A Horror Movie

by on September 9, 2016 at 7:22 am in Science | Permalink

From a new paper in Science.
Hat tip: Monique van Hoek.

1 anon September 9, 2016 at 7:26 am

“Good news, everyone!”

“I have found a way to sell 10,000 as much antibiotic!”

2 Dzhaughn September 9, 2016 at 3:47 pm

Yes, but at 1 millionth of the price.

3 anon September 9, 2016 at 7:30 am

For those who missed the news, there was a recent market intervention in this area.

FDA outlaws antibacterial soap

4 Brian Donohue September 9, 2016 at 8:50 am

Yes, coordination problems actually do exist.

5 dearieme September 9, 2016 at 7:36 am
6 TMC September 9, 2016 at 8:02 am

Fitting, but he won’t have the self reflection to know why.

7 msgkings September 9, 2016 at 1:09 pm

Haha! Sick burn, bro. Trump totally has the best self-reflection, yuge self-reflection.

8 Axa September 9, 2016 at 8:08 am

The video is short but full of content. I was wondering how to analyze the experiment and at 1m43s nodes and links fade in……..a quantitative analysis is possible, this is beautiful. Simple looking experiments are the drivers of fundamental insight.

9 Axa September 9, 2016 at 8:14 am

The nodes and links are a planar spatial graph, just wondering about the properties of this graph. Some specific fractal dimension? The diffusion of a random walker? It’s nice when biology and physics can talk each other.

10 Ronald Brak September 9, 2016 at 8:49 am

There are steps we can take to control and reduce antibiotic resistance. But it is going to take a large amount of resources, government oversight, and to do it properly it will have to be done on a global scale. And when I look at the inadequate response we have made to the clear danger of global warming over the past quarter century, I am not confident we will organize an appropriate response to antibiotic resistance for a decade or more.

11 Axa September 9, 2016 at 9:19 am

My glass is half-full and I cherry pick DDT/birds and CFCs/Ozone layer cases to prove we’ll organize an appropriate response.

12 anon September 9, 2016 at 9:34 am

It wasn’t that long ago that MR still had DDT diehards.

Some things just become a cultural belief. Lets hope antibiotic resistance does not become “another liberal lie.”

13 Ronald Brak September 9, 2016 at 9:44 am

We could have introduced controls on the use of antibiotics in agriculture across the developed world in the late 70s once the problem became apparent or in the late 90s when the first major controls were introduced in the EU. But today in 2016 we still do not have an organized global approach and so to me it it seems much more like the piecemeal approach we have seen taken with regard to global warming than the more rapid response taken with CFCs.

The example of DDT is interesting as where it was restricted from agricultural use DDT retained its usefulness in controlling insect borne disease as mosquitoes failed to develop significant resistance to it, but in South East Asia where it remained in use it became much harder to control malaria.

To really get a real handle on microbial antibiotic resistance we are going to have to use techniques similar to those used in agriculture to control pesticide resistance in insects on bacteria.

14 Dzhaughn September 9, 2016 at 3:56 pm

The problem of antibiotic resistant bacteria seems a thousand times more tractable than global warming. Because (1) a national policy will have a high national impact, (2) it is much easier to show the benefit of a marginal increase in an overused antibiotic is tiny, but much harder to show the same for the incremental benefit of another furnace, air conditioner, or car, especially in the developing world.

15 dearieme September 9, 2016 at 9:33 am

“the inadequate response we have made to the clear danger of global warming over the past quarter century”: aye, we’ve not hanged any of the lying bastards.

16 Ronald Brak September 9, 2016 at 9:48 am

Exactly.

17 Jim Clay September 9, 2016 at 11:28 am

I suspect dearieme has a different idea of who is lying.

18 anon September 9, 2016 at 10:04 am

Under current trends it will not be the liars who are first against the wall when the scientific rational revolution comes, but the scientists who burn their NSF cards, and try to blend in on the casino floor.

19 JC September 9, 2016 at 9:34 am

Impressive. They improve way faster than our body becomes resistant or immune… thank God there are biotechnologists…

20 dearieme September 9, 2016 at 9:35 am

I note that the voice-over chap has been infected by the micro-organism that makes people start sentences with “So”.

21 Philip Crawford September 9, 2016 at 11:20 am

Well….

Those dang teenage girls at it again.

22 Thiago Ribeiro September 9, 2016 at 12:35 pm

So what? It is, like, harmless.

23 Nicholas September 9, 2016 at 10:21 am

I’m gonna be the contrarian out there. Consider the following experiment:

Take several of the bacteria strains that evolved high resistance to antibiotics.
Take several of the original bacteria strains that were susceptible to even small amounts of antibiotics.

Now put them back into a dish without antibiotics. See who wins out?

Antibiotic resistance is scary, but the truth is that most patients don’t have high levels of circulating antibiotics all of the time, so the evolutionary pressure represents a bunch of blips that get diluted out quickly. I also suspect that many antibiotic resistance genes are costly in other ways that may decrease the fitness of the bugs, thus encouraging a loss of that resistance.

The truth is, most people with infections are easily treated with antibiotics that are decades old. How can that be if resistance genes are so easy to acquire and they have no cost to the organism? Yes some superorganisms are emerging, even they are few in number, and in most cases, they still can’t survive the onslaught of a healthy immune system.

24 Axa September 9, 2016 at 2:11 pm

Yep, the truth is that most infections are treated with decades old antibiotics. The curious problem is those antibiotics come from half understanding of what happens and half luck. There is no emergency, but in fat cows year it’s good to prepare for difficult times. Part of the preparation is getting fundamental comprehension of what happens with bacteria. Penicillin discovery was luck and it worked as “black-box” at the time of discovery.

25 Dzhaughn September 9, 2016 at 4:02 pm

+1. But what remains is a proof that some amount of research to produces antibiotics is valuable. But research of what type and at what level?

26 Li Zhi September 10, 2016 at 11:52 am

The “truth is” that most people don’t NEED antibiotics to fight an infection. So, it obviously logically follows that we should out-law them, right? Your entire argument is specious. The idea that people will comply with full-course regimes of ab when it costs them money and time they can not afford is just plain silly/futile. All central planners can do is talk about how we can “address the problem” and beg for more funding to “study the problem”. The rational way forward that I see is faster diagnostics (in office) so that Drs don’t feel compelled to hand them out like candy, and better education so that patients/parents don’t demand them as “insurance”. Regulating antibiotics is similar to mandating vaccinations: the community at risk isn’t the same as the community where compliance is needed. (ie the immune compromised)

27 Steven Kopits September 9, 2016 at 10:37 am

Right. There’s a second phase to that experiment.

Once you have the antibiotic resistant bacteria, you set up a new screen with no antibiotics. You put the resistant bacteria on one end and the original bacteria on the other end (color coded, if you can) and see who wins out.

If the resistant bacteria win out, then you will see persistence in the mutation. If the original bacteria win out, then the resistant bacteria will tend to disappear when antibiotic use is terminated.

28 Alex Tabarrok September 9, 2016 at 11:01 am

Yes, that happens at first, but (from the paper):

Mutations that increased resistance often came with a cost of reduced growth, which was subsequently restored by additional compensatory mutations (29–31). Although some resistance-conferring mutations allowed colonization of regions of high drug concentration without affecting growth, many lineages capable of growing in these regions were deficient in yield, particularly during CPR resistance evolution (as measured by optical density: Fig. 4, A and B, for CPR; fig. S3 for TMP). These yield-deficient mutations were followed by compensatory mutations allowing growth to full density

29 Steven Kopits September 9, 2016 at 12:36 pm

So you’re saying the superbug evolution is permanent, and evolved strains are superior–at least in some cases–to original strains. Probably not true if every case, but plausible at least in some cases.

If that were true, however, one would expect antibiotic resistant bugs to spread very quickly. After all, the mutations succeed in just eleven days in the video. So if that path were true, antibiotics should loose their efficacy in weeks to months. Clearly, they don’t.

On the other hand, chronic use of antibiotics, as in animal husbandry, and wide-spread, concentrated use with otherwise compromised populations, eg, elderly in a hospital, certainly would provide a good setting to develop some superbugs.

Still, wouldn’t this just encourage us to use gene drive to modify the superbug genetically?

http://www.nytimes.com/2015/11/24/science/gene-drive-mosquitoes-malaria.html?_r=0

30 Ronald Brak September 10, 2016 at 2:33 am

Steven, while bacteria can exchange genetic material, including between species, they don’t actually reproduce sexually so gene drive can’t be used against them. There are other things that can be done, however.

Currently it would be possible to construct hospitals out of materials that are extremely hostile to microorganisms and have robots sterilize all surfaces every 2 hours. This would be very useful for controlling infection, but until we work out a way to replace human flesh with something better, we can’t change the fact that human beings are covered in microorganisms, have guts full of them, and constantly spread them around by touch, breath, spittle when talking, sneezing, and so on.

Since we can’t eliminate these bacteria directly, we are going to have to make them less resistant. One way to do this would be to stop using antibiotics, but that has the drawback that a huge number of people would die as a result. And it would take an awful long time to get resistance down to 1940 levels. If some bacteria decide to keep their resistance genes because they help them do something unrelated to antibiotics it might never happen. And also bacteria can spore and go dormant for decades so if we went without antibiotics for a generation, fully resistant strains could pop right back up as soon as we started antibiotic use again.

One thing that can be done is culture bacteria that have no antibiotic resistance, or are even especially vulnerable to some, and slop them around where ever it will do the most good. This is no silver bullet, but done on a large enough scale it could eliminate many strains of resistant bacteria. Of course it has obvious limitations. It is probably not a good idea to just go spreading around mycobacterium tuberculosis no matter how non-resistant it is. Instead, we will have to directly eliminate TB from the world. Difficult, but it can be done. But it will take a huge amount of resources, global coordination, and so on.

31 austrartsua September 9, 2016 at 11:28 am

So what? This is why we have sex.

https://en.wikipedia.org/wiki/Red_Queen_hypothesis

32 Thiago Ribeiro September 9, 2016 at 12:36 pm

But what if I were British?

33 dearieme September 9, 2016 at 2:31 pm

You’d have more sex but you wouldn’t discuss it in public.

34 Thiago Ribeiro September 9, 2016 at 9:29 pm

“You’d have more sex but you wouldn’t discuss it in public.”
I know, I know. “The love that dare not speak its name.”

35 Yancey Ward September 9, 2016 at 12:20 pm

If the plate had only 3 bands- two outer bands with zero antibiotic and one inner band with 1000 times a lethal dose, how long would it take for the bacteria to expand into the middle?

36 Ronald Brak September 10, 2016 at 1:42 am

Well, from the film it looked as though a single mutation was enough for bacteria to spread into each new zone. So if they have to be carrying three mutations of the right sort to survive in the 1,000 times a lethal dose area, the chances of those three correct mutations occurring at once in a single bacterium would be incredibly small. But given enough time and opportunity it could happen. Unfortunately, it is difficult to create situations where there is either no antibiotic or enough to kill all bacteria.

37 Ronald Brak September 10, 2016 at 4:33 am

The abstract of this paper gives an example of how difficult it can be to develop a high level of antibiotic resistance:

http://science.sciencemag.org/content/312/5770/111

Unfortunately, once the right gene combination for resistance comes up it can be very hard to get rid of. As long as one bacterium with the functioning set of resistance genes is in existence it is always possible for it to make a comeback when exposed to the antibiotic.

38 Yancey Ward September 10, 2016 at 2:24 pm

It is simply an assumption that it took a “single mutation”, isn’t it? More appropriately, absent a comprehensive genetic study, visually it appears that it took only one bacterium with the correct combination of mutations to breach each band, though it is possible it was a single site mutation in each case. I don’t think this caveat undermines the mathematical probabilities, but I would have like to have seen the visual demonstration of this.

So, I don’t understand why the visual presentation doesn’t include my proposed experiment since it is clear that the experiment was designed to demonstrate the problems with the general overuse of antibiotics combined with not using them vigorously enough in specific cases.

It took 11 days to breach to the middle. Does it take 22 days, a year, 5 years to breach my experiment? It is question one has to answer to determine how worried one should be about resistance and some of the proposed methods for minimizing it.

39 Llort September 9, 2016 at 3:13 pm

Nice story, if only evolution existed.

40 Durrr September 10, 2016 at 3:09 pm

All bacteria are equal. Any measured difference in “antibiotic resistance” is the result of our racist, sexist, transmutationphobic bacteria society.

41 Dzhaughn September 9, 2016 at 4:03 pm

Interesting coming from Alex, who often opposes regulating use of drugs.

42 Cliff September 9, 2016 at 9:49 pm

Not exactly

43 cowboydroid September 9, 2016 at 11:29 pm

*government regulation

44 Tom Bri September 9, 2016 at 4:49 pm

I’m an RN in a hospital. We continue to use penicillins because they still work. All infected patients have cultures taken and tested against multiple antibiotics to see what resistance they have, and the appropriate antibiotic is given. In many cases, it is a first or second generation penicillin.
Certain populations, the elderly, gays, diabetics etc are more likely to need frequent antibiotics, and to acquire resistant strains.

45 Shane M September 9, 2016 at 6:03 pm

Nothing to add, but wanted to say “More of this, please.” One of the coolest illustrations of science I’ve seen in a while.

46 Ian Maitland September 9, 2016 at 9:19 pm

I agree with Shane M. And an interesting discussion as well.

47 Thanatos Savehn September 10, 2016 at 1:40 am

Bacteria, fungi, archaea, algae and protozoa have been creating their own antibiotics while defending against their enemies’ chemical warfare for eons and yet none have vanquished all comers. Ponder why that is.

48 J September 10, 2016 at 11:41 am

Very impressive. Evolution in action. Now say that instead of antibiotics, we a barrier of IQ loaded exam is put before a population. When the exam requires IQ 130 almost no one passes. Then one or two succeeds and reproduces. The next barrier will be an exam requiring IQ 150 and so on. In a number of generations, we may have a group that thrives with exams that require IQ 200 to pass. This, in fact, is the traditional Chinese exam system, that has been applied for something like 2000 years. Of course, with bacteria the process is neater.

49 Marian Kechlibar September 12, 2016 at 2:39 am

I do not think it works this way. There is regression to the mean.

50 Marian Kechlibar September 12, 2016 at 2:37 am

The antibiotics were once very useful, but they might be superseded by the next evolution in science, bacteriophagi.

It does not make any sense to kill bacteria wholesale, if we now know that many bacterial strains in our bodies protect us against allergies, hostile external bacteria, help us process food etc. It only makes sense to kill the hostile bacteria specifically, to discriminate. Which bacteriophagi can do very successfully.

Antibiotics are a mixed blessing, they have certainly saved lives of people, but the extent to which they contributed to the current epidemics of metabolic syndrome and allergies is still unknown.

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