bits and pieces together and eventually, a few people standing on the work of many others to produce a useful process that can be implemented everywhere, and it’s usually those last few integrative steps that get all the recognition. Our perception of who those deserving people are can be influenced by whoever writes the history of the development of the technique.
Seriously, people…this is a great example of the power of history.
So a paper came out this year — this past week, even — recounting The Heroes of CRISPR. Even the title gives away the purpose. Now we will truly know who the dedicated, deserving scientists behind this great work are.
Except…it’s written by Eric Lander. Lander is not a name I really associate with the pioneering work behind CRISPR, but he certainly is a well-known, big name, so it might be appropriate that someone outside the core of the field but with a prestigious reputation should summarize the history of the research. He’s a very smart fellow with a successful career.
Except…he’s the head of the Broad Institute, which is one of the factions currently embroiled in a patent dispute over CRISPR. Uh-oh.
Except…he doesn’t disclose this conflict of interest in the paper. Double uh-oh.
Except…when reading the paper, as an outsider myself with a strong interest in the technology, I was a little confused by who gets a solid mention. I appreciated the deep background in the beginnings of the story, but was baffled by some of the names. Maybe it’s because I have not been closely following every step in the development, but George Church is made prominent…but I’ve never associated him with the CRISPR story. The names I was most familiar with, Doudna and Charpentier, are mentioned, but they’re buried like secondary players.
This all makes sense when you learn that Church is also a well-known member of the Broad Institute, and that Doudna and Charpentier are the primary competitors with the Broad Institute for the potentially immensely lucrative patent on this technique. My uh-ohs have just gone exponential and flown off the chart.
This paper has suddenly acquired the aroma of self-serving bullshit. This is not good. It’s not good for Lander, and it’s not good for the field, and it’s not good for the two women, Jennifer Doudna and Emmanuelle Charpentier, who have done so much of the recent work.
Fortunately, people noticed. The Scientist is reporting on the growing firestorm. Michael Eisen has been rallying the masses. Nathaniel Comfort has an excellent summary of the problems.
This story is going to get nastier, and I expect that, if justice is served (it often isn’t), Cell will have to publish a retraction of the article. Of real concern is that both Doudna and Charpentier have weighed in with comments on PubMed Commons that directly refute a claim made by Lander.
JENNIFER DOUDNA 2016 Jan 17 10:31 p.m.
From Cell editor: “…the author engaged in substantial fact checking directly with the relevant individuals.”
However, the description of my lab’s research and our interactions with other investigators is factually incorrect, was not checked by the author and was not agreed to by me prior to publication.
Please picture a wall of unbroken “uh-ohs” descending in a cascade for page after page after page below.
George Church was my classmate at Andover — well, until they kicked me out. I hope he wasn’t a co-conspirator in this.
A bit OT, but the PCR was in fact the result of inspiration by a lone genius. Who then went stark raving bonkers. So maybe George should decline the credit.
George Church has also complained, per the Scientist link above:
Church is given to wild-eyed fantasizing about future applications, with which I frequently disagree, but he’s credible and essentially arguing against his own interest here.
The patent issue is huge to lawyers and institutions and the various companies founded by all involved, but the big public denouement is going to be the Nobel — and only three people can get it. Church did publish work on using CRISPR on human cells, at essentially the same time as the Broad’s Zhang, but I think his only chance for the big prize is for both Doudna and Charpentier to be discredited. It is greatly to his credit that he is critical of Lander’s paper. I admired Lander, and liked him the one time I met him, but this is looking like a big stain on his reputation.
So far we’re all in agreement. I think both Church and Lander are very impressive scientists, this is not good for Lander’s reputation, and Church is behaving with all propriety.
Although I disagree on one thing: Kary Mullis was stark raving bonkers from the very beginning.
PCR was still the result of iterative development of emerging technologies. Mullis’ story has become increasingly fabulous, and Kleppe, Sanger, Klenow are all portrayed as missing the potential of their own techniques, or perhaps as lacking the inspirational genius to fill in the gaps. The disputed inventive and translational inputs of the other Cetus employees have become a footnote and are largely not discussed.
Patents are a necessary evil and bad enough, but the Nobel prize is a unnecessary exercise in fictionalisation of scientific history which encourages rewriting of the narrative to exclude significant contributions. The idea that three people alone can claim priority in many areas of modern science is laughable, and I think is increasingly redundant given the trend towards collaborative, multidisciplinary research and literature accessibility.
The Nobel is a damaging competition which poisons public understanding of science, does little to encourage innovation, and not much to reward scientists.
It’s “Uh-Oh’s” all the way down.
It is sad to see a scientist behaving in this way, but it is human. I’m not saying that excuses what Lander did. He appears to me to have given in to those baser human desires and had sacrificed his integrity by doing so.
What Bernard @4 said.
On the PCR question, is there a write-up somewhere about its history that is more than “the awesome Kary Mullis’ awesome idea?”
I know I’ve seen Church on several CRISPR related Patents. Not necessarily as the primary author though.
CRISPR is freaking amazing. I was just looking at an application about it earlier today.
Regarding CRISPR/Cas 9 , do *not* forget the Chinese team.
Going off on a tangent, for science writers to get the public to take an interest they need a *short*, good nickname.
“Jet Engine” and “antibiotics” quickly spread through the public awareness, but CRISPR/Cas9 genetic scissors” will be dead in the water as far as public interest is concerned.
I was thinking “Gene Photoshop”, “DNA Legokit or “Aladdin’s Flashlight”.
If you are afraid of gene editing you can go with “Sauron’s Helix”.
You will have heard of the possibility of creating malaria-resistent mosquitos using CRISPR,
While we are at it, let’s make then immune to dengue too, and that nasty South American virus that causes microcephaly.
Also, I want biofuel crops that can make the chemical precursors of butanol (not ethanol, it is not user-friendly for a couple of reasons).
And I see no reason not to expunge the several hundred serious inherited diseases carried by humans.
@birgerjohansson:
As much as I’m following this technique with interest, we shouldn’t succumb yet again to breathless “GIMME GIMME GIMME” technotriumphalism. From the reportage of the Chinese embryo research team I gathered CRISPR can only modify a singular genetic locus, right? And complex traits are primarily encoded in multiple loci? So this limits the potential for human germline-editing. And then there’s the thing about how one gene can code for more than one trait. Inconsiderate modification could cause defects rather than healing. Weren’t there also fidelity issues with the Chinese set-up?
All in all, a fair bit of water will flow through the Rhine before we can see an impact on healthcare. Till then we should figure out how to safeguard against corporate abuse. It always starts with talk about eradicating inherited diseases just about anyone can agree on the world would do better without, before it shifts to creepy neo-eugenicist about “improvement.” Improvement according to what metric? To the benefit of whom? Human life is already uncomfortably strongly denigrated as is, and it will be even more commodified if we’re fully reduced to our genome, probably rated from “will make a good worker bee” at the top of the chart to “too much natural kludge.”
I am with y ou re. the scepticsm of potential eugenics. But biofuel crop development and using CRISPR for cancer research should not be controversial.
Miscellaneous:
Advance improves cutting and pasting with CRISPR-Cas9 gene editing http://phys.org/news/2016-01-advance-crispr-cas9-gene.html
Like it or not, biofuel crop development is controversial for many reasons:
1) Use of GM/GMOs
2) Land usage and localisation
3) Biofuel yields (particularly versus waste volumes and the impact of C1 gas outputs of non-valorisable crop wastes)
4) Competition with other and established fuel infrastructures
5) Crop pricing (related also to 2)
6) Lack of integrated biorefinery technologies (related to 3)
Genome editing techniques (which I think is probably the most common nickname I’ve seen applied to CRISPR, by the way) are going to remain controversial whilst all GM remains controversial, and even increasing public acceptance of the technology will not solve all of the associated problems. It is a great technique, but many of the barriers to uptake of Industrial Biotechnology and Medicinal Biotechnology are in the application, rather than the underpinning technologies.
Its is not the case that CRISPR can only modify a single locus; one of its big advantages over some (all?) other gene-editing tools is that it can be used to modify several specific ones at the same time. However, the multiple-loci problem is indeed enormous, as is the unintended consequences one, not to mention off-target and residual effects.
DuPont is working on using CRISPR to improve biofuel efficiency and economic viability; we may have to reconsider that.
Finally, isn’t the name CRISPR cute enough already? Crispr (c & lc) was floated for a while but the acronym seems to have reasserted itself.
Lander is one of those individuals who excels in self-promotion. Unfortunately his self-promotion includes pushing others down. I’m not in the field, but family members and friends are, and Lander’s name has come up at social gatherings for decades. The consensus is that he’s brilliant, but that he diminishes and destroys other people to enhance his own position. My opinion is that there are many brilliant people in the world. There are few intellectual endeavors that benefit from a handful of brilliant people crushing most of the others. That doesn’t select for brilliance, it selects for jerkiness.
Completely agree with the comment about the Nobel Prize, btw.