The Nobel Prize in Chemistry 2020 | Hacker News Reader

The Nobel Prize in Chemistry 2020

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The discovery is beyond doubt deserving of the award. It was also awarded only 8 years after the publication.

It's a bit sad though that Virginijus Šikšnys didn't get any credit for the discovery, because his paper sent over a month earlier was rejected by Cell.

https://en.wikipedia.org/wiki/Virginijus_%C5%A0ik%C5%A1nys#P...

Edit: The Nobel award paper writes this on his findings: https://www.nobelprize.org/uploads/2020/10/advanced-chemistr...

> Similar findings were also published in another report using the related CRISPR-Cas system in Streptococcus. As in Charpentier and Doudna’s work, this report also demonstrated that Cas9 cleaves within the protospacer, that cleavage specificity is directed by the crRNA sequence, and that the two nuclease domains within Cas9, each cleave one strand. However, the researchers did not notice the crucial importance of tracrRNA for sequence-specific cleavage of target DNA [29].

So I guess it's a bit more complicated than just having missed the publication.

Why is academia (at least in the physical sciences) so competitive? My partner is a molecular biologist and she can't collaborate with anyone outside of her lab because of the fear that they collaborators will take their research before they get a chance to publish it.

It seems this method of performing groundbreaking research and science is horrifically detrimental to our collective progress. There's no reason for these groups to compete when they could collaborate.

Isn't it because right now research is basically a zero sum game? A government sets a budget for research, so the more and the better papers the other lab publishes, the more funding they get and less funding YOUR lab gets.

Exactly, it encourages mafia like structures. It matters a ton who you know and who your PI was as a Postdoc and PhD.

Not just funding, also jobs for the members of your lab etc

> Isn't it because right now research is basically a zero sum game?

Someone really needs to change the game!

A better functioning science would be a huge boost for humanity as a whole.

I don't expect government to change how it operates, but maybe some billionaires can build alternative institutions.

People have been trying for well over a century now to form alternative institutions (including governments) based entirely on human cooperation rather than competition. The results have typically been less than impressive so far. Keep in mind that part of the reason our modern concept of "intellectual property" exists is to encourage people to share their discoveries instead of keeping them secret - that's how deeply ingrained in human nature this behavior is.

You would either need to be able to measure discipline-wide or sub-disclipline-wide performance, or measure unpublished collaborations between researchers.

For the first case, if molecular biologists make a lot of progress, then the molecular biology budget gets increased. Likewise if a discipline stagnates, its budget would be cut. This is probably how it already works to an extent. You still have the problem of a finite budget being shared between disciplines.

I think it's better to measure, and reward, collaboration directly rather than turn the gross knob of aggregate funding. First steps towards this would include publishing negative results, just so there's a data point. Then we reward such results insofar as they contribute to positive results (measured via citations maybe). Obviously positive results would be rewarded much more than negative results, but we shouldn't discount the efforts of the many researchers who diligently find dead ends and tell others to avoid them.

It's not just the research though, it's the credit. Here we are discussing a Nobel Prize awarded to what seems to be consensually agreed is a subset of deserving contributors, in part because of flaws in the review process?

Discussion of credit for CRISPR goes back years. The first controversy began with patents. It's been obvious to anyone following this that credit for it is difficult to attribute. Everyone agrees CRISPR is in need of recognition, and yet the major systems for doing so are still based on an erroneous "lone genius" paradigm (with modifications).

Because you can’t loose much but gain much with such behavior.

It actually relates to many things, but mostly it's because all the matters is getting credit for an idea. Realize that the process is basically to create something and then write about it to advance knowledge, thus sharing it with all. What's left at the end of that process is to recognize those who have done a lot of positive sharing. Those who are so recognized get the best jobs, the most funding, the best students, etc. As such, if an idea slips out of your lab and into some other lab, you might not get credit, and hence, all the craziness. It's one of those cases where it's not a great system, but it's also hard to figure out a better one.

On the other hand, physics seems to not have this issue. Experimentalists working on topics related to CERN publish jointly (with like 500 co-authors) and theoreticians regularly post pre-prints under review on arXiv. They are a much smaller community though.

This is a consequence of the required resources for the experiments. If it takes a ten billion dollar piece of equipment to produce your results then chances are you are going to be one little cog in a very big machine. There are not papers with 500 co-authors in any other field or even in sub-fields of particle physics that do not require massive accelerators to achieve results.

There are many large-scale projects in biology that benefit from open collaboration. In general, these require lots of work and produce useful resources used by a whole field. Insights that could revolutionize a field can sometimes be described in a sentence or two, and reproduced in a few days or weeks, so scientists are more uneasy sharing them.

This is a phenomenon that I've only just come to know since tiptoeing into the biotech space only half a year ago. Coming to recognise how poorly academics collaborate and the incentives underlying that has been one of my most saddening and de-motivating realisations since entering the space.

1) Because human beings aggressively pursue their self-interest, which extends to getting new credit for scientific discoveries.

2) Because scientific discovery often requires multiple competing approaches (because you don't know which one will work in advance), and top-down control tends to discourage that.

3) Because biomedical discovery is not an inherently directed process most of the time, and top-down control would risk missing out on important discoveries that only happened because we gave individual scientists the freedom to work on whatever they wanted (like bacterial immune systems).

Complaining about this state of affairs is like complaining that housecats aren't vegetarians yet. We have a new genetic manipulation technology that has already revolutionized molecular biology just a few years after it was discovered, and is already being investigated in clinical trials. Anyone who looks at this and says "you're doing it wrong" has a vastly distorted idea of what is actually possible in biomedical science, or any other line of work that requires actual humans to carry it out.

No, while those things are factors, the core problem arises from the structure of the funding and career advancement system. These are systems we've constructed, not aspects of human nature. It's sink-or-swim, and even those swimming are only barely doing so.

You are assuming that the construction of the system has nothing to do with human nature in the first place. I think there are a lot of godawful perverse incentives embedded in our current system, and I suspect we could come up with a much better system if we started over from scratch, but I am extremely skeptical that an ideal system would be any less dependent on competition. And in the current context, the burden is on those who say we should redesign the system to prove that their hypothetical ideal system will perform better in practice than the one that turns out all of these CRISPR-related discoveries at a furious pace.

I'm not sure which assumptions I've genuinely revealed, but I certainly would agree that the ideal systems are those that manage the good and the bad in human nature.

It's a straw man to say that a better system must be competition-free. Simply ameliorating the level of intensity and competition would go a long way. We need a more incremental seniority and funding system, where the difference between being able to do academic science and not to do so isn't defined by dramatic forks in the road. We have a vast separation-of-wealth in science funding and institutional power that must be addressed to get back to a healthier place.

I don't know why you saw "cooperative" and changed it to "top-down control"

I take it you haven't met very many university research professors. (But I probably should have used the term "central planning" instead since that is much closer to what I meant - the problem of over-coordination when a more distributed approach would have ultimately worked better.)

> 1) Because human beings aggressively pursue their self-interest

Some human beings work that way.

Others share and cooperate freely with their peers.

“We don't see things as they are, we see them as we are.”

― Anaïs Nin

"The Double Helix" by Watson delves into the highly competitive nature of this level of research. It is a candid and entertaining portrayal.

Well, and what about Francis Mojica who discovered CRISPR in bacteria?! He certainly deserved at least 1/3 of the award.

This effect even exists within the same lab (been there, seen it). It's a horrible environment.

> Why is academia (at least in the physical sciences) so competitive?

All human achievement is fundamentally agonistic.

The really bewildering thing is how so many people who clawed their way to the top apparently forgot about the competition it took to get there.

Not very much money (read: almost 0). If you get scooped you might be out of a job.

"Academic politics is the most vicious and bitter form of politics, because the stakes are so low." https://en.wikipedia.org/wiki/Sayre%27s_law

Maybe it's field specific. In my subfield of physics, I've collaborated with three other groups across the US without any fear of people running off with our work.

Reading "Heroes of CRISPR" [1] it sounds like that, after Cell rejected the paper, they shortened the claim but it was still very much known to them:

> Finally, Siksnys showed that the system could also be reconstituted in a second way—by combining purified His-tagged Cas9, in-vitro-transcribed tracrRNA and crRNA, and RNase III—and that both RNAs were essential for Cas9 to cut DNA. (They would ultimately drop the second reconstitution from their revised paper, but they reported all of the work in their published U.S. patent application filed in March 2012 [Siksnys et al., 2012]).

> Siksnys submitted his paper to Cell on April 6, 2012. Six days later, the journal rejected the paper without external review. (In hindsight, Cell’s editor agrees the paper turned out to be very important.) Siksnys condensed the manuscript and sent it on May 21 to the Proceedings of the National Academy of Sciences, which published it online on September 4. Charpentier and Doudna’s paper fared better. Submitted to Science 2 months after Siksnys’s on June 8, it sailed through review and appeared online on June 28.

[1] -- https://www.cell.com/cell/fulltext/S0092-8674(15)01705-5

While "Heroes of CRISPR" is a fairly detailed history of the whole affair, it's always worth noting that it was written by Eric Lander, the director of an institute with a strong vested financial interest in having the story interpreted in a particular way.

And in particular he of course wanted to make Feng Zhang (who worked for him at the time) to be the principal "hero" of the story.

There is something mesmerizing about an evil genius at the height of their craft, and Eric Lander is an evil genius at the height of his craft.

Lander’s recent essay in Cell entitled “The Heroes of CRISPR” is his masterwork, at once so evil and yet so brilliant that I find it hard not to stand in awe even as I picture him cackling loudly in his Kendall Square lair, giant laser weapon behind him poised to destroy Berkeley if we don’t hand over our patents.

This paper is the latest entry in Lander’s decades long assault on the truth...

http://www.michaeleisen.org/blog/?p=1825

Things are a bit better these days thanks to bioRxiv. I wonder which Nobel summary (if any) will cite a preprint for the first time...

This is a complex issue. The good news: Dr. S. has certainly received plenty of recognition (e.g., https://www.nature.com/articles/d41586-018-05308-5). Would love to hear an interview with him and his thoughts on who should be recognized.

Yeah, the good news is that everyone involved in the CRISPR discoveries has done extremely well both financially and scientifically, even if they're not getting a trip to Stockholm. It definitely shows the limits of the three-person-max approach, however.

> paper sent over a month earlier was rejected by Cell

Cell rejected an almost-nobel-worthy paper? Is this business as usual? Would they maybe have got the nobel price, if they had submitted to a lesser journal instead of Cell?

Can we make a rule of thumb, that in general you should submit your groundbreaking work to the most prestigious journal possible, but if you feel your work is of nobel caliber, then play it safe and submit to a mediocre journal to avoid the high publication threshold of the top level journals?

It's kinda common tbh.

https://www.sciencealert.com/these-8-papers-were-rejected-be...

Usually major breakthroughs are rare and extraordinary and might seem too off the norm for major journals.

Yes, very common. Bullshit gets published and great work is ignored EVERY DAY. Academic research is broken.

Because of the optics of giving the award exclusively to two women. If Siksnys was a woman she would have been the third winner.

There's a documentary on Netflix "Human Nature" that discusses the history of CRISPR and features interviews with both Emmanuelle Charpentier and Jennifer Doudna. [0][1][2]

[0] https://www.netflix.com/title/81220944

[1] https://www.youtube.com/watch?v=_1UkCfDnn6c

[2] https://en.wikipedia.org/wiki/Human_Nature_(2019_film)

I've heard a number of interviews/podcasts with Jennifer 'The Dude' Doudna about CRISPR/Cas9 over the years. Usually a great listen, she's pretty funny and from all indications has that great combo of taking her work seriously but not herself.

The part of the documentary where she relates the Hitler dream, weighing in on the impact of her work is a poignant moment. A very responsible scientist.

It's not on Netflix Germany.

It was also broadcast through PBS NOVA here in the US (and it is available on PBS Passport -- that is how I watched it). In fact, I thought it was a PBS NOVA episode, but it is apparently an independent film.

I haven't seen it yet, but there's a new Nova episode about CRISPR I've been meaning to watch: "CRISPR Gene-Editing Reality Check".

https://www.pbs.org/wgbh/nova/video/gene-editing-reality-che...

(Does Berkeley still have parking spots reserved for Nobel Laureates? They'll have to add a new one...)

Poor Virginijus Šikšnys, left out because the journal he sent it to rejected without review his paper which was sent before Doudna and Charpentier's.

https://www.statnews.com/2018/05/31/crispr-scientists-kavli-...

"But bad luck with a journal made Šikšnys the forgotten man of CRISPR: Cell rejected his paper in April 2012 without sending it out for peer review. In contrast, when Doudna, Charpentier, and their colleagues showed that Cas9 could be programmed to cut DNA, their paper sped through the review process at Science and was published online in late June 2012. Šikšnys and his co-authors, meanwhile, had scrambled to find a more receptive journal and landed at Proceedings of the National Academy of Sciences, which published their paper three months after the Berkeley team’s."

Poor Francisco Mojica

Francisco Juan Martínez Mojica (Elche, October 5, 1963), usually known as Francisco JM Mojica, is a Spanish scientist, molecular biologist, and microbiologist at the University of Alicante in Spain, known for his discovering research on the Clustered Regularly Interspaced Short Palindromic Repeats-CRISPR gene editing technique.[1]

https://en.wikipedia.org/wiki/Francisco_Mojica

I don't think it's a case of "poor" Mojica. He discovered some important properties around the palindromic nature of DNA in bacteria, as did others in Japan. While it was important, it is not the same level of contribution as Doudna and Charpentier. I don't think that there is much debate around this.

I disagree, he did not discovered a property, he discovered and described the CRISPR mechanism. He deserves a big part of the credit, without CRISPR there is no CRISPR-cas9. With this award, they are neglecting basic research and just rewarding the applications. Btw I highly recommend to read the Mojica story it is fascinating how he found it and understood how it worked.

>I disagree, he did not discovered a property, he discovered and described the CRISPR mechanism.

Exactly this! You cannot downplay his influence, at all. He also did speculate on plenty of those applications. Really weird to have him excluded.

I got interested in how often the chemistry prize goes to biology/biochemistry.

     2011: quasicrystals
    →2012: G protein-coupled receptors
     2013: modelling complex chemical systems
     2014: super-resolved fluorescence microscopy
    →2015: studies of DNA repair
     2016: molecular machines
     2017: cryo-electron microscopy for biomolecules
    →2018: directed evolution of proteins
     2019: lithium ion batteries
    →2020: genome editing

So let's say 4 out of 10 (2012, 2015, 2018, 2020). My initial assumption that biology would dominate was wrong, and the chemistry prize seems to have been going to very diverse topics in chemistry.

The prizes in 2014 (fluorescence microscopy) and 2017 (cryo-electron microscopy) weren’t strictly for biology but were tools for studying biology. Including them would make it 6 out of 10.

Thoroughly deserved. 9 years since publishing their paper in Nature. CRISPR/Cas9 is that revolutionary. Is that the fastest Nobel since breakthrough/discovery? Or was it Graphene Nobel (albeit in Physics) in 2010?

EDIT: Looks like fastest Nobel prize since discovery was in 1987 (in Physics) - for high temperature super conductivity. Bednorz and Mueller won their Nobel within 2 years (!!!!!)

Ref - https://science.sciencemag.org/content/238/4826/481

Yang and Lee got it 1957 for parity violation, work that they did in 1956 and which was experimentally confirmed the same year by Wu (who should have gotten a share, I think).

Wasn't the Nobel awarded for the observation of gravitational waves 1 year after the publication in Physical Review Letters?

Edit: here's the paper (2016) https://physics.aps.org/featured-article-pdf/10.1103/PhysRev...

There was a really interesting debate here on who should get credit for the patent (Charpentier & Doudna vs. Feng Zhang and to a lesser extent George Church, i.e. discovery + characterization vs. making things practical). I find it interesting, but not surprising, to see that only the former are getting the Nobel Prize.

It's a reasonably segmented group. Charpentier and Doudna deserve the breakthrough credit they're getting. Individually Feng Zhang did more to push CRISPR forward than anyone else has thus far. And George Church has had his hands all over the space for a very long time, while not fitting into either of the prior two groups.

It's so big it more than requires all of them, contributing in the ways they have (along with countless others, less heralded, at places like Berkeley or Broad).

George Church praised the Nobel committee’s choice and noted that there are plenty of ideas and companies to go around [1]. I wouldn’t be surprised if CRISPR in medical applications leads to future Nobel prizes, and there will be many winners on the commercial side (e.g. Editas cofounded by Church, Doudna, Zhang and others [2]).

[1]: https://www.statnews.com/2020/10/07/a-terrific-choice-george...

[2]: https://www.genengnews.com/topics/genome-editing/zhang-churc...

This is one of the most inevitable Nobels in recent memory. The only question was whether they would win it in Chemistry or Medicine.

Makes sense to give it to Chemestry first, but my guess is they'll win both.

That would be an interesting development! I believe that to date, Madame Curie stands alone in having won Nobel Prizes in more than one field.

Linus Pauling too (perhaps even more notable, as he shared none of the prizes). But neither won prizes in different fields for the same work, which would be quite unexpected.

Maybe a bit premature, but I'm glad this is going to Charpentier and Doudna rather than Zhang and the Broad.

Why?

why is premature? or why those two than the others?

Because they really showed their ugly side when it came to commercialization and the patent court case.

Sorry, I'm out of the loop on this. Can you explain it a bit more? I was aware of the lawsuit between Berkeley and MIT over the patent, but not of the specifics.

For instance, see http://www.michaeleisen.org/blog/?p=1825

Not that Michael is biased at all, either...

Anyway, I'm happy Jennifer and Emmanuelle won over others and thinks this was the right call. The discovery of the idea was the most important part here, bs showing it in human cells (which wasn't that hard afterwards).

It wasn't just that, it was the entire hype machine. Lots of schadenfreude going around today. I probably would have preferred they split the CRISPR award across chemistry and medicine prizes, but life isn't fair.

Two wrongs making a right. I see.

Agree. This was a good outcome, and the award went to two very deserving scientists.

For anyone interested in learning more, I highly recommend Doudna’s book, “A Crack in Creation” - very readable explanation of the process leading to discovering CRISPR/Cas9. https://www.amazon.co.uk/Crack-Creation-Editing-Unthinkable-...

I'll leave the scientific explanation links to people who know more but here's a fun song about this https://youtu.be/k99bMtg4zRk

This is interesting on several fronts. One because it’s a really cool discovery. But two because the Nobel tends to avoid situations where the full origin of the discovery is somewhat in dispute until things settle down. If you know the history here this is very much an active source of debate and the Nobel clearly picked sides here, which is interesting in its own right.

What's missing for reseting all / most of the DNA from an organ/a whole body in mammals?? Just reseting the DNA repair section of the DNA of a whole organ would enable massively slowing the ageing/cancer risks of said organ/body!

It is the key towards rejuvenation and preventing cancer, heizeimer and most diseases! I can't find a good resource on why this is not currently possible and where can I track scientific incremental progress towards making this breakthrough a reality, which would then become the biggest technological progress of the 21 century!

Why aren't an enormous amount (and diluted over days or months) of viral vectors enough?

https://en.m.wikipedia.org/wiki/Viral_vector#:~:text=Viral%2....

Don't underestimate the complexity of biological systems.

https://en.wikipedia.org/wiki/Gene_therapy#Hurdles

You have trillions of cells, each that contain billions of bases. Each cell can go wrong in its own way, and what you have to patch it back to is different for every person

All of these steps are currently not possible:

* establish a perfect sequence for an individual

* find mutations non-destructively (ie cell survives)

* send a specific edit to a specific cell in live animal

* perform just that modification (see https://en.m.wikipedia.org/wiki/Off-target_genome_editing)

Very deserved. This is, I think, the first time in the Nobel's history where a shared prize has only female laureates.

To Emmanuelle Charpentier [1] and Jennifer A. Doudna [2] for CRISPR/Cas9 gene editing [3].

[1] https://en.wikipedia.org/wiki/Emmanuelle_Charpentier

[2] https://en.wikipedia.org/wiki/Jennifer_Doudna

[3] https://en.wikipedia.org/wiki/CRISPR_gene_editing

Wow, neither Feng Zhang nor one of the earlier people in the discovery chain.

The CRISPR/Cas9 technique is so ground breaking. I am not surprised.

What about Feng Zhang?

I'm open to pushback. Nobel prizes usually reward basic science over applications thereof. My understanding is that Feng Zhang didn't discover anything fundamental. Sure, he was first with applying CRISPR to eucaryotic cells. Which indeed is an impressive feat: not because it was a huge theoretical leap but because of his labs strong work ethic managing to do so very quickly.

If that were the case then the prize should have been awarded to Yoshimuzi Ishino and Francisco Mojica (https://en.wikipedia.org/wiki/CRISPR#Repeated_sequences). This prize was specifically for a new method for gene editing.

Doudna, Charpentier, Zhang won joint prizes before for gene editing: Gairdner, Harvey, and Gabbay awards.

If Zhang was included in the Nobel prize, nobody would ask why he was included. But excluding definitely raises questions on why.

Didn't Church's very similar paper come out at the same time as Zhang's?

I think many people have similar ideas around the same time: Charpentier, Doudna, Zhang, Šikšnys etc. Zhang is the lastest to publish the result, but got the furtherest along in applying to human. I don't think anyone believes Zhang's work is based off others.

So CRISPR/Cas9 Nobel was a given since their breakthrough papers in 2011/2012. Lot of folks were speculating whether it will win in Chemistry or Medicine. Maybe Zhang/Church will win it in Medicine in few years. Also given the revolutionary nature of this technology, there could be be more Nobel prizes in this area in coming years

This guy learn it and use it on human DNA modification. https://en.wikipedia.org/wiki/He_Jiankui Sent to jail

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