Nobel Prize winner Gregg Semenza tallies tenth retraction (2023)

5. HARKing: "Hypothesis after results known" is also a problem to produce even "legitimate" papers by discarding the original hypothesis after negative findings and come up with a new one that fits the data. Its similar to p-hacking and also skews science into "promising" dead-ends.

> but seeing Nobel-prize-winning labs publish photoshopped blots

And they were caught because they edited poorly which could be detected automatically or by human eyes. Think about well versed image manipulators or generative AI...

I think this erosion of trust is the worst, AI can produce and it will propably come.

Even figures with images are typically assembled in Illustrator.

You past in the image of your cells or western blot or whatever, and then add all the labels etc.

> Pauling has been portrayed as a nobel-laureate-gone-quack

Oh, certainly. I wanted to emphasize that the quackery was only in regards to his views on vitamin C.

> in pop science media many times

To be clear, it's also told in the scientific literature by people with chemistry and medical training.

> so apparently the severity of relevant cold symptoms is indeed strongly decreased

My previous comment wasn't meant to be conclusive about the experiments that have been carried out, but to point out how experiments using >= 1 gram doses have been done.

I did this because you criticized studies which used sub-gram doses. I have no problems with that viewpoint, but since >= 1 gram studies exist, you surely need to address their conclusions.

I pointed to the Canadian paper because it was the earliest one I could find to investigate Pauling's claim.

> so I would figure that the real number is somewhere in-between the advocates and these "debunkers".

That's not how statistics works!

Yes, that paper shows that a couple of the findings were statistically significant ... but also remember the XKCD 882 on "green jelly beans linked to acne" https://www.explainxkcd.com/wiki/index.php/882:_Significant - if you test enough random data, you'll find statistical correlations due to random happenstance.

You need to run the experiment again and see if the signal is still present, otherwise you're chasing statistical noise.

Which the Canadians did the next year. See "Vitamin C and the common cold: a double-blind trial" at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1947567/pdf/can... where figure 1 shows no statistical difference in "days indoors" for 0.25, 1.0, and 2.0 grams taken prophylactically (or 4g and 8g taken therapeutically), contra Pauling's suggestion "on theoretical grounds that the beneficial effects of regular vitamin C supplementation should be proportional to the size of the daily dose."

So that's another >= 1 gram study, from the same people. From what I can tell from other summaries on the topic, there were dozens of these >= 1 gram studies by the 1990s or so.

Surely these are more relevant to your rabbit-hole exploration than the sub-milligram studies you complained about, yes?

> They say themselves that Pauling based his claims on studies showing 45% and 60% respectively (which you have not linked to for some reason).

I did not link to them because I wanted to understand your objections to the attempts at replication using >=1 gram of vitamin C/day, given that I know they exist, as I showed by demonstration. Both you and I know those publications exist.

Here's what I think is a copy of the original 1961 publication by Ritzel, https://www.mv.helsinki.fi/home/hemila/CC/Ritzel_1961_ch.pdf , "Kritische Beurteilung des Vitamins C als Prophylacticum und Therapeuticum der Erkältungskrankheiten". I lack the German to read it, but Tabelle 1 doesn't seem to match Tabelle 2? That is, Tabelle 1 says the number of krankheitstage ("sick days") is 31 for the vitamin C group and 80 for the placebo group, but Tabelle 2, with the individual breakdown, says there were 42 krankheitstage and

Here's Pauling's description of Reitzel, from his 1970 book "Vitamin C, the common cold, & the flu" https://archive.org/details/vitaminccommonco00paul/page/44/m..." pp 43-44:

"He reported a reduction of 61 percent in the number of days of illness from upper respiratory infections and a reduction of 65 percent in the incidence of individual symptoms in the vitamin C group as compared with the placebo group."

That 61% is computed from Tabelle 1, "Anzahl Krankheitstage" at 31 days vs. 80 days for the placebo group. (80-31)/80 = 0.6125. But oddly, Tabelle 2's columns for "Anzahl Krankheitstage" add up to 42 and 119, respectively, so I think Tabelle 1 swapped the value for Krankheitstage and Einzelsymptome?!?! (Both are ~60% reduction, so this doesn't affect the conclusion.)

Also, note the short time - the vitamin C was only delivered for two 5-day ski camps, and those with cold symptoms on the first day were excluded from the study. If 60% were replicable, and not a statistical fluke or flaw in the methodology, it should be easy to see in other studies.

Note also that earlier on page 44 Pauling says that 200mg to students as a girls school in Ireland (it look like teenagers) reduced the severity and duration of colds ("Duration of the symptoms in catarrhal colds was reduced from 14 days to 8 days in the children receiving ascorbic acid."), so at this point he believes there is supporting evidence that 200mg (or perhaps 500mg for adult body weight?) is enough to show a noticeable effect.

Though Pauling is sloppy, saying "Wilson and Low in 1970" when it's "Wilson and Loh". Plus, here's Wilson criticizing Pauling's interpretation at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1795409/pdf/brm... shortly after the book came out:

"Nothing can therefore be concluded about the relationship of ascorbic acid metabolism and the appearance of cold symptoms in the different experimental groups from the results of this trial. ... by modern standards of clinical trial methodology [Tyrrell's trials] could not be classified as a well conducted clinical trial on the relationship between development of the clinical features of the common cold and the administration of supplementary vitamin C ... Dr. Pauling did not provide this critical evidence necessary for support of his hypothesis about the relationship between the administration of supplementary vitamin C and reduction of the symptoms of the common cold" - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1795409/pdf/brm...

> About the cancer claims (which I agree should be treated with utmost suspicion, as for any medicine):

Does his "double nobel laureate" affect your interpretation of his views on vitamin C and colds more than your interpretation of his views on vitamin C and cancer?

Anyway, if Pauling has stopped with Vitamin C and the common cold, I don't think he would have been seen a quack. Eccentric, sure, but was his doubling down to say it also treats cancer, and his tripling down to promotes how it may treat a host of other diseases, which made him a nobel-laureate-gone-quack.

> People in the pharmaceutical industry's marketing departments

Okay, think back to the 1970s when Pauling promoted vitamin C for the treatment of the common cold.

What treatments did people use for the treatment of the common cold? Aspirin was generic. acetaminophen (Tylenol) was generic. Ibuprofen was under patent, but competed against the first two. I think pseudoephedrine was generic? ("first characterized in 1889" says Wikipedia).

I don't see much in the way of patent profits there .. and I still don't know.

Who produced and sold vitamin C? (Hint: a paper I mentioned earlier end "We are grateful to Dr. J. Y. Gareau of Hoffmann-La Roche Ltd. for supplying the vitamins and placebo tablets.").

So, what did the pharma industry have to lose by promoting 1g consumption of vitamin C every day, for prophylactic use against the common cold?

Why would pharma profits prevent the military from using an effective cold treatment?

Why would pharma profits prevent the Soviets from using an effective cold treatment?

Why would pharma profits prevent the national school systems in Europe from providing vitamin C megadoses to their students?

> I first noticed suspiciously professionally written "debunk" Wikipedia articles during the Séralini affair

I have no idea what that means. My initial understanding of Pauling's megadose idea predates the existence of Wikipedia. Séralini seems to be a post-2010 thing? How does that affect any of the earlier published experimental results showing that megadoses don't have the clear effect that Pauling claimed, and that megadoses come with some side-effects.

> I'm not sure why this overall topic triggers so much.

Because there's oodles of published research over the last 50 years showing Pauling's ideas don't work like Pauling saying it would? Do you really want to say "pharam conspiracy" for something so easily tested that groups around the world evaluated the possibility? And that people like you can conduct yourself?

Who stands to profit from promoting Pauling's megadose hypothesis if it is actually false? And who promotes that idea the most?

I'm glad the GP pointed this out, because nobody talks about it. The "PI" of a lab is manager, so these issues are like an accountant embezzling money without the manager knowing. Maybe the manage should have put better processes and monitoring in place, but they were trusting their team members to behave properly, which is not unreasonable IMO.

The real issue is that the people who conduct the fraud are usually grad students or postdocs, whose entire future depends on the success of their research project. Fake results are pretty much guaranteed.

Think about it this way: Imagine you have a lab group with 10 PhD students, each with their own hypothesis to investigate (e.g. intervention A will reduce the rates of disease B in mice). What are the odds that all 10 students will prove their hypothesis and generate publishable results? No way it's 10/10 obviously...it's more like 5/10. So what is supposed to happen to those 5 students that were tasked with investigating the bad hypotheses? Our current system implicitly penalizes these students to the extent that their careers in academia are over, and even earning their PhD is not certain. BTW, I know I am being overly general here, and the student will likely have several parallel projects on-going, can pivot to other things, etc, but hopefully my general point is clear.

He works at Johns Hopkins, which is a private university that works closely with a health system called Johns Hopkins and the Johns Hopkins hospital (the medical school). When you say "for profit", be aware that they definitely take money from the government and patients and use it to develop new intellectual property that generates large amounts of money for them (although I guess the "profit" from that doesn't benefit the shareholders).

These "non-profits" have multi-billion dollar budgets and are highly "profitable" depending on how you like to define it. https://www.nytimes.com/2020/02/20/opinion/nonprofit-hospita... In these cases, the non-profits are given tax incentives provide a certain amount of community benefit.