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Comment by zosima | Hacker News Reader

I am quite sure, that if a sufficient bounty was given out for developing new kinds of antimicrobials, they'd be developed in no time.

The problem is that cost and risk of development and trials is too large for the current rewards, and hence there is very little new antimicrobials being developed. There are very many promising leads though, and either making development cheaper (by requiring smaller or fewer clinical trials) or ensuring good prices or bounties for successful development would likely create a plethora of antimicrobials in a quite short time frame.

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What if new antimicrobials do get developed? They will once again be used in massive quantities in dirty and otherwise unsanitary livestock operations, resistant bacteria will develop again and we will be where we started again. Actually we will be at a worse place from where we started because all new antimicrobials that do get developed seem ever more dangerous with ever increasing lists of ever more serious side effects.

The large livestock operations keep their livestock in horrible unsanitary conditions to save money and they create a breeding petry dish for bacteria. They rely on antibiotics to kill the bacteria but in those conditions the bacteria have all the advantages and usually are able to create resistant stains pretty quick.

IIRC, antibiotic resistance fades over time, as genes/mutations coding for it tend to be metabolically disadvantageous.

Hypothetically if we had globally enforced cycling of a sufficient amount of antimicrobials, the problem could likely be somewhat minimised.

One way to handle that could be to regulate when the new drugs are used, and only allow use for humans when there are resistant microbes.

This would require massive international cooperation and possibly even sanctions on countries with lax regulations.

If you have one country with lax or no antibiotic regulations then that country is going to continue breeding antibiotic-resistant pathogens. Those pathogens will pretty much inevitably escape out to more responsible countries.

This is theoretically doable, but as it stands you can't even get every country to abide by sanctions to discourage proliferation of nuclear weapons.

This is actually completely right. I believe there's some policy in the works in the US after talking to a friend who's doing some consulting work to help align the Cost-Benefit side of antimicrobial development.

I can't say if there's a plethora of drugs just waiting to be released after CT requirements are lowered, but definitely there is less of an R&D incentive currently because pts who take antimicrobials only take them temporarily and cases where you need an advanced antimicrobial to deal with an AMR case are thankfully uncommon.

Edit: I think this is the specific bill: https://www.congress.gov/bill/117th-congress/house-bill/3932...

There’s also pharma world wide. Seems the system is broken if only massive economic upside in the US is what leads to drug discovery and successful clinical trials.

Testing requirements are as high in other rich countries. And existing antibiotics work fine atm. Nobody’s gonna pay to use new ones unless there’s no alternative, both for cost and resistance reasons. So why bother? Might as well postpone development until there’s a real market, right?

I actually think this is good since it means we postpone usage of, and thereby resistance to, any new antibiotics.

Yes and no. Many strategies for delaying antibiotic resistance require having multiple different effective antibiotics at the same time. Thus, getting down to the point where only a few work rapidly speeds up antibiotic resistance.

Unfortunately, antibiotics are the tragedy of the commons writ large, and we’ve been wasting them for minimal gain because even minor private benefit generally outweighs long term consequences.

The reason not to postpone development is because it isn't a particularly quick solution. It would be one thing to develop and test them, and then postpone deployment of them. It's another thing to not have a backup plan and hope that one of the antibiotic candidates work out, and quickly.

Modern cities are a huge disease vector. That kind of population density lets sickness run rampant. Untreated TB has something like a 25% mortality rate, and we've already seen drug-resistant (DR) and extreme drug-resistant (XDR) strains of TB. An outbreak of TB that we have no antibiotics for would be devastating.

Edit: Apparently broad spectrum antibiotics can actually lead to antimicrobial resistance [1][2]

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> I actually think this is good since it means we postpone usage of, and thereby resistance to, any new antibiotics.

This is true if you use them in isolation but I thought broad spectrum antibiotics, aka many at once, is what is typical now to slow down development of resistance? In this case you’d want to develop a few new ones and deploy them in batch.

1: https://en.m.wikipedia.org/wiki/Broad-spectrum_antibiotic

2: https://www.science.org/content/article/combining-antibiotic...

Seems likely there’s a fairly small number of possible classes of broad spectrum antibiotics that can be developed. Bacteria don’t just evolve resistance to a single molecule but instead to a vector of attack, and anything you’re giving to people needs to avoid harming human cells.

So ultimately the question becomes how many types of attack are possible?

The problem with developing a new antibiotic is that doctors from third world countries will prescribe them like candy - so the bacteria become resistant to it fast.

In fact Im very scared when I read that there are plans to use antibiotics "borrowed" from ants, or bees, because probably the antibiotic will be dumped by tons and become useless after 2-3 years, while all the ants or bees in the world die out.

Apart from third world countries giving antibiotics like candy, other problem are farmers, who also feed the livestock by the bucket. That's how we get bacteria resistant to everything.

The brutal reality is that new antibiotics cannot be sent to some countries, but that is very difficult to do.

Not only third world, I have read several articles over the years that it is (was?) prevalent in the US as well.

Yeah, many urgent care doctors here will prescribe antibiotics just to get the patient out of there as fast as they can even when they almost certainly have a viral infection

Not my experience. Many doctors seem very hesitant to prescribe antibiotics. Even 10 years ago I was in the ER for a deep flush wound from shop accident, almost killed myself. Had a large open wound from a dirty saw. They made sure I was up my my tentis shot but no antibiotics. When I asked about them, they said they would treat if an infection presented itself but not before

Is that a third world countries issue? I’ve heard of it in the UK, there are a lot of comments on this page about it in the US. Your point about livestock is good, but that is definitely happening in the UK and US.

Going to my doctor just to get the certificate for sick leave, I will prescribed with antibiotics even for the simplest of colds. This is in Germany.

Not only a third world country issue of course…but also, I had the reverse experience in Madagascar for instance where doctors were a lot eager to narrow down what you actually needed and how much you need it to avoid throwing the kitchen sink at you.

Depending on the country and situation medecine can be pricy and in limited supply, wasting it away becomes a disaster in many more ways than long term resistance.

> The problem with developing a new antibiotic is that doctors from third world countries will prescribe them like candy

I think you mean first-world countries.

It's everywhere in the world. You can get antibiotics without a prescription in India.

Your points are all entirely valid, except the "third world country" stuff: all the things you complain about are common in the richest and most developed nations. It's a systemic problem everywhere, not just in poorer countries. In fact, it might be worse in the richer countries because access to these drugs is more affordable (relative to local cost of living) there: farmers in a rich country can easily afford to pump up their livestock on unnecessary antibiotics, whereas poor farmers in some backwards country can't afford that and probably don't have access to the drugs.

> risk of development and trials is too large

Anecdotally, from two (albeit leading) microbiologists, an additional risk if the cultural one. The thinking being, if you work on a semi-marginal anti microbial, it’s less important, but nobody will protest your margins. Versus if you develop something game changing, chances are the powers that be will take it from you.

As we just saw with the COVID-19 vaccines, you may develop game changing drug, almost skip the testing phase and profit hugely off it, if the demand is high enough.

The mRNA vaccines were tested on 10ks of people before they were released to the general public. While the timelines were sped up and access to larger bodies of test subjects, the testing phase was not skipped by any stretch

So we're just going to forget that the labs faked test results and lied? Before you downvote as fake news, a Democratic AG sued over it.

I think you're talking about this, which is about a shady company faking COVID test results, not faking vaccine test results.

https://blockclubchicago.org/2022/01/19/center-for-covid-con...

I'm not sure. Not only do you need to kill bacteria, you need to not kill or harm humans at the same time. That is a high bar.

You need to kill bacteria, not kill humans and print money. The optimal strategy is to wait as long as possible as the value of a novel drug goes up as resistance goes up.

Hot take, but I actually think this is good since it means we postpone usage of, and thereby resistance to, any new antibiotics. The second there’s a new antibiotic, poor countries are going to over-use generics of it and create resistance.

If the economics were rational, I’d agree with you.

Humans inability to effectively organize doesn’t matter to the bacteria. As a species, we have the ability to understand that what happens in impoverished areas impacts us all. The smart move would be to rethink healthcare, globally.

Otherwise, those bacteria, who can’t argue, will just relentlessly keep evolving.

> The problem is that cost and risk of development and trials is too large for the current rewards,

This kind of invesment has been traditionally done by governments. But with a reduction of taxation governments do not have animore money to do this. And for private companies it makes more sense to spend that kind of money in advertisment than in developing new products.

> ensuring good prices or bounties for successful development would likely create a plethora of antimicrobials in a quite short time frame.

If one woman has a child in 9 months. How many months takes to 9 women? More money may accelerate development, but there is a limit on how much faster one can go. Give a big enough reward and you will find more corporations cheating and lobbyng to get that money without delivering any actual antimicrobials.

Public research institutions seem a very good middle ground. Give pasionate scientist funding and they will come with solutions. Give passionate CEOs money and you get the next big scam.

> But with a reduction of taxation

I’m pretty sure government tax revenue is still at or near all time highs. As the population grows there’s more and more taxes to spend for this purpose. It’s just a matter of priorities.

> As the population grows there’s more and more taxes to spend for this purpose.

but so does the cost to service that growing population.

Basic research scales in a way that treating specific individuals doesn’t. Treating specific individuals can be handled by insurance.

Any increase in general tax revenue generated by an increase in population is going to used for the new population. For example NASA's budget didn't increase just because of an increase in population

This feels like a misdirection, though. Revenue may be high, but the same forces that drive this being a trivial statement also mean that expenses are at an all time high.

> Give passionate CEOs money and you get the next big scam.

This has been the case for decades, yet we still seem to have not learned this.

This is my observation, from having seen this happen in a couple of industries, and hearing of it happening in others.

There seems to be a "sweet spot," in new money-making stuff, where real value is produced, rewards are reaped, and scamming is low.

The industry starts off with small-scale passion projects, and relatively low rewards. Virtually no scamming, but also modest financial gains, as the passion-players start to establish the infrastructure.

Then it starts to "catch on," and a more professional approach is applied. The industry starts to scale, and the first folks on the upswing start to make some good money.

Then, after that, the scale goes up exponentially, the quality of the work nosedives, the rewards pile up, and the scamming becomes more prevalent. Many of the originators fall down, because they can't adapt to the new darwinian order.

Eventually, the whole thing becomes so corrupted, that it collapses under its own weight.

Rinse and repeat.

i think you’re hitting the nail on the head emphasizing passion.

so often people entirely disregard passion for the work when theorizing that no one would be a ceo for less than $40million.

i haven’t ever seen studies done surrounding the issue, but i’d bet far more innovation comes from people doing something because they’re passionate than it does from monetary reward.

there’s a tipping point somewhere when innovation takes a backseat to greed.

often greed directly leads to a willingness to destroy a things essence or just chip away at the thing completely ignoring the passion which brought it about in the first place.

edit: forgive me if this seems a bit heavy handed—just watched Its a Wonderful Life with the family for Christmas so maybe i’m feeling a bit jaded towards greed.

> big scam

If you have reasonably honest people who are not starting from scratch, and honest trials, you likely are going to get a real thing. Case in point: mRNA vaccines against COVID.

> The problem is that cost and risk of development and trials is too large for the current rewards, and hence there is very little new antimicrobials being developed

If that is so, then that research should be done by the state. The well-being of entire human race cannot be tied to monetary incentives of profiteering.

What are examples of the state actually achieving a research objective better than free enterprise?

The majority of research advances in medicine have been done with NIH grants and the free enterprise only afterwards did the "productization" of it.

I’m not sure, but what about the space program in the 1960s?

I thought of that too. I don't know enough about it to know if it's a legit counterpoint. My view is that real competition is necessary to efficiently and effectively get to a solution, versus focusing on the bureaucratic mechanics of running the machine that's supposed to be building the solution, which is what happens when government takes things on.

But the space program, and maybe the Manhattan project, actually had real, credible competition, even if it wasn't economic, so maybe were able to escape the bureaucratic trap. Something less urgent (even if it is on paper) like antibiotic resistance, I'm not convinced presents the kind of competition that would actually substitute for a competitive market.

> I don't know enough about it to know if it's a legit counterpoint.

Its a gigantic counterpoint. A large swath of the technology used today was developed by NASA and then turned over to the private corporations for them to profit. Socializing the costs. Privatizing the profits.

The Internet iself an argument. It was developed at DARPA with taxpayer money. Then turned over to the private corporations so that they could profit. Another case of socialism for the corporations.

With the Internet the government got their pound of flesh through taxation of all the new enterprises that sprung up because of their investments , so I wouldn’t make it sound so negative.

> With the Internet the government got their pound of flesh through taxation of all the new enterprises that sprung up because of their investments

Really. With all the tax breaks and ongoing lowering of the top tax bracked for corporate profit. Even as they offshore their legal entity to dodge taxes...

Even if the capital gains taxes were 90% like back in Eisenhower era and it was actually enforced, that still wouldn't justify handing over publicly funded research to private actors to profit. Publicly funded everything should be made publicly available and usable.

I think this is overstatement as to 'turning it over.' DARPA paid for research and operated communications systems in furtherance of a standardized packet network. This was done largely with privately developed tech like commercial telephone wires, commercial modems, commercial minicomputers, commercial solid state RAMs, commercial storage tech. The benefit of DARPA's big funding boost was consolidation, sharing, selection of objectively reasonable choices like tcp/ip, and allowing international collaborators. This sped up the process of having a viable, unified internet wherein other researchers who were not even in the United States contributed tech like the web (on Next computers, with Next software stacks, Motorola chipsets, Sony CRT tech, etc).

> This was done largely with privately developed tech like commercial telephone wires, commercial modems, commercial minicomputers, commercial solid state RAMs, commercial storage tech

Same happened with all of those. The government created the tech, then paid private corporations to implement it, literally funding the everything from scratch while the private corps grabbed the profits.

> This sped up the process of having a viable, unified internet

That's false. Chile's Socialist president was at the point of launching their Internet in mid 70s. Which was ended by the US backed coup.

The ENTIRE technology core of the US. The government channels taxpayer money to state research organizations like DARPA. They invent things like the Internet. Then they turn over those to the private sector for profit.

The majority of core research has been backed by government funds for a while now. Commercialization and mass market adoption is typically where private enterprise steps in.

Nuclear Energy and space telescopes come to mind.

Not sure I agree. Take a look at recently developed antimicrobials. It’s not like there haven’t been any new ones. The problem is this: they are very expensive compared to older antimicrobials (so don’t get used at all except in wealthy healthcare systems) and they are tightly held in reserve for only the most resistant cases (so very small market). The latter point is particularly insurmountable, since widespread use will make the new antimicrobial less useful. It isn’t really worth it for a drug maker. The article talks about this, indicating that public-private partnerships are the way forward.

They also tend to not be new families of antimicrobials with novel mechanisms of action, which is what's needed for more significant gains against resistance.

>I am quite sure, that if a sufficient bounty was given out for developing new kinds of antimicrobials, they'd be developed in no time.

It's dangerous to think such problems can just be solved by throwing money at them...

Another factor to consider is it’s much better for social good to wait until you have 2-3 working new antibiotics to mix together to reduce the survival rate exponentially. But that would require delaying the short term profits of selling the single-cocktail twice.

antibiotic cocktails are tricky - sometimes using multiple antibiotics can reduce clearance. This is a really good paper on the topic: https://www.nature.com/articles/s41586-022-05260-5

Just need some governments to mandate them, then no worries

why do we need "rewards"? just have a national lab produce them

If this ends up being the approach, I really hope it will be led by a country with a few decades experience in successfully being socialist. The US really has no business doing this, the government departments and oversight boards that exist today are much too compromised by the pharmaceutical industry to pull this off.

A national laboratory is not a socialist idea. If it were then the US would actually be an extremely socialist country given its government spending. Doesn't the US put out the most research in the world, and have the most Nobel prizes? That hardly seems like a country that can't manage this. Nowhere is free of bureaucracy.

Nationalization of research laboratories is a very socialist idea. That doesn't make it bad or inefficient, but government takeover of research and education has pretty solid roots in socialism, Marxism, and fascism.

The US does spend the most and that leads to output, but that doesn't mean it's the most efficient or does the best job of prioritizing the populations best interests over political or business concerns.

The selection process of awards like the Nobel Prize is also at risk of bias given that many of the people involved in picking the winners are themselves part of the national laboratory machine.

Regardless, my point was simply that we probably have a better chance at a Swedish effort leading to less biased and more efficient research than one from the US right now. I wasn't aiming for a debate on the relative political roots or leanings of publicly funded research labs.

I agree with you here. A parallel example being the IRS and tax reform that's prevented by private companies in the tax preparation domain.

That's as far from socialism as possible, so I'm really not sure how your example is in agreement.

A 'national lab' does not have anything to do with 'nationalisation'. Nationalisation means to take over an existing privately run lab, whereas a national lab can be established from scratch without even the hint of a takeover of any private organisation. In the post you replied to there was zero suggestion of nationalisation.

That said, nationalisation is sometimes the correct move as the opposite of privatisation which is also sometimes the correct move, so attaching labels like 'socialist' to it to tar the policy is not productive (just as tarring something as 'capitalist' also does not beget good thinking about policy).

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