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Comment by koolba | Hacker News Reader

> That is an especially pressing challenge in the development of new antibiotics, because a lack of economic incentives has caused pharmaceutical companies to pull back from the search for badly needed treatments. Each year in the U.S., drug-resistant bacteria and fungi cause more than 2.8 million infections and 35,000 deaths, with more than a third of fatalities attributable to C. diff, according to the the Centers for Disease Control and Prevention.

How big does the market have to be to commercially viable for research and development? Nearly 3M potential patients at a couple hundred dollars per course is nearing a $1B/year.

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At least one disincentive is that if you do find an amazing new antibiotic effective against certain strains of antibiotic resistant bacteria, antibiotic stewardship means the medical community will try and use it only where necessary to slow any adaptation to the new drug. That makes your potential patient population much smaller.

If we develop new ways to invent anti-biotics, such that we have a reasonable expectation of new ones being produced yearly, then maybe anti-biotic stewardship will become less important.

Yeah, this seems game theoretically problematic. We clearly want a deep warchest of antibiotics, but new antibiotics won't sell in any meaningful quantity likely, or even hopefully, until after their IP rights expire. I don't see how you make money here.

Maybe the government should structure some new incentives for stocking the antibiotic warchest.

Here's an interesting thought. Let's say that the number of possible antibiotics that can be discovered is so high that bacteria cannot simultaneously be resistant to all of them (plant immune systems, which involve a lot of small moleculea, indicate that this may be possible). Then, this game theory trap where stewards are guarding what we have so that pharma doesn't want to make anything new is both pointless and self-perpeuating, because we will never reach the point where we realize we've beaten resistance.

The second-order costs avoided by treatments developed so innovatingly could be included in a "value to society" estimation.

"Acknowledgements" lists the grant funders for this federally-funded open access study.

"A Deep Learning Approach to Antibiotic Discovery" (2020) https://doi.org/10.1016/j.cell.2020.01.021

> Mutant generation

> Chemprop code is available at: https://github.com/swansonk14/chemprop

> Message Passing Neural Networks for Molecule Property Prediction

> A web-based version of the antibiotic prediction model described herein is available at: http://chemprop.csail.mit.edu/

> This website can be used to predict molecular properties using a Message Passing Neural Network (MPNN). In order to make predictions, an MPNN first needs to be trained on a dataset containing molecules along with known property values for each molecule. Once the MPNN is trained, it can be used to predict those same properties on any new molecules.

The issue is that no pharma company wants to make drugs that will be carefully stewarded as last lines of defense vs super bugs. You won't see 3M patients per year because every hospital system worth its salt has antimicrobial stewardship programs which will interrogate every case of antibiotic use. Doctors are trained and pushed into using these drugs as infrequently as possible because they all know Darwinian selective pressure will render antibiotics less useful the more they're used.

But it's a different story in developing nations with lower standards, where they will steal your IP and bombard the microbial population with every antibiotic they can.

Furthermore, agriculture will surely love to grab new compounds to blanket their herds with. They will not give pharma great profits either, and they'll increase resistance to your fancy new drug that you spent billions developing.

So overall, it's a grim financial picture for pharma and antibiotics. They would prefer to make cancer drugs, chronic disease drugs, biologics, and not these carefully stewarded and easily ripped off antibiotics. IMO, antibiotics will come from altruistic scientists working on their own, and not from the CFOs and bottom lines of pharma.

A couple of good recent article to understand this complex problem (USA perspective): https://endpts.com/can-we-make-the-antibiotic-market-great-a... and https://endpts.com/biopharma-has-abandoned-antibiotic-develo...

Reasons are mainly: No incentive to develop antibiotics from a legal perspective (FDA), as insurance companies prefer to reimburse the cheap and generic, still working mostly "well enough" for now.

Insurers pay for in-patient antibiotics as part of a lump sum to hospitals known as a Diagnosis Related Group (DRG). Using a cheap antibiotic increases hospital profit margins, while using an expensive new drug could mean that a hospital might lose money by treating a given patient. As a result, hospitals are incentivized to use cheaper antibiotics whenever possible. This puts significant pricing pressure on new antibiotics, which are one of the only type of medicines paid for like this.

Here is a prior HN submission that talks about the economics of new drug development for rare diseases:

https://news.ycombinator.com/item?id=19787367

tl;dr: a hypothetical drug with an expected profit of $547 million, adjusted for discounting and risk, has an expected value of negative $6 million.

In terms of your numbers, 2.8M is all drug resistant infections - even the best drug would only work for a fraction of those..

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