Is the Great Stagnation soon over?

by on January 7, 2015 at 7:42 pm in Current Affairs, Medicine, Science, Sports, Uncategorized | Permalink

The method, which extracts drugs from bacteria that live in dirt, has yielded a powerful new antibiotic, researchers reported in the journal Nature on Wednesday. The new drug, teixobactin, was tested in mice and easily cured severe infections, with no side effects.

Better still, the researchers said, the drug works in a way that makes it very unlikely that bacteria will become resistant to it. And the method developed to produce the drug has the potential to unlock a trove of natural compounds to fight infections and cancer — molecules that were previously beyond scientists’ reach because the microbes that produce them could not be grown in the laboratory.

Studies on people will start in about two years, the NYT article is here.  Here is the underlying Nature article.

Alternatively, here is a claim that James Harden is the future of basketball.

I thank numerous MR readers for related pointers.

1 Eric Crampton January 7, 2015 at 7:59 pm

Is there any good reason that trials on people couldn’t start now? Like, on people who are about to die because c.difficile is about to kill them and nothing else has worked?

2 E. Harding January 7, 2015 at 8:06 pm
3 E. Harding January 7, 2015 at 8:07 pm
4 Curt F. January 8, 2015 at 12:10 am

Much more relevant to Eric’s question is the fact that supplies of teixobactin are probably not sufficient for trials in people yet. (See Mark Thorson’s point in one of his posts below.)

5 dearieme January 7, 2015 at 8:00 pm

“the drug works in a way that makes it very unlikely that bacteria will become resistant to it”: is evolution really about to be beaten?

6 Patito January 7, 2015 at 8:20 pm

“…for maybe 30ish years” is the end of that sentence if you read the source material. So… evolution decidedly not beaten.

7 carlolspln January 7, 2015 at 8:51 pm

Most antibiotics work by interfering with a particular protein in a prokaryote. Teixobactin works by interfering with formation of peptidoglycan cell walls, which is a more complex process.

The bigger story: the researchers actually developed a new technic for identifying future antibiotics, by cultivating them in situ:

http://www.theguardian.com/science/2015/jan/07/antibiotic-drug-resistance-teixobactin

8 Quite Likely January 8, 2015 at 10:16 am

It’s just saying it’s helpful. Like how copper has antibacterial properties. Obviously if there was some sufficiently huge evolutionary pressure bacteria could probably find a way to survive on copper, but so far it hasn’t happened. Presumably there is some way bacteria could survive and evolve a resistance to this drug, but it’s not unreasonable that it could be more difficult to do so against some drugs than others.

9 E. Harding January 7, 2015 at 8:02 pm

Don’t think so. I’m typing this on a computer made in 2005 by a company which no longer exists as an independent entity. The rate of CPI deflation for personal computers and peripheral equipment has risen (fallen?) from under -36% in January 1999 to a mere -8% today. The computer revolution is definitely over. And the discovery of a new antibiotic hardly signals the end of a forty-plus-year trend.

10 zbicyclist January 7, 2015 at 11:57 pm

Yes, the Desktop to Tower to Laptop thing has pretty much run its course.

But are you still using the same phone you were using in 2005? If so, why?

11 E. Harding January 8, 2015 at 12:11 am

I have three phones (all cell; none landline) which I use: one small one from before 2008, an Android-based phone built in 2011, and a BlackBerry. I do not use phones to take pictures, and hardly ever browse the Internet with the Android phone.

12 Axa January 8, 2015 at 3:02 am

The world is not responsible of your shortsightedness not shared by the global under 35 year old population……most of people. 😉

13 dead serious January 8, 2015 at 8:18 am

You forgot to add: “Get off my lawn!”

14 E. Harding January 7, 2015 at 8:12 pm

Also, I think there’s a law that says that every title that begins with a yes-or-no question has an answer of “no”.

15 Mark Thorson January 7, 2015 at 8:31 pm

This isn’t even reporting an animal trial. It’s an in vitro study. This is so far from being ready for trial in humans it’s not even worth talking about among non-biochemists. Lots of potential antibiotics fail because of some kind of toxicity. If it kills your liver or kidneys, that’s a show stopper.

16 Adrian Ratnpala January 7, 2015 at 9:27 pm

It’s a Nature paper. That means it is supposed to be of interest outside the field. That might not be how things work in real life, but at least that’s the principle.

In this case I think it is of interest. They point towards a whole new strategy for coming up with antibiotics along with discovering a whole new mechanism for antibiotic action. That’s intersting science, big enough news to be at least a blip on the mental radar of all scientifically literate people, even if no specific drug comes out of this.

17 Curt F. January 8, 2015 at 12:18 am

Amen Adrian and +1.

First of all, Mark, there is some in-vivo data from mice in the paper. (Blood clearance lifetime data, I believe.) Also, toxicity was tested against mammalian cells, but admittedly, that was in vitro.

Adrian, it’s definitely a new way to come up with antibiotics. The mode of action is new but similar-ish to vancomycin (peptidoglycan biosynthesis inhibition), arguable perhaps if it is a “whole new” mechanism but still very cool, very Nature-worthy, and interesting.

Lastly, it isn’t just a Nature paper, but it’s a Nature Research Article. It’s an absolutely huge amount of work. It could easily have been divided up into 3 or 4 different papers. (One paper for isolating the strain, another paper for purifying the molecule and doing the structure, another for finding the resistance mechanism, and another for genome sequencing, etc., etc.) But it isn’t. It’s one paper and it tells one clean story of a huge research project that undoubtedly took decades of person-time. It’s nice that rigorous, complete papers like this one can still happen — apparently the publish-or-perish push for the “minimal-publishable-unit” hasn’t yet completely won.

18 carlolspln January 8, 2015 at 3:08 pm
19 Ray Lopez January 7, 2015 at 11:16 pm

@MT – yes agree. I’ve seen many inventions that cure cancer in vitro and in mice but not in humans. Still, it’s good news.

OT, On soapbox now. Imagine, as I’ve written before, if strong, fairly enforced patent laws of the kind AlexT seemingly disfavors, and cash prizes going to inventors of the kind AlexT favors, were in existence for the last 100 years (and imagine the US stayed out of WWI which arguably would have prevented WWII, as Germany was going to settle with France, UK due to stalemate probably). We’d be at least a couple of hundred years further in the technology curve than now. Today’s society is geared towards B.S-ing (arts), rent seeking (lawyers and politicians included), keeping old people who are arguably not productive anymore alive for a few more years (doctors), middlemen (buy low, sell high, duh!), and front running legitimate inventors (on this last point, it’s true the first to market does well–the original inventor– but it’s equally true that the *second* to market does very very well with very little risk. In fact, a rule of thumb in the VC world is to see how many other startups are ‘already doing this successfully’, Peter Thiel would be the expert here but that’s my understanding, maybe I read it from Thiel). Off soapbox now.

20 Jan January 8, 2015 at 6:32 am

Yeah…because the last 150 years have been really terrible for innovation…

21 ElijahGonzalez76082 January 8, 2015 at 9:26 am

Dunno, an awful lot of 20th century innovation came out of Bell Labs, which was a weird deal with the government that AT&T could keep its phone monopoly as long as it was liberal with licensing the non-phone technologies they developed. I don’t know how that fits in your story.

22 Steve Sailer January 7, 2015 at 8:33 pm

In the later 20th Century, pharmaceutical companies decided mostly en masse that the traditional way of looking for new drugs by reviewing existing natural organic compounds was outdated and the future belonged to designing molecules based on first principles. That appears now to have been, on the whole, a mistake.

23 Keith January 7, 2015 at 9:23 pm

They also used massive high throughput screening techniques. A mistake or not? I don’t know.

24 Mark Thorson January 7, 2015 at 9:47 pm

That’s what the iChip is — a high-throughput screening device for bacteria difficult to grow outside of their natural dirt environment.

http://www.novobiotic.com/about/

The increment they have contributed is the ability to culture bacteria not previously cultured by embedding the culture system in dirt, so unknown chemicals from the dirt can diffuse into the culture system and support the growth of these difficult-to-culture bacteria.

Once you identify a promising molecule, what do you do next? You aren’t going to be growing the bacteria in big tanks, like you would for more friendly bacteria. You might make the molecule synthetically, but look at the structure of teixobactin. That’s not going to be an easy or cheap molecule to make, and you’ll need hundreds of grams of the stuff to go through animal and clinical trials.

25 Curt F. January 8, 2015 at 12:05 am

Once you identify a promising molecule, what do you do next? That’s an interesting question. First, I wouldn’t be so sure that those bacteria wouldn’t be amenable to “domestication”. Often times “bizarro” strains can be forced to evolve into things that are much friendlier for growth in giant fermenters than not. And even more likely, the pathway for the synthesis of the product is known. These days with gene synthesis being what it is, the pathway could be recapitulated in E. coli or yeast without too much trouble.

I blogged a bit about this paper here: http://minglingken.com/2015/01/07/learning-to-listen-to-the-silent-majority/ Learning to grow “ungrowable” bacteria is good for lots of fundamental scientific reasons, not just finding new antibiotics.

26 Curt F. January 8, 2015 at 12:06 am

the pathway for the synthesis of the product is known. I should have said “suspected”, not known.

27 Jeffrey January 8, 2015 at 1:33 am

The bacteria grows inside the iChip. Once there is a sufficiently large colony of the bacteria within the iChip they are able to cultivate it within the lab.

28 Curt F. January 8, 2015 at 2:23 pm

Just because it grows in the lab doesn’t mean it will grow economically in giant industrial fermentation tanks.

29 Ray Lopez January 7, 2015 at 11:25 pm

“Alternatively, here is a claim that James Harden is the future of basketball” – does anybody notice that the Rockets, from the graphic, sink a higher percentage of shots from the side of the three-point arc rather than the top of the key? I thought shooting from the side, where you cannot see the backboard or use it as reference, as the hardest shot in basketball? Paradoxical.

30 eqbal January 7, 2015 at 11:37 pm

But is TC just throwing us a time-waster WRT Harden? (I mean, I can’t comment on the bio stuff, but sheesh, did I need to pour 15 minutes of my life into James Harden as Magic Johnson?)

31 Shane M January 7, 2015 at 11:39 pm

I can’t find any stats, but I wouldn’t automatically think a corner 3-pointer is a lower percentage shot than one from the top of the key, or from the wing. It’d be an interesting stat to see, but there very well could be reasons to think that a 3-point shot from the corner might be more likely to be uncontested than at other points on the floor.

Again, I’d love to see the stats of 3-point filed goal % by location on the arc.

32 Alexp January 8, 2015 at 12:02 am

Three point shots from the corners are a few feet closer to the basket than ones from the top of the key. This results in an average of a few percentage points higher shooting percentage, so that’s why most teams aim to shoot from the corners nowadays. I assume most professional basketball players (or at least the ones who regularly attempt three point shots) have stopped needing to use the backboard as reference years before entering the NBA.

33 triclops January 8, 2015 at 12:24 am

True, but two more things to add. Shots that are in uniquely identifiable spots on the floor(elbow shots and corner threes) are easier to gauge, and therefore, gain proficiency with. Also, missed corner 3s lead to a significantly higher chance the team with the ball will retain possession with an offensive rebound.

34 zbicyclist January 8, 2015 at 12:01 am

I’m puzzled. Why add the James Harden bit to this post. Shouldn’t that just be a miscellaneous link? Is there some synergy between sabremetrics and bacteria culturing that I’ve missed?

35 FC January 8, 2015 at 1:09 am

salary cap:basketball teams::petri dish:bacterial colonies

36 triclops January 8, 2015 at 2:00 am

The claim is that Harden is a new kind of star, based on analytics. So an end to NBA stagnation.

37 mkt January 8, 2015 at 3:46 am

Yup, in recent years various analytic techniques have become more and more widespread in basketball, analogous to the Moneyball movement in baseball which has resulted in a new type of baseball executive, exemplified by the Red Sox hiring a 28 year old Yale alumnus to be their general manager. Not so coincidentally, the Houston Rockets were one of the first teams to take strong steps in this direction when they hired a 35 year old Northwestern and MIT alum, Daryl Morey, to be their GM.

The guy who was so to speak the Bill James of basketball analysis, Dean Oliver (he wrote what is still the best book on the subject, _Basketball on Paper_), was basically an outsider who finally convinced an NBA team to hire him, the Seattle SuperSonics. He then went to the Nuggets, then became ESPN’s director of research or some such, and recently was snapped up by the Sacramento Kings’ new owner.

38 stan January 8, 2015 at 1:41 pm

The future of basketball is Steph Curry.

As for Dean Oliver and his Four Factors, I think that possession efficiency metrics suffer when there is no recognition that all possession are not independent. The outcome of the previous possession has a tremendous influence on the following one. E.g. a turnover not only hurts offensive efficiency, it often leads to an easy basket for the opponent which hurts defensive efficiency — yet the defense may not have had any opportunity to defend at all.

39 Todd Kreider January 8, 2015 at 2:52 pm

Scientists are discussing the antibiotic at in the pipeline blog by Derek Lowe ( so far not much mentioned on basketball)

The Great Stagnation has got to be the weirdest long term view put out by an economist. well, at least up there in the Top 10.

40 Derek Lowe January 8, 2015 at 3:38 pm

To answer some of the questions in this comment thread, the paper does report data in mice, so it’s not just an in vitro study. And (something I was glad to see), they’ve done a number of the preclinical studies that you’d want to do for a new compound: pharmacokinetics, metabolic stability, plasma protein binding, preliminary toxicology, interactions with liver enzymes and with ion channels that are known to be correlated with cardiac problems, etc. Much more than the usual “Hey, neat molecule!” paper, and I wish that this were the case more often.

And animal models in infectious disease tend to be about the most predictive in all of drug discovery. (Diabetes is probably next in line, and cancer is way down there near the bottom, next to something like Alzheimer’s). Add that to the fact that the compound is not bacteriostatic (just keeps them from growing) but actually bacteriocidal, and this is a legitimate candidate. As mentioned, though, scaling it up will be the next challenge – not impossible, by any means, just requires some work. The genes for this compound’s biosynthesis are known, so if all else fails, you could try splicing them into some more amenable species for the fermentation.

The biggest problem is that this compound, teixobactin, is not active against gram-negative bacteria. Those are much harder to find a drug against – as I can attest from personal and futile experience in the lab – and we already have several options for the gram-positive ones that teixobactin does kill. It’s not some amazing compound that’s going to save us from the bacterial hordes, but it’s worth taking further. The platform used to find it, and the principles behind it, may yield even more interesting compounds in the future.

41 Todd Kreider January 8, 2015 at 7:42 pm

hey Derek!

cancer-man here…. thanks for infusing MR with your thoughts on this!

while hard to believe, economists are ripe to become scientists.

seriuously, you heard it here first.

42 Cassandra January 12, 2015 at 9:45 am

You’ve really captured all the esteisnals in this subject area, haven’t you?

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