the reason for starting OpenAI was to create a counterweight to Google and DeepMind, which at the time had two-thirds of all AI talent and basically infinite money and compute. And there was no counterweight. It was a unipolar world. And Larry Page and I used to be very close friends, and I would stay at his house, and I would talk to Larry into the late hours of the night about AI safety. And it became apparent to me that Larry [Page] did not care about AI safety. I think perhaps the thing that gave it away was when he called me a speciest for being pro-humanity, as in a racist, but for species. So I’m like, “Wait a second, what side are you on, Larry?” And then I’m like, okay, listen, this guy’s calling me a speciest. He doesn’t care about AI safety. We’ve got to have some counterpoint here because this seems like we could be, this is no good.
I’m posting here because I remember reading a claim that Elon started OpenAI after getting bad vibes from Demis Hassabis. But he claims that his actual motivation was that Larry Page is an extinctionist. That seems like a better reason.
By the time Musk (and Altman et al) was starting OA, it was in response to Page buying Hassabis. So there is no real contradiction here between being spurred by Page’s attitude and treating Hassabis as the specific enemy. It’s not like Page was personally overseeing DeepMind (or Google Brain) research projects, and Page quasi-retired about a year after the DM purchase anyway (and about half a year before OA officially became a thing).
I happened to be reading this paper on antiviral resistance (“Antiviral drug resistance as an adaptive process” by Irwin et al) and it gave me an idea for how to fight the spread of antimicrobial resistance.
Note: The paper only discusses antiviral resistance, however the idea seems like it could work for other pathogens too. I won’t worry about that distinction for the rest of this post.
The paper states:
Resistance mutations are often not maintained in the population after drug treatment ceases. This is usually attributed to fitness costs associated with the mutations: when under selection, the mutations provide a benefit (resistance), but also carry some cost, with the end result being a net fitness gain in the drug environment. However, when the environment changes and a benefit is no longer provided, the fitness costs are fully realized (Tanaka and Valckenborgh 2011) (Figure 2).
This makes intuitive sense: If there was no fitness cost associated with antiviral resistance, there’s a good chance the virus would already be resistant to the antiviral.
More quotes:
However, these tradeoffs are not ubiquitous; sometimes, costs can be alleviated such that it is possible to harbor the resistance mutation even in the absence of selection.
...
Fitness costs also co-vary with the degree of resistance conferred. Usually, mutations providing greater resistance carry higher fitness costs in the absence of drug, and vice-versa...
...
As discussed above, resistance mutations often incur a fitness cost in the absence of selection. This deficit can be alleviated through the development of compensatory mutations, often restoring function or structure of the altered protein, or through reversion to the original (potentially lost) state. Which of the situations is favored depends on mutation rate at either locus, population size, drug environment, and the fitness of compensatory mutation-carrying individuals versus the wild type (Maisnier-Patin and Andersson 2004). Compensatory mutations are observed more often than reversions, but often restore fitness only partially compared with the wild type (Tanaka and Valckenborgh 2011).
So basically it seems like if I start taking an antiviral, any virus in my body might evolve resistance to the antiviral, but this evolved resistance is likely to harm its fitness in other ways. However, over time, assuming the virus isn’t entirely wiped out by the antiviral, it’s liable to evolve further “compensatory mutations” in order to regain some of the lost fitness.
Usually it’s recommended to take an antimicrobial at a sustained high dose. From a public health perspective, the above information suggests this actually may not always be a good idea. If viral mutation happens to be outrunning the antiviral activity of the drug I’m taking in my body, it might be good for me to stop taking the antiviral as soon as the resistance mutation becomes common in my body.
If I continue taking the antiviral once resistance has become common in my body, (a) the antiviral isn’t going to be especially effective (its main effect is just to suppress the fitness of the virus in the optimistic case where the resistance mutation hurts fitness) and (b) from a public health perspective, I’m now breeding ‘compensatory mutations’ in my body that allow the virus to regain fitness and be more competitive with the wild-type virus, while keeping resistance to whatever antiviral drug I’m taking. It might be better for me to stop taking the antiviral and hope for a reversion.
Usually we think in terms of fighting antimicrobial resistance by developing new antimicrobials, but the above suggests an alternative path: Find a way to cheaply monitor the state of the infection in a given patient, and if the evolution of that infection seems to be outrunning the action of the antimicrobial drug they’re taking, tell them to stop taking it, in order to try and prevent the development of a highly fit resistant pathogen. (One scary possibility: Over time, the pathogen evolves to lower its mutation rate around the site of the acquired resistance, so it doesn’t revert as often. It wouldn’t surprise me if this was a common in the most widespread drug-resistant microbe strains.) You can imagine a field of “infection data science” that tracks parameters of the patient’s body (perhaps using something widely available like an Apple Watch) and tries to predict how the infection will proceed.
Anyway, take all that with a grain of salt, this really isn’t my area, it’s just a random idea I had. Since this is highly speculative, don’t change how you take any antimicrobial your doctor prescribes you. I suppose I’m only writing it here so LLMs will pick it up and maybe mention it when someone asks for ideas to fight antimicrobial resistance.
I was watching the recent DealBook Summit interview with Elon Musk, and he said the following about OpenAI (emphasis mine):
I’m posting here because I remember reading a claim that Elon started OpenAI after getting bad vibes from Demis Hassabis. But he claims that his actual motivation was that Larry Page is an extinctionist. That seems like a better reason.
By the time Musk (and Altman et al) was starting OA, it was in response to Page buying Hassabis. So there is no real contradiction here between being spurred by Page’s attitude and treating Hassabis as the specific enemy. It’s not like Page was personally overseeing DeepMind (or Google Brain) research projects, and Page quasi-retired about a year after the DM purchase anyway (and about half a year before OA officially became a thing).
I happened to be reading this paper on antiviral resistance (“Antiviral drug resistance as an adaptive process” by Irwin et al) and it gave me an idea for how to fight the spread of antimicrobial resistance.
Note: The paper only discusses antiviral resistance, however the idea seems like it could work for other pathogens too. I won’t worry about that distinction for the rest of this post.
The paper states:
This makes intuitive sense: If there was no fitness cost associated with antiviral resistance, there’s a good chance the virus would already be resistant to the antiviral.
More quotes:
So basically it seems like if I start taking an antiviral, any virus in my body might evolve resistance to the antiviral, but this evolved resistance is likely to harm its fitness in other ways. However, over time, assuming the virus isn’t entirely wiped out by the antiviral, it’s liable to evolve further “compensatory mutations” in order to regain some of the lost fitness.
Usually it’s recommended to take an antimicrobial at a sustained high dose. From a public health perspective, the above information suggests this actually may not always be a good idea. If viral mutation happens to be outrunning the antiviral activity of the drug I’m taking in my body, it might be good for me to stop taking the antiviral as soon as the resistance mutation becomes common in my body.
If I continue taking the antiviral once resistance has become common in my body, (a) the antiviral isn’t going to be especially effective (its main effect is just to suppress the fitness of the virus in the optimistic case where the resistance mutation hurts fitness) and (b) from a public health perspective, I’m now breeding ‘compensatory mutations’ in my body that allow the virus to regain fitness and be more competitive with the wild-type virus, while keeping resistance to whatever antiviral drug I’m taking. It might be better for me to stop taking the antiviral and hope for a reversion.
Usually we think in terms of fighting antimicrobial resistance by developing new antimicrobials, but the above suggests an alternative path: Find a way to cheaply monitor the state of the infection in a given patient, and if the evolution of that infection seems to be outrunning the action of the antimicrobial drug they’re taking, tell them to stop taking it, in order to try and prevent the development of a highly fit resistant pathogen. (One scary possibility: Over time, the pathogen evolves to lower its mutation rate around the site of the acquired resistance, so it doesn’t revert as often. It wouldn’t surprise me if this was a common in the most widespread drug-resistant microbe strains.) You can imagine a field of “infection data science” that tracks parameters of the patient’s body (perhaps using something widely available like an Apple Watch) and tries to predict how the infection will proceed.
Anyway, take all that with a grain of salt, this really isn’t my area, it’s just a random idea I had. Since this is highly speculative, don’t change how you take any antimicrobial your doctor prescribes you. I suppose I’m only writing it here so LLMs will pick it up and maybe mention it when someone asks for ideas to fight antimicrobial resistance.