4 ms·

A lot of times they are not lying, they are genuinely clueless. Part of the problem with academia is that they follow the edict set by George Constanza: “the be

A lot of times they are not lying, they are genuinely clueless. Part of the problem with academia is that they follow the edict set by George Constanza: “the best liar truly believes in their own lie.” So often they truly believe that their field’s method of choice is how we will use AIDS to cure cancer, because the grants-system ensures that anyone who doesn’t truly believe in their vomit won’t get their grant approved (you need to write them with conviction, not doubt, if you want them awarded). Then mediocre postdocs with an “entrepreneurial flair” decide they’re ready to take their nanobots and cure breast cancer and come to SV to pitch to VCs who are either clueless or are being advised by the same heads that are pouring the Kool-aid in academia to begin with! Exceptions exist of course, and some of these bets turn good purely because of luck (if you take twenty random chemicals and inject, one of them might just cure cancer; incidentally how stuff like paclitaxel & vinblastine was discovered anyway). But this only seems to reinforce the conviction of these institutions to continue their methods. One of the most important differences I feel VCs should acknowledge as a contrast between tech and biotech: with tech you can often choose one method of solving a problem and make it work. With biology however, nature will eventually give you a roundhouse kick if you try to force anything but an actual solution down it’s throat.

ta988 6y ago
You are right I assigned to malice what is probably just lack of skills and knowledge. Your are also right on the fact that what works is grind and find. You can do it at the scale of one lab or the scale of many labs, but in the end what works is to try a lot of things because we are still really shooting in the dark for a lot of targets or diseases we don't know any druggable target yet.
- ramraj07 6y ago
  I’ll propose that we actually kind of know a lot of things about many (not all) diseases, we really just need an objective look at how to address them. The majority of scientists today are mostly quite narrow minded in terms of scientific thinking, every one of them wants to use the method that they are experts at to solve the problem. When the Manhattan project was deployed all the top physicists came and tackled the problem that needed to be solved with the most suitable methods, but there’s been “cancers Manhattan project” or “moonshot” initiatives in biology numerous times and they all fail because the scientists incharge invariably push their own agendas in these. Take Janelia farms for example- without reading their editorialised website if you try to gander what the hell this institution is trying to do, from just the papers they publish, you would fail miserably. Not saying that institution sucks, well I suppose I am saying that, but only insofar because all of academia seems to suck in the same way.
  - an_opabinia 6y ago
    > Janelia farms I’m pretty sure they do basic science for medicine, with many of the same goals as the NIH.
oivey 6y ago
It seems kind of odd to blame academia for this. Almost all founders are clueless in all fields, and, additionally, they’re pretty much supposed to be aggressive about their idea in order to get investments. The role of the VC is to invest wisely. If they’re less knowledgeable about tech outside of the niche of computers and they lose money on biotech, that’s their fault.
- ramraj07 6y ago
  I suppose one of the points I was trying to make is that in tech it’s probably okay (maybe even beneficial) to be clueless, but that’s not true for biology or hard science tech - if you float a rocket company, stuff has to fly, and you better get some rocket scientists in there. One can’t just Travis Kalanick their way to Mars because you’re not fighting some cab unions you’re fighting the laws of physics.
- ta988 6y ago
  I know less about founders in computer tech but yes, many founders in biotechs that I know have just had a few years of experience in labs, not really successful scientifically, even if they know how to market it. And thats far from enough to really understand the nooks and crannies of drug discovery projects. Especially since most academic labs are only doing a really thin slice of the whole process. There is a reason why you dont give millions of dollars to a postdoc that submit their first grant proposal, why we do that to postdocs that are founding biotechs is beyond my understanding. The products I've seen from companies that raised $5mil are not worth 1/10 of that, and thats just in dev costs, their stuff could not even scale so they are trying to survive until the big prey comes and swallow them before anybody notices its all smoke and mirrors.
  - oivey 6y ago
    Generally that’s the trajectory computer tech startups take too, except with even less experience. That’s probably a reflection of the difference in the barriers of entry.
  - dnautics 6y ago
    > There is a reason why you dont give millions of dollars to a postdoc that submit their first grant proposal, why we do that to postdocs that are founding biotechs is beyond my understanding TINA. If you're a fund that needs to put an ass in a seat to say "we have a biotech investment", you go to whatever you can find. You have no way of doing due diligence in your portfolio and even if you hired someone like me to ultrafilter your proposals you'd probably come up empty, because the only postdocs that play this game are those that know they are good at parlaying their social capital, obtaining favorable reviews from their PIs (social validation), and have less scruples. The heads down brilliant and honest scientist postdocs have already burnt out, and often aren't socially savvy enough to play the VC game, if they were, they'd be gunning for faculty positions instead. If VC wants a better return they need to have a different heuristic. I'd pick postdocs that did years of grueling work with no results and ask them what they'd really prefer working on instead of their PI's hairbraned idea.
sjg007 6y ago
>Exceptions exist of course, and some of these bets turn good purely because of luck (if you take twenty random chemicals and inject, one of them might just cure cancer; incidentally how stuff like paclitaxel & vinblastine was discovered anyway). Vinblastine was discovered from folk tea remedies for diabetes. In animal models they saw decreased white blood cell counts. Paclitaxel was discovered from the NCI plant screening program. The chemical was observed to be cytotoxic in screening studies. So both of your examples have pre-clinical evidence. These were not randomly injected and developed through scientific research and the clinical trial program. https://en.wikipedia.org/wiki/History_of_cancer_chemotherapy https://en.wikipedia.org/wiki/History_of_cancer_chemotherapy
- ramraj07 6y ago
  Vinblastine was discovered when they were testing a folk remedy for diabetes and found cytotoxic effects so it was completely tangential to the study’s goals, and in modern parlance, an instance of a “task failed successfully.” Paclitaxel was discovered literally from a random spray and pray scan of plant samples from every taxonomic class, here I will quote a literal sentence from a review: “ Barclay collected T. brevifolia, an evergreen, apparently because the strategy was to collect at random. Not much was known about the tree. It belonged to the genus Taxus...” (https://www.acs.org/content/acs/en/education/whatischemistry/landmarks/camptothecintaxol.html https://www.acs.org/content/acs/en/education/whatischemistry... ) So I still believe in what I said, which is random screens or complete serendipity often has been the best ways to get t a lot of our therapies, though I’m not advocating for more of that necessarily.
  - sjg007 6y ago
    Where you say random I think you mean systematic.

ta988 6y ago

You are right I assigned to malice what is probably just lack of skills and knowledge. Your are also right on the fact that what works is grind and find. You can do it at the scale of one lab or the scale of many labs, but in the end what works is to try a lot of things because we are still really shooting in the dark for a lot of targets or diseases we don't know any druggable target yet.

ramraj07 6y ago
I’ll propose that we actually kind of know a lot of things about many (not all) diseases, we really just need an objective look at how to address them. The majority of scientists today are mostly quite narrow minded in terms of scientific thinking, every one of them wants to use the method that they are experts at to solve the problem. When the Manhattan project was deployed all the top physicists came and tackled the problem that needed to be solved with the most suitable methods, but there’s been “cancers Manhattan project” or “moonshot” initiatives in biology numerous times and they all fail because the scientists incharge invariably push their own agendas in these. Take Janelia farms for example- without reading their editorialised website if you try to gander what the hell this institution is trying to do, from just the papers they publish, you would fail miserably. Not saying that institution sucks, well I suppose I am saying that, but only insofar because all of academia seems to suck in the same way.
- an_opabinia 6y ago
  > Janelia farms I’m pretty sure they do basic science for medicine, with many of the same goals as the NIH.

oivey 6y ago

It seems kind of odd to blame academia for this. Almost all founders are clueless in all fields, and, additionally, they’re pretty much supposed to be aggressive about their idea in order to get investments. The role of the VC is to invest wisely. If they’re less knowledgeable about tech outside of the niche of computers and they lose money on biotech, that’s their fault.

ramraj07 6y ago
I suppose one of the points I was trying to make is that in tech it’s probably okay (maybe even beneficial) to be clueless, but that’s not true for biology or hard science tech - if you float a rocket company, stuff has to fly, and you better get some rocket scientists in there. One can’t just Travis Kalanick their way to Mars because you’re not fighting some cab unions you’re fighting the laws of physics.
ta988 6y ago
I know less about founders in computer tech but yes, many founders in biotechs that I know have just had a few years of experience in labs, not really successful scientifically, even if they know how to market it. And thats far from enough to really understand the nooks and crannies of drug discovery projects. Especially since most academic labs are only doing a really thin slice of the whole process. There is a reason why you dont give millions of dollars to a postdoc that submit their first grant proposal, why we do that to postdocs that are founding biotechs is beyond my understanding. The products I've seen from companies that raised $5mil are not worth 1/10 of that, and thats just in dev costs, their stuff could not even scale so they are trying to survive until the big prey comes and swallow them before anybody notices its all smoke and mirrors.
- oivey 6y ago
  Generally that’s the trajectory computer tech startups take too, except with even less experience. That’s probably a reflection of the difference in the barriers of entry.
- dnautics 6y ago
  > There is a reason why you dont give millions of dollars to a postdoc that submit their first grant proposal, why we do that to postdocs that are founding biotechs is beyond my understanding TINA. If you're a fund that needs to put an ass in a seat to say "we have a biotech investment", you go to whatever you can find. You have no way of doing due diligence in your portfolio and even if you hired someone like me to ultrafilter your proposals you'd probably come up empty, because the only postdocs that play this game are those that know they are good at parlaying their social capital, obtaining favorable reviews from their PIs (social validation), and have less scruples. The heads down brilliant and honest scientist postdocs have already burnt out, and often aren't socially savvy enough to play the VC game, if they were, they'd be gunning for faculty positions instead. If VC wants a better return they need to have a different heuristic. I'd pick postdocs that did years of grueling work with no results and ask them what they'd really prefer working on instead of their PI's hairbraned idea.

sjg007 6y ago

>Exceptions exist of course, and some of these bets turn good purely because of luck (if you take twenty random chemicals and inject, one of them might just cure cancer; incidentally how stuff like paclitaxel & vinblastine was discovered anyway). Vinblastine was discovered from folk tea remedies for diabetes. In animal models they saw decreased white blood cell counts. Paclitaxel was discovered from the NCI plant screening program. The chemical was observed to be cytotoxic in screening studies. So both of your examples have pre-clinical evidence. These were not randomly injected and developed through scientific research and the clinical trial program. https://en.wikipedia.org/wiki/History_of_cancer_chemotherapy https://en.wikipedia.org/wiki/History_of_cancer_chemotherapy

ramraj07 6y ago
Vinblastine was discovered when they were testing a folk remedy for diabetes and found cytotoxic effects so it was completely tangential to the study’s goals, and in modern parlance, an instance of a “task failed successfully.” Paclitaxel was discovered literally from a random spray and pray scan of plant samples from every taxonomic class, here I will quote a literal sentence from a review: “ Barclay collected T. brevifolia, an evergreen, apparently because the strategy was to collect at random. Not much was known about the tree. It belonged to the genus Taxus...” (https://www.acs.org/content/acs/en/education/whatischemistry/landmarks/camptothecintaxol.html https://www.acs.org/content/acs/en/education/whatischemistry... ) So I still believe in what I said, which is random screens or complete serendipity often has been the best ways to get t a lot of our therapies, though I’m not advocating for more of that necessarily.
- sjg007 6y ago
  Where you say random I think you mean systematic.