We Made One Gram Of Remdesivir • Hacker News Board

Re: We Made One Gram Of Remdesivir

#151

Post by barkingcat » Sun, Apr 05, 2020, 3:35 PM UTC

auxym wrote: post #123

yjftsjthsd-h wrote: post #45

Earlier quoted context omitted.

So... Why does anyone do it? We're talking about throwing years of your life at this work; how on earth is it pulling people in if it can't pay bills?

That's why I'm clueless at all the politicians and journalists claiming we have a STEM shortage, we need to boost STEM education, need more kids interested in STEM careers... STEM = science technology engineering math CS/software has huge demand and salaries to go with it (yay, ads) Traditional (civil/mech/ee/chem/etc) engineering is OK. You'll never be rich but you'll always be comfortable. (I've had plumbers claim…

To be fair, plumbers do make more than the average code jockey doing maintenance type programming at regular computer jobs (outside of the faang universe, there are a lot of average paying computing/coding jobs - think programming forms for web stores, coming up with fillable pdf forms for ordering, etc)

Plumbing is an essential service, and in emergencies, hourly rates can go into $300+/hour. So why don't everyone go into plumbing? Cause it's a shit job (/s)

Jokes aside, my take on the science job contradiction is that current American society does not respect nor want the products of science.

Think vaccines - when we have an emergency, everyone wants one, but in "normal times", think about where the pockets of the anti-vaccination movement have taken hold: rich communities in California where science should have had the best chance of surviving, but is struggling.

Communities in the American Southern states who are having trouble keeping evolution and science curriculums in tact are another example.

Re: We Made One Gram Of Remdesivir

#152

Post by vageli » Sun, Apr 05, 2020, 3:36 PM UTC

jschwartzi wrote: post #146

missosoup wrote: post #122

Earlier quoted context omitted.

In a vacuum yes. In the world of academia and its perverse incentives, no. Publishing something that goes against the grain means a lot more scrutiny on your work and bigger humiliation for any mistakes made. If you're publishing against the grain, you have to double triple check every single detail to make sure it's all iron-clad. This costs a lot of additional time and money. When publishing research that preaches…

Really academia needs a way to request comment on an experimental procedure without requiring results or conclusions. Then you could publish negative or questionable results and seek speculation from other researchers.

> Really academia needs a way to request comment on an experimental procedure without requiring results or conclusions. Then you could publish negative or questionable results and seek speculation from other researchers.

I feel like anonymity could possibly go a long way for this.

Re: We Made One Gram Of Remdesivir

#153

Post by ridaj » Sun, Apr 05, 2020, 3:37 PM UTC

darawk wrote: post #91

djaque wrote: post #84

Earlier quoted context omitted.

I'm in acceleraror physics and study photocathodes. Unfortunately the state of those projects is that we thought a material should have great photoemission properties under some very specific circumstances. When we measured it, the material was actually terrible and we don't understand why it's that way outside of some speculation. Unfortunately it also feels like our lab doesn't have the type of expertise to explain…

> My advisor's explanation on publishing was that if we had great results that followed our initial theory of what's going on then we could write a paper and nobody would question it. But, now that we contradict theory the threshold of evidence is much higher and he doesn't want to go ahead with it. Isn't that sort of the most important thing to publish? Something that contradicts theory means something new. Seems li…

It reminds me of the paper reporting that neutrinos had been detected going faster than the speed of light[0]. It turned out to be an instrumentation issue. Some of the folks involved had to step down.

Yes, it is important to publish results that violate established theories, but if there's already a lot of validation of those theories through experimentation, you're going to have legitimate pushback, especially if your method of experimentation isn't the most sophisticated.

If the result of your publication is a theoretical breakthrough, then that's great, but unless you're in the top tier within that discipline, the likely outcome is that your research turns out to have a big flaw which you missed, and you invite a bunch of people to point out to the world that you can't do science properly...

[0] https://www.sciencemag.org/news/2012/06/once-again-physicist...

Re: We Made One Gram Of Remdesivir

#154

Post by xg15 » Sun, Apr 05, 2020, 3:38 PM UTC

cowboysauce wrote: post #147

xg15 wrote: post #102

Earlier quoted context omitted.

Out of curiosity: We seem to have a very good understanding how synthesis in biological processes works (from DNA to the eventual molecules), we are able to create DNA/RNA molecules with arbitrary content and we're increasingly able to simulate what molecule a particular nucleotide sequence would produce. So, putting the three together, would it be possible to use actual biosynthesis for designed molecules by basical…

in theory it's possible, in practice it's not. DNA encodes the information on how to produce to proteins. Proteins can catalyze chemical reactions. But there's no straightforward to look at a nucleotide sequence and figure out what it's corresponding protein does. Nor can we design proteins with arbitrary functions. The entire thing is so unimaginably complex. For example, for a lot proteins that are catalysts (aka e…

Thanks a lot for the info.

> Proteins fold into their final shape from the chain of amino acids that DNA encodes. Protein folding in general is a hard problem.

My hope was that we had made progress in exactly that domain. Yes, the relationship between a nucleotide sequence and the resulting protein is extremely complex, but my impression was that we have tools to simulate the folding process for a given chain of amino acids (Folding@Home comes to mind).

So I was imagining a brute-force like process, where you (somehow) start with some candidate sequences, simulate how they would fold and use the sequence that comes closest to the molecule you wanted to have in the first place. Of course this only works if your target molecule can be assembled out of amino acids.

Re: We Made One Gram Of Remdesivir

#155

Post by ridaj » Sun, Apr 05, 2020, 3:40 PM UTC

jschwartzi wrote: post #146

missosoup wrote: post #122

Earlier quoted context omitted.

In a vacuum yes. In the world of academia and its perverse incentives, no. Publishing something that goes against the grain means a lot more scrutiny on your work and bigger humiliation for any mistakes made. If you're publishing against the grain, you have to double triple check every single detail to make sure it's all iron-clad. This costs a lot of additional time and money. When publishing research that preaches…

Really academia needs a way to request comment on an experimental procedure without requiring results or conclusions. Then you could publish negative or questionable results and seek speculation from other researchers.

It does: for example, as djaque's comment points out, in their case this was published at conference proceeding. And of course advice can be sought in private as well.

Re: We Made One Gram Of Remdesivir

#156

Post by rwmj » Sun, Apr 05, 2020, 3:56 PM UTC

malwarebytess wrote: post #98

lisk1 wrote: post #94

Earlier quoted context omitted.

There are a lot more RNA virus specifically targeting antivirals surprised that most of them are not yet tested.

sounds like we should get on it

According to this radio programme[1] I was listening to at the weekend, scientists have been warning about the potential of coronaviruses to cause a pandemic for a long time, and saying we should work on general antivirals for them. Obviously that didn't happen.

[1] https://www.bbc.co.uk/programmes/m000gvd1

Re: We Made One Gram Of Remdesivir

#157

Post by ggcdn » Sun, Apr 05, 2020, 4:01 PM UTC

wenc wrote: post #135

Vaslo wrote: post #34

In my former life I was a graduate organic chemist, but I “quit” with a Masters. I loved Synthetic Chemistry as an undergrad and thought I wanted a PhD in. There were three lousy things (for me) about the career that made me bail. 1). So many syntheses have horrible yields just like this one. You’d start with grams of material to end up with micrograms. I loved solving these problems as an undergrad in books, but rea…

> They need a journal of failed chemistry because only the working stuff gets published. I think there's theoretical value in this, and many have tried, but the incentives/disincentives for doing so isn't favorable. Here's some reasons why I think it's difficult to motivate people to publish negative results: 1) Negative results, while important in advancing science, don't get you grants. 2) Negative results need to…

Maybe instead of full-fledged journal model, negative results should be published in a short (few pages) failure report. This addresses at least a few of the points you highlight. Skip all the cruft: here’s what we tried to do, here’s our methodology, and here’s the result.

Then these could be classified by methodology/process/chemicals/etc for people to look up before starting their research.

Re: We Made One Gram Of Remdesivir

#158

Post by djaque » Sun, Apr 05, 2020, 4:02 PM UTC

ridaj wrote: post #153

darawk wrote: post #91

Earlier quoted context omitted.

> My advisor's explanation on publishing was that if we had great results that followed our initial theory of what's going on then we could write a paper and nobody would question it. But, now that we contradict theory the threshold of evidence is much higher and he doesn't want to go ahead with it. Isn't that sort of the most important thing to publish? Something that contradicts theory means something new. Seems li…

It reminds me of the paper reporting that neutrinos had been detected going faster than the speed of light[0]. It turned out to be an instrumentation issue. Some of the folks involved had to step down. Yes, it is important to publish results that violate established theories, but if there's already a lot of validation of those theories through experimentation, you're going to have legitimate pushback, especially if y…

Thanks, this is in line with what I feel is going on. I woke up this morning to see a lot of comments on how my experience is proof that academia is broken. Instead, it just feels like everybody is being very cautious about our results.

We don't understand why our data doesn't line up with theory and this isn't some super well funded experiment like the ones at the LHC with like a million grad. students. This is just me in the lab alone with the hundreds of subtle ways the experiment could have gone wrong or needed a slight modification to the theory. It would take us a lot of effort to distinguish an experiment gone wrong from an interesting new development and that's not always worth it. Especially for such a niche area of research like I'm in.

Also, we did publish our data. We just did it in a conference proceeding with a lot of caveats attached to it instead of in a big journal article. That's the aspect that I was complaining about, but I do understand my advisor's decision.

I have to strongly disagree that science is broken here.

Re: We Made One Gram Of Remdesivir

#159

Post by djaque » Sun, Apr 05, 2020, 4:09 PM UTC

BurningFrog wrote: post #150

djaque wrote: post #84

Earlier quoted context omitted.

I'm in acceleraror physics and study photocathodes. Unfortunately the state of those projects is that we thought a material should have great photoemission properties under some very specific circumstances. When we measured it, the material was actually terrible and we don't understand why it's that way outside of some speculation. Unfortunately it also feels like our lab doesn't have the type of expertise to explain…

Yet another example of how 2020 institutional science is broken. For the purpose of producing knowledge. It does other things.

Could you please explain why you think this means science is broken?

There are real issues in academia, but I disagree that what happened here is wrong. We did publish our data, we just didn't do it in a journal article. In my fields, this is actually fairly typical and journals are less of the norm unless you have a big result.

The whole problem is that extraordinary claims require extraordinary evidence. Sometimes when you don't have much funding and there's only a few grad. students in the lab, that evidence is no longer worth the time to collect.

See the comments below about the "neutrinos travel faster than the speed of light" paper. There is a real danger in publishing theory-breaking results when you don't have 100% confidence in them.

Re: We Made One Gram Of Remdesivir

#160

Post by djaque » Sun, Apr 05, 2020, 4:14 PM UTC

ridaj wrote: post #155

jschwartzi wrote: post #146

Earlier quoted context omitted.

Really academia needs a way to request comment on an experimental procedure without requiring results or conclusions. Then you could publish negative or questionable results and seek speculation from other researchers.

It does: for example, as djaque's comment points out, in their case this was published at conference proceeding. And of course advice can be sought in private as well.

Yes, exactly. I also gave an invited talk about it at the largest domestic conference in my field. This is kind of unusual for a grad. student which should give you an idea of how unique the problem is. We actually received good advice about our experiment that we might try later. The issue is just how niche what I study is. There's probably less than 10 experts in the world on the specific problem I was tackling.