Founder-driven life sciences companies • Hacker News Board

Re: Founder-driven life sciences companies

#21

Post by echelon » Sun, Jul 05, 2020, 10:21 AM UTC

shoyer wrote: post #18

echelon wrote: post #15

Earlier quoted context omitted.

This will change when we can spin up whole human bodies for experimentation and discard them at will. We need to clone decephalized humans. Turn off neural plate development. Downregulate genes that cause brain development. Before we get this right we can supplement it with surgical techniques to ensure the clones never have brains and never become sentient. Hook the embryos up to artificial life support that innerva…

What makes you think that (1) that it’s even possible to create such beings, (2) that these would even be good disease models or (3) a lack of model organisms is the main factor holding back medical breakthroughs? None of these is at all obvious...

1. It'll be an incredibly difficult engineering task with many large hurdles. But it's possible, because life found its solution in us. We culture human cells all the time, just like bacteria or plants - this is just a higher structure. In fact, you can think of this entire process like growing humans as plants.

2. We spend a lot of time "humanizing" model organisms by creating chimeras. But even then the results are frequently not portable. How many animal studies fail to make the jump to advanced clinical trials?

3. A human is the system you want to study. It has the same genome, the same transcriptome, the same proteome, the same metabolome, and the same kinetics and thermodynamics. Animal models are 17th century dentistry in comparison.

Re: Founder-driven life sciences companies

#22

Post by strogonoff » Sun, Jul 05, 2020, 11:38 AM UTC

echelon wrote: post #21

shoyer wrote: post #18

Earlier quoted context omitted.

What makes you think that (1) that it’s even possible to create such beings, (2) that these would even be good disease models or (3) a lack of model organisms is the main factor holding back medical breakthroughs? None of these is at all obvious...

1. It'll be an incredibly difficult engineering task with many large hurdles. But it's possible, because life found its solution in us. We culture human cells all the time, just like bacteria or plants - this is just a higher structure. In fact, you can think of this entire process like growing humans as plants. 2. We spend a lot of time "humanizing" model organisms by creating chimeras. But even then the results are…

Placebo research and documented cases of physiological diseases treated via mental health therapy puts in question the viability of using theoretical human-like creatures that possess no consciousness, and therefore no mental state to speak of.

To draw an analogy, this would introduce such a huge gap between “staging” and “prod” environments that the effort and the ethical risk of ending up with “staging” entities possessing any degree of human consciousness cannot even remotely be worth it. (I’m somewhat alarmed that I feel the need to spell that out.)

Re: Founder-driven life sciences companies

#23

Post by DrAwdeOccarim » Sun, Jul 05, 2020, 12:27 PM UTC

jl2718 wrote: post #10

Hi. This is pretty early for this, but I’m looking for some advice for starting a seed fund to advance early-stage startups in cancer immunotherapy. It’s not for me, but someone whom I did some machine learning work, and angel investment with. He’s one of the top names in the field from the early days of cloning to today, veteran of several biotech startups, and likely recent Nobel and Lasker winner advising. There’s…

I am relatively new to the cancer IO space, but unless you discovered a new check-point idea (e.g., TIGIT) a lot of the ideas are flushed out already. If you're thinking cell-therapy, there are a number of autologous ideas already on CMC for p1 testing. If you're trying to make TILs angry, or modulate M1/M2 CD11b macrophages, anything that requires transcriptional re-programming, you have a lot of catching up to do.

Re: Founder-driven life sciences companies

#24

Post by Eridrus » Sun, Jul 05, 2020, 12:29 PM UTC

est31 wrote: post #3

t_serpico wrote: post #2

This is one key comment that fundamentally differentiates software/hardware from biotech: "Overall the power of recombinant technology and its rapid growth in the 1970s/1990s didn’t necessarily translate into success for new technologies." Powerful abstractions and pervasive feedback loops across the hardware and software stack is what fundamentally enabled rapid innovation in tech; those same ideas haven't developed…

One of the reasons why biotech has so low success is that we see it as kinda ok to unleash a half tested app onto people, basically most startup apps out there, while new drugs are extremely hard to get tested. It's kinda understandable given that some drugs can have serious negative long term effects on people, whereas a buggy CRUD app can't really do much harm in comparison. While the costs of a "buggy" drug are us…

I don't think this comparison holds up. In software, the reason to release something early is because it is hard to tell if there is demand for what you have built and getting feedback from the market is vital.

In pharma, I think the success criteria are much better understood, but it's just really hard to do what people want.

Not so say our regulatory system isn't a shitshow that needs reform, but I don't think there is the same benefit of releasing buggy versions.

Having said that, there are a lot of arguments for reforming how we do later stage clinical trials to provide access to potentially life saving drugs as well as reducing the costs of drug development https://reason.com/2018/02/02/right-to-try-fda-drug-trials/

Re: Founder-driven life sciences companies

#25

Post by echelon » Sun, Jul 05, 2020, 12:38 PM UTC

strogonoff wrote: post #22

echelon wrote: post #21

Earlier quoted context omitted.

1. It'll be an incredibly difficult engineering task with many large hurdles. But it's possible, because life found its solution in us. We culture human cells all the time, just like bacteria or plants - this is just a higher structure. In fact, you can think of this entire process like growing humans as plants. 2. We spend a lot of time "humanizing" model organisms by creating chimeras. But even then the results are…

Placebo research and documented cases of physiological diseases treated via mental health therapy puts in question the viability of using theoretical human-like creatures that possess no consciousness, and therefore no mental state to speak of. To draw an analogy, this would introduce such a huge gap between “staging” and “prod” environments that the effort and the ethical risk of ending up with “staging” entities po…

> Placebo research and documented cases of physiological diseases treated via mental health therapy

How is cancer something you can fix with mental health therapy? Tell them to go home and feel better, that it'll all be over soon?

What about a host of other genetic and immune disorders, many of which can be fatal?

I don't mean to come across as harsh or mocking, but there are a host of diseases where your solution does not work.

> I’m somewhat alarmed that I feel the need to spell that out

I understand your argument, but I reject it because I don't think we're seeing the same picture of where things now stand or could be. I'll counter with an analogy of my own.

Right now we're attempting to fix issues in prod by looking at another company's software, decompiling it, bit fiddling a bit, then trying to hot patch it into our own production instance. We run some smoke tests before releasing things, but these can't always identify long-term effects.

I want to have an actual honest to god dev and staging environment. Not just that, but a system that looks remarkably like prod that we can burn down and spin up on demand for each investigator trying to solve novel problems.

We can actually test at scale (and duration!) and pick apart the system to see that no part of it goes into failure mode or disease state.

Development goes much faster when you have an actual dev kit to run your code on or tear apart.

We don't have anything like that right now.

I get that the notion that human beings being equated to fungible software or disposable hunks of meat is uncomfortable. But the special ingredient in both you and me is consciousness, and this design ensures we never bring new consciousness to life. We turn off the gene expression that causes the brain to develop, and we can double down with mechanical amputation.

It sounds macabre, but so too did dissecting cadavers a century ago.

Re: Founder-driven life sciences companies

#26

Post by Eridrus » Sun, Jul 05, 2020, 12:47 PM UTC

neilv wrote: post #4

est31 wrote: post #3

Earlier quoted context omitted.

One of the reasons why biotech has so low success is that we see it as kinda ok to unleash a half tested app onto people, basically most startup apps out there, while new drugs are extremely hard to get tested. It's kinda understandable given that some drugs can have serious negative long term effects on people, whereas a buggy CRUD app can't really do much harm in comparison. While the costs of a "buggy" drug are us…

I think "move fast, and break things" isn't as catchy, when it's harder to ignore that "things" being broken are often people.

Most of the cost in pharma trials is not due to safety testing, it is in testing whether it is effective and whether it is better than the competition.

I'm not really involved in pharma, but there seems to be a decent argument for selling the drug with provisional approval after safety has been established and collecting outcomes data for those who use provisional drugs https://reason.com/2018/02/02/right-to-try-fda-drug-trials/

Re: Founder-driven life sciences companies

#27

Post by [deleted] » Sun, Jul 05, 2020, 1:36 PM UTC

echelon wrote: post #25

strogonoff wrote: post #22

Earlier quoted context omitted.

Placebo research and documented cases of physiological diseases treated via mental health therapy puts in question the viability of using theoretical human-like creatures that possess no consciousness, and therefore no mental state to speak of. To draw an analogy, this would introduce such a huge gap between “staging” and “prod” environments that the effort and the ethical risk of ending up with “staging” entities po…

> Placebo research and documented cases of physiological diseases treated via mental health therapy How is cancer something you can fix with mental health therapy? Tell them to go home and feel better, that it'll all be over soon? What about a host of other genetic and immune disorders, many of which can be fatal? I don't mean to come across as harsh or mocking, but there are a host of diseases where your solution do…

[deleted]

Re: Founder-driven life sciences companies

#28

Post by goblin89 » Sun, Jul 05, 2020, 1:37 PM UTC

echelon wrote: post #25

strogonoff wrote: post #22

Earlier quoted context omitted.

Placebo research and documented cases of physiological diseases treated via mental health therapy puts in question the viability of using theoretical human-like creatures that possess no consciousness, and therefore no mental state to speak of. To draw an analogy, this would introduce such a huge gap between “staging” and “prod” environments that the effort and the ethical risk of ending up with “staging” entities po…

> Placebo research and documented cases of physiological diseases treated via mental health therapy How is cancer something you can fix with mental health therapy? Tell them to go home and feel better, that it'll all be over soon? What about a host of other genetic and immune disorders, many of which can be fatal? I don't mean to come across as harsh or mocking, but there are a host of diseases where your solution do…

> Right now we're attempting to fix issues in prod by looking at another company's software, decompiling it, bit fiddling a bit, then trying to hot patch it into our own production instance.

The staging/prod analogy is flawed.

What we are doing is manipulating board wiring, while what we could do is further our understanding of and abilities to alter the OS and firmware running on it.

Very unfortunately, but understandably, scientifically oriented mindset tends to dismiss the latter route. After all, so far it seemingly rules out any notion of dev environment. Where is reproducibility, if all we can do is SSH into a snowflake live system (or more like XSS inject it, right)? A daunting limitation, but perhaps not impossible to overcome.

That is not to say the former has no place and your point is invalid. Still, when all you have is a hammer…

Re: Founder-driven life sciences companies

#29

Post by TomMarius » Sun, Jul 05, 2020, 1:53 PM UTC

echelon wrote: post #20

d_silin wrote: post #16

Earlier quoted context omitted.

Bioethiticists will have a field day with you. Also multiple angry mobs from left, right and center.

There's absolutely nothing wrong with what I've proposed. Typically only people that believe in a soul or that humans "should die" take issue. Neither of these is correct in my world view. I can understand the religious perspective, but the romantic idea that limited live spans are good is incredibly twisted. I think people should be immortal, but that's just not feasible. The next best thing is using all of the tool…

Well, many people disagree, so I'd like to voice my support. Maybe more of us should team up in a chat room.

Re: Founder-driven life sciences companies

#30

Post by Emergently » Sun, Jul 05, 2020, 2:32 PM UTC

echelon wrote: post #20

d_silin wrote: post #16

Earlier quoted context omitted.

Bioethiticists will have a field day with you. Also multiple angry mobs from left, right and center.

There's absolutely nothing wrong with what I've proposed. Typically only people that believe in a soul or that humans "should die" take issue. Neither of these is correct in my world view. I can understand the religious perspective, but the romantic idea that limited live spans are good is incredibly twisted. I think people should be immortal, but that's just not feasible. The next best thing is using all of the tool…

I'm an emergency physician and I think what you have proposed is unethical and immoral. Good luck getting any type of experimentation through the Institutional Review Boards(IRB), bioethicists, and scientists.

Call us Luddites but this type of science is not looked at kindly. There's no argument or debate to be had when what you are proposing is a red line for many and a non-starter.