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DBL%20Hendrix%20small.png College chemistry, 1983

Derek Lowe The 2002 Model

Dbl%20new%20portrait%20B%26W.png After 10 years of blogging. . .

Derek Lowe, an Arkansan by birth, got his BA from Hendrix College and his PhD in organic chemistry from Duke before spending time in Germany on a Humboldt Fellowship on his post-doc. He's worked for several major pharmaceutical companies since 1989 on drug discovery projects against schizophrenia, Alzheimer's, diabetes, osteoporosis and other diseases. To contact Derek email him directly: derekb.lowe@gmail.com Twitter: Dereklowe

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May 22, 2007

Evolution In Action

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Posted by Derek

As the cost of sequencing goes down, a lot of once-crazy experiments become feasible. There's a good case in point this week in the preprint section of PNAS. A team of researchers looked at a single patient undergoing treatment with vancomycin for a serious infection. (Just saying "vancomycin" makes the "serious infection" part redundant, since it's often the last resort). They periodically isolated Staphylococcus aureus bacteria from the patient's blood during the course of the treatment to look at how resistance to the antibiotic developed.

Fine, fine - except the way they watched the process was to sequence the whole genome of each bacterial isolate. What they found were a total of 35 mutations, which developed sequentially as the treatment continued (and the levels of resistance rose). Here's natural selection, operating in real time, under the strongest magnifying glass available. And it's in the service of a potentially serious problem, since resistant bacteria are no joke. (Reading between the lines of the PNAS abstract, for example, it appears that the patient involved in this study may well not have survived).

The technology involved here is worth thinking about. Even now, this was a rather costly experiment as these things go, and it's worth a paper in a good journal. But a few years ago, needless to say, it would have been a borderline-insane idea, and a few years before that it would have been flatly impossible. A few years from now it'll be routine, and a few years after that it probably won't be done at all, having been superseded by something more elegant that no one's come up with yet. But for now, we're entering the age where wildly sequence-intensive experiments, many of which no one even bothered to think about before, will start to run.

Comments (34) + TrackBacks (0) | Category: Infectious Diseases


COMMENTS

1. Zak on May 22, 2007 8:51 AM writes...

Want to hear something scary? My wife is a doctor here in Japan, and she has been in medical institutions where the antibiotic of first resort, for everything and anything, is vancomycin. Why? Because it results in a bigger profit.

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2. RKN on May 22, 2007 9:00 AM writes...

Here's natural selection, operating in real time, under the strongest magnifying glass available. And it's in the service of a potentially serious problem, since resistant bacteria are no joke.

I agree resistant bacteria are a serious problem for us, and any number of experiments have shown resistance is mediated by mutations that, for instance, render beta-lactams useless. But scientifically speaking I'd like to see some controls here. Is it possible, for instance, that blood-borne bacteria show functional mutations in their beta-lactamse absent any so-called "selection pressure," i.e. absent any drug treatment? I realize it might not be proper to collect the control data in a clinical setting, but in the course of doing good science such controls are important.

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3. Keith Robison on May 22, 2007 9:27 AM writes...

Your comment about the patient is poignant. Historical note: the first patient ever treated with penicillin died as well -- despite heroic attempts (such as extracting it back out of the patient's urine), there just wasn't enough of the stuff.

WRT to the comment about control data, it is a well placed point. Not quite what the writer was looking for, but in the abstract the authors mention that during the same timecourse the bugs became resistant to the unrelated antibiotic daptomycin.

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4. Chris on May 22, 2007 10:38 AM writes...

(Reading between the lines of the PNAS abstract, for example, it appears that the patient involved in this study may well not have survived).

In the introduction, the authors explicitly state that the patient, who suffered from congestive heart failure and ednocarditis, and had a heart valve replaced, died after ~12 weeks on vancomycin.

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5. Brian on May 22, 2007 11:36 AM writes...

After cloning my first gene in grad school (about 10 years ago), I remember thinking that had I been doing this just 10 years before that, I could be defending my thesis instead of setting up to make mutations.

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6. RPM on May 22, 2007 12:26 PM writes...

Along the same lines as RKN, the appearance of mutations does not guarantee that natural selection is operating on them (it's very rare to see mutation and natural selection as coupled processes). From a quick glance, it appears they may actually have the data to infer whether natural selection is acting on any of those mutations.

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7. SynChem on May 22, 2007 12:44 PM writes...

So what? This work merely shows what we already know--creatures/organisms can change. The bacteria mutations constantly occur with or without the stress. It proves absolutely nothing as far as the particle-to-life evolution is concerned. It's equally logical and scientific to say that such ability of the organisms was nothing but, dare I say the word, "designed" in its genetic makeup.

Again, it all depends on through which world view one chooses to interpret the same facts.

Evolution in action? Yes, this piece of work definitely nailed it! This is it.

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8. ctate on May 22, 2007 1:22 PM writes...

How long does each isolate take to sequence?

I see that the sequencing itself was done at the Joint Genomes Institute... am I reading this correctly that all of the genetic analysis was done post hoc?

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9. Palo on May 22, 2007 1:30 PM writes...

Creationists and Evolution-deniers are always moving the goal posts. Now they don't 'care' about Evolution of species, but only about the "particle-to-life" transition. So, if you cannot make a 'living' organism out of your molecules toolbox in the lab, then, Evolution is disproven.
The paper shows that change occurs, that change is sequential, and that sequential changes resulted in an adaptative new function. If that is not Evolution I don't know what it is.

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10. SynChem on May 22, 2007 1:53 PM writes...

Palo,

"If that is not Evolution I don't know what it is."

To the "true" evolutionists, evolution ultimately means life comes from particles. And you can wait till the cow comes home for their evidence supporting this one.

Let me also ask you this. How is the notion of "sequential changes resulted in an adaptative new function" inconsistent with the creation point of view? Exactly my point. The facts/physical observations are the same. It's how you choose to interpret.

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11. Clark Kent on May 22, 2007 2:14 PM writes...

This paper is another example of showing evolution can occur. However, knock-out mice, Round-up Ready corn and Golden rice prove that intelligent design can occur. We can never prove what happened in the past, so we should focus our energy on how these processes affect the present and future. Drug-resistant bacteria and bioengineered crops are two examples where more research is needed, but if we turn this into a creation vs. evolution debate, we may lose the science.

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12. Ugh on May 22, 2007 2:15 PM writes...

I don't know why I even bother, but ... there is absolutely no state of events that is incompatible with the creation point of view. If your argument is that there is an invisible, omnipotent man who transcends time and space, can do anything and has created everything according to his whims, then obviously literally nothing can disprove that (because he's omnipotent you know!). Whether or not the intelligent people of the world want to believe this is up to them. We'll keep using evolution as a tool in science where it's valuable (from psychology to genetics). You can keep using creationism for ... whatever use it has (?). I sincerely wish you the best of luck getting NIH funds with it.

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13. SynChem on May 22, 2007 2:32 PM writes...

Ugh

Are you implying creationists don't care about logic :)?

Your NIH comment is very telling of the very unscientific attitude of many of the evolutionist scientists. Science is all about finding working models that are consistent with observations, and keep an open mind while doing it. But sadly you're right about NIH ( the whole scientific community actually). In the current climate, it's "you're not a real scientist or a second rate one" if one doesn't wholeheartedly embrace evolution.

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14. Wavefunction on May 22, 2007 2:52 PM writes...

"In the current climate, it's "you're not a real scientist or a second rate one" if one doesn't wholeheartedly embrace evolution."

I think that's ok. Of course it depends on what you mean by "wholeheartedly", but if we accept the general definition, that's ok, because believing in creationism is believing in something that does not have a shred of evidence to support it. On the other hand, since creationism does not need or cannot demonstrate any proof, of course it will be consistent with everything around us. And not just Judeo-Christian-Islamic creationism. Every African tribal creation tale, as well as the hypothesis that we are actually a mental simulation created by an extraterrestrial.

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15. anonymous on May 22, 2007 3:23 PM writes...

Zak - that's because doctors dispense and get reimbursed for dispensing in Japan. The reimbursement is a percentage of the drug's price, so the incentive is to prescribe higher cost drugs. That is also why lower-priced generics have very little penetration in Japan.

Some institutions also used to dispense only half the dose so that the patient had to come back for another reimbursed visit to get their whole dose. When Zithromax launched with its 3 day dose schedule in Japan (shorter even than the 5 day US schedule), some doctors resisted prescibing it.

The MHLW is slowly changing the dispensing situation, but they also look at South Korea, where when the doctor dispensary system was eliminated overnight with no mechanism to fill in the hole in the doctors' compensation, many docs went on strike. The MHLW is using a slower approach to incent pharmacy dispensing, and now IIRC, pharmacies provide about half of all dispensed drugs, versus less than 10% a decade ago.

I have not yet seen any one look at the rates of development of bacterial resistance to anti-biotics in Japan versus the US, that might be an interesting public health project.

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16. Jose on May 22, 2007 3:51 PM writes...

Hmmmm. I wonder why polls generally show a strong correlation between populations that believe in evolution and those that don't believe in global warming.

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17. qetzal on May 22, 2007 9:00 PM writes...

SynChem,

If you care about logic, you should reconsider a statement such as this:

To the "true" evolutionists, evolution ultimately means life comes from particles.
Permalink to Comment

18. Evolution all the way baby! on May 22, 2007 10:24 PM writes...

It's truly sad, although very clever, that creationists have taken their fight to the blogs - a place where they actually get any kind of attention. I guess the saying still holds "there is no such thing as bad press." So maybe the best thing we can do is not react every time of these people jump on any news relating to evolution on the internet. I seriously would not be surprised to find out they have a well organized team that scours the internet for discussion boards/blogs for mentions of evolution so they can add in their poor 2 cents.

Permalink to Comment

19. SynChem on May 23, 2007 8:55 AM writes...

To post 17, I couldn't figure out what you meant.

To post 18, I'm just a fellow chemist working among you. And you'd be surprised at how many of us there are, and what a great job some of them are doing.

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20. Still Scared of Dinosaurs on May 23, 2007 9:25 AM writes...

It's really unfortunate that this thread has been polluted by one poster with a political agenda. I found the statement "it's very rare to see mutation and natural selection as coupled processes" thought provoking. I was thinking that they could be interdependent processes in cases such as antibiotic treatment on the assumption that the drug is putting tremendous pressure on the population of bacteria which, absent something else taking over the niche they are occupying, will respond by multiplying to refill the space. Therefore the increase in the reproduction would increase the observed mutation in the population.
I recognize this isn't an Nobel-worthy addition to scientific thinking on my part, but I was wondering if the article gave any insight as to the kinetics of such a process. Were populations of the target organism fairly constant over the sampling period, and if not was there any relationship between the counts and the genes?
But nooooooo.......
The next poster diverts the whole thread into neoCon blogtrash and the science whithers into opinion. Well here's an opinion for you: Anyone who doesn't believe that, broadly speaking, Evolution is the best scientific explanation of the origins and diversity of life on Earth is unfit to be the President of the United States.

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21. RKN on May 23, 2007 9:45 AM writes...

Anyone who doesn't believe that, broadly speaking, Evolution is the best scientific explanation of the origins and diversity of life on Earth is unfit to be the President of the United States.

The theory of evolution does not provide an explanation for the origin of life. Abiogenesis is the prevailing scientific hypothesis that accounts for the origin of life. I guess I'll never be the president :-(

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22. MolecModeler on May 23, 2007 10:07 AM writes...

You can be religious and believe in evolution I think, although this requires a more advanced idea of creation than the 7 days of Genesis.

The 6000 year old earth notion is absurd, obviously.

The whole evolution vs. creation argument is just a wedge issue to try and inject a particular brand of religious instruction into public schools, nothing more.

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23. SynChem on May 23, 2007 10:16 AM writes...

The belief in either creation or evolution requires a lot of faith. I find it appalling when people in the business of science refuse to acknowledge that and call people fools when they doubt evolution, as if there's no debate on this issue among "true" scientists. People with this mentality obviously are dismissing or unware of many of the greatest past and present scientists who believe in a creator (Einstein, etc)

In the end, I'm not sure who has the political agenda here. As a fair minded truth seeker, I'd want to examine the hypothesis, models and evidences from both sides with my head, and not emotions. Judging by some of the hostile and demeaning comments here, emotions definitely seem to be in control.

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24. Still Scared of Dinosaurs on May 23, 2007 10:37 AM writes...

RKN -
I was speaking really, really broadly. Could it be said that random change and positive feedback of some type is a characteristic of both evolution and abiogenesis, and that it's reasonable to see the two as segments of a continuum? Please? Or do I have to go back and amend my statement?

Maybe you can still have my vote. Where do you stand on the "US out of North Dakota NOW" issue?

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25. Paul Dietz on May 23, 2007 11:13 AM writes...

Could it be said that random change and positive feedback of some type is a characteristic of both evolution and abiogenesis, and that it's reasonable to see the two as segments of a continuum?


IMO, it would not be reasonable to say that.

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26. Wavefunction on May 23, 2007 12:04 PM writes...

I don't want to get into a debate here, but to say that belief in evolution needs a lot of faith is really absurd. Faith is defined as belief without evidence. I don't want to say more.
Also, we will be glad if you don't bring up the standard Einstein argument. Einstein never believed in a personal god, and used the word as a metaphor for the ultimate mysteries of the universe. There are many sources that document his lack of belief in a creator. Also, no one is calling people who doubt some exact details of evolution fools, but evolution as a whole itself?...Houston we have a problem.

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27. A Theist on May 25, 2007 8:35 AM writes...

STFU SynChem, go back to bible school. And to your point, Clark Kent: you can go shake hands with the "intelligent designers" in the cases you mentioned.... big difference.

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28. A Lienist on May 25, 2007 10:45 AM writes...

You people... arguing about whether some invisible, epiphanic creator seeded life on earth or whether it spontaneously formed from blind matter out of a nearly mathematical principal... it is clearly an argument that can only be settled by examining the inhabitants of other stars and asking them what they believe in. If they all believe in maths, then it's maths, if they all believe in epiphany, then it is epiphany. One giveaway will be aliens like extras in startrek. That means God. Lem/Hoyle type aliens implies evolution. Personally, I think machines made us, which will make things harder to work out.

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29. force on May 25, 2007 11:34 AM writes...

"The belief in either creation or evolution requires a lot of faith."


Let's accurately define this "faith" that you are talking about because it skews the truth by saying the belief in either or is the same.


"Faith" in creation comes from believing in a book about an aloof intelligence. "Faith" is excepting this is how it is because we feel it must be true.


"Faith" in evolution comes from our belief in the scientific method. These "true" scientists make specific hypotheses as explanations of natural phenomena, and design experimental studies to test these predictions for accuracy. We believe in it -- the scientific method, evolution, etc. -- because it has proven itself a thousands of overs.


Our "faith" in evolution comes with a mountain of supporting evidence on how this theory came about. Your "faith" comes from believing in something that by definition can never be proved.


That is the differences between these two beliefs.


And I believe we are still wanting for your experiments to prove your theory of creation. I have faith we'll be waiting for a while.

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30. Tbag on May 25, 2007 1:40 PM writes...

Synchem is no chemist. If he were, he'd know that Darwin's Theory of Evolution MAKES NO CLAIMS WHATSOEVER ABOUT THE ORIGIN OF LIFE.

That field of study is known as abiogenesis, and would require a lot of "faith" to nail down any 1 theory.

It takes absolutely no "faith" to understand evolution. Just pull your head out of your ass and open a book.

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31. Wilson Fowlie on May 25, 2007 1:55 PM writes...

People with this mentality obviously are dismissing or unware of many of the greatest past and present scientists who believe in a creator (Einstein, etc)

Maybe other scientists, but not Einstein:

It was, of course, a lie what you read about my religious convictions, a lie which is being systematically repeated. I do not believe in a personal God and I have never denied this but have expressed it clearly. If something is in me which can be called religious then it is the unbounded admiration for the structure of the world so far as our science can reveal it.

From a letter Einstein wrote in English, dated 24 March 1954. It is included in Albert Einstein: The Human Side, edited by Helen Dukas and Banesh Hoffman, published by Princeton University Press.

(Note: I stole this from http://atheistempire.com/greatminds/quotes.php?author=9)

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32. Flinthart on May 26, 2007 1:22 AM writes...

Dear Synchem:

You're a twat.

The question of particle-to-life in the field is unresolved, but in the lab it was done years ago. Unless, of course, you're of the "viruses aren't alive" stance.

Yep. In 2003, they built a polio virus from the ground up. It behaved... well, exactly like the viruses that were used to provide plans/models for it.

Don't take my word for it:

http://www.connotea.org/add?uri=http://www.nature.com/news/2003/031110/full/031110-17.html

By the way, I take it back. You're not a twat. I like twats. There are excellent uses for twats. They make the world a better place. You are definitely not a twat.

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33. Newcomer on May 28, 2007 4:15 PM writes...

Most people on either side of this issue tend to not recognize the fact that it actually is possible to believe in a personal, Creator God who used evolution to create the world. I, and many others, hold this view. The Bible was not written as a science textbook. It was written by ancient Middle East nomads who had no knowledge nor use for what we call Evolution.
It really does make me sad to see so much heated debate about this. Not to mention the fact that scientists such as myself are not only seen as second-class scientists by the professional world, and second-class Christians (sorry to make this even more politically heated) by my fellow church-goers. Evolution does nothing to undercut Religion. Religion does nothing to undercut Evolution (nor science). However, I know as well as many others that this debate probably will not end.

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Summary of the morning session on day two at the European Indoor Championships

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