We Made One Gram Of Remdesivir • Hacker News Board

Re: We Made One Gram Of Remdesivir

#171

Post by wenc » Sun, Apr 05, 2020, 4:47 PM UTC

ggcdn wrote: post #157

wenc wrote: post #135

Earlier quoted context omitted.

> 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.

Yes, sounds like that could work. Like a wikipedia of experiments tried, with contact details and a public discussion forum for anyone interested in going deeper into the results.

In many fields, you can generally tell if someone is faking it about from how they respond and what they say. It's not that easy to fake specialized knowledge. This will help increase the signal-to-noise ratio.

The trick is to bootstrap a high-quality community, where top people in the field will want to engage. MathOverflow managed to do this for pure math. Quora on the other hand used to be good in the early days (many SV names) but has struggled to maintain quality. There's also the problem of moderating professional rivalry and reputation-maintenance in academia -- these are non-trivial issues in some smaller fields.

Re: We Made One Gram Of Remdesivir

#172

Post by Balgair » Sun, Apr 05, 2020, 4:59 PM UTC

djaque wrote: post #164

joshvm wrote: post #148

Earlier quoted context omitted.

Instrumentation is field-specific. It really depends how bespoke your requirements are. Some places buy stuff off the shelf, others fabricate in-house. In astronomy it's called instrumentation. Astro has relatively sane nomenclature. You have observational (looking at stuff and gathering data), theoretical (theory and simulations) and instrumentation (building stuff). Everyone in the field understands those terms. Th…

Exactly, the instruments I was talking about are used to measure the properties of photocathodes. It's such a niche field that there's no off the shelf solution. Everybody makes their own device and ours is one of like two in the world with it's grade of sensitivity. There is one professional engineer in the lab my group is a part of, but they primarily work on the bigger projects. For this, I have to do all of the C…

I'll echo this too. Instrumentation is field specific. I was in bioeng, but my work was photo-chem/physics and optics. Basically, building novel nanoscopes.

Pro-Tip: Want a 'quick' nobel? Do optics for ~3/4 years. Then never touch it again. Making new kinds of microscopes is crazy useful and high impact, but you either get lucky or you waste 45 years in a lab. Try it out for a bit, throw a few on red, then walk away from the table.

Re: We Made One Gram Of Remdesivir

#173

Post by Josh_Bloom » Sun, Apr 05, 2020, 5:02 PM UTC

ebg13 wrote: post #3

The writing is so good, I had to double check that it wasn't written by Derek Lowe.

Thank you! That may be the biggest compliment I’ve ever gotten. Derek is the god of carbon as far as I’m concerned. Josh

Re: We Made One Gram Of Remdesivir

#174

Post by OscarCunningham » Sun, Apr 05, 2020, 5:03 PM UTC

tikej wrote: post #120

CamperBob2 wrote: post #101

Earlier quoted context omitted.

I asked this question once. I couldn't figure out why there's no SPICE for chemistry (SPICE being any of several accurate, refined, and well-understood simulation programs for EE work). You know the whole deal with the three-body problem? How closed-form solutions become intractable in a hurry once you go past two or three mutually-influential orbiting bodies? As it was explained to me, that's why there's no SPICE fo…

(Quantum) Many body problem is indeed at the very heart of chemistry. If it was solved creation of new materials and chemicals would be less of trial and error. In principle it comes down to the fact that problem space explodes tensorially with number of electrons e.g. in principle you need grid size of 3N dimensions per every electron so for helium a^6 where a is number of points in the grid (and you probably need a…

Excitingly, this is one of the problems that quantum computers will be good at. We might see a time when chemists can run experiments faster on a computer than they can in the lab.

Re: We Made One Gram Of Remdesivir

#175

Post by aazaa » Sun, Apr 05, 2020, 5:12 PM UTC

> n-BuLi is short for n-butyllithium, which bursts into flame if exposed to oxygen or water.

It looks like the author is overselling some of the dangers here.

While you really don't want to dump n-BuLi into water, you have no reason to either.

The problem child of the class to which n-BuLi belongs is t-BuLi. That will spontaneously ignite in air, whereas n-BuLi will not. There was a very high-profile case I believe at UCLA a few years back in which a student using t-BuLi in the lab caused a fire with it and ended up dying.

https://cen.acs.org/articles/87/i31/Learning-UCLA.html

Also, I find this article confusing in the way it's written. Take the title, for example. It gives the impression that the author is describing his own efforts to make remdesivir ("we").

What he's really describing is some preps he found in the literature. And with a little too much hyperbole for my taste.

Re: We Made One Gram Of Remdesivir

#176

Post by alkonaut » Sun, Apr 05, 2020, 5:26 PM UTC

alkonaut wrote: post #96

roenxi wrote: post #19

Although very interesting, this article isn't a great introduction because a critical part of the picture is missing - the availability of the inputs. Sticking to simple stuff; mines produce iron at a rate measured in thousand-tonnes per hour with yields of potentially sub-30% compared to volume of earth moved. Ammonia and many acids are presumably measured in tonnes or kilograms produced per day. Low yields make the…

Exaxtly this. Are the inputs available and we can spend just a few tens of billions on building gigafactories to make this process parallel and controlled? Then it’s like making microchips from silicon or gold from ore. Terrible yield but cheap inputs and a scalable process. If the inputs are expensive or the process can’t scale (to a billion doses in 12 months, say) then that’s worrying and perhaps indicates this is…

Edit: remdesivir is a therapeutic, not a vaccine, so it is useful in much smaller quantities than a vaccine.

Re: We Made One Gram Of Remdesivir

#177

Post by dang » Sun, Apr 05, 2020, 5:38 PM UTC

nik_0_0 wrote: post #77

Josh_Bloom wrote: post #37

@ebg13 Thank you! That may be the biggest compliment I’ve ever gotten. Derek is the god of carbon as far as I’m concerned. Josh

You missed the reply, but I hope ebg13 finds this! Great writing.

I briefly moved the comment, then saw that Josh_Bloom had posted another copy of this reply to the right place.

Re: We Made One Gram Of Remdesivir

#178

Post by whatshisface » Sun, Apr 05, 2020, 5:42 PM UTC

koboll wrote: post #161

kccqzy wrote: post #22

Remdesivir is an analog of adenosine, one of the four building blocks of RNA. Just look at the main structure and you'll agree they look similar. It turns out the mechanism of action of this drug is that it's supposed to be confused with adenosine, so that the viral RNA replication process uses remdesivir instead of adenosine, which later breaks the RNA†. Our body, or really, all biological processes can synthesize i…

This is such a great description. Compare how Wikipedia describes the same process [ https://en.wikipedia.org/wiki/Adenosine#Research ]: > The adenosine analog NITD008 has been reported to directly inhibit the recombinant RNA-dependent RNA polymerase of the dengue virus by terminating its RNA chain synthesis. This interaction suppresses peak viremia and rise in cytokines and prevents lethality in infected animals, ra…

Gibberish to someone with limited knowledge of biology, but significantly more informative for someone who is using Wikipedia as a reference source and not a textbook.

Re: We Made One Gram Of Remdesivir

#179

Post by dang » Sun, Apr 05, 2020, 5:43 PM UTC

nbabitskiy wrote: post #32

kccqzy wrote: post #22

Remdesivir is an analog of adenosine, one of the four building blocks of RNA. Just look at the main structure and you'll agree they look similar. It turns out the mechanism of action of this drug is that it's supposed to be confused with adenosine, so that the viral RNA replication process uses remdesivir instead of adenosine, which later breaks the RNA†. Our body, or really, all biological processes can synthesize i…

>> look at the main structure and you'll agree I don't know much about RNA, but this sentence is pure bs. How would I know where to look in RNA sequences?

This comment broke the site guidelines. Even if you're right, it is a problem to address another user this way, because the container isn't strong enough to hold that level of (let's call it) energy. When you post like this, you're breaking the already-weak bonds that hold this community together, which is what makes it a moderation issue.

Would you mind taking a look at https://news.ycombinator.com/newsguidelines.html and sticking to the rules when posting? Those rules are all there because of past problems in the threads. Note this one: "Have curious conversation; don't cross-examine."

Re: We Made One Gram Of Remdesivir

#180

Post by oefrha » Sun, Apr 05, 2020, 5:53 PM UTC

koboll wrote: post #161

kccqzy wrote: post #22

Remdesivir is an analog of adenosine, one of the four building blocks of RNA. Just look at the main structure and you'll agree they look similar. It turns out the mechanism of action of this drug is that it's supposed to be confused with adenosine, so that the viral RNA replication process uses remdesivir instead of adenosine, which later breaks the RNA†. Our body, or really, all biological processes can synthesize i…

This is such a great description. Compare how Wikipedia describes the same process [ https://en.wikipedia.org/wiki/Adenosine#Research ]: > The adenosine analog NITD008 has been reported to directly inhibit the recombinant RNA-dependent RNA polymerase of the dengue virus by terminating its RNA chain synthesis. This interaction suppresses peak viremia and rise in cytokines and prevents lethality in infected animals, ra…

Scientific articles on Wikipedia aren’t written for laymen, although some could be understood by laymen as a side effect. For example as a physicist/mathematician I expect precise and physically/mathematically accurate statements rather than hand-wavy analogues that the average Joe might be able to make sense of, and that’s how I edit. Now, it’s okay to also include more approachable explanations, but they’re not a must.