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Dr. Kariko’s experience makes me wonder how many other potentially groundbreaking research nodes are being ignored and whether organizations like YC actually ha

Dr. Kariko’s experience makes me wonder how many other potentially groundbreaking research nodes are being ignored and whether organizations like YC actually have adequate mechanisms to identify such potential bio-science startups. "Dr. Kariko’s struggles to stay afloat in academia have a familiar ring to scientists. She needed grants to pursue ideas that seemed wild and fanciful. She did not get them, even as more mundane research was rewarded. “When your idea is against the conventional wisdom that makes sense to the star chamber, it is very hard to break out,” said Dr. David Langer ... Leading scientific journals rejected their work. When the research finally was published, in Immunity, it got little attention. ... “We talked to pharmaceutical companies and venture capitalists. No one cared,” Dr. Weissman said. “We were screaming a lot, but no one would listen.[1]” [1] https://www.nytimes.com/2021/04/08/health/coronavirus-mrna-kariko.html https://www.nytimes.com/2021/04/08/health/coronavirus-mrna-k...

anonporridge 3y ago
Of course they are. Almost every groundbreaking idea that surfaced went through a period of obscurity and dismissal.
- thomasahle 3y ago
  Are you saying this is a fact of life, or that it is true by definition? Like, "any idea, to be truly groundbreaking, can not be easily distinguished from noise / crackpot theories".
  - whatisyour 3y ago
    It's surprisingly difficult to look at an idea and figure out from first principles if its any good. Most of the scientists (and people really) rely on comparing it with what they have already seen and using their experiences from things they know to judge the new idea. So, its really difficult to judge a revolutionary theory. Crackpot theories are easier to judge however. They often have very provable falsehoods.
  - inglor_cz 3y ago
    "any idea, to be truly groundbreaking, can not be easily distinguished from noise / crackpot theories" This is an interesting insight. Yeah, I think you are onto something here. Groundbreaking ideas, as opposed to new technologies, tend not to have obvious real world applications/results for years. As such, they aren't easily distinguishable from random crackpottery. We tend to validate ideas by their later applications, or, at the very least, a heap of corroborating evidence. Both takes a lot of time to aggregate.
    - MichaelZuo 3y ago
      It's practically a tautology, if the idea was easily distinguishable from 'random crackpottery' then it wouldn't be so groundbreaking, because it necessitates that the other party in a 30 to 60 minute meeting could confidently distinguish it.
- maronato 3y ago
  “It’s true because it has always been true”
Lionga 3y ago
It mostly shows that gov. funded research grants are broken and just fund echo chambers. Even if it was not easy pharmaceutical companies finally did invest.
- funcDropShadow 3y ago
  > It mostly shows that gov. funded research grants are broken and just fund echo chambers. No, it shows there are weaknesses in the government-funded research grants. But it is far from clear which other system would be better overall not just in this case.
hintymad 3y ago
"A new scientific truth does not triumph by convincing its opponents and making them see the light, but rather because its opponents eventually die, and a new generation grows up that is familiar with it" -- Max Planck
- m463 3y ago
  Makes me think of that Feynman commencement speech - hopefully we can get better: We have learned a lot from experience about how to handle some of the ways we fool ourselves. One example: Millikan measured the charge on an electron by an experiment with falling oil drops and got an answer which we now know not to be quite right. It’s a little bit off, because he had the incorrect value for the viscosity of air. It’s interesting to look at the history of measurements of the charge of the electron, after Millikan. If you plot them as a function of time, you find that one is a little bigger than Millikan’s, and the next one’s a little bit bigger than that, and the next one’s a little bit bigger than that, until finally they settle down to a number which is higher. Why didn’t they discover that the new number was higher right away? It’s a thing that scientists are ashamed of—this history—because it’s apparent that people did things like this: When they got a number that was too high above Millikan’s, they thought something must be wrong—and they would look for and find a reason why something might be wrong. When they got a number closer to Millikan’s value they didn’t look so hard. And so they eliminated the numbers that were too far off, and did other things like that. We’ve learned those tricks nowadays, and now we don’t have that kind of a disease. https://calteches.library.caltech.edu/51/2/CargoCult.htm https://calteches.library.caltech.edu/51/2/CargoCult.htm
  - bsder 3y ago
    While it's a nice story, I seem to remember that it isn't true. There was some article a while back that talked about the fact that measurements from the oil drop experiment pretty much moved as the input data got better.
    - emmelaich 3y ago
      As far as I know, the story is true. If the input data just got better, you'd expect measurements above and below the real value. IIRC, the experimental value went in one direction, from Millikan's to the currently accepted value.
deepsun 3y ago
> She needed grants to pursue ideas that seemed wild and fanciful. You cannot even realize how many people in academia are running for wild and fanciful ideas. Don't blame the scientists, they are probably the most open-minded to the new ideas. But filtering out bad ideas is a part of their job, and they grew thick-skinned from constant bombardment of fancy ideas, we cannot pursue them all. So I'd say this story is pretty traditional in the history of revolutionary ideas (e.g. a similar story of John Snow vs. cholera -- how many years and lives it took).
sn9 3y ago
As an aside, this is maddening: "Published April 8, 2021 Updated Oct. 2, 2023, 9:59 a.m. ET" The original article is gone! Just an constantly evolving page that likely has things deleted for reasons other than accuracy (e.g., like narrative coherency). Just write another article! Damn!
- nathancahill 3y ago
  Interesting. I diffed the original with the current. They added this paragraph: > On Monday, they were jointly awarded the Nobel Prize for Physiology or Medicine for their research. And added "Long Overlooked" to the title.
manicennui 3y ago
YC is basically a non-entity when it comes to such startups.
- civilitty 3y ago
  For good reason. YC has no business investing in biotech because that’s how we get shit like Theranos. The biotech VC industry is mature with as much or more deal flow in dollars than software VC every year, with tons of people with experience in science and entrepreneurship.
throwaway2037 3y ago
The pipeline for fundamental biology research is much longer and more complex compared to pure tech. This is the reason why there are so many fewer bio-tech start-ups. The same can be said about hardware vs software in pure tech. There must be 100x start-ups in software, compared to hardware. The greatest hope for more break-thrus that can be commercialised is an increase in gov't research funding (say: 10x) and/or the gov't offering bounties with guaranteed contracts for commercial products. Example: If you can create a malaria vaccine with 75% efficacy for children under 12, then US/EU/Japan/UN will guarantee an order for 25B USD or 1B doses. (Something enormous, to really move the needle.) Wiki tells me that she started publishing about mRNA in 2005. The first mRNA vaccine was not approved until Dec 2022. That kind of timeline is impossible for private investment to fund. It needs to come from gov'ts and non-profits.

anonporridge 3y ago

Of course they are. Almost every groundbreaking idea that surfaced went through a period of obscurity and dismissal.

thomasahle 3y ago
Are you saying this is a fact of life, or that it is true by definition? Like, "any idea, to be truly groundbreaking, can not be easily distinguished from noise / crackpot theories".
- whatisyour 3y ago
  It's surprisingly difficult to look at an idea and figure out from first principles if its any good. Most of the scientists (and people really) rely on comparing it with what they have already seen and using their experiences from things they know to judge the new idea. So, its really difficult to judge a revolutionary theory. Crackpot theories are easier to judge however. They often have very provable falsehoods.
- inglor_cz 3y ago
  "any idea, to be truly groundbreaking, can not be easily distinguished from noise / crackpot theories" This is an interesting insight. Yeah, I think you are onto something here. Groundbreaking ideas, as opposed to new technologies, tend not to have obvious real world applications/results for years. As such, they aren't easily distinguishable from random crackpottery. We tend to validate ideas by their later applications, or, at the very least, a heap of corroborating evidence. Both takes a lot of time to aggregate.
  - MichaelZuo 3y ago
    It's practically a tautology, if the idea was easily distinguishable from 'random crackpottery' then it wouldn't be so groundbreaking, because it necessitates that the other party in a 30 to 60 minute meeting could confidently distinguish it.
maronato 3y ago
“It’s true because it has always been true”

Lionga 3y ago

It mostly shows that gov. funded research grants are broken and just fund echo chambers. Even if it was not easy pharmaceutical companies finally did invest.

funcDropShadow 3y ago
> It mostly shows that gov. funded research grants are broken and just fund echo chambers. No, it shows there are weaknesses in the government-funded research grants. But it is far from clear which other system would be better overall not just in this case.

hintymad 3y ago

"A new scientific truth does not triumph by convincing its opponents and making them see the light, but rather because its opponents eventually die, and a new generation grows up that is familiar with it" -- Max Planck

m463 3y ago
Makes me think of that Feynman commencement speech - hopefully we can get better: We have learned a lot from experience about how to handle some of the ways we fool ourselves. One example: Millikan measured the charge on an electron by an experiment with falling oil drops and got an answer which we now know not to be quite right. It’s a little bit off, because he had the incorrect value for the viscosity of air. It’s interesting to look at the history of measurements of the charge of the electron, after Millikan. If you plot them as a function of time, you find that one is a little bigger than Millikan’s, and the next one’s a little bit bigger than that, and the next one’s a little bit bigger than that, until finally they settle down to a number which is higher. Why didn’t they discover that the new number was higher right away? It’s a thing that scientists are ashamed of—this history—because it’s apparent that people did things like this: When they got a number that was too high above Millikan’s, they thought something must be wrong—and they would look for and find a reason why something might be wrong. When they got a number closer to Millikan’s value they didn’t look so hard. And so they eliminated the numbers that were too far off, and did other things like that. We’ve learned those tricks nowadays, and now we don’t have that kind of a disease. https://calteches.library.caltech.edu/51/2/CargoCult.htm https://calteches.library.caltech.edu/51/2/CargoCult.htm
- bsder 3y ago
  While it's a nice story, I seem to remember that it isn't true. There was some article a while back that talked about the fact that measurements from the oil drop experiment pretty much moved as the input data got better.
  - emmelaich 3y ago
    As far as I know, the story is true. If the input data just got better, you'd expect measurements above and below the real value. IIRC, the experimental value went in one direction, from Millikan's to the currently accepted value.

deepsun 3y ago

> She needed grants to pursue ideas that seemed wild and fanciful. You cannot even realize how many people in academia are running for wild and fanciful ideas. Don't blame the scientists, they are probably the most open-minded to the new ideas. But filtering out bad ideas is a part of their job, and they grew thick-skinned from constant bombardment of fancy ideas, we cannot pursue them all. So I'd say this story is pretty traditional in the history of revolutionary ideas (e.g. a similar story of John Snow vs. cholera -- how many years and lives it took).

sn9 3y ago

As an aside, this is maddening: "Published April 8, 2021 Updated Oct. 2, 2023, 9:59 a.m. ET" The original article is gone! Just an constantly evolving page that likely has things deleted for reasons other than accuracy (e.g., like narrative coherency). Just write another article! Damn!

nathancahill 3y ago
Interesting. I diffed the original with the current. They added this paragraph: > On Monday, they were jointly awarded the Nobel Prize for Physiology or Medicine for their research. And added "Long Overlooked" to the title.

manicennui 3y ago

YC is basically a non-entity when it comes to such startups.

civilitty 3y ago
For good reason. YC has no business investing in biotech because that’s how we get shit like Theranos. The biotech VC industry is mature with as much or more deal flow in dollars than software VC every year, with tons of people with experience in science and entrepreneurship.

throwaway2037 3y ago

The pipeline for fundamental biology research is much longer and more complex compared to pure tech. This is the reason why there are so many fewer bio-tech start-ups. The same can be said about hardware vs software in pure tech. There must be 100x start-ups in software, compared to hardware. The greatest hope for more break-thrus that can be commercialised is an increase in gov't research funding (say: 10x) and/or the gov't offering bounties with guaranteed contracts for commercial products. Example: If you can create a malaria vaccine with 75% efficacy for children under 12, then US/EU/Japan/UN will guarantee an order for 25B USD or 1B doses. (Something enormous, to really move the needle.) Wiki tells me that she started publishing about mRNA in 2005. The first mRNA vaccine was not approved until Dec 2022. That kind of timeline is impossible for private investment to fund. It needs to come from gov'ts and non-profits.