We Made One Gram Of Remdesivir • Hacker News Board

Re: We Made One Gram Of Remdesivir

#121

Post by ImaCake » Sun, Apr 05, 2020, 12:04 PM UTC

ashildr wrote: post #74

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 mode of action is fascinating, some HIV medications work in a similar way. What I’m curious about is why this huge group attached to the adenosine-like group is needed. It seems to be rather complex for being a shoe to be thrown into cellular gear. Do you have an idea or pointer into the mode of action of this group?

So looking at the wiki page image of Remdesivir [1] I can see that this looks a lot like the sugar-phosphate backbone that is integral to DNA and RNA. If you imagine DNA as a curling ladder, the nucleoside (adenosine) is the steps, and the sugar-phosphate pairs make up the rails on either side of the steps.

The adenosine bit is attached to a five carbon sugar (pentagon with O at top) which is identical to the sugar it would be attached to in RNA. The next thing along is a phosphate with some oxygens double bonded to it, which is part of the "backbone" of DNA. The stuff attached to that phosphate is nothing like DNA or RNA.

Hope this makes sense and provides a little insight for you :)

1. https://en.wikipedia.org/wiki/Remdesivir

Re: We Made One Gram Of Remdesivir

#122

Post by missosoup » Sun, Apr 05, 2020, 12:06 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…

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 to the choir, no such considerations are required.

In an ideal world, publishing against the grain should be encouraged and there should be no extra reputational penalty for getting caught with errors in that type of research (heaps of errors go unnoticed in mainstream papers, even popular ones). But that's not how it works sadly.

Re: We Made One Gram Of Remdesivir

#123

Post by auxym » Sun, Apr 05, 2020, 12:28 PM UTC

yjftsjthsd-h wrote: post #45

barkingcat wrote: post #18

Earlier quoted context omitted.

If they don't have grants, $0. If they work in a lab for someone who has a grant, $0, but with credit on the papers (that's why there's 35 authors on the paper, 1 person got paid, the rest got name credit in the hopes that they get noticed by a commercial company wanting to monetize this process, so in the future they get their own gig). If they work in a commercial lab, maybe they make a little.

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 theye make more than me).

Science and math have really bleak career outlooks. Tenure track faculty jobs are a crapshoot. Industry jobs are scarce. Most people I know from college that went into the sciences are either still stuck in PhD or postdocs, or quit after BS/MS and now working as lab technicians or equivalent. Not even glorified, just plain old overqualified lab techs in QC departments and such.

Edit: As a final note, here's a 2015 report from OSPE, an organization representing engineering professionals in Ontario, Canada: https://www.ospe.on.ca/public/documents/advocacy/2015-crisis... An except:

"Information referred to in this report is derived from the Canadian National Census 2011 National Household Survey (NHS). According to the 2011 NHS1, only about 30 per cent of employed individuals in Ontario who held a bachelor’s degree or higher in engineering were working as engineers or engineering managers. Fully two-thirds of engineering-degree holders were not working in engineering at all. Many had jobs that didn’t necessarily require a university degree."

Re: We Made One Gram Of Remdesivir

#124

Post by fouc » Sun, Apr 05, 2020, 12:32 PM UTC

spockz wrote: post #108

fouc wrote: post #59

Earlier quoted context omitted.

Sharing failures seems like the best way to make progress. I mean we're talking about SCIENCE here. If we don't have a comprehensive list of what does not work, that's just going to make progress so much slower.

I also wonder how many breakthroughs we would not have because of somebody saying that something didn’t work.

That's true. Failures need to be reproduced too.

Re: We Made One Gram Of Remdesivir

#125

Post by tikej » Sun, Apr 05, 2020, 12:37 PM UTC

I want to make remark about organic synthesis from the perspective of person who is engineer of chemistry by training as did his fair share of organic synthesis (and eventually moved to computational atomic and molecular physics).

It is one of the oldest and very established fields. Unfortunately practices aren’t great. The preparation formulas are often vogue, imprecise and difficult to reproduce. This comes from the fact that often the sizes and types of glassware are not specified, some informations are omitted (how quickly something is changed not only to what value e.g. heat up to 100 degrees but it does not say over what time) etc. Chemists usually (except some theoretical/computational specialisations) don’t have any training in algorithms or programming.

There are novel developments such as https://www.gla.ac.uk/news/archiveofnews/2018/november/headl... and references therein. I’m optimistic about them but I expect strong opposition from older faculty. They see synthesis as more than art and think that one has to have “good hand” in order to be a good organic chemist.

I think some generational shift will be necessary in order to change this discipline to more reproducible, strict and reliable. It will come but not that soon :)

Re: We Made One Gram Of Remdesivir

#126

Post by Symbiote » Sun, Apr 05, 2020, 12:53 PM UTC

ngngngng wrote: post #36

I've never learned a bit of Chemistry. I assume there are formulas to determine how substrates and reagents will react with each other? And the process chemists understand these formulas better than most? Apologies for the assumptions in these question, but are there many reactions in organic chemistry that are completely unknown? This actually seems pretty fun. I'd love to have a reason to study it and a means to do…

Which country's education system doesn't have any chemistry at all?

Chemical formulae are required study for 11-14 year olds in England, for what it's worth. (Probably starting with words: methane + oxygen → carbon dioxide, and later writing a balanced equation: CH₄ + 2O₂ → CO₂ + 2H₂O.) The reaction presented is obviously much, much more complicated, but the same concept.

Edit: catalysts are covered too, although I don't know if the notation of putting them above the → is introduced at this age. https://www.bbc.co.uk/bitesize/guides/zqd2mp3/revision/6

Re: We Made One Gram Of Remdesivir

#127

Post by saalweachter » Sun, Apr 05, 2020, 1:03 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…

I believe I've seen occasional reports on chemistry sims on HN; the last I saw, someone had managed to simulate an "interesting" number of atom at a rate of 1 ns / week.

Re: We Made One Gram Of Remdesivir

#128

Post by stevespang » Sun, Apr 05, 2020, 1:06 PM UTC

joshvm wrote: post #64

djaque wrote: post #49

Earlier quoted context omitted.

That's kind of my experience with research, but in physics. Already have three projects under my belt w/ no publishable results. All of them involved much more work than the other grad. students in my lab including building like three different instruments from scratch, but the other students have published. Their projects were much more "safe" than mine and their papers are pretty small, but at least they have paper…

Don't worry. Instrumentation is a pain for publishing because often it creeps into engineering territory. I spent a year of my PhD trying to get something to work, it didn't and I ended up building an entirely new instrument in the third year. That's how it goes. I know people who came out of their PhDs with five papers (in the UK that's a big deal), but they're in fields where its relatively easy to publish and/or g…

Fortunately, you can't censor whoever you disagree with over in this forum Josh. You aren't a tyrant and a dictator over here like your forum.

Re: We Made One Gram Of Remdesivir

#129

Post by Glosster » Sun, Apr 05, 2020, 1:25 PM UTC

perlgeek wrote: post #83

eyegor wrote: post #20

This article really reinforces my choice to drop ochem in college. It's funny how deciphering assembly code seems downright mundane compared to this jargon. Like, I get how given the process you could recreate things, or you could devise possible reactions based on electron shells and bonding tendencies, but how do researchers even figure out how to make these reactions happen? Especially when they require -100C, or…

> but how do researchers even figure out how to make these reactions happen? Especially when they require -100C, or +5atm of pressure. That part, at least in theory, is easy to understand. Chemical reactions are typically of the form: ingredients + energy -> products + byproducts If the energy is on the left-hand side, making the environment warm makes the reaction go faster. If energy comes out (so it's on the right…

Thanks for taking the time to explain at a basic level, this was very interesting!

Re: We Made One Gram Of Remdesivir

#130

Post by Scoundreller » Sun, Apr 05, 2020, 1:32 PM UTC

"(2) The one-gram dose is a guess based on the doses of other antiviral medicines."

You're in luck, the first dose is 200mg, and then 100 mg daily after that.

Unfortunately, it's also IV, so you have a number of extra steps after synthesis to ensure sterility.