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We Made One Gram Of Remdesivir

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Re: We Made One Gram Of Remdesivir

#81

Post by tralarpa »

dguest wrote: post #70
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…

In point 3: did you try to contact the authors of the paper you were trying to reproduce? I don't know organic chemistry, but in my field the authors are often willing to discuss their results, especially if it might mean more citations for them.

May I ask what your field is? Is it CS? I am asking because we computer scientists are sometimes a little bit naive when it comes to research and publications. In other fields, like pharmaceutics, where future patents can be worth hundreds of millions of dollars, authors are very careful what they tell others.

Re: We Made One Gram Of Remdesivir

#83

Post by perlgeek »

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-hand side), making it cooler is better. You also need to control the temperature to be in a range where both the ingredients and products can survive.

As for the pressure, if the products and by-products have more total volume than the ingredients, low pressure is good. If it's the other way round, high pressure encourages the reaction.

The more complicated part is that if multiple reactions can happen with the same ingredients, or if the products can do further, unwanted reactions. Then you have to balance out the parameters to encourage just the reaction you want, and to discourage all the others.

Re: We Made One Gram Of Remdesivir

#84

Post by djaque »

dguest wrote: post #73
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…

What branch of physics? There are hundreds of published null results looking for dark matter or Supersymmetry, for example. Instead of documenting a failed search, the papers focus on what versions of the theories the experiment excludes to 95% confidence.

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 why it's so bad either at least not without years of learning.

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.

We trust our data, but he's concerned about getting it through peer review. For what it's worth we did publish it in a conference proceeding, but it doesn't have the same weight as a journal article.

Re: We Made One Gram Of Remdesivir

#85

Post by dguest »

avian wrote: post #72
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…

As someone who spent 4 years working on a PhD (wireless/RF technology) and then quit, your points 2 and 3 ring a lot of bells. I think "journal of failed experiments" is a wonderful idea.

Anyone can put a paper on arXiv. The bigger problem is that most journal editors will be skeptical of citing arXiv. If you're collaborating with more traditional academics it can be a challenge to even submit a paper with such citations.

I've had to push my colleagues to cite a number of non-traditional sources: arXiv, github, and zenodo for example. Fortunately most of them agree that citations are cheap and that giving more people credit is generally a good thing.

One thing that helps is publicly stating how you want your research cited. If you don't have a peer reviewed publication in the pipeline, tell people how to cite your work on a blog or your github page or somewhere. Most people default to peer-reviewed journals for citations and get confused when one doesn't exist, so an explicit statement really helps.

Re: We Made One Gram Of Remdesivir

#86

Post by rwmj »

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…

To what extent can synthesis steps be automated? Do you use a computer to plan how to get to a chemical? Do you use robots to carry out some or all steps?

Re: We Made One Gram Of Remdesivir

#87

Post by unnouinceput »

Quote: "Fortunately, there are creatures called "process chemists" – guys who laugh at the discovery synthesis, insult as many of us as possible, and then make it better so that the yields are higher and some of the most dangerous chemical reagents and solvents – ones you really don't want to use on a large scale – are replaced by others. They are generally a bunch of mutants, but they do a great job in "fixing" the synthesis used by the discovery chemists."

This really cracked me up. In my IT world the equivalent for "mutant" would be refactoring, right? I did "mutated" this way a few times in the past to much of the horrors of my boss(es)/manager(s) when they learned the next day.

Re: We Made One Gram Of Remdesivir

#88

Post by rwmj »

rocqua wrote: post #68
est31 wrote: post #66

Earlier quoted context omitted.

There is no RNA cloning machinery in our cells. The RNA is instead copied from the DNA in the nucleus. Viruses like the coronavirus actually bring their own RNA cloning machinery that's assembled by the cell. Remdesivir only blocks the RNA cloning proteins of the virus.

Doesn't that mean that Remdesivir would essentially defeat _all_ RNA viruses? Or is the effectiveness dependent on the exact RNA cloning mechanism used by the virus?

Yes, it was originally invented to treat ebola, but it's thought to have general antiviral properties against RNA viruses.

Re: We Made One Gram Of Remdesivir

#89

Post by wodenokoto »

djaque wrote: post #49
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…

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…

I never got published in the field I have a masters in, for what I'd like to think of as somewhat comparable reasons.

However, my take-away was that the successful researchers were the ones who could take any decent experiment and figure out what was publishable about it, or at least steer it into a publishable direction.

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