The Questionable Authority

Natural Selection, Antibiotic Resistance, and Interesting Questions.

Posted by Mike Dunford on March 13, 2008
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Dr. Michael Egnor, of SUNY Stony Brook and the Discovery Institute, doesn’t think that evolution is relevant to trying to figure out how to combat the spread of antibiotic resistance. The interesting areas of research, he believes, lie in other areas of biology:

The important medical research on antibiotic resistance in bacteria deals with how the mutations that give rise to resistance arise, exactly what those mutations are and how they work, and what can be done to counteract them. The important medical research involves genetics, molecular biology, and pharmacology. Darwin’s theory is of no substantive value to the research because, as Mr. Dunford admits, there is no difference between antibiotic resistant bacteria that emerge through artificial intelligent selection and antibiotic resistant bacteria that emerge through natural selection. Antibiotic resistance is a phenomenon that occurs because there are often a few bacteria in a large population of bacteria that have a mutation that renders them less sensitive to the antibiotic. These bacteria that aren’t killed by the antibiotic eventually outnumber bacteria that are killed by the antibiotic. Survivors survive. Does this mundane observation really help Mr. Dunford understand things he may not have otherwise understood? It certainly doesn’t advance medical research in any meaningful way. New insights into genetics, molecular biology, and pharmacology do advance medical research.

I realize that I’m just begging for Dr. Egnor to take what I say out of context again, but he is not entirely wrong. If I was working on ways to fight antibiotic resistance, I would certainly want to focus more on the molecular mechanisms that are involved in the development of resistance than on the question of how resistance spreads through a population of bacteria after it appears.

The fact of the matter is that we already have a very good idea of how antibiotic resistance spreads through a population of bacteria.

Bacteria reproduce at a very high rate. In bacteria, as in all other living organisms on this planet, the process of reproduction is not perfect. The new copy of the bacterial DNA is not always exactly the same as the old one. Sometimes, the errors in reproduction have no effect on the bacteria. Sometimes, the errors in reproduction kill the bacteria. Sometimes, the errors in reproduction result in the bacteria gaining or losing the ability to do certain things. Because these errors take place in the DNA, they will be passed on (imperfectly) as the bacteria continue to reproduce.

If the environment that the bacteria live in changes, and bacteria that have an “error” that allows them to do something new become much more likely to reproduce than bacteria without the “error”, the entire population is going to change very quickly. The bacteria that have the “error” will produce more bacteria that have the “error”. The bacteria that lack the “error” will produce fewer bacteria without it. Soon, the vast majority of the bacteria in the population will have the “error”.

Antibiotics change the environment that bacteria live in. Bacteria that have DNA copying mistakes that result in them being better able to survive and reproduce in the presence of the antibiotic will produce more bacteria like themselves. After a relatively small number of generations, the vast majority of bacteria in the population will be resistant to the

That’s a relatively simple version of the explanation, of course. I’ve left out quite a few details. Still, it’s a pretty reasonable summary of our understanding of how a new trait (in this case, antibiotic resistance) can spread through a population (in this case, bacteria).

It’s also a reasonable summary of the process of evolution through the mechanism of natural selection. This is the mechanism that was first outlined in the Darwin and Wallace papers in 1858, and it’s the process that Darwin discussed in depth in The Origin of Species.

If researchers are focusing more of their attention on the question of how resistance arises in the first place than they are on how resistance spreads through a population after it arises, it’s because we have a reasonably good understanding of how resistance spreads. In science, the interesting questions are the ones that still need to be answered.

The fact that a question has been answered does not mean that either the question or the answer are unimportant. In the case of antibiotic resistance, both remain extremely important. It’s our understanding of evolution that informs the measures that doctors need to take to reduce the risk of developing new strains of multiple drug-resistant bacteria. It’s our understanding of evolution that leads us to restrict the veterinary use of certain antibiotics in order to better preserve their effectiveness when used by people. The importance of evolution in this case is not in any way reduced simply because we understand how it works.

In fact, we understand how evolution works so well that we can actually use evolution as a tool to aid in researching other questions about antibiotic resistance. In the research project that kicked off this latest burst of Egnorian rhetoric, scientists used natural selection to obtain a population of antibiotic-resistant bacteria. They then studied those bacteria to figure out what made them resist the antibiotic. The importance of evolution in this case in not reduced simply because we understand it well enough to make it work for us.

Dr. Egnor apparently wants to object to all of this because it’s not one of the areas of evolutionary biology that he finds objectionable:

Antibiotic resistance is irrelevant to the inference to design or to chance in biology, and therefore it is irrelevant to the debate over Darwin’s theory.

That assertion is very difficult to justify. “Darwin’s theory” is just what I outlined above: if a heritable trait makes it more likely that those who possess it will successfully reproduce, the trait will spread through the population. That process drives the spread of antibiotic resistance. That may not be something that Egnor objects to, but it’s still part and parcel of “Darwin’s theory”.

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Comments

  1. #1 _Arthur
    March 13, 2008

    “Antibiotic resistance is irrelevant to the inference to design or to chance in biology, and therefore it is irrelevant to the debate over Darwin’s theory.”

    Egnor’s right. Facts are irrelevant tho the Design Inference.

  2. #2 sinned34
    March 13, 2008

    Egnor is such a tool!
    The theory of evolution is not the simplistic tautology that Egnor seems so enamored of: “survivors survive”. Rather, it’s the study of how those “survivors” obtain the traits which allow them to survive!
    I worries me that such a simple concept can escape the understanding of a neurosurgon. Egnor reminds me of a mechanic who didn’t learn to drive – he can work on an engine (the brain), but has no idea how to use it himself.

  3. #3 pathologist
    March 13, 2008

    Heehee. There are reasons behind the choice of specialty. I once asked a friend of mine why she went into surgery rather than medicine and she told me it was because she was more of a doer than a thinker. Probably applies to Egnor. I myself gravitated toward pathology because I was crappy at surgery. I like to think about what I’m cutting on in order to figure out how it got to be in the condition it is in, rather than worrying about keeping it alive and fixing it! Perhaps faith healers don’t like to think OR do?

  4. #4 harold
    March 13, 2008

    Some replies from another physician, albeit one who was less prestigious than Dr Egnor.

    The important medical research on antibiotic resistance in bacteria deals with how the mutations that give rise to resistance arise, exactly what those mutations are and how they work, and what can be done to counteract them. The important medical research involves genetics, molecular biology, and pharmacology.

    In other words, Dr Egnor now appears to have changed his mind, and accepted the theory of evolution. He agrees that genetic diversity occurs, that mutations can be beneficial to the host in some circumstances, and that phenotypes can be selected for.

    He now accepts the theory of evolution (there’s more to it than just that, random genetic drift and so on, but he’s accepted the basic story). Case closed. Thanks Dr. Egnor. Glad we cleared that up.

    Darwin’s theory is of no substantive value to the research because,

    I’ll explain why this is wrong in a minute, but Dr Egnor is on a roll here, let’s not let one mistake slow us down.

    as Mr. Dunford admits, there is no difference between antibiotic resistant bacteria that emerge through artificial intelligent selection and antibiotic resistant bacteria that emerge through natural selection.

    Glad to hear that you agree with mainstream scientists and physicians here, Dr. Egnor. Your “champions” Paul and “Keith Eaton” (who is probably actually a parody poster) were screaming all day about this.

    Antibiotic resistance is a phenomenon that occurs because there are often a few bacteria in a large population of bacteria that have a mutation that renders them less sensitive to the antibiotic. These bacteria that aren’t killed by the antibiotic eventually outnumber bacteria that are killed by the antibiotic. Survivors survive.

    Minor caveats here. Survivors don’t just survive, they reproduce at a relatively higher rate (in this case more or less an infinitely higher rate, if all others are being prevented from reproducing), too, otherwise it wouldn’t matter. Also, it’s a bit more complex than just a point mutation in many cases, plasmids and so on, but Mike simplified, too, and the simplifications are not deceptive. But basically, correct again.

    Does this mundane observation really help Mr. Dunford understand things he may not have otherwise understood?

    It sure does. Understanding that we were looking for mutations/alleles (including on exchangeable elements) that allowed the expression of an antibiotic resistant phenotype that would be selected for allowed us to figure out what’s going on with resistance in the first place, for one thing.

    If scientists thought that “there are no positive mutations”, or “mutations can never add information”, or hadn’t studied classical and molecular genetics and natural selection, we wouldn’t have had a clue. The theory of evolution was applied, but it was taken so for granted that no-one even mentioned its name.

    It certainly doesn’t advance medical research in any meaningful way. New insights into genetics, molecular biology, and pharmacology do advance medical research.

    First of all, technically, no-one said that the theory of evolution would “cure” antibiotic resistance. What people said was that antibiotic resistance is a clear example of evolution. You’ve admitted that above yourself. But there’s still a further problem here…

    No, Dr Egnor, understanding what’s happened so far, understanding it completely and in an unbiased way, very much does help, indeed is necessary for, advancing medical research.

    Resistance is still a problem, new problems will arise, and new insights will be applied to old problems.

    Understanding how life works as well as we can, which very much includes a recognition of the role of evolution, will continue to be critical.

    For the record, Dr Egnor, you’ve advanced light years beyond your creationist “brethren” here. I doubt if it will last. But let me just state that whatever your religious or political beliefs, you could stop right now, admit you were initially mistaken, no-one will think the least of you, and it won’t have a thing to do with God or how the country should be run.

  5. #5 harold
    March 13, 2008

    Former hematopathologist here, by the way.

    It would certainly suit the conceits of my former specialty to hope that we might be the first to react strongly to any effort to associate medicine with pseudoscience.

    Unfortunately, I already know that there is at least one creationist pathologist out there. Still.

  6. #6 T. Bruce McNeely
    March 13, 2008

    Harold, I am also a pathologist who has recently changed direction to working in microbiology. A large part of my work involves infection control and antibiotic stewardship, both of which rely on knowledge of evolution for success. Development of new infection control measures and treatment of infections also relies on evolutionary principles. To say that evolution doesn’t advance medical research is simply stupid. Like I said in another post, if Dr. Egnor were practising at my hospital, I would be lobbying for suspension of his antimicrobial prescribing privileges.

  7. #7 Kevin
    March 13, 2008

    Antibiotic resistance is a phenomenon that occurs because there are often a few bacteria in a large population of bacteria that have a mutation that renders them less sensitive to the antibiotic. These bacteria that aren’t killed by the antibiotic eventually outnumber bacteria that are killed by the antibiotic. Survivors survive. Does this mundane observation really help Mr. Dunford understand things he may not have otherwise understood?

    This is so plainly wrong, I can’t imagine how he believes it himself.

    Let’s imagine for a second that “darwin’s theory” was not established and accepted.
    Well then, it would not make much sense just to study how resistance arises would it? Because resistance in one individual or small population wouldn’t mean much — maybe it wouldn’t spread, or maybe it would just die out, etc. Instead we’d have to study all sorts of random ideas. Maybe the resistance appears everywhere all at once? Maybe it doesn’t spread by inheritance, but has to appear in each individual?

  8. #8 George
    March 13, 2008

    I find it amazing that a doctor is not interested in how a new trait of antibiotic resistance spreads in bacterial populations. Seems this amazing ignornace has led to very unfortunate state where wild bacteria have resistance to our best antibiotics – I wonder how this might have happened?

    Wild bacteria have evolved antibiotic resistance. Natural selection plays a vital role.

  9. #9 fun
    March 14, 2008

    Wild bacteria have evolved an antibiotic resistance from existing genes correct? Can a new gere evolve without an existing gene present- or can a new gene emerge from organic material?

  10. #10 Malc
    March 14, 2008

    @Fun

    I’m not practicing biologist – but my understanding is that one way new genes emerge is when an existing gene is duplicated (which happens relatively frequently).
    If a mutation then occurs in one copy of the gene the other copy continues to provide the original function in the organism and it’s descendants, while natural selection etc can act freely on the mutated version.

    I’m sure that’s a vastly simplified version and welcome corrections :-)

  11. #11 Wounded King
    March 14, 2008

    @Fun

    While Malc is right in his description of the importance of duplication to allow for genetic divergence there is one very popular example of a gene thought to have arisen arguably without an existing gene being present, that of the nylon digesting enzyme NylB.

    The NylB protein in Flavobacterium is thought to be derived from a frameshift mutation in a previously existing open reading frame, although whether this was an actual gene is debatable, which produced a new reading frame encoding the nylon digesting enzyme. The mutation in question is a simple 1 base pair insertion which is sufficient to produce and entirely new reading frame, with a substantially altered sequence from the original, encoding the new enzyme.

    For the original research on this mutation see …

    Ohno S. (1984 Apr). Birth of a unique enzyme from an alternative reading frame of the preexisted, internally repetitious coding sequence. Proc Natl Acad Sci U S A , 81, 2421-5.

    The full text is available at http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=345072 .

    This sort of occurence seems a much less likely source than gene duplication and neofunctionalisation as an origin for most new genes. In both cases there needs to be some genetic material to work with, genes don’t just appear from ‘organic material’ other than organic material in the form of nucleic acids.

    TTFN,

    Wounded

  12. #12 Torbj�rn Larsson, OM
    March 14, 2008

    Maybe I’m wrong, but I would imagine that neurosurgeons sometimes helps fight cancers by removing tumors. If so, it is amazing that Egnor doesn’t care that those tumors are the likely result of evolutionary processes (mutation and selection, including preoperative treatments, among precancerous and cancerous cells), nor that the operations may kick off another round of evolution among suppressed daughter cells. IIRC there is research here, as it concerns pre- and postoperative treatments as well as the operations.

    One could even imagine that it would be against medical integrity and good practice among surgeons to not avail themselves and their patients of best knowledge and practices.

    Can a new gere evolve without an existing gene present

    IANAB, but it is my understanding that new genes evolve in the genome without necessarily being descended from a functioning gene (which happens most often, say by gene duplication). Retrotransposons (SINEs and LINEs) is claimed to have been exaptated for exonic (AFAIU functional) gene parts. Pseudogenes, formerly functional genes, may have evolved to have new function. Haven’t read the papers, but it seems feasible to this layman.

    or can a new gene emerge from organic material?

    That’s abiogenesis, not (resistance) evolution.

  13. #13 Jeff Webber
    March 14, 2008

    re. “…Darwin’s theory is of no substantive value to the research…”
    perhaps a useful analogy for Dr. Egnor would be:
    Although you as a surgeon may not understand or even think about anything to do with mining, smelting, metal casting or metallurgy, nonetheless these fields are necessary to produce the tools that allow you to do your job. So it is with MET, “Bacterial Resistance Theory” is built on it.

  14. #14 George
    March 14, 2008

    @fun

    I think your question points out the greatness of science. It is the discovery of the details that is so exciting. I suppose some day there will be enough details known that general rules about how changes occur are known. Changes occur to existing genes, to duplicate genes, perhaps inserted genes (viral), what else. I think it will be fun to find out.

    While I view Dr. Egnor as a liar, he is trying to avoid the issue by pointing to the the lab research that attempts to discover the details of natural evolution. This battle between nature (evolving antibiotic resistance) and human efforts to develop new antibiotics can be obfuscated – that is the trick Dr. Egnor attempts.

    The reality is that if evolution did not occur in the first place, then antibiotic resistance would not be an issue. Kinda makes Dr. Egnor’s claim that eveolution is not an important consideration look stupid. When the whole problem exists only becasue of evolution in the first place.

  15. #15 Philip H.
    March 14, 2008

    Interestingly, I went to a seminar this week here in the D.C. area that described an analogous question to this one (Emerging disease research). The seminar’s presenter described to us how, even though we can discern the high degree of ecological specialization in disease organisms, and we can discern the pathways that could lead to their spread (not unlike the pathways leading to antibiotic resistence) we humans still refuse to operat ein a way that elucidates those pathways and shuts them down. his exact comments was “there’s no profit in curing disease.” He also had some itntereting things to say about how humans got to this cross roads.

  16. #16 trrll
    March 14, 2008

    There are still some mysteries in antibiotic resistance. For example, as Steve Projan points out, some bacteria fail to develop resistance in response to antibiotic use. Syphilis is still vulnerable to penicillin, for example. Projan suggests that this may be related to genome size, with large genome bacteria perhaps having leeway to evolve. This also suggests that small genome bacteria may be somehow “locked in” to a limited genome size, perhaps having some mechanism that prevents expansion of the genome such as by duplication.

  17. #17 Christophe Thill
    March 14, 2008

    Isn’t Egnor condemning himself with his statements? Isn’t he actually saying that Darwinian evolution processes are so obvious that pointing them explicitely doesn’t add anything, because they’re always working in the background anyway?

  18. #18 Unsympathetic reader
    March 15, 2008

    Egnor is completely missing the boat when he writes, “Antibiotic resistance is irrelevant to the inference to design or to chance in biology, and therefore it is irrelevant to the debate over Darwin’s theory.”

    Actually, antibiotic resistance is perfectly germane to the question of design. In fact, the acquisition of resistance seems to align quite well with the role of ‘chance in biology’ (& other Darwinian mechanisms) and is a pretty clear example of evolutionary change that does not require ‘inference to design’.

    I predict that in Egnor’s next round he’ll ‘pull a Spetner’ by moving the goalposts as to what constitutes ‘significant’ evolutionary change.

  19. #19 Paul Burnett
    March 15, 2008

    Philip H quoted a speaker whose exact comment was “there’s no profit in curing disease.”

    Exactly. In a capitalist economy, it makes more sense to minimize disease prevention, keep people sicker longer, and help them live as long as possible – preferably sick. That’s the American versus European model – more money spent on health care for less health.

    A couple of years ago the Journal of the American Medical Association published a study, “Disease and Disadvantage in the United States and in England,” which found being American seems to damage your health regardless of your race and social class. A New York Times report on diabetes pointed out that insurance companies are generally unwilling to pay for care that might head off the disease, even though they are willing to pay for the extreme measures, like amputations, that become necessary when prevention fails. ( http://www.pekingduck.org/archives/003688.php )

  20. #20 harold
    March 16, 2008

    Paul Burnett –

    Exactly. In a capitalist economy, it makes more sense to minimize disease prevention, keep people sicker longer, and help them live as long as possible – preferably sick. That’s the American versus European model – more money spent on health care for less health.

    There is a large amount of truth to your post, especially with regard to the perverse payment policies of many private insurers.

    However, it doesn’t help anything to indulge in oversimplified conspiracy theories or overgeneralizations.

    1) The countries with the best health records, i.e. Western Europe, Japan, Australia/NZ, Canada, and some others like Costa Rica, are all democratic capitialist countries. Cuba is the rare example of a non-capitalist, non-democratic society that has surprisingly good health statistics. Yes, these countries have universal health coverage – that’s a characteristic of developed, capitalist countries; the US is an exception (and see below) – and most have more generous social programs and less extreme division of wealth than the US, as well. But they’re still capitalist countries. To deny this is to empower the Fox News version of reality.

    2) The US does have a very good national health program for the elderly and disabled, efficient and well-accepted by patients and providers. It’s called Medicare. Our problem is that it’s not universal enough. In fact, in overall terms, the US is simply the “worst” of the countries I listed in “1)” above (as well as a fair number of others that now exceed us a bit in life expectency and favorable infant mortality statistics; nearly all democracies).

    I am an extremely strong advocate of universal health coverage in the US. My personal view is that just extending Medicare to everyone regardless of age (which would not cost anywhere near as much as it sounds, because the sickest people who generate overwhelmingly the most costs are already covered) would be one simple solution (the complexities of Medicare notwithstanding).

    The word “socialism” and its derivatives are totally useless, because there is no agreement as to what that word means. To some people, the presence of “social programs” within a system makes it a “socialist” system (eg calling the Netherlands “socialist”); to others, near total government control of all economic transactions is implied. Misunderstandings are common and people with English as a second language are continually confused.

    One thing is certain. To argue that the US cannot have universal, effective health care coverage without “becoming socialist”, or otherwise engaging in some sort of overarching societal change, is logically about the same as arguing that we can’t have publicly funded fire departments without being “socialist”.

    Publicly funded universal health care coverage could be easily achieved, and need not at all be tied to any other, more controversial, economic, political, or social change. It is only in Fox News reality that a country whose Medicare system probably already covers almost a majority of true health care costs, could not provide its citizens with health care fairly easily.

  21. #21 Kaleberg
    April 5, 2008

    Isn’t Egnor one of those religious nuts who argue that antibiotics resistance flows from the fact that bacteria worship a superior god to the one that we worship?

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