Weekend Reading & Selected Links
Happy weekend! Here are some links to things I've been reading or watching that you might also enjoy:
1. My new podcast conversation with Katalin Karikó. She is one of the inventors of mRNA technology and likely to win a Nobel prize in the next several years. This was her first properly longform podcast interview. (Some of my favourite excerpts at the bottom of this email.)
2. 'Shamir Secret Sharing', the story of a catastrophic software bug that Max Levchin briefly introduced into the PayPal codebase "that almost cost [them] the company".
3. Howard Maclean Twitter thread on spatial thinking in Australian policy-making.
4. 'Donald Horne, citizen intellectual', Frank Bongiorno reviews Ryan Cropp's new biography of Horne.
5. 'Democratic Backsliding in the World’s Largest Democracy', a recent paper by Sabyasachi Das.
6. 'Sydney's Millennial Exodus', a new research note by Elyse Dwyer of e61.
7. The story of Gödel's US citizenship examination.
8. 'Rand and Oppenheimer: The Atomic Bomb Movie that Wasn’t'.
9. 'A Room-Temperature Superconductor? New Developments'. In case you missed the possible news.
10. The Day After Trinity, reels of the 1981 documentary.
11. 'Surname Diversity, Social Ties and Innovation', a new paper by Max Posch, Jonathan Schulz, and former guest of the pod Joseph Henrich.
Have a great weekend,
Joe
Excerpts from my podcast with Katalin Karikó
1. On why the funding of biosciences is broken
WALKER: I guess this is more of a historical or sociological question about the community of researchers, but something that's been puzzling me is, if we go back to that central dogma of molecular biology — DNA makes RNA makes protein —, you've essentially got three kind of playgrounds there to experiment with for therapeutics. Although I'm sure that's simplifying it, because it's not as if the opportunities within each of those three are necessarily equal. But it's fair to say that at least one of the big playgrounds is RNA.
Moreover, there's something very intuitive about using mRNA to develop vaccines because conceptually it's almost like the mirror image of how a virus works, because the virus hijacks cells using mRNA and then replicates.
And so I get that the immune response problem seemed really difficult, maybe intractable. But the history of science is just filled with problems that seemed intractable. And so maybe there was only like a really small chance of solving that problem. But given that the payoff was so large, the positive benefits that could come from it were so large, surely in expected value terms (if you multiply that very small probability by the massive positive benefit), it was still worth dedicating a lot of research to.
So what's the answer here? Why were people so dismissive, so sceptical? Was it that academia and the funding system distorted the incentives of other scientists? Or did RNA just genuinely seem like a delusional thing to be working on? Why were people so sceptical? I don't understand.
KARIKÓ: I have to say, Joe, that recently there have been more papers about me than I have ever published. And they are trying to identify why I never got the money, why [funding bodies] didn't give this proposal money.
One interesting thing was published about that. There is a “centre” where the money, the fame, is; most likely your proposal gets funded because it’s on the most favourable topic. Maybe today, RNA is [most favourable]. If you are working with mRNA, maybe that's the centre there.
And then there are people in the periphery. There is no fame, there is no money, no nothing there. The only thing in the periphery is freedom. You can do what you like to do, what you feel is important.
Here’s what a proposal is: why they should give me money. And they should question that. “She came from university nobody knew about.” “She never had a mentor who was famous.”
And somehow it gravitates always to the same people, same circle. They get published there, they get the money. And that's another explanation: I was not famous enough or didn't have anybody who would support me in a way that somebody that’s a famous and well-established scientist stands behind you and says, “Oh, look at this, it’s good.”
You know, our [2005] paper had to be discovered by scientists at Harvard. In 2011, they published. That's when people started to pay attention — when they used it to generate induced pluripotent cells, stem cells.
2. More on science funding
WALKER: Have you ever calculated what percentage of your grant applications were successful?
KARIKÓ: No. It has to be zero point zero something, because I had one grant when we established the company after our discoveries. The first grant we submitted was for a small business grant to the US government, NIH. Then we received that grant. That was the only time I was PI on a grant.
3. On selling her car on the black market to emigrate from Soviet-era Hungary to the US with her husband and young daughter
KARIKÓ: We had a Russian car, which we could sell officially. We just had to change the money from the black market because there were students from Arabic countries that I could exchange with. Actually, he didn't have dollars, he had pounds. And so I exchanged and we get something — 1,000 dollars; 800 pounds. It was like $1,200 equivalent. In Hungary, the Hungarian currency was not convertible and you couldn't go and purchase freely from your foreign Hungarian currency to dollars. And if somebody would give you money, foreign currency, like a dollar, you had to go to the bank and give it to them and they will give you whatever Hungarian currency. You are not allowed to have [foreign currency]. It was against the law. But we have to live somehow. And so this $1,000 was like a lot of money.
Later it turned out that we had to hide it in Susan’s teddy bear, because it was smuggled. She smuggled it out.
WALKER: We can blame Susan.
KARIKÓ: Yeah, Susan smuggled the money. Other Hungarians also send me letters and emails that say: “Where did they hide?” Everybody had to come out with some extra money. You just cannot come with a family to America with $100.
WALKER: Yeah. So did you sew it into the teddy bear?
KARIKÓ: So I put it in, I wrapped it up and then I stitched it back. And then we watched her at the airport to make sure...
WALKER: "Don't let go of that bear!"
KARIKÓ: "Don't leave that bear there.”
WALKER: Did she know the money was in it or was she too young?
KARIKÓ: No, she was two and a half years old.