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Philly scientist behind COVID vaccine tech was demoted by UPenn (billypenn.com)
316 points by apsec112 on Jan 3, 2021 | hide | past | favorite | 183 comments



As a few other commenters have mentioned, this is a story about how Karikó was sidelined early in her career. The Penn demotion occurred in 1991. She eventually left in 2013 when, despite publishing groundbreaking research in the mid 00s, she was never returned to a tenure-track position.

Nonetheless an impressive story of conviction and perseverance. Penn has decades-old egg on its face, rather than months-old fresh egg.


I did my PhD at a top US institution in the 00s, and post-doc in the late 00s, working on somewhat related stuff.

Working with synthetic mRNA was hard during my time. I would imagine that it was many times more difficult in the 90's. Just as an EE analogy, working on mRNA in the 90s is like working on extreme UV lithography in the 80s. It was too far into the future to be useful, and there were better research funding opportunities for other things. But if one was smart, one could see the potential. It's not so surprising that she got passed for tenure, working on something so crazy wild. It was around 2005-2010 time frame when mRNA synthesis became affordable enough to become an applied science rather than basic research.

It sounds like Kariko lost her associate professor position in the 90s, but continued her work as a postdoc for more than 10 years. That's some awesome dedication to something that almost nobody thought would work out. It's not so surprising she jumped ship around 2010 when the mRNA tech caught up.

I hope she gets her Nobel prize. She deserves it.


>I hope she gets her Nobel prize. She deserves it.

If she and the others involved in identifying the root cause and coming up with the vaccine, do not get the Nobel in Medicine/Chemistry i will consider the whole "Nobel Prize" system to be a complete tool and sham.


Some people already consider it a sham, after a certain peace prize attribution.


Woah woah woah. Just take a breath and recognize that the "Nobel prize in Chemistry/Physics/Whatever" is soon 110% completely different from them "Nobel Peace Prize". It is a shame they share 2 common words.

They are different.


O have a favourite zen koan.

"Hakuin used to tell his pupils about an old woman who had a teashop, praising her understanding of Zen. The pupils refused to believe what he told them and would go to the teashop to find out for themselves.

Whenever the woman saw them coming she could tell at once whether they had come for tea or to look into her grasp of Zen. In the former case, she would server them graciously. In the latter, she would beckon to the pupils to come behind her screen. The instant they obeyed, she would strike them with a fire-poker.

Nine out of ten of them could not escape her beating."

If a big part of the nominations is obviously politically motivated, should the others get the tea or the poker?


If you put a rotten egg by accident into an 20 egg omlett, it is still spoiled.

If you dilute a brand name with controversial actions or products, it drags the whole brand down. And it does not matter of parts of it are still good.


Everyone can be nominated


Edit: Please do not bring up "Nobel Peace Prize" in these discussions since we are dealing with basic hard sciences and not subjective social awards.


the Nobel Peace Prize is sort of a sham.


> i will consider the whole "Nobel Prize" system to be a complete tool and sham.

What was Obama given the Nobel Peace Prize for?


"For 108 years, the Norwegian Nobel Committee has sought to stimulate precisely that international policy and those attitudes for which Obama is now the world’s leading spokesman. The Committee endorses Obama’s appeal that 'Now is the time for all of us to take our share of responsibility for a global response to global challenges.'

Oslo, October 9, 2009"

https://www.nobelprize.org/prizes/peace/2009/press-release/


Really? That deserves a Nobel Peace Prize in this day and age? Is that what we have reduced the Prize to?


Well, Al Gore won it for "a really good Power Point Presentation" several years earlier, so, yeah.


And two really good books, and a really good documentary film, and eight years in high political office pushing for action that aimed to saved millions of people now doomed to be displaced from climate change in the next decades. Awarding it to Obama for not being GW Bush is one thing, awarding it to Gore something entirely different.


droning pakistanis children


No, he got the peace price before that.

That said, AFAIK Obama himself found it somewhat cringeworthy when he was awarded the price, which - if it is true - makes it a lot less embarrassing on his part.

Also it seems they really haven't had reason to be happy with a couple of other candidates too, one leading a country that massacred Rohingas under her leadership and one starting another war in Africa.


War is Peace


Reading this, it struck me that we're quite fortunate that COVID-19 hit in 2020, and not in say 2000, when there would have been much less hope for development of a quick and effective vaccine.


Reminds me of Howard Temin, whose widely dismissed research in the 1960s and 1970s was critical for our understanding of HIV/AIDS a decade later. https://en.wikipedia.org/wiki/Howard_Martin_Temin


I mean, we basically had a test run with SARS.

Only through good fortune did SARS flame out.


I feel COVID-19 is the real test run.

Im in SA and the new strain is the real deal. Four people I know have perished in one week. I don't even know who to call or what to say.


I am sorry for your loss.

I have not seen any research that the new strains are more deadly, only that they are more infectious.


The rate from infection to mortality has increased notably. Our government is trying their best to paper over the seriousness. Just now people on social media are demanding a harsh lockdown like March because its getting out of hand. Maybe news outlets will cover something I can link to.


You must cite your sources, you cannot simply state this.

It is not enough to write something and promise to link a source later.


https://thezvi.wordpress.com/2020/12/24/covid-12-24-were-fed... from Christmas Eve is an early (secondary) source for some of this.


Good fortune and damn hard restrictions super early.


SARS infected 60 million Americans, right? I don't remember any restrictions, so I think it was just "good luck".


There were only 8,096 confirmed cases of SARS worldwide.


On the other hand it might not have spread quite as far before people realised the danger. Global air traffic almost tripled between 2000 and 2019.


Sinopharm has an old school vaccine there you put disinfectant on the virus and then inject it which seems to work well.

Info on the vaccine https://blogs.sciencemag.org/pipeline/archives/2020/08/17/si...

They were using it in a limited way back in June https://www.fiercepharma.com/pharma-asia/china-s-sinopharm-t...

and has recently got approval. I can't help but wonder if they'd offered it generally with a not fully tested warning when it was offered to "employees of some large state-run companies" presumably in April/May, how many lives would have been saved.


I am genuinely curious how well this works.



Well, both Russian and Oxford vaccines seem very effective, even though they are using conventional technologies. Without BioNTech or Moderna, an effective vaccine would have been delayed by maybe 3-6 months, which isn't too bad.

But now that mRNA vaccines have been proven, they might be mass distributed in about 9 months in a future pandemic.


Conventional? It's a virus vector with replaced genetic sequence produced by sequencing and genic manipulation.


an effective vaccine would have been delayed by maybe 3-6 months, which isn't too bad.

You realize such a delay would mean many more people would die not to mention the overall damage to society from lockdowns? I can’t understand how that would possibly be not “too bad.”


Sorry, my "not too bad" comment was based on the initial estimate for the vaccine, which was 18-24 months from the start of the pandemic. That would have been July or Dec 2021.

Science really came through this time. We not only had a new vaccine platform that arrived just in time (mRNA), but our conventional vaccine development was also able to get a good vaccine out much sooner than scientists originally thought.


(Not OP)

> You realize such a delay would mean many more people would die not to mention the overall damage to society from lockdowns?

Yes.

> I can’t understand how that would possibly be not “too bad.”

Compare it to not having a vaccine ever.


We don't know how effective the vaccines will be, and we have no data on long-term immunity. Its a bit early to celebrate :)


[flagged]


Epidemiologists existed in 2000 and were quite capable of recognizing the difference between a global pandemic and "a really bad flu season".

Hell, the 1918 pandemic literally was flu, unlike COVID, and it predated a lot of what we think of as modern medicine, and it was heavily censored by governments around the world, and it was still obvious that it was more than just "bad flu season."


Those who compare COVID to a really bad flu season don't seem to understand just how bad a bad flu season can get. The estimated deaths from 1918 are thought to be 17-100x what COVID has caused so far.


For some people, maybe. For others, it's merely recognizing and stating that we've gotten through bad or even worse epidemics than this. Often without the sensationalized hoopla. Eg,1968.

I'd argue it's the people saying it isn't comparable to a bad flu season who are the ones less familiar with the flu's devistating history.


The fact that we've gotten through worse doesn't mean it's not a major issue. There's a large gap between "human civilization will survive this" and "not a big deal."


Peak deaths in Sweden from COVID this year are about the same as from Swine Flu in 2009:

https://swprs.org/wp-content/uploads/2020/10/sweden-monthly-...

Also the population would have been younger, with fewer vitamin-D deficient migrants.

It would have been explained as a very bad flu season.


When was the last time 350,000 Americans died in a 'really bad Flu season", even without lockdowns? When was the last time deaths per day were measured in the thousands?

If you don't trust me perhaps you'll listen to Donald Trump, who told Bob Woodward in early February 2020: "And so that's a very tricky one. That's a very delicate one. It's also more deadly than even your strenuous flus.... This is more deadly,” he said. “This is five per — you know, this is 5 percent versus 1 percent and less than 1 percent, you know. So, this is deadly stuff.”


And don't forget scientists have continued to gather and evaluate data since. We now have a much clearer (albeit still imperfect) picture of the disease and its behaviour.

For example, COVID's current "death rate" estimate is ~3x worse than flu. Versus Trump's "~5x" in your quote from Feb 2020¹.

People love to argue about such overall rates but for practical purposes, they're too crude a hammer – too aggregate, too high-level to be actionable. More importantly, we now have a better understanding of the groups at risk.

> [Infection fatality rate] measuring 0.002% at age 10 and 0.01% at 25. However, the rate progressively increased with age, growing from 0.4% at 55 to around 15% at 85.

Age and certain comorbidities seem critical. This knowledge shapes the global COVID response, allowing help to be significantly more targeted and effective. For instance, when rolling out national vaccination plans.

___

¹ Whichever rate Trump was talking about – there's case fatality rate, crude fatality rate, infection fatality rate


Oh sure, that was just a best estimate at the time, bottom line is we and he knew it was going to be bad from the start and that his public "just a flu" statements were false.

Yet still we have people to this day repeating his knowingly and now admittedly false claims as though they are true. That's how deep the hook line and sinker got swallowed. It's fascinating psychology. Even when the con artist admits and explains the con, some people prefer to stay conned.


> For example, COVID's current "death rate" estimate is ~3x worse than flu. Versus Trump's "~5x" in your quote from Feb 2020¹.

COVID-19 Infection Fatality Rate is estimated at around 0.6% whereas H1N1/09 Flu infection fatality rate was estimated to be less than 0.03%. Not sure where you get “3x”, I think the correct number would be 20x based on these numbers.

* Covid-19 IFR source: https://www.cdc.gov/library/covid19/112420_covidupdate.html where a chart indicates an IFR between 0.5 and 0.75% for USA and England

* H1N1/09 IFR source: https://www.bmj.com/content/339/bmj.b5213.full “We estimate that 0.026% (range 0.011-0.066%) of these individuals died from causes related to this infection”


I compared Covid's estimated IFR of < 0.23% to flu's < 0.07% [1].

But that's exactly the discussion I called out as not terribly relevant: The variance within Covid (due to age, location, comorbidities…) is much greater than variance between Covid and flu.

In other words, even a Covid-vs-flu rate difference of 20x (as you say) is dwarfed by the 1000x difference between Covid age groups (which you didn't contest). Can we agree on that?

My point is that a broadly aggregated statistics like "global IFR" is too crude to be actionable. Easy to put in a headline, sure, but more potential for confusion than good.

[1] https://www.who.int/bulletin/online_first/BLT.20.265892.pdf


Disagree strongly. An IFR of 0.6% when considered across the entire population is indeed cause for much more alarm than one of 0.02%. It is very relevant.

0.6% of the population in the USA, for instance, would mean about 2 million people would be killed by uncontrolled and massive COVID-19 spread.

Focusing down to small subgroups would only be relevant if you have a magic wand and could, for instance, seal off all over-60 year olds from human society for a year.

P.S. the paper you cited is by John Ioannidis. He has become notorious in 2020 attempting to prove Covid-19 isn’t very dangerous. Worth consideration as this version has managed to pass peer review, but keep in mind it’s outside the mainstream of opinion. IMO, the 0.2% estimate is pretty clearly low and I’ve read a good debunking of that specific paper in the past. https://threadreaderapp.com/thread/1316511734115385344.html


I'll put it bluntly: fixating on an average ("average IFR") of a wildly heavy-tailed distribution (e.g. exponential for IFR-vs-age) is idiotic.

Technically yes, such average exists – the population is finite. But taking a population-wide decision based on such estimate is suboptimal. We already know a population parameter (age, comorbidities) that gets us an actionable segregation!

I personally see such "hiding behind an average of an exponential" as scientific fraud. Misinformed at best; disingenuous and murderous at worst (such as with Covid).

> He has become notorious in 2020

Interesting, thanks. I wasn't aware of John Ioannidis' pedigree. For those curious – this article does a good job summarizing the controversy (April 2020):

https://undark.org/2020/04/24/john-ioannidis-covid-19-death-...

> Focusing down to small subgroups would only be relevant if you have a magic wand and could, for instance, seal off all over-60 year olds from human society for a year.

A magic wand to seal off over-60 olds? How do you feel about sealing off everyone?


> A magic wand to seal off over-60 olds? How do you feel about sealing off everyone?

Worked great in New Zealand and Taiwan, and pretty dang good in Singapore, Australia, and even China. A pity we weren’t fast enough to do it here.

I haven’t seen any society successfully execute a strategy to exclude the aged from human society or viral transmission yet, and we’ve had 9 months to experiment. If such a strategy existed and was proven to work, your theory that it was idiotic to ignore it would make sense. Unfortunately, it doesn’t seem to exist.


Overdose deaths are up 40%, to 81,000 in 2020:

https://www.cdc.gov/media/releases/2020/p1218-overdose-death...

Suicides and homicides also up. Given that these deaths will occur for people with a typical age of 40, vs 80 for COVID, substantially more years of life have been lost from lockdown (which seems to have achieved little anyway), than from COVID.


And the last year with record overdose deaths was: 2019. And with the exception of 2018 every other year backwards from 2017 to 1999 was also a record drug overdose death year.

That is the opioid crisis.

Source: The CDC WONDER database, group by year, and by "UCD - Drug/Alcohol Induced Case". (Deep link doesn't work)


The US is a flaming pit of despair right now, for reasons stretching far beyond any impact COVID-19 may or may not have had. It's not reasonable to take the state of specifically that society as any sort of benchmark for how bad things are.


Removing her from tenure track prior to her reasearch gaining traction may have been short sighted but excusable - more an embarrassment than anything.

Not returning her to tenure track once her research proved fortuitous is much more concerning.

Trying to take credit now for facilitating her research when they actively worked against it at the time is damning.


All of this seems to be normal in most universities. I have seen my PhD advisor's video for a TV channel recorded, later presented in TV with his face cut off and another Professor (unrelated to our team) explaining it on TV. The response from the TV channel ?, We signed off the video rights to do as they please with them.


Plus, Karikó said UPenn sold her patents for just $300k to CellScript as they wanted quick cash:

https://elpais.com/ciencia/2020-12-26/la-madre-de-la-vacuna-...


Is UPenn being run by "Administrative Tools" or do they still have somebody with a "Scientific Mind" in charge of things?


"Administrative tools" is the name of the game at most or many universities now.


The Penn president is an inauthentic talking head whose primary qualification for the job is being able to schmooze with Joe Biden and Comcast executives.


Ugur Sahin, who now leads BioNtech with his wife, where Kariko now works, told a story in an interview: His elementary teacher recommended that he be enrolled in the "Hauptschule", the lowest of the three-tier German high school system. A neighbor intervened, and had he not Sahin would not have been able to study medicine.


This is a story about how the academic system failed twice to retain talent due to short-sighted metric gaming. It's a story where if Karikó believed that life would be easier if she just started churning out meaningless papers, we likely would not have an mRNA vaccine.

edit: Also very curious about the "attempt to have her deported" as I've heard of many threats of that nature against foreign post-docs.


>how the academic system failed twice to retain talent due to short-sighted metric gaming

Very right! I fear that the cancer of "shortsighted quick returns" in the Research field has been the death of many a talented researcher. Research/Education should really be treated very differently from Industry/Productization and the same yardstick should not be applied to both.


It's a little gobsmacking how many, and how often post-secondaries stifle and ostracize research and development that is more than a safe and comfortable stretch from existing bodies of knowledge.

Is innovation required to be only in safe and comfortable baby steps.. Or whatever can be controlled or understood..?

Maybe this is in part a reason why so many of our leaders, institutions and experts in so many fields revealed themselves not to be .. during COVID.

There are more voices starting to speak that the clock is starting to tick on some academic brands for failing to exist in the future, and the digital transformation of society has already left them behind.. While some remain at maintaining a present that is anchored in the past.

I'm passionate about the value of an education to improve your life and hope this rapidly improves with the the other rapid changes occurring during the pandemic.

Still, devaluing someone, marginalizing their contributions, and then continuing to own their intellectual property for the long game doesn't seem entirely reassuring behavior for any post secondary.

If it wasn't valuable then, why not let the prof walk with IP ownership if it's so worthless?


It's also a depressing tale for wannabe academics, however. mRNA vaccines are an impressive, groundbreaking development. Dr Kariko (and others) may get a Nobel for that. And yet, she was kicked off the tenure track because she failed to secure VC investments, for chrissake.


University research is a business now, like most things in higher-ed.


If it was really a business, they would support ideas like "developing a revolutionary and extremely important technology." It's worse than a business - it's an amorphous political and bureaucratic mess.


I mean, there are plenty of actual businesses that also do short-sighted things (and up going out of business).


there are also plenty of business that do short-sighted things but continue making money because they have a cash-cow or two which allows them to be idiots everywhere else.

I mean this is really the ABCs of modern business.


Something similar to this actually happened to Neil Degrasse Tyson too ... the University of Texas basically failed him out of his PHd, he went to Columbia, got his Phd and the rest is history https://alcalde.texasexes.org/2012/02/star-power/


I think a relevant point is that UPenn has been publicizing their past affiliation with her and her research, in order to bask in some reflected glory for developing the vaccine technology.

If not for that, it would indeed be decades-old egg on their face. I think they’ve done a fair job of freshening up that egg, though.


7 year old egg (but in hindsight good for the world). They pushed her out, so she went to BioNTech. There she helped to create the world's first Corona vaccine:

https://biontech.de/sites/default/files/2019-08/20140202_Bio...


She's a senior vice president at BioNTech now. I guess she laughed last.


I think you're being too hard on the University. The reality is that Universities are full of a spectrum of brilliant people, some of whom become superstars, some of whom don't. Some of them work really hard and spin their wheels, go down blind allies, or just miss their luck. From a University perspective, how should it evaluation its faculty? How does it measure the output of minds that are pretty much by definition beyond simple comprehension? How do you measure brilliance when you cannot possibly absorb their output due to the sheer size of it? There isn't a good answer. But the machine cranks on. It makes mistakes. It looks like an unfortunate one here, and I'm glad that her persistence paid off. But there are thousands of stories like this, some of them with ground-breaking top-notch scientists in there, and some not. If you're sniffing around for a villain here, I don't think you'll find it.


Not only was she demoted, Penn is trying to portray her as if she played a minimal role:

> "We are grateful for Dr. Karikó's important contributions both during her time at Penn," said university spokesperson Maccarthy, "where she continues to hold an appointment as an adjunct associate professor." The school's promo video about mRNA technology focuses on Weissman, mentioning Karikó only in passing.

It should be pointed out that the university holds the patent for the vaccine:

> In 2005, Karikó and Weissman published their groundbreaking study. The University of Pennsylvania licensed the technology and patented it. (Researchers' patents are often held by the institutions where they work).

It seems unfair that UPenn gets the patent in spite of practically thwarting the research on the subject (cutting Dr. Karikó's salary).


It's a bit like getting fired from a job (w/o recognition) or rejected at an interview, and then proceeding to do exceedingly well in life. Happens very rarely, but you do tend to hear about the famous cases. Good for that person, but I don't believe in karma.


1991 was a long time ago, is she even close to the same person today as she was then? I don't know the details but she may have very well deserved the demotion. Just because someone does something amazingly great now doesn't mean they were always great.


Oh, come-on ! We don't have to get into "ad hominem" space. The article makes it clear that it is her research from that time period (whether nascent or otherwise) which has led to today's success.


Saving the world is one thing, but she failed at the most important metric: securing grant funding for her institution. Probably her impact factor was terrible too.

/S


You get what you measure. We get publications.


The follies of human organizations since time immemorial summed up in a single point.


I feel like this saying would be better phrased as, "you get what you reward," because as long as you don't directly incentivize the metric it can still be useful.


“When a measure becomes a target, it ceases to be a good measure.” https://en.wikipedia.org/wiki/Goodhart%27s_law


Indeed, never heard of her until a few months ago. How many followers has she?


How many citations? Clearly it's those that count.


She has an impressive h-index (51) and citation count (12000+) currently. Her pre-2013 count isn’t that impressive as current, but good.

https://scholar.google.com/citations?user=PS_CX0AAAAAJ&hl=en...


I wonder how easy it will be for her to get any funding now... and how easy it will be for Penn to get funding. :)


> Penn officials declined to comment on their relationship with Karikó, previous or current. “We are unable to discuss specifics about faculty or staff employment matters,” spokesperson Stephen Maccarthy told Billy Penn.

Privacy is the such a convenient and perfect excuse for institutions to cover up their mess.


What would you have them do? You can't have privacy only for things you want privacy for, and transparency for things you don't want privacy for.


I would argue for institutional transparency, tempered by individual privacy.

For example, in this situation UPenn is not sharing the information out of "Privacy concerns". These could be alleviated by the scientist in question saying that they are free to share information about that time -- leaving no reason to continue hiding the information except for embarrassment.


Interesting idea. But that sounds dystopian. If the scientist declines, then does the university get to publicize that they wanted to release the information but the scientist blocked it (thus casting suspicion on the scientist)? If not, then people wouldn't be able to tell if the university asked the scientist for release, or the scientist prevented it, which is still the same problem as before (the public doesn't know what happened).

Basically, it sounds like an institution at any time can announce "hey we did nothing wrong, and we would like to explain why, and have just asked the employee if they accept but they haven't responded yet" while the employee would need to confer with lawyers how to control what now becomes a public spectacle (along with its usual problems of libel, PR, fake news, etc.).


> the university get to publicize that they wanted to release the information but the scientist blocked it (thus casting suspicion on the scientist)?

The situation without this rule, is that the university can and will release information that is in its interest and fail to release information that is not. This status quo is worse than what you are describing.

The point is that this biased information about a private individual shouldn't be public information. If the private individual is lying or misrepresenting the situation, then take it to court: don't use their private information against them for public spectacle.


I don't know why you've been downvoted, there are valid criticisms that you've brought up. Especially:

> the employee would need to confer with lawyers how to control what now becomes a public spectacle (along with its usual problems of libel, PR, fake news, etc.).

I don't think I even have a good armchair solution for this, let alone a real one.

--

I think in general it's a difference of where I would draw the line. This:

> Basically, it sounds like an institution at any time can announce "hey we did nothing wrong, and we would like to explain why, and have just asked the employee if they accept but they haven't responded yet"

seems like a feature to me, not a bug. If an employee is making accusations against a organization, than the organization should have a chance to clear their name.

---

However I don't have a good response to the issues of libel, PR, fake news, etc., except possibly to have a requirement that whatever is put out in the press release from the organization be approved by the ex-employee in question.

This guarantees that

A) The organization is not lying in a way that the employee is harmed by.

B) The employee is not lying in a way the organization is harmed by.

If it's impossible for the two to come to a conclusion, than either party can say something about it, or contest what the other says. This also allows the employee to say "I wanted to do a joint press release with $org, but we could not come to an agreement about what to release.", so at least the damage from this can be turned either direction.

Edit: Formatting


They could have said "However, we can say we are happy that she has found success in her career and, as many should be, we are grateful for her contributions in finding a vaccine"


Put away your pitchfork, this demotion was in the 90s


And the demotion was for focusing on the less and less popular mRNA with idea of using it for vaccines, instead of something that would bring grant funding.

She was demoted precisely for doing what led to the techniques used by Biontech and Moderna.


It wasn't political or that someone had some beef with her research at Penn. Ultimately a requirement for academic labs is that you need to find a way to pay for your own research, because there just isn't money otherwise. Schools provide some startup funds to early career professors to get things going and equipment purchased, maybe a few salaries covered for a time, but the expectation is that they start securing their own funding themselves by writing grants to funding agencies calling for research in certain areas. This is why most Principle Investigators (PIs) are in their offices writing grants and keeping up with calls for proposals from funding agencies, and not in the lab toiling over experiments; gotta keep the funding coming and everyone under your wing employed. In my experience when PIs failed to secure grant money, at that point the lab had already spooled down and there isn't any more salaries to pay, and they usually just transitioned to a teaching professor role or a more administrative role in the department, covering their salary through those efforts rather than grant funding.


That mostly means we could have mRNA vaccines a decade earlier.


perhaps, or maybe it means we would have mRNA vaccines decades later.


Exactly. Her moving to BioNTech seems to have been the best outcome possible... even though I completely understand her sourness at Penn. But it sounds like she’ll get the last laugh and can call out Penn for its lack of vision.


yeah, and it is entirely possible that developing mRNA technology simply wasn't a good fit for Penn, even if it was long term viable and within their ability to fund.

It it seems pretty unfair to say that "the school wasn’t very supportive of the scientist who led the charge."

They gave her 6 years runway while she tried to find external funding and get the technology off the ground before kicking her off tenure, and kept her on payroll until the she made her breakthrough another 10 years later.

If I understand the timeline right, she started at Penn in 89, was kicked off tenure in 95, published her major mRNA paper in 2005, then left Penn to be a senior VP in 2013.


Academia gives you six years to publish top-tier papers and obtain significant grant funding to impress one's peers. Failure to do that and have a mediocre, but not an abysmal, teaching record means dismissal (i.e., not being on the tenure track any longer - not necessarily being fired outright). In general, the system works okay, but one has to play the game. Winning grants is extraordinarily hard, even more so today than it was in the 1980s. To me it is unclear whether to blame the university, the grant agency reviewers, or her writing (one must make a convincing arguments to the reviewers, which is very hard if one is breaking with dogma). Her university peers may not have been able to see how revolutionary her work was at the time and so they fell back on the metrics. Getting tenure is extremely difficult. I applied for it this year at my university...


If the system disregards revolutionary research because it's too hard to understand (which, by the way, there is evidence that established members of a field actively block revolutionary research because they "know" it won't work out) then it is the system that should be changed.


Well said!


Sure, but universities are old and stodgy. Maybe it’s people who want to be professors in the first place that should be changed. With hindsight, moving to BioNTech seems like the best decision she could have made, and now she can enjoy the final laugh.


Unfortunately, research that may lead to amazing results can take decades, yielding little commercial value or shiny tech that grant givers want to throw money at. They too are likely evaluated against the short-term outcomes of the grants they award.

Also unfortunately, it is very difficult to distinguish between one decades-long research path that will, eventually, yield significant results, and another one that will end in failure with nothing to show for it.


>unfortunately, it is very difficult to distinguish between one decades-long research path that will, eventually, yield significant results, and another one that will end in failure with nothing to show for it

But that is the very nature of Research in basic hard sciences. We have to have systems in place which have such monetary/time losses factored in. The problem today is that Academia is using the same "short-term gains" yardstick used in the Industry which is completely wrong. The nature of the subject should dictate your manner of funding it.


>We have to have systems in place which have such monetary/time losses factored in.

Sure, everyone agrees with that. Can you propose a model that will work?


The "University Framework" already exists to support such a system. The problem is that Industry has infiltrated itself into the system and turned the "Research Objective" into "Profit Motive". This has to be eradicated completely. Others in this same thread have also proposed some ideas and i will try to add to it;

* Establish a network of "Research Universities" from each country in the World (sort of UN of Universities). The poorer countries can be partially funded by richer countries. This is to ensure that knowledge flows are not constrained due to lack of resources.

* Research in the various Sciences have to be clearly identified as "Critical" or Not. The former is funded and managed completely differently than the latter. For example, research in vaccines/cancer is considered critical while research in "battery chemistry"(currently a hot area of research) is not. In the former case, all we keep tabs on is "some progress" and not necessarily an external deadline i.e. researchers are given the freedom to keep working on it with self-imposed and self-defined milestones.

* All "money making" (eg. licenses/patents/royalties etc.) from Research is to be shared between Researchers, Institution and Industry (where applicable).

* All "Research" in Universities get funding from the following sources, some with constraints and some without;

----- 1) Govt. grant as part of yearly budget with no strings attached. This is taxpayer money and any output is available to the public.

----- 2) Academia/Industry tie-up (eg. VC/Angel money) where all stakeholders needs are considered. However if the research is considered "critical" Industry needs may be waived.

----- 3) "Corporate Social Responsibility"(CSR) money from all large corporations/rich folks etc.

----- 4) Revenue/Profit from University "businesses" like Education etc.

* Finally, No "Research" project should ever be overseen by purely "Administrative/Finance/MBA" types. Only Core Domain Experts should be granted oversight with the above mentioned helping as needed.


Or do it like Germany does:

* Fundamental groundbreaking science research is done in research institutes without pressure to teach or get industry grants, with 100% state funding - the Max Planck institutes

* Industry-relevant research runs in entirely separate teams, either in applied-science institutes - the Fraunhofer Institutes - or universities, with mixed public and private grant funding

Presto, no more pressure for industry sponsors of blue-sky fundamental research.


>* Establish a network of "Research Universities" from each country in the World (sort of UN of Universities). The poorer countries can be partially funded by richer countries. This is to ensure that knowledge flows are not constrained due to lack of resources.

Agreed, a lot of grant funding now has an open access rider on it, so research doesn't get stuck behind a paywall.

> Research in the various Sciences have to be clearly identified as "Critical" or Not. The former is funded and managed completely differently than the latter.

How do you ensure that this classification of critical/non-critical happens accurately? How do you hire for this team, and what metrics would you use to judge their performance? How do you ensure that this 'non critical' funding isn't simply a waste of money? This solution seems to just push the same problem further down the road.

>For example, research in vaccines/cancer is considered critical while research in "battery chemistry"(currently a hot area of research) is not.

I work in vaccines, and I don't agree with this blanket assertion. How do you deal with vaccine technology that is junk and will never produce a safe and efficacious product?

>In the former case, all we keep tabs on is "some progress" and not necessarily an external deadline i.e. researchers are given the freedom to keep working on it with self-imposed and self-defined milestones.

So unlimited funding for unlimited projects as long as they are critical according to some review committee? We might have a tiny problem doing that.. :)

>* Finally, No "Research" project should ever be overseen by purely "Administrative/Finance/MBA" types. Only Core Domain Experts should be granted oversight with the above mentioned helping as needed.

We should have a large tent. Financial management is a critical component of any successful project. "Core Domain Experts" will likely have limited time, given their other commitments and own personal research to work on. Also, there needs to be a thorough vetting and oversight to make sure that these experts aren't just funding projects that their buddies are working on.

I think you have some good ideas, but as you can probably imagine too, its no easy task proposing a working model, and getting it adopted world-wide :)


Your objections are just the low hanging ones :-) You surely do not expect a iron clad proposal here with all the t's crossed and i's dotted? However here are some resolutions to your objections;

>How do you ensure that this classification of critical/non-critical happens accurately?

Define "accurately". We are playing the balance of probability based on the "domain experts" knowledge base. In some cases it would be obvious. For example take this mRNA research; this great article from https://www.statnews.com/2020/11/10/the-story-of-mrna-how-a-... states;

  In the natural world, the body relies on millions of tiny proteins to keep itself alive and healthy, and it uses mRNA to tell cells which proteins to make. If you could design your own mRNA, you could, in theory, hijack that process and create any protein you might desire — antibodies to vaccinate against infection, enzymes to reverse a rare disease, or growth agents to mend damaged heart tissue.
A moderately scientific mind can easily see the vast life-saving potential here (analogous to stem cell research promise but from a different direction) so why wouldn't we label it "critical" and keep funding it until the breakthrough is found? Note the issue was not of Science but of Mechanism which is almost always solved with Time and Technology. UPenn failed this test miserably and completely.

>How do you ensure that this 'non critical' funding isn't simply a waste of money? ... How do you deal with vaccine technology that is junk and will never produce a safe and efficacious product?

This is where the system has to absorb the losses when you do decide to cut the chord but this should not be based on imaginary "market/financial needs". Revenue generation from various sources somewhat guarantees that.

>So unlimited funding for unlimited projects as long as they are critical according to some review committee? We might have a tiny problem doing that.. :)

Of course, this is nothing new; we are dealing with Humans after all. Just make your criteria for "critical" very stringent and the people in charge knowledgeable. This is how Science has always worked when the "bean counters" don't get involved.

Think of it this way; in any project there is always the core/essence/kernel Science/Technology/Whatever which is the primary reason for its existence while the others are ancillary which exist only to support the primary. If you make the mistake of taking the ancillary for the primary, you will lose almost always (i put "almost" to factor in the role of Chance :-).


So you might ask why we have research universities anymore.


Please note that the [1] NIH, for e.g., does fund speculative/exploratory research. You will not however, get unlimited funding. So if you fail to show at-least something you probably wont get renewed. There isn't a perfect funding model that also prevents wastage.

[1]

https://grants.nih.gov/grants/funding/funding_program.htm


If there is not an appropriate award that already exists then it should be created and then given to her and any other unsung heroes in this area. If no institution does it then it should be crowd funded and presented by a new foundation. I will donate!!


There is some talk of a Nobel Prize in chemistry for Dr Katalin Karikó and her collaborator Dr Drew Weissman. From what I’ve heard, mRNA as a technique is quite an advance — if true then they deserve all the accolades they get to make up for the years of fruitless, unappreciated research.


Agree 100%. All the people involved in this vaccine should be given the Nobel in Medicine/Chemistry.


This is actually quite a good background story on the mRNA COVID-Vaccines, that also explains Karikós role in more detail.

https://www.statnews.com/2020/11/10/the-story-of-mrna-how-a-...

WSJ also has a number of good articles:

https://www.wsj.com/articles/how-pfizer-delivered-a-covid-va...

https://www.wsj.com/articles/how-a-couples-quest-to-cure-can...

https://www.wsj.com/articles/how-pfizer-partner-biontech-bec...

What I found quite interesting was the latest news release from BioNtech where they thank all their partners. Some parts of the supply chain are only served by very small companies.

https://investors.biontech.de/news-releases/news-release-det...


Curious that they mentioned their local pharmacy (Phoenix-Apotheke Mainz, on the same street as their office). I wonder what it supplied.


The first "statnews" link is excellent! Everybody should read it; really explains the technology for the layperson in simple language.

Thanks for the link.

PS: The WSJ articles are all behind a paywall and hence inaccessible.


The result of running universities like a business. People are more concerned about publications and conference and funding than actual science which is slow and unremarkable most of the time.


I don't understand why the current failure of at least the US university system to actually promote long-term thinking and research isn't a bigger issue. How many people's lives could have been saved by research that was never done? How might society have been improved? Like, there's literally millions (billions?) of human lives on the line.


Also another case where

"Researchers’ patents are often held by the institutions where they work."

I wonder what the law is around that ... what percentage are the discoverers legally entitled to?

If the answer is obscene, what efforts have been made to fix that?


Not a lawyer but I've participated in "technology transfer" at a university.

At University of Washington one of the standard deals is 27% for the inventors (for patent license revenue). Of course every deal is negotiable. When you use university resources such as lab space and students the university will take some financial share.

When it comes to equity stake in a startup the deal negotiated becomes much more tricky of course and the university may maintain an equity stake in the company in exchange for exclusive licensing of the patents.

https://comotion.uw.edu/what-we-do/startup-related-services/...

http://www.washington.edu/admin/rules/policies/APS/59.04.htm...


A similar article was published in Wired about a month ago: https://www.wired.co.uk/article/mrna-coronavirus-vaccine-pfi...


Pretty good article; mentions the others involved in the whole "mRNA" research.

Thanks for posting the link.


Reminds me of the Doctor who was ostracized by the medical community for his theories on what causes an Ulcer.

He ended up giving himself an Ulcer to show he could cure it.

https://www.discovermagazine.com/health/the-doctor-who-drank...


Funny how biases work. It is "Philly" when positive. "Immigrant" when negative.


Researcher fails to make money for half a decade because they were working on something that they wouldn't figure out for an additional two decades.

Okay...?

If this still bothers you, please tell me what kind of organization would exist to support 25 years of false starts, and what needs to change to make that kind of organization exist.


You realize that academic research can take years or decades to pay off right? Look at nuclear fusion research. Should we give up just because we are still decades away even after decades of research?

I think this is a major problem in our society. We expect immediate profits off of research, but that limits us to research that is less bold and innovative. We should allow our brilliant scientists to follow their passions instead of following grants.


You have to give up on some research, since there are only finite resources available.

This means you will abandon some projects that would ultimately have been very successful. That's true for every possible strategy.


I understand that argument, and it is usually in the context of the folly of quarterly results in the private sector, which is a far cry from six years and twenty five years.

Regardless, back to my question, what needs to change to support all the other researchers toiling away right now that won't gain any consensus or utility till the year 2050.


Government funding? More "charity" from billionaires?

Our society has plenty of money to support people like her and her research. That's the point of the academy in the traditional sense: not a vocational school, but a gateway to new understandings of the world.


We need a mindset of doing research for its own sake rather than just as a way to profit. What profit could come of going to the moon? Yet we developed many technologies along the way.

Realistically, the funding would probably need to come (and already does come) from the government. The government should be funding manned missions to Mars and investing much more in longshot technologies like nuclear fusion, to name a couple obvious ones.


See lb504's answer.


Such an organization used to exist; it was called a university, and it offered tenure in part, in theory, to support researchers whose work might bear no fruit for decades.


> what needs to change to make that kind of organization exist.

Stop modelling universities, national education and research systems on profit-seeking businesses.

Businesses already cover that niche; it's entirely unhelpful for universities to exist with a profit-making premise.


> If this still bothers you, please tell me what kind of organization would exist to support 25 years of false starts, and what needs to change to make that kind of organization exist.

Academic research is supposed to be for such long-term research. Plenty of scientists research for entire life, just to explore dead ends.

Also, WTF it is considered as OK to base scientific research decisions on profit generated within 5 years? (I know how it happens and why, but considering it as OK is ridiculous)


> If this still bothers you, please tell me what kind of organization would exist to support 25 years of false starts, and what needs to change to make that kind of organization exist.

A Federal Universal Basic Income along with a Single Payer Healthcare system would go a long way to supporting 25 years of false starts for projects where the primary initial investment is intellectual labor. Many science, engineering, and cultural projects fit this description.


Single payer healthcare, absolutely. Negotiating a market rate between professionals and the entire public is the most optimal approach for the consumers whom; in a moment of need, won't really be able to shop around and choose.

While I do believe there needs to be a first world floor to living conditions, I've come to more understand UBI as one more way of killing the middle class. It's the Supply side, a lack of competition, that is out of whack for many of the most expensive things in the US, and probably most other industrialized nations.

UBI increases how much the poorest can pay, it does nothing to limit how much can be demanded by the rent-seeking rich. In effect UBI is a subsidy to the rich and an attack on the middle class.


But the same supply side problem is also an argument against single payer healthcare. Maybe you've negotiated an awesome rate for the public, but then this comes back to bite you in the form of shortages and/or reduced R&D of new treatments. I mean, essentially it is one big monopsonistic price control regime, right? On the other hand if we can somehow bolster competition, increase doctors trained, etc., then maybe prices can come down on their own to a level accessible to the public again.


If a thing is desired by society but the market is unable to fulfill that need that sounds like an area the government (the people's organization of foundation, first / last resort) should apply work. Though sometimes government can be the cause if regulations aren't well thought out and there's a failure to minimize unintended consequences.

If there aren't enough doctors as a whole, that's a sign that either the incentives and detriments offered by society are incorrect or that barriers to entry are too high for the market to function. (In the case of medical professionals in the US I've heard that a combination of artificial scarcity and malpractice worries are the issue. For the latter I'd like to see criminal (reckless endangerment, etc), rather than economic, outcomes for egregious cases; which should also apply to institutions training and certifying doctors. With that layer of protection the 'insurance' against being harmed should instead be covered by normal disability programs at the society level.

In the case of insufficient doctors in an area, that sounds like a great place for the military to have a base and provide civilization; though the doctors (and possibly other professionals) not existing there might also be a sign of larger issues.

If a place isn't economically viable anymore it is important to identify the root cause and fix it, or offer assistance to relocate to places that are useful for their residents and society.


Doubt that. We have full socialized healthcare and great unemployment benefits. Yet we also suffer from the same problems in academia.

Having those is pretty orthogonal to actually getting results in science. No need to mix them in.

Universities should actually fund (so indirectly by the goverment from taxes) long term research. That’s kinda the whole point of Universities, in addition to education. Long term research that doesn’t have immediate short them commercial interest. Not make the scientists be basically startup founders that must constantly pitch to get money.

And the reason we want to support that is because on long term there often is very useful commercial benefits that then improve everyones lives.


You're implying she could've done all this research in her bedroom? I doubt it.


No, they're not. They're implying that a world where the government takes an even more active role in promoting economic activity, and secures the fundamental aspects of human dignity for its citizens, would be a society where more people can spend time on their passions, which often are things like "develop a groundbreaking new style of vaccination".


there's already a country where the government is taking a very active role in promoting economic activity, specifically North Korea


Come on, are we being serious here? "Developing a groundbreaking new style of vaccination" requires far, far more support than just a salary. UBI/social safety nets are totally irrelevant here.


And yet, it was developed under free market principles and delivered to market with no one getting a UBI.

UBI is a fantasy for children.


My opinion is that this sort of long-term and/or high-risk research and development is precisely what universities and governments (and government grants) are for.


and what needs to change, for the researchers right now who won't have any useful milestone or breakthrough until the year 2050.


> If this still bothers you, please tell me what kind of organization would exist to support 25 years of false starts

Government, academia, VCs in industries with slower payoffs than software (i.e., most, including biotech).

OTOH, deciding which series of decades of false starts are worth continuing to support and which to cut off is...well, not an exact science would be an epic understatement.


I would expect academia to absolutely be the place for long-term, speculative research to be at the heart of what they do.


>If this still bothers you, please tell me what kind of organization would exist to support 25 years of false starts,

This is basically the whole point of academia.


This mRNA technology is amazing. One of the great hopes is that it may be possible to target specific cancers with great accuracy thereby saving many lives. Hopefully these vaccines are just a start.


I’m surprised there are few articles in the news about how they work, and why it’s a big deal. One of the other vaccines developed in China uses a common adenovirus as a carrier for the SARS-COV-2 genetic material and that was why it had lower efficacy. The Oxford vaccine uses some less-common adenovirus, which is somewhat better, but mRNA lets you bypass using viruses as a vector altogether.


You're right, but what matters much more is that the investors realized the potential (5x in 1 year after the correction). Moderna was on the roadmap for ARK invest for a long time (and compensated for it heavily).

Now that mRNA is proven technology, it can bring all other gene technologies up with it.


While the title of this article is accurate it’s deceiving. She was demoted sometime in the 1980-1990s. The article even says she stopped working for the school in 2013 and went to work for a pharma firm. The article even says she went pack to UPenn this year to get her vaccine.


It's also misleading in other ways (perhaps unintentionally). For example:

> After six years, her bosses at Penn were reportedly so frustrated by the lack of momentum that they cut her salary and demoted her.

Actually, she was denied tenure. At most universities, going up for tenure after 6 years is just part of the process, and it's fairly common for people to be denied. It's not like they singled her out.


... and being denied tenure is a pretty clear signal that it's time to move on. You're branded now, and there isn't much hope for advancement if you stay.


Not just any pharma firm, she joined BioNTech, which created the Pfizer vaccine.


Why is it always called "the Pfizer vaccine" when it's clearly a joint operation between Biontech and Pfizer with Biontech being the inventor of the vaccine and Pfizer being the pharma giant that is able to help with resources and producing it at scale?


Because Pfizer has a marketing department many times bigger than all of BioNTech.


Because the vaccine is manufactured and distributed by Pfizer, so that's who you buy it from and that's what it says on the packaging.


Easier to say. Just like "Oxford" vaccine instead of "Astrazeneca/Oxford".


GNU/Linux please.


this escalated quickly


That’s essentially the opposite situation, though. Presumably Oxford has better PR people than BioNTech. It also has the great advantage of being easier to spell.


But in this case it's the BioNTech vaccine then.


> Why is it always called "the Pfizer vaccine"

False supposition, in most cases in my reading it is called Pfizer/BioNTech in reference


It sounds like she was not able to raise the money to continue her research. That’s not really UPenn’s fault. No one can know in advance which ideas are promising enough, so it isn’t reasonable to blame them.

This isn’t a scandal or an embarrassment. If, after working for decades, no one is willing to fund you, it’s kind of expected that they have to cut their losses at some point. She was apparently working on it for over 20 years! It turned out that all of the grant money and VC money didn’t see the right risk/value potential in it, so they declined to provide their money, but BioNTech did and hired her as a VP. I suspect this ended much better for her than staying at Penn would have.


Isn't it slightly embarrassing that we:

a) can't predict the impact of most research programs very well but

b) make pretty drastic decisions based on them, and

c) [for Penn specifically], never revisit those decisions.

Her publication record from 2005 onwards is pretty solid: Immunity and Nature papers with a thousand citations each, an out-licensed patent, and a bunch of other papers too.

It probably wouldn't kill anyone for UPenn to say "The value/success of her work wasn't obvious to our P&T committee at the time" or something vaguely apologetic.


>It probably wouldn't kill anyone for UPenn to say "The value/success of her work wasn't obvious to our P&T committee at the time" or something vaguely apologetic.

Yes! UPenn needs to publicly own up to their short-sightedness and apologize to the researcher. If you want the bouquets you should also be ready for the brickbats.


An institution of the prestige UPenn aspires to is supposed to provide research leadership, and not just be a place for VCs to subcontract their work.


So they should fund all research for all time?

No, that's not reasonable. I know, they should just fund the research that will eventually be proven to be ground breaking. Seems pretty straight forward. Of course they are dependent on the research at Penn for the crystal ball.


That’s great, but assuming she (and everyone else working on research that they felt was important) expected to be paid, the money has to come from somewhere, right? Tuition costs are already too high and we are calling in the government to pay for student loans. So what do people expect? Obviously with a crystal ball they probably would have kept her funded (if this is even the full story - and it probably isn’t), but we shouldn’t blame them for not having one. 20+ years with no takers sounds like a pretty fair shake. Are they just supposed to fund everyone indefinitely so they can never be accused of missing something good?

Not even VCs have a great track record at picking winners, and they do this for a living.


> Are they just supposed to fund everyone indefinitely so they can never be accused of missing something good?

No, of course not - that is just an unhelpful false-dichotomy straw man reply (like the whole of wuwuno's).

The issue of funding both fundamental research and that which lacks a pathway to short-term profitability is a difficult one, much more subtle than you presented in your original post, where getting VC funding was presented as the sole criterion that mattered (the point of view given in that post amounted to saying that delegating all decisions to VCs was the proper way to go about it.)

One of the reasons vaccine reasearch hasn't been attracting a lot of VC funding is that vaccines are not nearly the money-makers that drugs and tests are. We're lucky that some research was kept going despite this, and the lesson from that is that we should not trust in VC funding being the predominant determinant of funding.


> It sounds like she was not able to raise the money to continue her research. That’s not really UPenn’s fault. No one can know in advance which ideas are promising enough, so it isn’t reasonable to blame them.

As one had wrote 2-3 grant proposal during graduate studies, my takeaway is that the system failed to give the really impactful ideas the right amount of resources.

That's matching a 2-day-old submission [1] about peer-reviewed research papers are becoming boring, as another sign that the existing research management systems are not producing interesting results, even just from reading the papers, which presumably is already the most interesting thing can be produced from a research project.

[1] https://news.ycombinator.com/item?id=25605156


It seems like having the scientists do their own fundraising is the wrong way to do things. You'd have to be an expert in both the science and the fundraising, to compete against the other scientists who are fundraising. Obviously, since learning how to raise funds competes with learning and developing the science, this system is going to prioritize greater-skilled-fundraisers/lesser-skilled scientists. If you're a great fundraiser, why do you even need the University?


> If you're a great fundraiser, why do you even need the University?

Because funds don't cover certain operational costs. You also lease lab space/equipment/staff from the university, etc.

Everyone can identify problems with the existing model, its rather difficult to propose workable solutions!


That makes sense, but if you’re a fundraiser and not a scientist, how do you evaluate the claims and the potential for every project that wants you to raise for them? If that were my job, I’d have no idea how to tell a Theranos apart from what this research was, other than going with my personal rule of favoring the one who doesn’t put on a fake voice.

But there is a limited supply of money, and someone has to figure out how to get the right amount to the right people for the right length of time. If you know how to do that, I’ll definitely fund you, and every project you recommend!


shouldn't it be the university administration's job to find funding and allocate it? sure nobody can know the future, but people in positions of power should at least understand the potential results and implications of the projects they decide to terminate or support. researchers themselves shouldn't have to waste time essentially paying rent to a parasitic bureaucracy.


If you've never published you should be banned from discussing this topic at all, the dunning krueger effect is infuriating for such an integral part of human progress.




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