People talk about Karys inexplicable beliefs about HIV. Why does nobody point out, as written in the speech, the fact that prior to PCR Kary explained the process of PCR to all of the biochemists around him in great detail, and nobody even raised an eyebrow. nobody believed him. How could anyone call himself a biochemist if they couldn’t recognize a biochemical revolution after being slapped in the face with it by the person who invented it? There wasn’t a single missing step according to Kary, the entire process was mapped out and consisted of procedures and chemicals that already existed. This amazing paradox is lost on most people. They overlook it just like those fools overlooked PCR-on-a-silver-platter.
It’s the dark truth. Most scientists and doctors are basically frauds. They just memorize what the real scientists have figured out so far.
> Monday morning I was in the library. The moment of truth. By afternoon it was clear. For whatever reasons, there was nothing in the abstracted literature about succeeding or failing to amplify DNA by the repeated reciprocal extension of two primers hybridized to the separate strands of a particular DNA sequence. By the end of the week I had talked to enough molecular biologists to know that I wasn’t missing anything really obvious. No one could recall such a process ever being tried.
> However, shocking to me, not one of my friends or colleagues would get excited over the potential for such a process. True. I was always having wild ideas, and this one maybe looked no different than last week’s. But it WAS different. There was not a single unknown in the scheme. Every step involved had been done already. Everyone agreed that you could extend a primer on a DNA template, everyone knew you could melt double stranded DNA. Everyone agreed that what you could do once, you could do again.
There's lots of things that sound good on paper. People have been working on things like fusion energy for decades. Actually demonstrating a breakthrough is very different.
That people were unimpressed until the point of demonstration is just rational. If someone were excited and impressed by every promising-sounding hypothetical they would end up on a lot of wild goose chases.
I don't think any of this shows any deficiency in the scientific community. Quite the opposite. A strange guy with off-beat ideas was able to come in and demonstrate an achievement, and he was awarded recognition for it and his technology adopted on a widespread basis.
You lack good reading in history. If everyone thought like you, science would stagnate. You make the common error: to see all “on-paper,” unproven ideas as equal. Comparing the reaction mechanism of PCR to the equations involved in human-scale fusion. They aren’t the same, no two hypotheses are the same. Real scientists actually read hypotheses and try to understand what’s going on in this hypothetical scenario — reason about it. People that do this are often excited about “wild goose chases” because they aren’t actually wild goose chases. They are hypotheses that contain pieces that work with a lower level of ambiguity than most ideas. And here’s another detail the phonies gloss over: sometimes the pieces are better than other times. Most times there’s some ambiguity but sometimes there’s very little and you can be more sure. That was the case with PCR. That’s how real scientists think. They think with models, trying to understand the world. Most people don’t do it and they are utterly unmoved by convincing ideas. They can’t distinguish between convincing ideas and rubbish. It’s the hallmark of someone who doesn’t get it.
On one hand he did create one of the most revolutionary technologies of the 20th century, the PCR.
OTOH he was a denier of the HIV virus role as a cause of Aids and actively supported South Africa's president Tabo Mbeki on a disastrous policy of ignoring the transmission of the disease.
I take that everyone's opinions must always be taken cautiously, even the opinion of smart men in their own areas of expertise.
> he was a denier of the HIV virus role as a cause of Aids
I did a deep dive into this back in the 90s, during the course of which I had a chance to talk to Kary. I looked up his phone number on the internet (this was long before doxxing was a thing), cold-called him, and he picked up the phone. We talked for about half an hour. That's the kind of guy he was. I more or less asked him how can a smart guy like you buy into this conspiracy theory? His answer was: he wasn't buying in to the conspiracy theory. He was not endorsing the idea that HIV did not cause AIDS. All he believed was that there was not yet enough data to conclusively show that HIV was the cause, and so people should keep an open mind. And frankly, given what was known at the time, I thought he had a valid point.
He remained a denialist for the rest of his life, though. And besides there was plenty of evidence in the early 90s that HIV caused AIDS. It was conclusive.
> there was plenty of evidence in the early 90s that HIV caused AIDS. It was conclusive.
That is far from clear, at least to me. The main thing that bothered me at the time, and which I've never seen satisfactorily explained, is that 1) AIDS was widely believed to be 100% fatal, 2) believed to be caused by HIV, but 3) the HIV virus had incubation periods of [EDIT: up to] ten years or more. I don't see any way to validly conclude that HIV causes AIDS at a time when the virus had only been known for ten years or so. One could advance this as a plausible hypothesis (one which ultimately proved to be correct), but in the mid-90s I think there was still room for valid doubt.
But I'm very open to being convinced that I was wrong about this (not that it matters much at this point, but it is of historical interest to me).
That incubation period doesn't sound right. Google tells me: "The interval from HIV infection to the diagnosis of AIDS ranges from about 9 months to 20 years or longer, with a median of 12 years." (https://www2.health.vic.gov.au/public-health/infectious-dise...)
So yes, median of 12 years. Not minimum.
Wikipedia's entry on HIV/AIDS denialism links to this document from a committee organized by the National Academy of Sciences in 1988 where the committee says they find the evidence of a causal link between HIV and AIDS conclusive (page 33): https://www.nap.edu/read/771/chapter/4 The rest of that section explains the evidence they have: extremely high correlates for HIV infection and subsequent AIDS prevalence in at-risk communities, no cases in populations that were not at risk, near 100% detection rate of HIV in the blood of AIDS patients, and the tracing of HIV infected blood donors to transfusion patients acquiring AIDS.
I didn't say minimum. The point is, in the mid-90s you had a lot of people with HIV infections. Some of them were dying, but a lot of others carried infections for many years with no apparent ill effects. I don't see how you can get definitive causality from that data.
You said incubation periods of "ten years or more," which was clearly false. The rest of my comment addresses the rest of yours. Not everybody who is infected with a virus gets the most severe symptoms, I would assume we know this intuitively after 10 months in a different pandemic situation ;)
I thought it was implausible that you meant less than ten years by saying that, because your argument rested significantly on it. Other than that our disagreement seems to be on whether there was good reason to be significantly out of line with the scientific consensus on HIV/AIDS in the early 90s, which there doesn't seem to be from my research.
No, it didn't. If you think that then you haven't understood my argument. Let me try again:
HIV was first identified in 1983, so by the mid-90s the virus had been known for just a little over 10 years. Part of the prevailing hypothesis at the time was that the virus occasionally had incubation periods in excess of 10 years, but that it would inevitably kill you sooner or later. I do not see, on the basis of the data available at the time, how you could definitively rule out the possibility that, for example, some people could successfully defend against HIV indefinitely based on some to-that-point unidentified immunological mechanism. Or that AIDS was caused by some unidentified factor that weakened the immune system, and that HIV was an opportunistic infection that was harmless if you happened to have it without the actual unidentified causal factor for AIDS. Or maybe HIV was a co-factor. I can think of a lot of possibilities that AFAICT could not have been definitively ruled out based on what was known in 1995.
Yes, the establishment got it right. But it is far from clear to me that it wasn't for the wrong reasons. The history of science is full of examples of the establishment getting it wrong. It's possible they just got lucky with HIV.
If the epistemic standard is a well-understood mechanism for HIV causing AIDS then yes I would say that hadn't been identified at the time, but the review I linked admits as such.
Moreover if what you disapprove of is the standard of evidence demonstrated by the medical community at the time then I think I can understand that even if I disagree with it. What I can't understand is why you think this is relevant to why Kary Mullis was a denialist, since it's clear he remained as such long after the evidence was overwhelming, the mechanism was demonstrated, etc.
By 1983 it was known that the HIV virus affected T-cells, and the hypothesis that destruction of T-cells causes the observed immunodeficiency isn't such a long stretch.
Yes, I specifically said it was a plausible hypothesis. But the fact that there were people with HIV infections who had no apparent ill effects for years still left room for reasonable doubt for quite a while (like well into the late 90s) particularly since one of the alternative hypotheses was that the treatments then being given for HIV were actually killing people.
Mullis subscribed to the theory that AIDS is caused by infection with too many viruses at any given time. You go to the gay sauna, have sex with dozens of people, and the sheer multitude of infectious agents is what causes breakdown of the immune system. That doesn't square up with how we know the immune system works, not then, not now.
one of the alternative hypotheses was that the treatments then being given for HIV were actually killing people
That hypothesis was advanced and defended by Peter Duesberg, a professor of molecular and cell biology at the University of California, Berkeley. In retrospect we can tell that Duesberg was obviously wrong, but to simply dismiss it as "plain bonkers" is being far too facile.
You'd like to know how Duesberg came up with his hypothesis because the results from early clinical trials speak for themselves. T-cell count went up in the treatment group, amelioration of symptoms, progression to more severe disease delayed.
Of course the virus evolved to defeat the medication, and the disease came back, that's why we nowadays use combination therapy.
You'd really like to know why, despite the obvious successes of combination therapy, Duisberg continued to advance his theory, by 2000 it was totally disproved.
If nothing else you have to muse on the separability of man and idea, at least a little.
PCR is an amazing idea. It’s inventor was a deeply weird guy with a large pile of really bad ideas and an even larger pile of not-even-false ones (e.g., the raccoon spirit animal thing).
Like Pauling, or Watson, a lesson to learn here is that just because someone got a Nobel for true and legit reasons doesn’t mean that what they have to say about other things is of the same caliber. Or even in the same neighborhood of that caliber. Or that a Nobel is a mark of moral character, or anything of that sort.
William Shockley, one of the primary inventors of the first practical transistor, was basically a Nazi, as was Henry Ford. Thomas Edison tried to build a radio to talk to ghosts. Nikola Tesla claimed his inventions were channeled in dreams. Jack Parsons, one of the key rocket scientists of the early space age and the primary inventor of modern solid fuel boosters, was a follower of Aliester Crowley who tried to invoke supernatural entities with sex magic while high on peyote. I know two biology Ph.D's who are Biblical-literalist 6000 year creationists, and one of the most brilliant artists and writers I've met thinks we faked the Moon landing. In the Silicon Valley orbit I've met many neo-reactionaries and neo-fascists and on the flip side people who are so "woke" they see every human interaction in terms of racial and cultural power dynamics. I've met yet more engineers who are into occultism, ghost hunting, and... I could do this for a long time.
In my experience the more intelligent a person is the more likely they are to believe bizarre and extremely heterodox things.
One of my issues with the modern skeptic movement has always been how they try to whitewash the history of science and engineering and forget about all the wild ass shit all these people believed (and that present-day scientists and engineers believe when you get a few beers into them).
You forgot the father of scientist-nutcase-weirdos, Isaac Newton himself!
Perhaps there's a different lesson here: at some level of intelligence, you pierce through the patterns of stability your fellow men had weaved for their survival and sanity (and yours). And then anything goes.
Maybe you also realize the "should of giants" are really the shoulders of men? Capricious and agenda-driven and haphazard, if you care to zoom in with enough resolution.
For Christmas I got Freeman Dyson's "Disturbing the Universe". I never realized how poetic the man was. I always admired Dyson for his courage to speak out and his scientific insight, but he makes beautiful connections between poetry and science, Faust and Newton, creativity and sanity, integrity and death (he served in WW2 and died last year). A chillingly honest and humane read.
add to this the neopuritan “un-person them and all their works” reaction when it is remembered that people are people and that common features of our technology and culture are due to people with occasionally pretty godawful other ideas.
Like, what do you want me to do, refuse to have a COVID test because the guy who figured out how to make it work had some extremely bad ideas about HIV? I assert without proof that i could find someone making that claim somewhere deep in the depths of alternet or salon or tumblr, but i think it's specious.
A worldview that admits of more complexity and tangled-up-ness is more robust against that kind of insanity.
That's not what I meant. I was talking about what I see as a whitewashing of history, an attempt to take the wild thrashing punk concert that is the actual history of human thought and render it down into soft rock for easy listening.
I take a different conclusion from the facts you present, but I know better than to get into it in HN, other than maybe to say: wow, lots of the primary discoverers of scientific principles, and inventors of basic technology, had this shamanic side, maybe there's something to that.
You're probably getting dinged for describing Shockley as "basically a Nazi". I mean, I hope it's not for describing Henry Ford that way, since yeah, that's accurate. Shockley sued someone for that characterization and won. I'd hazard that characterizing him as a racist, and proponent of eugenics, would be less controversial; I'm not at all interested in litigating William Shockley's reputation.
Worth point out, though, that both Ford and Shockley were pretty boring "normies" whose opinions were widely held by others. So your point would have been better made by dropping the first sentence, or even burying it a bit further down.
You are putting the cart before the horse here. People who think outside the box and challenge society and norms are the ones who push the limits of our current knowledge. Conformist and those who seek approval from others will not risk their credibility or reputation on untested ideas.
Science, when done properly, is supposed to divorce itself from our biases. The whole point of the scientific method is that someone like Kary who is a bonafide crackpot, can still make one of the most influential valid scientific discoveries of all time.
As a process in its truest form, it works. And we should all be very glad of that, and use it as a lesson to be aware of how biased we can be, and how a biased person can still wield the tools to arrive at the truth.
He also would give scientific presentations, then slip in some completely unrelated slides of scantily clad women. I've never understood why old-school male scientists think that is appropriate.
I didn't mean to tar lots of old-school male scientists. I only meant that, during my long career, I've only seen old-school male scientists show this sort of stuff, or approve of it. But I didn't mean to imply that large numbers of them did it. However, it was generally tolerated and not spoken up against.
By academic credentials, Mullis was a 3rd rate scientist. Then he had that one brilliant invention. Then he went back to being almost a crackpot.
For comparison, the inventor of the fundamentals of the now famous mRNA vaccine technology, Katalin Karikó, was 2nd rate scientist by academic credentials. Could not get tenured permanent position, but was able to stay employed in the normal workforce at a university.
Of course, by scientific importance they are both first rate scientists, because of their important inventions.
I recall a quote by an introspective and humble Nobel winner (I think it was one of the guys who discovered/verified the cosmic microwave background radiation) that was basically "They don't give Nobels for being the best scientist, they give it for the most important discoveries." He was basically saying he happened to be at the right place at the right time (working on a team that had access to the proper telescopes), and that he was no Einstein.
The fact that Mullis made a huge discovery and is also a third rate scientist and crackpot are not mutually exclusive.
If he was a third rate chemists there's no way he would invent PCR, even if it seems obvious after the fact and with current automation. He wasn't just at the right place at the right time; unless you want to credit it to aliens that he claims to have met.
amusingly, Mullis got high on LSD while at Berkeley, went to Golden Gate Park, and wrote a paper about universal time reversal that got published (single author!) in Nature. Boy, publishing was a lot easier then.
Thanks, I always have a hard time finding it. Ah- it's only a letter, not a full publication. To be honest I can't really tell if it's clever or stating the obvious (I'm a biologist/computer scientist).
Max Gergel, mentioned in passing here, wrote a delightfully insane memoir entitled “Excuse Me Sir, Would You Like To Buy A Kilo Of Isopropyl Bromide?” full of some pretty hair-raising stories:
The area where the Columbia Organic Chemicals Company was located was restored in 2007-2008. "A total of 1,436.40 tons of soil was removed and disposed of."
From the speech:
> There were no government regulators to stifle our fledgling efforts, and it was a golden age, but we didn’t notice it.
What an amazing speech blending personal and technical. I wish I could have heard him actually give this lecture (is there a video? I can't find it). And a great conclusion:
> In Berkeley it drizzles in the winter. Avocados ripen at odd times and the tree in Fred’s front yard was wet and sagging from a load of fruit. I was sagging as I walked out to my little silver Honda Civic, which never failed to start. Neither Fred, empty Becks bottles, nor the sweet smell of the dawn of the age of PCR could replace Jenny. I was lonesome.
I like his observation about unsupervised tinkering with dangerous chemicals as a childhood gateway into the sciences, but I don't know what to do with it. How do you _effectively_ convince your community that the gain in scientific curiosity is worth the small potential for disaster?
"The first successful experiment happened on December 16th. I remember the date. It was the birthday of Cynthia, my former wife from Kansas City, who had encouraged me to write fiction and bore us two fine sons. I had strayed from Cynthia eventually to spend two tumultuous years with Jennifer. When I was sad for any other reason, I would also grieve for Cynthia. There is a general place in your brain, I think, reserved for “melancholy of relationships past.” It grows and prospers as life progresses, forcing you finally, against your grain, to listen to country music."
I know, just glad I worked in a molecular biology lab after Taq was discovered. My lab experience was akin to his first hopes — put the reagents in, place it in the thermocycler, and pick it up the next morning.
you probably worked in a lab during the period where scientists, annoyed that PCR machines required purchase of licensed Taq, simply cloned and expressed their own and used it instead.
It’s the dark truth. Most scientists and doctors are basically frauds. They just memorize what the real scientists have figured out so far.