[sgarlatm]

It's nice to know that despite all the alarmist articles about the end of antibiotics, good progress is being made. If this works, it could completely replace traditional antibiotics. In that case, I could see dozens of new drugs in this class developed by the antibiotic companies. This would be similar to the race to develop new antidepressants, HIV drugs, and erectile dysfunction drugs. Any drug you have to take over and over again is a huge draw for the pharmaceuticals.

[giarc]

This won't completely replace traditional antibiotics. As the article states this acts on Gram positive persister cells (a very specific group). The coming storm is from Gram negative bacteria such as Klebsiella, Actinetobacter and Pseudomonas.

There is actually very little activity occurring in the field of antibiotic drug discovery and you identified the issue; no money in drugs that someone takes for 14 days and stops. Pharmaceutical companies are driven by stockholders and therefore they want them developing drugs that someone takes for the rest of their life (anti-depressants). Much of the research for abx discovery comes from academia who struggle with budgets that are pennies compared to what Pfizer, GSK, Wyeth, Astra can afford.

[JunkDNA]

You're right that it's about profits when pharma is involved, but you are wrong about the reason (otherwise vaccines would not exist). I can tell you from firsthand experience that the length of time someone is on a drug makes almost no difference in where research priorities are.

The primary issue with antibiotics is that since the late 1990's, if you succeed, and you develop the best antibiotic the world has ever seen, the FDA will require it to be a "drug of last resort". It will therefore sit on the shelf and be guaranteed to not be prescribed very much during the life of its patent. Once enough time goes by, and other drugs come out if (and that's a big if) it is no longer a drug of last resort, it is likely off patent and therefore can be made in generic form for pennies by generic manufacturers. Regardless of what you think about patents, these incentives are completely misaligned with companies going all-in and taking a risk on new antibiotics.

[giarc]

Vaccines are a bit of a different class as some are exempt from adverse reaction lawsuits and therefore risk is reduced for the companies manufacturing the vaccine.

I think your assessment that my argument is "wrong" is inappropriate. You'll see that my argument is supported by the WHO (Bulletin of the World Health Organization 2011;89:88–89).

>Another reason is commercial. Antibiotics, in particular, have a poor return on investment because they are taken for a short period of time and cure their target disease. In contrast, drugs that treat chronic illness, such as high blood pressure, are taken daily for the rest of a patient’s life. “Companies have figured out that they make a lot more money selling the latter drugs than they do selling antibiotics,” Spellberg says, highlighting the lack of incentive for companies to develop antibiotics.

[Fomite]

And yet in a recent survey of drug development costs, "Difficid", by Optimer Pharmaceuticals, was one of the most inexpensive to develop.

I also really don't buy the "return on investment" argument, as curing a bacterial disease rarely provides immunity.

It's also not my experience as a researcher in the area - several drug companies are actively funding research.

[giarc]

Fidaxo also may not be that great or cost effective[1]. Optimer, I believe has been bought by Cubist and delisted from Nasdaq. 1. Clin Infect Dis. 2013 Aug;57(4):555-61

[Fomite]

I do know their most promising findings don't get reflected in clinical trials well. But "The Drug Companies aren't there" isn't addressed by a small drug company specializing in ID getting bought about by another drug company that has tons of ID products for half a billion dollars.

[vxNsr]

As a citizen of earth and a member of humanity it hurts to hear that people who's very business is saving lives are largely driven by profits for their company and not the goal of the company: saving lives. While I know this naive I wish it weren't.

[maxerickson]

Do you know if NIH uses any of their funding in a DARPA like manner?

[JunkDNA]

They do this to a certain extent, but the problem here is that the "R" part of "R&D" is not really at issue. While there's a lot of focus in the popular press on "finding" new antibiotics, that part can be addressed by basic research grants. I don't believe we're wanting for proof of concept kinds of things. Unlike with engineering, where once you've got a proof of concept, you can refine and iterate to make it production quality, biology is completely arbitrary.

The issue comes with the "D" part of R&D. That is the expensive part with drugs because you start having to do very tightly controlled animal model studies progressing further into clinical trials with humans. The popular notion that you "discover" a drug is not how things work in reality. Often you discover a whole raft of closely related chemical entities that appear to do what you think they do. You tweak based on further studies in order to improve efficacy and safety. But the system is sort of nondeterministic in the sense that even altering the structure slightly often has knock-on effects you can't predict. Assuming you get something decent, that's what gets made into the an actual medicine. There's a whole branch of applied chemistry that specializes in this called medicinal chemistry. In many cases, you'll read about some promising new antibiotic that has been discovered in an academic lab, but once the chemists take a look at it, you realize there's no way to make a drug out of it. The reasons can be any or all of: the therapeutic dose would be too high, it blows out the liver, it can't be made into pill, the compound is unstable and can't have a good shelf life, it can't be taken orally, etc... Working out all those kinds of problems has always been the realm of pharmas and biotech startups. Academics aren't interested in that stuff because it's not basic research, it's highly applied and is mostly trial and error based on decades of doing this kind of work.

At a macro-level, this is fundamentally what ails the entire pharma sector right now. The development part of making drugs is so expensive and such a complete and utter crap-shoot, that few new drugs of any sort are actually being produced. The last decade has been one of prolonged decline in the industry in terms of truly new drugs and there is no obvious mechanism available to us to make it less so.

[Fomite]

In fairness, the NIH has started pushing "translational research" really hard in recent years.

[larrys]

"no money in drugs that someone takes for 14 days and stops. Pharmaceutical companies are driven by stockholders"

You wonder of course why, if that is the case (and I do agree), that the government doesn't get involved with more funding or subsidies for these types of less profitable drugs. The same way they spend countless dollars on other things for the public good (and company profit obviously).

[Fomite]

They have gotten involved in lightening the regulatory burden for certain drugs that are orphaned or for rare diseases, which is essentially a subsidy.

Also, the number of drug company booths at a recent infectious disease conference I went to suggests this whole "No interest in drugs that cure in three weeks" thing is...well...not actually true. These are incredibly common infections, there's plenty of market for them. Hell, the compound was initially discovered by Bayer.

[maxerickson]

I wondered about this and looked it up (leading to my other comment in this thread). NIH has a $30 billion medical research budget. DARPA is a couple of billion. Of course the $30 billion is not all directed at less profitable drugs.

Apparently there are a bunch of hard problems there.

[giarc]

The government is involved, but through academia. For example in Canada we have the CIHR (Canadian Institutes of Health Research) which would fund develop of drug develop (among many other health research).

[w1ntermute]

Sounds like something the Gates Foundation should get on.

[im3w1l]

The scary thing is what would happen if these bacteria fell into the hands of terrorist extremists. They could potentially create bio-weapons of mass destruction. Or imagine if some suicide cult decided that the time has come for the doomsday of reckoning. Al-Qaeda anthrax letters are nothing compared to this. It could also be used to threaten mutually assured destruction in asymmetric warfare. Iran could probably develop it more easily and stealthily than their (not very) secret nuke program. Developing countermeasure to this is a matter of national security. Insha'Allah people will come to their senses and please think of the children: We must secure the existence of our people and a future for white children before it is too late.

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[zabraxias]

This is really fantastic news but I too am skeptical of the drug companies being interested in a cure as opposed to a repeatable treatment.

As a side note the article seems very well written for non-medical folks like myself.

[Fomite]

This line of reasoning doesn't really apply to antibiotics - because you're likely to get another infection in your lifetime, and many people have infections at any given time, they're perfectly fine eradicating this one.

Believe me, in the infectious disease space, drug companies tend to look for cures and prevention. For example, Merck and GSK spent staggering amounts of money on the HPV vaccine.