How a Researcher 'Clinging To the Fringes of Academia' Helped Develop a Covid-19 Vaccine (nytimes.com) 64
Long-time Slashdot reader destinyland writes:
The New York Times tells the story of Hungarian-born Dr. Kariko, whose father was a butcher and who growing up had never met a scientist — but knew they wanted to be one. Despite earning a Ph.D. at Hungary's University of Szeged and working as a postdoctoral fellow at its Biological Research Center, Kariko never found a permanent position after moving to the U.S., "instead clinging to the fringes of academia."
Now 66 years old, Dr. Kariko is suddenly being hailed as "one of the heroes of Covid-19 vaccine development," after spending an entire career focused on mRNA, "convinced mRNA could be used to instruct cells to make their own medicines, including vaccines."
From the article: For many years her career at the University of Pennsylvania was fragile. She migrated from lab to lab, relying on one senior scientist after another to take her in. She never made more than $60,000 a year... She needed grants to pursue ideas that seemed wild and fanciful. She did not get them, even as more mundane research was rewarded. "When your idea is against the conventional wisdom that makes sense to the star chamber, it is very hard to break out," said Dr. David Langer, a neurosurgeon who has worked with Dr. Kariko... Kariko's husband, Bela Francia, manager of an apartment complex, once calculated that her endless workdays meant she was earning about a dollar an hour.
The Times also describes a formative experience in 1989 with cardiologist Elliot Barnathan: One fateful day, the two scientists hovered over a dot-matrix printer in a narrow room at the end of a long hall. A gamma counter, needed to track the radioactive molecule, was attached to a printer. It began to spew data.
Their detector had found new proteins produced by cells that were never supposed to make them — suggesting that mRNA could be used to direct any cell to make any protein, at will.
"I felt like a god," Dr. Kariko recalled.
Yet Kariko was eventually left without a lab or funds for research, until a chance meeting at a photocopying machine led to a partnership with Dr. Drew Weissman of the University of Pennsylvania: "We both started writing grants," Dr. Weissman said. "We didn't get most of them. People were not interested in mRNA. The people who reviewed the grants said mRNA will not be a good therapeutic, so don't bother.'" Leading scientific journals rejected their work. When the research finally was published, in Immunity, it got little attention... "We talked to pharmaceutical companies and venture capitalists. No one cared," Dr. Weissman said. "We were screaming a lot, but no one would listen."
Eventually, though, two biotech companies took notice of the work: Moderna, in the United States, and BioNTech, in Germany. Pfizer partnered with BioNTech, and the two now help fund Dr. Weissman's lab.
Now 66 years old, Dr. Kariko is suddenly being hailed as "one of the heroes of Covid-19 vaccine development," after spending an entire career focused on mRNA, "convinced mRNA could be used to instruct cells to make their own medicines, including vaccines."
From the article: For many years her career at the University of Pennsylvania was fragile. She migrated from lab to lab, relying on one senior scientist after another to take her in. She never made more than $60,000 a year... She needed grants to pursue ideas that seemed wild and fanciful. She did not get them, even as more mundane research was rewarded. "When your idea is against the conventional wisdom that makes sense to the star chamber, it is very hard to break out," said Dr. David Langer, a neurosurgeon who has worked with Dr. Kariko... Kariko's husband, Bela Francia, manager of an apartment complex, once calculated that her endless workdays meant she was earning about a dollar an hour.
The Times also describes a formative experience in 1989 with cardiologist Elliot Barnathan: One fateful day, the two scientists hovered over a dot-matrix printer in a narrow room at the end of a long hall. A gamma counter, needed to track the radioactive molecule, was attached to a printer. It began to spew data.
Their detector had found new proteins produced by cells that were never supposed to make them — suggesting that mRNA could be used to direct any cell to make any protein, at will.
"I felt like a god," Dr. Kariko recalled.
Yet Kariko was eventually left without a lab or funds for research, until a chance meeting at a photocopying machine led to a partnership with Dr. Drew Weissman of the University of Pennsylvania: "We both started writing grants," Dr. Weissman said. "We didn't get most of them. People were not interested in mRNA. The people who reviewed the grants said mRNA will not be a good therapeutic, so don't bother.'" Leading scientific journals rejected their work. When the research finally was published, in Immunity, it got little attention... "We talked to pharmaceutical companies and venture capitalists. No one cared," Dr. Weissman said. "We were screaming a lot, but no one would listen."
Eventually, though, two biotech companies took notice of the work: Moderna, in the United States, and BioNTech, in Germany. Pfizer partnered with BioNTech, and the two now help fund Dr. Weissman's lab.
In other words... (Score:1, Insightful)
She should have given up. The science was settled.
In other words...fusion. (Score:2)
Kind of like that fusion article [slashdot.org] we looked at earlier.
Re:In other words... (Score:5, Insightful)
For people like you, the science will never be settled until it tells you what you want to hear.
Re: (Score:2)
"Sometimes people donâ(TM)t want to hear the truth because they donâ(TM)t want their illusions destroyed" --Friedrich Nietzsche (b. 1844)
Re:In other words... (Score:5, Insightful)
Re:In other words... (Score:5, Informative)
The proposal was rejected by reviewers at the National Science Foundation because "the science is settled." I personally believe that making that statement in science is pretty bold, particularly given the state of knowledge about global warming in the early 90s. The issue is that the grant reviewers were all climatologists and the proposal from an astronomer was not aligned with the prevailing view in their field. The acculturation that happens within fields of studies makes it difficult to accept outside or unorthodox ideas. The speaker recommended that we don't waste our time writing proposals that stray into other fields.
Dr Kariko experienced the same scientific tribalism that the speaker had experienced. Having an independent (people outside the field) review of grant proposals by competent (people with established scientific research backgrounds), particularly when the consequences are high, is vitally important.
Re: (Score:3)
Re: In other words... (Score:1)
Re: (Score:2)
Re: (Score:2)
Re: (Score:2)
This is why funding Basic Science is so critical (Score:5, Insightful)
It's stories like this that underline why funding basic science, with no foreseeable near-term application is so critical. What looks to be on the fringes today, may easily become critical in the future. You never know when or where an application for something might pop up.
And even if it doesn't ever pan out, keeping researchers employed, suppliers employed, students funded, etc... is a net benefit for society.
This is why dead-ends is so crucial. (Score:2)
It's stories like this that underline why funding basic science, with no foreseeable near-term application is so critical.
Assuming that's what the grant reviewers were looking for. They could have also thought it was a dead end like the em-drive or cold fusion.
Re: (Score:2)
Well they were wrong then, weren't they?
And the cost was nearly very high.
Re: (Score:2)
If you want a jobs program just have those researchers work on replicating existing studies. We've got enough crap that doesn't actual
Re:This is why funding Basic Science is so critica (Score:5, Interesting)
You're basically asking for the angel investment model of funding 100 startups where they'll almost all fail in the hopes that one manages to be the next big thing.
Strangely enough, that sounds exactly like the current tech industry.
Re: (Score:2)
Re: (Score:2)
Funding for basic science doesn't solve this kind of problem. It just leads to tenured professors who, like in this case, end up saying "the fool didn't know it was impossible, so she did it". The core problem is cultural, within the academic and research community, rather than financial.
Re: (Score:2)
I got myself in a lot of trouble for assuming that other people with advanced degrees in positions of public trust and responsibility had the same high level of integrity that I do
It's not about integrity! Ask your advisor how many other committees they were on, or chairing, at the time. Your advisor is putting in a lot more work than you realize, for more than just you, on top of their normal responsibilities. You want to make things harder on everyone else just to pursue your own ideas? Wait until after you drop the 'c' at then end of your name, okay?
It may be too late for you, but this advise could have saved you, and everyone around you, endless frustration:
Your dissertatio
Re: (Score:3)
It isn't just that basic science gets short shrift, it's that *risky* but in this case the problem is also that risky but interesting science doesn't get funded. She was impressive enough that a parade of senior researchers wanted her on their team, but her ideas couldn't get funding because they were too original.
RNA had a bad rap (Score:2)
Re: (Score:2)
Well look at what we use to think of microglia. [youtu.be]
Re:RNA had a bad rap (Score:5, Interesting)
No, you are thinking of so-called junk DNA [wikipedia.org], which usually just means DNA that doesn't code for any known protein, and often cannot code for protein because of stop or invalid codons. Non-coding DNA sometimes looks like corrupted copies of protein-coding genes, sometimes like viruses, sometimes like other things or not like anything obvious. Even though it doesn't code for proteins, though, it can affect which genes are expressed (copied into RNA and potentially into proteins) -- this kind of epigenetic behavior is very important in practice.
Re: (Score:3)
The problem with mRNA is it works best in those who least need it and fails in those who most need it. So sounds like a good idea but a bit of a fools vaccine. In the case of covid it works the best in those who are asymptomatic or suffer only minimal symptoms because their immune system already reacts early to limit the impact of the virus.
Do you have a citation for this rather specific assertions?
Re: (Score:2)
Re: (Score:2)
The problem with mRNA is it works best in those who least need it and fails in those who most need it. So sounds like a good idea but a bit of a fools vaccine. In the case of covid it works the best in those who are asymptomatic or suffer only minimal symptoms because their immune system already reacts early to limit the impact of the virus.
That is complete nonsense.
The mRNA vaccine provokes your body cells to produce spike proteins of the virus in question.
Regardless who yo are or what your outcome would
Re: (Score:3)
Nice troll. The mRNA COVID vaccines are quite effective. More effective, in fact, than many conventional vaccines (also more effective than the conventional vaccines for COVID). They have proven effective in the elderly who tend to get the worst COVID symptoms.
Since the entire mechanism of action for ANY vaccine is to prime the immune system, it stands to reason that no vaccine is at all effective in people with no immune system (nothing to prime)
I only bother to reply because there are so many trolls out t
Re: (Score:2)
Yeah, academia is mostly a fraud (Score:2)
That's not to say that the Platonic Ideal of academia is a fraud, or that the Platonic Ideal of science is a fraud, but it is to say that academia as it exists in the US comes nowhere near how it presents itself.
Academia as a collective strawman markets itself as an idea factory: people (almost exclusively young people go in, money (the more the better) goes in, a crank gets turned, and good, actionable, marketable ideas, inventions, products come out. That's of course nowhere near universally true. A few s
Re: (Score:2)
That's not to say that the Platonic Ideal of academia is a fraud, or that the Platonic Ideal of science is a fraud, but it is to say that academia as it exists in the US comes nowhere near how it presents itself.
Then that means stories like what's presented here would have never happened in foreign countries. Oh like say...Hungary.
Re: Yeah, academia is mostly a fraud (Score:1)
I didn't say the US invented stupid. Administrative stupid is an ancient tradition and a cultural universal.
For a brief time, however (probably sometime immediately after the war but before the time of thr moon landings), American academia was sufficiently small and self-selected to make good use of the insane amount of money being pumped into it be the federal government through DoD, NSF, NASA and the like.
But that was almost two generations ago and the people in charge now have grown up being incentivized
Re: (Score:2)
Not every acorn will become an oak. But if you want a forest of oaks, you need thousands of times the acorns that will become oaks, in the hopes that a handful will germinate, and of those, a handful will grown to modest height, and of those, a handful will tower.
My concern would be the growth of more junk science. A poster higher up talked about focusing on replicating studies. That would be useful. There's a lot of junk social science, and junk economic science, and more time spent on refining those as we
Re: Yeah, academia is mostly a fraud (Score:1)
This is true and is quite often the go-to retort to concerns about academics wasting taxpayer/donor/tuition money.
However, it can be (and frequently is) a misdirection. If you want an oak, you want an acorn. But sometimes you get sold two halves of an acorn (two postdocs on a short clock and short on experience vs one experienced and thus higher paid research scientist or engineer) or six fifths of an acorn (a gaggle of grad students who have even more distractions, are all but guaranteed to ghost the pro
If anyone should get a Nobel Prize (Score:2)
it should be Dr. Kariko
Re: (Score:2)
Re: (Score:3)
I don't know exactly how crucial her research was to the production of mRNA vaccines (it is a newspaper article, they like to embellish things...), but yes, a Nobel Prize wouldn't surprise me.
Buy saying that mRNA vaccines saved civilization is a bit of an hyperbole. Out of the 10 or so currently deployed vaccines, only 2 are mRNA. They may be the best, but even without them, we are not powerless anymore. And researchers are not sitting still, more than a hundred vaccines using a wide variety of techniques a
Re: (Score:3)
They were the first, still work the best, and are the most likely to be quickly modified if a mutant strain makes that necessary. It's a BIG advantage.
Re: (Score:2)
It's an inspiring story (Score:2, Interesting)
And I'm happy that she stuck with it. But the line "never made more than $60000 a year" was kind of annoying. The median income in the US is around $65K - so she wasn't exactly starving. Sure, she didn't have tenure... but the vast majority of people don't have guaranteed income and jobs.
Re: (Score:2)
Right, sounds like she was a moderately successful scientist
Re: (Score:2)
I should have been clearer - $65K is the median household income in the US.
Re:It's an inspiring story (Score:5, Informative)
. According to Contract-Awarded Labor Category [gsa.gov] GSA database, a subject matter expert like Dr Kariko would be billed at $168/hr to $297/hr. Modulo overhead, a person with her background could probably make $150K/year.
So, she was making 20% less than the low-end of the average professor pay. In many universities, the university does not over 100% of a professor's pay--they are expected to bring in grant money. Her low pay likely reflects the lack of grant money.
So, I have to give her props to staying with her research when she probably could have ditched it and doubled her salary.
Science is not immune from hype (Score:5, Interesting)
First off, RNA was not ignored. In fact people were trying to make RNA vaccines for a while but the RNA would degrade fairly quickly. It was known that mRNA didn't *have to* degrade because it normally did stick around in the cell. The question was why, and how did the cell recognize introduced mRNA from regular RNA. It was well known, that the cell modifies RNA about a hundred different ways .. so nobody was sure *which* of the modifications triggered the intracellular immune response. Based on research into proteins called TLRs, in the early 2000s some people had guessed that it might be methylation. As it turns out, it was the methylation was the answer. Now I don't know what grants Kariko and Weissman were turned down for, but it seems that when they *did* apply for a grant to investigate this aspect, they did get it. If the other grants they applied for weren't given .. who knows what rabbit holes they would have been searching in and have never gotten to this?
While figuring out that methylation was an important key (of a few) to making RNA persist in the cells .. objectively it was just a step no different than the other steps needed to make this thing work. Everything from the people who discovered that TLR proteins were triggering the RNA persistence problem and how they worked.. figuring our RNA was being methylated .. the ones who attempted the first RNA vaccines in the 1990s .. the ones who discovered which NLPs can safely deliver it . ALL of those contributed equally in my opinion .. so yeah Kariko made an important contribution .. by determining which RNA modification was the important one .. but apparently the media thinks they should influence determining which was the most counter-intuitive step or difficult.
TL;DR: A large number of scientists all over the world persisted on this problem and contributed directly to enabling RNA vaccines. The hype machine shouldn't determine whose contributions were they most difficult or key.
Re:Science is not immune from hype (Score:5, Informative)
True, but you should have put references. So here are some references to the above:
First mRNA vaccine tried on mice, in 1993: https://onlinelibrary.wiley.co... [wiley.com]
Some examples of RNA vaccines in the 1990s (there are others btw, not listed here): https://www.onlinelibrary.wile... [wiley.com]
Two examples where others had figured out that a TLR was somehow triggering on synthetic or foreign RNA: https://www.cell.com/immunity/... [cell.com] AND https://pubmed.ncbi.nlm.nih.go... [nih.gov].
Example of prior hint that methylation may be the cause: https://www.jimmunol.org/conte... [jimmunol.org]
Re: (Score:2)
Oh so familiar (Score:2)
Harlen Bretz comes to mind. Same story but geology and and the Missoula Floods. Laughed at for years, with "where'd the water come from". Till one day another geologist was pointing out large ripple marks in northern Idaho. Then BINGO.
Similar to a woman who lived with us when I was a child, she was trying to get Phd in solid state Physics. Women were not particularly welcome.
They (Score:1)
Considering the very first word in the article is "She", do we really need to use a gender-neutral pronounce to refer to Dr. Kariko?
As a woman in science who was ignored for years, erasing the fact that she's a woman seems like pouring salt on the wound. I'm sure she dealt with a lot of sexism throughout her life and now that she's been vindicated, she is turned into they.
Correct timeline of mRNA vaccines (Score:5, Informative)
1990: Synthetic mRNA used to express proteins: https://science.sciencemag.org... [sciencemag.org]
1993: First mRNA vaccine tried on mice: https://onlinelibrary.wiley.co... [onlinelibrary.wiley.co] [wiley.com]
Some examples of RNA vaccines in the 1990s (there were many others btw, not listed here): https://www.onlinelibrary.wile... [www.onlinelibrary.wile] [wiley.com]
1990s and 2000s: Two examples where others had figured out that a TLR was somehow triggering on synthetic or foreign RNA: https://www.cell.com/immunity/ [cell.com]... [cell.com] AND https://pubmed.ncbi.nlm.nih.go... [nlm.nih.go] [nih.gov].
2000s: Prior hints that lack of methylation may be the specific cause of the TLRs triggering on introduced RNA: https://www.jimmunol.org/conte [jimmunol.org]... [jimmunol.org]
2005: Proof from Kariko that indeed methylation can help mRNA vaccines persist in the cells by evading TLR detection
Not included in timeline .. parallel track of NLP technology that can finally be used to safely deliver mRNA in to cells.
Science advances one funeral at a time (Score:3)
Rather, as German physicist Max Planck somewhat cynically declared, science advances one funeral at a time. Planck noted “a new scientific truth does not triumph by convincing its opponents and making them see the light, but rather because its opponents die, and a new generation grows up that is familiar with it.”
Science Set Free: 10 Paths to New Discovery
https://www.amazon.com/Science... [amazon.com]
Hopefully it doesn't backfire! (Score:1)
Nobel Price 2021 (Score:3)
Re: (Score:1)
"settled" and "consensus" science are... (Score:2)
not actual science, they are marketing terms.
Science is wonderful, and useful, but it's not "TRUTH". If done properly, science is a method of producing a constantly updating and increasingly accurate approximation of reality, which provides humans with a better framework for living, and being productive, in this place we call the universe. The moment somebody, often with an agenda, steps in and asserts that certain ideas are not to be examined, or certain people are not to be allowed, and justifies this ba
Definitely not "fringe" (Score:2)
I hate the usage of the word "fringe" in this context. It puts this reasearcher in the same basket with people babbling in pseudoscience and other whacky ideas. Then some looneys can point to articles like this and (usually without reading them) claim stuff like "This idea was fringe too when it started! Don't dismiss my soul energy cancer therapy method! Big Pharma fights me because I'm a threat to their chemotherapy profits!".
This scientist went to college, throught the grind of earning a PhD, publishing,
Re: (Score:2)
Everyone pivot, pretend they don't do this... (Score:2)
Everyone pivot, pretend they don't do this...
The group when called out on their wrongthink, won't change course or stop preventing future correct-think.
To them this isn't proof they shouldn't be gatekeepers, it's proof they sometimes make "human" mistakes while remaining at the helm to ban and stifle others.
They misunderstand this is less about saying they were wrong in the past and more about saying they clearly lack vision and thus shouldn't be gatekeepers anymore. THAT is the message.
Re: (Score:2)