Texas cancer researcher was called ‘foolish’, then won the Nobel Prize (2018) | Hacker News Reader

Texas cancer researcher was called ‘foolish’, then won the Nobel Prize (2018)

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160 pointsnew_guy43 comments

In the very early 80s, as a middle-school student in the suburbs of Houston with a new Apple ][+, I attended a personal computing show downtown.

One of the booths was showing off a game, called "Killer T-Cell" if I remember correctly, based on some local university research. You'd move a little T-Cell around, through a changing pink maze of good tissue, to absorb & destroy any cancerous (purple?) cells that popped up.

It used hi-res mode but seemed to be played on a grid based on the Apple ][+'s low-res mode – and sometimes that mode flashed through as well. (I can't remember if that was a glitch or purposeful effect.) It was pretty crude in graphics and gameplay, but we bought it, for maybe $5 or $10, on a 5.25" floppy – moreso for the novelty and intellectual content than anything else.

Over 37 years ago, that game conveyed to me the idea that people probably get a lot of microcancers all the time, which are routinely cleaned up by the immune system's T-cells, and only become a problem when the immune system is finally overwhelmed or tricked.

Dr. Allison's Wikipedia page suggests he was at Houston's MD Anderson Cancer Center at that time, in his early 30s. I wonder if the game was motivated by his research... or even if he was the person who sold me that game.

The professor that created "Killer T-Cell" was Dr. Elton Stubblefield[1][2]. Both Dr. Elton Stubblefield and Dr. James Allison were at University of Texas MD Anderson Center in Houston.

[1] https://www.upi.com/Archives/1982/10/28/Beating-cancer-the-v...

[2] http://jplaffont.photoshelter.com/image/I0000BBbrdiNVlfI

Thank you! My searches had turned up nothing. (Was something like Lexis-Nexus needed to find that old UPI story?)

I'm not a scientist, medical researcher, nor even very knowledgeable about biology. However, as part of my work, we deal with some prominent medical research institutions.

Over visits and dinners I've got to talk with a few of their leading anti-cancer researchers. One thing that was explained to me was a researcher saying that current findings are pointing out that cancer would be better thought of as a "immune deficiency" disease, rather than anything else.

For something to be "cancerous", must meet two basic conditions: (a) It short circuits the genes in the cell which limit reproduction, cancers instead reprogram to reproduce continuously. (b) Are in stealth-mode to the bodies immune system.

Evidently, your body can detect "A" and self-contain those micro-tumors basically in cysts as it was explained. However when "A" and "B" combine, your body can't deal with it because it can't even see it.

This particular professors research involved genetically altering cancer cells so that they could again be visible to the bodies immune system and marked as "defective". Thus, the body could rid itself of the cancer naturally.

Yes, the microcancer idea is correct, however in most of these cases the cells also produce signals that notify the immune system that they have gone out of control, which then promptly kills them. It's also why patients that suffer from a specific type of skin cancer( can't recall the name) are usually HIV carriers while that type is very rare in the general population. So the cancers that we do see in the general population ( i.e. not immunosuppressed) are usually the ones the immune system can't deal with.

As some context, in 2001, a couple of scientists many might consider to be the closest to the "leaders of cancer research" wrote a seminal review in the journal Cell called as "hallmarks of cancer" where they set out to define 7 essential (or what they thought was essential) things that a tumor has to do to be defined as cancerous.

That list did not include any mention whatsoever of the immune system. IIRC the only mention of the immune system was in one sentence deep in the review where they just casually disregard it.

I was still in high school when this review came out so I probably can't say I would have thought differently but at least to me that review was indicative of the fairly myopic way research happens in general, even today. Imagine this - two of the leaders of the field who are supposed to fill out ten pages of all the things that could affect or be affected by a developing cancer, and it did not fathom to the that the immune system had something to do with it?

The more outrageous thing is its not unheard of that the immune system has a role to play. People had suspected a long time that even chemo therapy in general only works via the immune response. It's the level of insulation between immunologists and cancer biologists that was to blame. People just decided to stick to one gene or disease and really didn't want to give a shit about anything else happening in biology with serious thought. No wonder it has taken us so long!

And if you think Im being too harsh, a decade later in 2011 the same authors wrote an amended review to update their original. By now it had become obvious that the immune system presented both a formidable barrier at first and an essential ally in later steps for any cancer to be able to grow and thrive. Don't know about you, but that sounds like an essential "Hallmark" of cancer to me. But then of course lest we correct ourselves, the researchers just grouped the immune checkpoint as one of the several other "supplemental" hallmarks that were discovered since.

Being factually incorrect does not mean they made a mistake.

The correct response to every science idea is extreme skepticism without evidence. That’s not to say we should avoid gathering evidence, just that the default needs to be conservative.

The point though is that there _was_ evidence. They just didn't see it (at first) or chose to wittingly or unwittingly undermine it (a decade later).

Skepticism of results is one thing, but wilful pursuance of the "only way to approach things is the way I know of, every other way has to be proven beyond any other metric I would need for my own way to be considered" is another.

They can only respond to evidence they have.

This is the entire point of publishing research. It’s the people collecting evidence’s job to make it public. Especially if it’s groundbreaking.

And again, that’s using a position of authority to dismiss new evidence on speculation rather than facts or science. Good science exercises restraint in quickness to judge new evidence, allowing time for discovery to work as needed. The opinionated orthodoxy of science doesn’t contemplate a wait and see approach, because the scientific method takes a backseat to other concerns such as politics, pride, prestige, funding, and innumerable other unscientific motivations in opinionated science.

The problem is that the more established scientists can play politics and deny/reduce funding for the "crazy" idea.

There needs to be balance. I see people religiously hold to the orthodoxy of scientific knowledge rather than the scientific method. But there's also the case where established scientists are financially reliant on what the orthodoxy is as that's what their research is about.

The world is complicated and not intuitive and I'm aware there's a distinction between rejection and skepticism, but I feel that people err to rejection much too easily.

Some examples of the weirdness of the world: Quantum mechanics and the fact that it's possible to build a windpowered land vehicle that travels directly down wind faster than the wind.

Trying to find other examples, I've run across Boltzmann who committed suicide in 1906 likely due to all the pressure he faced trying to get people to accept the idea atoms exist.

"I see people religiously hold to the orthodoxy of scientific knowledge rather than the scientific method. "

this seems to be the real problem. a lot of people want to find the final solution for a problem and then close the case once and for all.

Edit: That need is probably why we have religions.

It's especially bad since sometimes you can combine orthodox science in novel ways to get a result that is seemingly ridiculous.

I remember there was a paper[1] where someone proved (mathematically mind) that you can change your position in curved space time by simply changing your internal configuration in a loop. By taking advantage that your center of mass behaves weirdly in curved space time.

Essentially, this would allow you to move in space without having to throw mass out via a thruster.

However, sadly, the displacement is too tiny to be practical.

[1] stackexchange which explains this and links the paper: https://physics.stackexchange.com/questions/46180/can-a-defo...

>The problem is that the more established scientists can play politics

One of my favorite examples of how religiously dogmatic scientists can be about existing theory is centered around the discovery of quasicrystals.

Daniel Shechtman won the Nobel prize for discovering a form of crystals that formed regular non-repeating patterns like Penrose tiles or the tiles used on some Mosques.

As evidence, he had electron microscope images of the materiel, very clearly proving the veracity of his discovery, yet double Nobel laureate Linus Pauling took particular pleasure in making his life a living hell, declaring that "there is no such thing as quasicrystals, only quasiscientists".

>In an interview this year with the Israeli newspaper, Haaretz, Shechtman said: "People just laughed at me." He recalled how Linus Pauling, a colossus of science and a double Nobel laureate, mounted a frightening "crusade" against him. After telling Shechtman to go back and read a crystallography textbook, the head of his research group asked him to leave for "bringing disgrace" on the team.

https://www.theguardian.com/science/2011/oct/05/nobel-prize-...

You would think that scientists would be willing to accept physical evidence even if it isn't covered by existing theory, but sadly, they are perfectly willing to reject it.

I think we need to separate cases with actual evidence like what you are describing from default behavior. With a little evidence you can defend spending a little more resources studying the same thing. Over time that feedback loop works to both efficiently spend money and change orthodoxy.

That’s different from saying X seems likely based on gut feeling or whatever. In the case with zero evidence the goal is to find the cheapest way to gather any support and this initial effort is generally cheap enough to self fund. If not, looking for funding outside of normal channels is a viable option.

That proof of concept stage is something of a road block, but less so than generally portrayed.

This is particularly interesting because Pauling has been widely panned for his advocacy of high-dose Vitamin C usage.

Many of the great scientists I respect seem to have this dynamic. They challenge existing scientific authorities, only to succeed and become the scientific authority that limits other challengers.

I think it would be great if there were several parallel and in some sense competing science systems.

Like if Chinese science grew to be an independent force with its own standards and systems. Or if the Gates Foundation and other high spending billionaires managed to build up a parallel eco system that could give brilliant misfits a seconds chance.

My PI did this work in Jim Allison's lab. They published in 1996 showing they could shrink tumors with CTLA4 blockade; this went on to become the drug Yervoy, the first successful immunotherapy.

For years people in cancer ignored this work until just a few years ago when it became clear the previous hoped for cure (tyrosine kinase inhibitors) were a bust. Then, suddenly, it became all anyone cared about.

This wasnt because there was no evidence it was important. We knew it was important, we knew we had to study the tumor microenvironment to understand the disease fully. The reason we didnt was because people thought they had a better idea (targeting therapy based on tumor genetics) and no one wanted to miss the gold rush in order to do the painstaking work required to learn all the immune biology.

Lots of understanding about how to prevent and cure cancer is ignored and is based on strengthening the immune system and giving it the building blocks it needs to do its job (or avoiding poisons that make it harder for the immune system to work). Maybe some of it is just too cheap and easy -- and yet also expensive and difficult in the sense that it involves a radical change to culture and lifestyle?

See, for example: "We Can Win the War on Cancer - Right Now - with Author Joel Fuhrman" https://www.youtube.com/watch?v=-qOKsPkfIWw "The underlying theme of this presentation today is that the diseases that afflict Americans are unnatural. They're not the result of genetics [or] predominantly from aging -- in other words cancer, heart attacks, strokes, [and] dementia don't have to happen and they shouldn't [happen] if we live in .. the way [our] bodies have been made and [are] biologically designed -- if we live a natural life [and] consume the nutrients humans require to be normal. Being normal means no cancer. ..."

As just one example, he explains how animal products, especially dairy, raise IGF-1 which contributes to cancer, and a white-bread bagel drives insulin levels high which also contributes to cancer -- with both driving normally useful hormones into cancer causing ranges. How many oncologists probably still eat bagels and have dairy?

There are some funny animations about this in "Fat Sick & Nearly Dead 2". https://www.youtube.com/watch?v=UDeTKomY4P8

Here is one of those animations on the immune system needing enough good food to do its job: "Understanding The Root Cause of Chronic Illnesses" https://www.youtube.com/watch?v=OlDPzdTciM8

(Ironic to see this modded down within minutes...)

A heathy lifestyle can reduce the rate of cancer, but not eliminate it.

Animals got cancer hundreds of millions of years ago. Long before any of our modern toxic lifestyle. https://www.nationalgeographic.com/science/2019/02/ridiculou...

Note, most types of cancer would not show up in the fossil record becase they don’t obviously impact bones. But, even still there are plenty of known examples of prehistoric cancer.

So what? The immune system in a healthy person can eliminate most cancer. That's part of what it does. The problem is most people are not healthy -- in terms of eating a healthy diet similar to what Dr. Joel Fuhrman outlines as well as other healthy lifestyle aspects (lower stress, avoiding toxins, periodic calories restriction even if just eating dinner earlier, etc.). Healthy nutrition eliminates most cancer through boosting the immune system and also by avoiding mutagens. If we get rid of, say, 90%+ of cancer, that is a tremendous win even if there is still 10% to be dealt with. That is a far bigger win than most experimental therapies overall are promising.

As just one example from the video, over the course of 30 years, Korean women's rate of breast cancer went up 500% by eating less vegetables and eating more animal products, oils, and sugar. While correlation is not causation, and there are other complicating factors like younger Korean women having children later in life, and they are getting less sleep from using computers more (sleep also helps prevent cancer https://www.businessinsider.com/what-happens-when-you-dont-g... ), when you consider the basic nutritional science and many other studies, is a very clear example of dose-response in the Western diet causing cancer. Reverse that process, and return to a diet with more vegetables (and get more sleep), and presumably about 80% of breast cancer in Korea will go away. That would be a big win for Korean women. And not only would breast cancer rates go down, all cancer rates would go down. And so would rates of other lifestyle disease like heart disease, dementia, and diabetes.

And in any case, even if we had a magic bullet that eliminated 100% of cancer after you got it like so many researchers are pursuing using billions of dollars of research funds (so the result can be patented and profitized) -- that magic bullet would still not prevent diabetes, heart disease, and dementia which are also primarily consequences of Western diet and lifestyle. Nor would that magic bullet make most people feel tremendously better the way a healthier diet and lifestyle can.

As priorities go, we are almost totally ignoring the low hanging fruit of promoting healthy diet and health lifestyle in all sorts of ways that will prevent most of this suffering. For a community level intervention on all this, see the book "BlueZones" and related web site ( https://www.bluezones.com/services/blue-zones-project/ ).

"Health" insurance will pay $50,000 for a heart bypass but it will pay $0 for the vegetables that would prevent or even reverse heart disease. Likewise, health insurance will pay $100,000 for oncology drugs for cancer but $0 for the vegetables that will prevent it. As health priorities go, that is insane.

And insane national health priorities make it harder for those individuals who want to eat healthier and live healthier -- because there is less community-level social support and less supportive infrastructure (sidewalks, walking trails, nearby groceries with fresh produce, restaurants with healthier menus, employee wellness plans, nutritious school lunches, and so on.)

As one more example of how this is a broader social problem, the subsidies the USA gives to agribusiness are completed inverted compared to what humans need to stay healthy: http://www.nbcnews.com/id/8904252/ns/health-fitness/t/farm-s... "The government will spend $17 billion subsidizing farmers this year. Rather than focusing on the producers of good-for-you fruits and vegetables — half its subsidies go to grain farmers, whose crops feed animals for meat, milk and eggs and become cheap ingredients in processed food."

I think you are missing the point of that paper. It doesn't sound like it was some forward looking paper but rather an effort to put what we already knew into words. Since then a big row of antibody treatments have entered the market with big success, which in turn means that our current understanding of cancer has evolved. The idea of the immune system playing a big role was not proven back then.

This stuff matters. I was fortunate enough to join a [trial](https://www.clinicaltrials.gov/ct2/show/NCT00636168) for Yervoy the summer before it was approved by the FDA. Based on my reading of the outcomes, there's a 1-in-4 chance that I'd be dead if I hadn't gotten the drug through that trial. (It was initially double-blind but has since been unblinded, so I know I was dosed with it.)

I wonder if there are Nobel prize winners that were never called foolish.

Yeah that's why I hate headlines like this. It's so easy for modern writers to find that validating tweet or comment to present the narrative that supports their article. Was 'foolish' a consensus? I'm willing to bet that an equally factual headline would be "Researcher called 'genius' then won Nobel Prize"

It reminds me of the "sounds like a bad idea" / "is a good idea" Venn diagram for startups.

If it sounded like a good idea and was a good idea, then a bunch of people would have already tried it. There would be steady progress by many people, and steady competition. There would be no "breakthrough" by a single person / company.

If it sounded like a bad idea and was a bad idea, then either nobody tried it, or a contrarian tried it and quietly failed.

At least there are a lot of fools who never won a Nobel prize.

This reminds me of a book called The Power of Starting Something Stupid, by Richie Norton. The book tells several stories just like this one, where it seems like peers or others are criticizing your work as “stupid” but you get it done anyways because you know it is worthwhile, then finally the world rewards you handsomely for it.

Nothing new. Read the about paradigm shift. You cannot work if you doubt every library you used may be hacked (or your assumption or idea is wrong about field X). Even if it is wrong obviously eg black body radiation you still continue. What one should know how it is not if but when the library was hacked (or your assumption is wrong), ...

https://outline.com/D2GuNJ

Relevant: https://slatestarcodex.com/2019/02/26/rule-genius-in-not-out...

tl;dr

The kinds of ideas that people who innovate come up with are found at the extremes of convention, and are not distinguishable from crazy whether they are right or wrong, and

You should expect an innovator to produce dumb ideas all the time. In other words, forgive the smart, for they know not when they dumb.

Edit: this is also why we can be justified praising Elon Musk for SpaceX and, to a lesser extent Tesla, and also ignore complete and utter nonsense like Hyperloop and his cave submarine.

Tyranny of success..

I think this lends credence to the Thiel/Eric Weinstein notion of allowing scientists and innovators to be irreverent because many new discoveries have to run against the grain. I've heard Weinstein postulate one of the great strengths of Western education is the fostering of such irreverence.

I've heard physicist Michio Kaku say something similar, that western thought historically has rewarded the mavericks but that eastern thought has tended towards a "the tallest blade of grass is cut down first" mentality. I think it was him who said that had Bill Gates been born in China, his peers would have made his success very unlikely.

This is simply historically false. From Galileo and copernicus to even the scientists positing germ theory in the 1800s, mavericks who fought against orthodoxy have been persecuted. Even today, in our colleges, "mavericks" are punished and attacked. Our most famous maverick, Socrates, was forced to commit suicide.

It's true bill gates wouldn't have amounted to much had he been born in 1950s china because china was heavily undeveloped. But had he been born later in the 60s or 70s with china opening up, he could have been a Jack Ma.

Full Title: A Texas scientist was called ‘foolish’ for arguing the immune system could fight cancer. Then he won the Nobel Prize.

It got a little mangled with the length constraint.

And in-between the critiques of his idea and the prize winning, Allison actually showed evidence that checkpoint blockade worked. That's what kind of annoys me about stories that describe science in these terms. It's as if the authors want the reader to take away the moral "Don't criticize scientists with seemingly crazy ideas; they might be right!". But criticizing crazy ideas up until the point where they are shown not to be crazy is exactly how science works.

True, but it is also important to be aware of the hand-wavy hubris/entrenched viewpoints that might prevent those ideas from having the chance to prove themselves right. “Science proceeds one funeral at a time”

It’s a fundamental tension in the scientific method. We create models for how reality works. We _know_ that they are imperfect and incomplete, but at times we forget and therefore treat an idea or even observation that violates the model as “impossible”.

Multiple observations ultimately dispel this failure but single observations are easy to dismiss. This is also why crazy but ultimately correct ideas are difficult to distinguish from crazy and wrong ideas.

And academics spend a lot of time teaching people to understand the models, and are always looking for errors that arise from an incomplete or incorrect understanding of the models. So, it is very natural to treat new theories that violate an incomplete model the same way. Especially in fields like medicine where it is nearly impossible to truly isolate single factors and outcomes.

True, though there is a difference between criticizing by saying "you have a logical mistake here and wrong data here", and saying "you are a fool, this will never work". Even to a crazy idea.

No idea is above scrutiny. Ridicule is mostly harmful.

I agree with the first part. "You are a fool!" is not scrutiny.

Edit: sorry, I read it wrong. I agree with the second part too

Is that really the moral? I am more of the opinion that we're just suckers for an underdog.

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