5 ms·

The full text is available here: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7915550/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7915550/ It's always good

The full text is available here: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7915550/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7915550/ It's always good to remember just how crazy complicated and unusual HIV is, with its self-rewrite immune escape functionality. The mRNA vaccine for covid-19 was very lucky, not only because coronaviruses are not the devilishly clever co-evolving with the host's immune system HIV type of things, but also because the spike protein was already "solved" ahead of the pandemic. By that i mean we knew how to create a version of the spike protein that doesn't require the full envelope to fold properly. The mRNA sequence was ready in January 2020, the rest was just manufacturing, testing and distribution. The HIV vaccine will be most likely much more complicated, as the authors point out in the last chapter. PS. Sometimes I wish I was a research doctor instead of a computer scientist, but I guess the grass is always greener :)

Traubenfuchs 5y ago
> Sometimes I wish I was a research doctor The reality of being a researcher appears to be quite disappointing. Trapped between grant hunting and p-hacking the papers you need to churn out into high impact journals appears to be the grim reality.
- bipson 5y ago
  I am (kind of) in research on the CS side, and I wish I was on the medical side. The grant hunting, bullshitting, old-stuff-in-new-covers is all the same, but the problems and the topics are just so much more approachable, relevant, interesting, and the community seems to be "nicer". But then of course, I know people that are in that area an were getting into research, and they did not paint a nice picture. And the community obviously can suck also once you're on the inside. And being a "researcher" without clinic duties is really not easy getting into in Europe it seems. Also, who wants to stop doing clinic completely, when this is what he trained for so long... There are upsides and downsides to everything - I think it really depends on where your interests are.
  - vanderZwan 5y ago
    > the community seems to be "nicer" Having worked as a programmer for molecular neurobiologists for two years: yeah, they are. Everyone's just hyped at how insanely fast things are developing. Everything I saw when I worked there felt cutting-edge. The engineering involved, the science produced, the speed at which new insights were being gained. > And being a "researcher" without clinic duties is really not easy getting into in Europe it seems. The trick is to go the molecular biology route instead, it seems
  - twic 5y ago
    I've done both. The crucial difference is that computer work is far more productive than bench work. If you spend a month at your computer, you will get something out of it. You can easily spend a month at the bench and come away with nothing at all. Part of the secret to success in bench work is finding a seam which you can mine productively. You have some technique or system set up and working, and you can grind out findings from it. But it takes time to establish that seam, and it isn't necessarily anywhere near where the actually interesting problems are. I worked on cell migration. We used a particular cell type that had very good, consistent migratory behaviour, which made it a good system. But it was a primary culture, made fresh from dissected tissue every day. Primary cultures are highly resistant to having DNA put into them. Pretty much all modern cell biology hinges on putting DNA into cells. I spent a year or so trying different techniques (including making adenoviral vectors!). Eventually, i found something which worked okay. But that was just the start of actually doing interesting work - the year up to that point had produced nothing. This is completely normal in bench work, but would be pretty shocking with computers.
    - macrolime 5y ago
      I've done both too, but after a couple months at the bench, I always find myself spending most of my time trying to create robots to automate the work instead. Haven't gotten that to work out in the long run, so I just do programming now.
    - mathw 5y ago
      I guess at one point computing was more like that, in that to solve a new problem you may well have had to build yourself a new kind of computer or compiler first.
- f6v 5y ago
  The reality of software engineering can be disappointing as well. Incompetent non-technical managers, business metric hacking before the funding round, and a ton of technical debt. But it pays much more.
  - Traubenfuchs 5y ago
    Don't get me wrong. I hate software development just as much as academia. After 7 years in the industry, there is not a single shred of positive emotion towards software engineering left in me.
    - stuff4ben 5y ago
      Wow, I'm incredibly sad for you. If I felt that way towards a field I've been working in since I was in the sixth grade and now for some 30 years of my life... well it wouldn't be pretty. Sounds like you're burned out. If software development is your passion, perhaps take a break and reconnect with yourself?
- refurb 5y ago
  Working in R&D in private companies can be not only well paid but very rewarding as well. A lot less struggle for resources if your idea pans out.
- DrAwdeOccarim 5y ago
  I mean, you're just talking about an academic research doctor. Which really only accounts for a small percentage of total researchers out there. I appreciate your trying to frame that his grass is actually quite green, don't just throw the baby out with the bathwater : )
eMGm4D0zgUAVXc7 5y ago
> with its self-rewrite immune escape functionality. Interesting! Could you elaborate on this or provide a link? > but also because the spike protein was already "solved" ahead of the pandemic. I would also be interested in further information on that? Thanks
- H8crilA 5y ago
  For the first you can just Google for "hiv rapid mutation", example: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5414815/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5414815/. The OP article contains a lot of details too. For the second see something like "covid spike sequence modification", for example this seems like an accessible article: https://cen.acs.org/pharmaceuticals/vaccines/tiny-tweak-behind-COVID-19/98/i38 https://cen.acs.org/pharmaceuticals/vaccines/tiny-tweak-behi... It was all thanks to the research on previous coronaviruses, MERS specifically. The Pfizer/Moderna vaccines have just copied it (of course that simple modification is not all it took, but that was definitely required for success).
alsobrsp 5y ago
> ... because the spike protein was already "solved" ahead of the pandemic. ... The mRNA sequence was ready in January 2020, the rest was just manufacturing, testing and distribution. Could I get some more context on this or a direction to start researching? I feel this would be great information to share with the vax hesitate crowd. I have heard a few people say the vaccines are too new and not tested enough.
- Naga 5y ago
  Off the top of my head, I believe it was due to research done during the SARS epidemic in the early 2000s that trailed off as funding dried up when it was no longer an immediate threat.
  - H8crilA 5y ago
    This is a good article on that specific sub-topic of the covid mRNA vaccines: https://cen.acs.org/pharmaceuticals/vaccines/tiny-tweak-behind-COVID-19/98/i38 https://cen.acs.org/pharmaceuticals/vaccines/tiny-tweak-behi... Also, replying to the grandparent: vaccines per se are not necessarily safe out of the door, they're medical products and as such can have potentially many unforseen and troubling consequences. However, in the past all the unforseen consequences of any vaccine (whether still used, or since then retracted from the market due to problems) would become known a few months and a few tens of million people into the phase 3. That's when it is very, very safe to jump on board. And this is definitely already the case with all the popular covid vaccines. To summarize: human data trumps everything in medicine, and we've had A LOT of data points.

Traubenfuchs 5y ago

> Sometimes I wish I was a research doctor The reality of being a researcher appears to be quite disappointing. Trapped between grant hunting and p-hacking the papers you need to churn out into high impact journals appears to be the grim reality.

bipson 5y ago
I am (kind of) in research on the CS side, and I wish I was on the medical side. The grant hunting, bullshitting, old-stuff-in-new-covers is all the same, but the problems and the topics are just so much more approachable, relevant, interesting, and the community seems to be "nicer". But then of course, I know people that are in that area an were getting into research, and they did not paint a nice picture. And the community obviously can suck also once you're on the inside. And being a "researcher" without clinic duties is really not easy getting into in Europe it seems. Also, who wants to stop doing clinic completely, when this is what he trained for so long... There are upsides and downsides to everything - I think it really depends on where your interests are.
- vanderZwan 5y ago
  > the community seems to be "nicer" Having worked as a programmer for molecular neurobiologists for two years: yeah, they are. Everyone's just hyped at how insanely fast things are developing. Everything I saw when I worked there felt cutting-edge. The engineering involved, the science produced, the speed at which new insights were being gained. > And being a "researcher" without clinic duties is really not easy getting into in Europe it seems. The trick is to go the molecular biology route instead, it seems
- twic 5y ago
  I've done both. The crucial difference is that computer work is far more productive than bench work. If you spend a month at your computer, you will get something out of it. You can easily spend a month at the bench and come away with nothing at all. Part of the secret to success in bench work is finding a seam which you can mine productively. You have some technique or system set up and working, and you can grind out findings from it. But it takes time to establish that seam, and it isn't necessarily anywhere near where the actually interesting problems are. I worked on cell migration. We used a particular cell type that had very good, consistent migratory behaviour, which made it a good system. But it was a primary culture, made fresh from dissected tissue every day. Primary cultures are highly resistant to having DNA put into them. Pretty much all modern cell biology hinges on putting DNA into cells. I spent a year or so trying different techniques (including making adenoviral vectors!). Eventually, i found something which worked okay. But that was just the start of actually doing interesting work - the year up to that point had produced nothing. This is completely normal in bench work, but would be pretty shocking with computers.
  - macrolime 5y ago
    I've done both too, but after a couple months at the bench, I always find myself spending most of my time trying to create robots to automate the work instead. Haven't gotten that to work out in the long run, so I just do programming now.
  - mathw 5y ago
    I guess at one point computing was more like that, in that to solve a new problem you may well have had to build yourself a new kind of computer or compiler first.
f6v 5y ago
The reality of software engineering can be disappointing as well. Incompetent non-technical managers, business metric hacking before the funding round, and a ton of technical debt. But it pays much more.
- Traubenfuchs 5y ago
  Don't get me wrong. I hate software development just as much as academia. After 7 years in the industry, there is not a single shred of positive emotion towards software engineering left in me.
  - stuff4ben 5y ago
    Wow, I'm incredibly sad for you. If I felt that way towards a field I've been working in since I was in the sixth grade and now for some 30 years of my life... well it wouldn't be pretty. Sounds like you're burned out. If software development is your passion, perhaps take a break and reconnect with yourself?
refurb 5y ago
Working in R&D in private companies can be not only well paid but very rewarding as well. A lot less struggle for resources if your idea pans out.
DrAwdeOccarim 5y ago
I mean, you're just talking about an academic research doctor. Which really only accounts for a small percentage of total researchers out there. I appreciate your trying to frame that his grass is actually quite green, don't just throw the baby out with the bathwater : )

eMGm4D0zgUAVXc7 5y ago

> with its self-rewrite immune escape functionality. Interesting! Could you elaborate on this or provide a link? > but also because the spike protein was already "solved" ahead of the pandemic. I would also be interested in further information on that? Thanks

H8crilA 5y ago
For the first you can just Google for "hiv rapid mutation", example: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5414815/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5414815/. The OP article contains a lot of details too. For the second see something like "covid spike sequence modification", for example this seems like an accessible article: https://cen.acs.org/pharmaceuticals/vaccines/tiny-tweak-behind-COVID-19/98/i38 https://cen.acs.org/pharmaceuticals/vaccines/tiny-tweak-behi... It was all thanks to the research on previous coronaviruses, MERS specifically. The Pfizer/Moderna vaccines have just copied it (of course that simple modification is not all it took, but that was definitely required for success).

alsobrsp 5y ago

> ... because the spike protein was already "solved" ahead of the pandemic. ... The mRNA sequence was ready in January 2020, the rest was just manufacturing, testing and distribution. Could I get some more context on this or a direction to start researching? I feel this would be great information to share with the vax hesitate crowd. I have heard a few people say the vaccines are too new and not tested enough.

Naga 5y ago
Off the top of my head, I believe it was due to research done during the SARS epidemic in the early 2000s that trailed off as funding dried up when it was no longer an immediate threat.
- H8crilA 5y ago
  This is a good article on that specific sub-topic of the covid mRNA vaccines: https://cen.acs.org/pharmaceuticals/vaccines/tiny-tweak-behind-COVID-19/98/i38 https://cen.acs.org/pharmaceuticals/vaccines/tiny-tweak-behi... Also, replying to the grandparent: vaccines per se are not necessarily safe out of the door, they're medical products and as such can have potentially many unforseen and troubling consequences. However, in the past all the unforseen consequences of any vaccine (whether still used, or since then retracted from the market due to problems) would become known a few months and a few tens of million people into the phase 3. That's when it is very, very safe to jump on board. And this is definitely already the case with all the popular covid vaccines. To summarize: human data trumps everything in medicine, and we've had A LOT of data points.