Getting away with “heresy”

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Conspiracy mongering and accusations of censorship have become standard fare in the writings of even the supposedly more serious Intelligent Design advocates, perhaps paralleling their progressive realization of utter scientific irrelevance. By their own meter, in the Wedge document ID leaders confidently set themselves a goal of 100 published scientific, technical or academic articles by 2003. Since this goal has not even remotely been achieved, nor seems likely to be achievable in any distantly foreseeable future, unsubstantiated claims like:

"To question Darwinism is dangerous for all professional scholars but especially biologists." W.A. Dembski, The Myths of Darwinism, in Uncommon Dissent

or

"There's good reason to be afraid. Even if you're not fired from your job, you will easily be passed over for promotions." M. Behe, quoted in Harvard Political Review, 5/12/02

and hyperbolic accusations of "stifling orthodoxy" or "Stalinist repression" have understandably replaced the bold forecasts of yore.

Contrary to these accusations, however, it can be easily shown how in the last few decades evolutionary biology has seen a number of unorthodox ideas gain acceptance, probably even more than most other branches of science. The symbiotic origin of mitochondria and plastids, the catastrophic theory of the dinosaurs' extinction, the neutral theory of molecular evolution, the existence of an entire new kingdom of organisms (Archaebacteria) and punctuated equilibria are all examples of unconventional hypotheses which have become mainstream within a few years from their original formulation, based on the strength of evidence. This is not to claim that science does not suffer from a reluctance to change - just like any other human activity - but rather that, when a new idea has merit, it arguably has more chances of receiving a fair hearing in science than, say, in politics or business (let alone activities that thrive on strict adherence to tradition, like kabuki theatre or religion).

But what about ideas that actually challenge the most fundamental tenets of evolutionary theory, especially its darwinian components? Are those being censored?

One of the fundamental neo-darwinian principles is that of undirected heritable variation, i.e. that every new generation of organisms bears changes from their parents, and that such changes are unrelated to the organisms' immediate or future biological needs. It is this vast pool of continuously generated new traits, most - but not all - useless or harmful, that, passed through the sieve of natural selection, drives evolution. This is also the sticking point for many of the anti-darwinian critiques of evolutionary theory, including ID's, since undirected variation eliminates the need for any divine or vitalistic teleological action in evolution. More than the idea of natural selection (an obvious and undeniable fact), or the principle of common descent (at least to any extent permitted by their religious beliefs), it is undirected mutation as the source of new biological adaptations (especially complex ones) that most ID advocates find hard to accept.

In light of the ID advocates' censorship claims, therefore, it may come to a surprise that this very key evolutionary principle, most sacred tenet of darwinian "orthodoxy", has been in fact openly challenged in some of the most prestigious scientific journals, and that this challenge spurred not witch hunts and Stalinist purges, but a research effort that is now almost two decades old, to which both "heretics" and "traditionalists" equally contributed with prominent publications. The story started in 1988... actually, no, it started in 1943, when my compatriot Salvador Luria and his mentor Max Delbruck wrote a now classic paper demonstrating how mutations in bacteria are unrelated to the selective pressures to which the bacteria are exposed [1].

This is how their clever experiment went. Starting from an isolated, clonal (that is, genetically identical) population of bacteria, they grew up many independent cultures, over many generations, in a nutrient-rich, non-selective broth. Then, they plated small amounts of these cultures onto solid medium plates (a kind of bacterial Jell-O), onto which they sprinkled a preparation containing a bacterial virus, or bacteriophage. Bacteriophages, "phages" for short, infect bacteria and hijack their replication machinery to make thousands of copies of themselves, until the bacterium bursts, releasing more phages and propagating the infection. If enough phages are sprinkled on a plate of growing bacteria, within a few hours they can kill the entire culture. Occasionally however, infection-resistant colonies of mutant bacteria can appear on the plates. The question is, are the mutants arising as a direct response to phage challenge, or are they generated spontaneously, regardless of selective pressure?

Luria and Delbruck reasoned that, if the phage-resistance mutations occurred as a specific response to the selective challenge, every single plate from their parallel cultures should display more or less the same number of resistant colonies, since every plate contained the same number of bacteria under the same selective conditions. On the other hand, if the mutations occurred even before the onset of selection, while the bacteria were happily growing in non-selective broth, the predicted distribution would be much less homogeneous: plates from liquid cultures in which the mutation had appeared would display many resistant colonies, while plates from liquid cultures in which no mutant arose would be completely killed by the phage. This is akin to a Powerball lottery draw: if ticket buyers had any way to influence the outcome, one would predict to find many winners of relatively little amounts, while if the lottery is truly random, rare winners with huge jackpots would be expected. Luria and Delbruck found that the latter was the case for their bacteria. In the genetic mutation lottery, the bacteria had no foresight about what the winning numbers would be, and the vast majority of the mutations occurred as the bacteria were growing in non-selective medium, unaware of what awaited them on the selection plates.

This simple approach, subsequently perfected by many investigators and extended over the years to many different systems, led eventually to the general conclusion that indeed mutations are not directed by the selective needs of the organism, or in evolutionary lingo, that they are "random with regard to fitness". These results were critical in the development of the neo-darwinian New Synthesis. And there sat this "orthodoxy", this "dogma", for 45 years, so routinely and extensively confirmed in bacteriology and toxicology labs that everyone took it for granted, until 1988.

In that year, a paper was published in Nature, one of the very top science journals, by John Cairns, a very well known geneticist, and his collaborators [2]. Titled "The origin of mutants", the paper described an experiment not much unlike Luria's: in this case, mutants were selected for their ability to re-activate a crippled gene that allowed them to metabolize the sugar lactose, the only source of energy avaliable on the selection plates. However, unlike phage selection, starvation does not kill the bacteria immediately, but allows them a certain time to try to escape their dire situation. To everyone's surprise, Cairns reported that in these conditions, besides a number of early-growing mutant colonies that followed the expected Luria-Delbruck distribution, he could observe many late-growing resistant clones with a much more homogeneous distribution, which indicated that the mutations followed, and not preceded, the exposure to selection. Even more strikingly, when mutations at a different gene were analyzed in the lactose revertants, no mutations were observed. In other words, the mutations appeared to be "directed" by the selection process specifically to the gene under selection. Cairns and co-workers concluded therefore that at least in some cases, mutations could be specifically directed by selective pressures. Bam. The door was opne for teleology. Adieu, "darwinist orthodoxy". Cairns even "brazenly" raised the specter of possible Lamarckian hereditary mechanisms - one cannot get more heretic than that!

It's not that the paper flew below the radar - everybody understood its implications. In the same issue of Nature, Franklin Stahl, another one of the founding fathers of bacterial genetics, endorsed its conclusions and ventured his own model of how directed mutations may happen [3]. In the following weeks, several letters about Cairns' findings were published in the same journal, most of them raising questions with the experimental design. For instance, it turns out that, for experimental reasons, the gene under selection was located not on the main bacterial chromosome, but on a separate genetic element called a plasmid; some possible implications of this positioning for the mutation process had escaped Cairns. Others argued that his selection of "control" non-selected gene was not ideal, also based on some genetic considerations regarding that gene's functional properties.

No one called for Cairns' metaphorical head, no one argued how Nature could have dared publishing anti-darwinian material. In fact, bacterial geneticists all over the world set out to investigate the new claims in their own labs. Cairns' basic observations were throroughly replicated, ruling out basic artifacts, and several investigators set up different experimental models to test the principle, and also obtained results suggesting "directed" mutations. From the skeptic side, alternative mechanistic explanations for the "directed" mutation claim were tested, which ultimately confirmed that the new phenomena fell within the darwinian framework. Although its conclusions were often criticized on an evidence basis, Cairns' paper not only was not suppressed, but was directly referenced in hundreds of articles (497 to date, accorsding to the ISI Citation Index). The back-and-forth papers and scientific correspondence in major journals make for excellent (and often entertaining, if that's your kind of thing) reading on the matter [4].

Within a few years, evidence accumulated for non-teleological models of mutation. By 1998, essentially everyone in the field, including Cairns and his closest collaborators, agreed that the original observation did not reflect "directed" mutations, which by that time had been re-baptized with the less loaded term "adaptive mutations" [5, 6]. Nevertheless, several interesting features of bacterial biology had been discovered in the process. One alternative model for the observations proposes that starved bacteria enter a "hypermutable" state , either by virtue of a specific genetic "rescue" program, or as a result of breakdown of normal cellular control mechanisms [7]. In this state, high levels of mutations are introduced throughout the bacterial genome, but selection for specific mutants makes it appear as if the environmental conditions preferentially targeted mutations to the selected gene. Importantly, this mechanism has relevance for the onset of bacterial resistance to antibiotic drugs, and possibly to certain cellular states involved in cancer development [5]. In another novel mechanism which has been observed, a multiplication of the copies of the crippled gene ("amplification") is first favorably selected because it leads to a small but detectable increase in its product's minimal activity [8]. This massive gene amplification makes for better chances of mutation, and when these occur the extra gene copies become a burden, and are eliminated by selection. The final result is the appearance of highly targeted mutations. Research on all these mechanisms is actively ongoing [9].

Cairns today is Professor of Microbiology at the Radcliffe Infirmary, one of the medical teaching hospitals of Oxford University, and remains a recognized leading authority in mutation genetics. His 1988 article is one of the highest cited papers in the field, and has spawned an entire new area of study.

Perhaps, if ID advocates stopped dedicating most of their efforts to political pamphlets and challenges to grade school education standards, and attempted some real scholarship, their complaints could be taken more seriously. With the advent of the internet, avenues for disseminating unorthodox scientific results outside of any imaginary or real "censorship" system are more abundant than ever, and it's a safe bet that ID advocates, who even edit their own electronic journal, would have published them if they had any. Given however their deafening scientific silence, they might as well claim that the dog ate all their manuscripts.

I'll let Dr. Cairns have the last word:

[Scientific] truth is quite unlike the verdict of a court of law, because it does not depend on advocacy. [10]


Acknowledgements
I would like to thank Dr. John Cairns for kindly replying to my e-mails, and sharing his thoughts on the adaptive mutation controversy and scientific fairness in general.

References
1. S. E. Luria and M. Delbruck (1943). Mutations of bacteria from virus sensitivity to virus resistance. Genetics 28:491-511
2. Cairns J, Overbaugh J, Miller S (1988). The origin of mutants. Nature 335: 142-5
3. Stahl FW (1988) Bacterial genetics. A unicorn in the garden. Nature 335:112-3
4. For example, see correspondence in Nature 336, 525-8 (1988); Lenski RE and Mittler JE (1993). Science 259, 188-94, and related correspondence in Science 260, 1221-24 and 1958-60 (1993).
5. Cairns J. (1998) Mutation and cancer: the antecedents to our studies of adaptive mutation. Genetics 148: 1433-40.
6. Foster PL (1998). Adaptive mutation: has the unicorn landed? Genetics 148: 1453-9.
7. Hall BG (1992). Selection-induced mutations. Curr. Opin. Genet. Dev. 2:943-6.
8. Hendrickson H, et al (2002). Amplification-mutagenesis: evidence that "directed" adaptive mutation and general hypermutability result from growth with a selected gene amplification. Proc Natl Acad Sci U S A. 99: 2164-9.
9. A good review is found in: Rosenberg SM (2001). Evolving responsively: adaptive mutation. Nat Rev Genet. 2: 504-15.
10. Cairns J (1991) Nature 352, 101. From a letter regarding the Imanishi-Kari scientific fraud allegations (later proven unfounded).

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14 Comments

Andrea - I think you once suggested the prion story might be instructive along these lines, too. I wonder if Prusiner has ever weighed in on ID?

I’ve read a lot of rebuttals of Behe’s arguments and complaints, as well as many expose’s of his claims in Darwin’s Black Box. Why does Behe, a professor and biochemist, continue to stand behind his arguments, even though parts of them have been proven wrong (ie his claims about evolution in textbooks, silence within scientific community, etc)? This is the one question that always bugs me. I don’t usually listen to ID advocates, except behe cuz he seems to have some credibility.

Russ: The prion story indeed is another good example of highly unorthodox idea being relatively quickly recognized, although it doesn’t have to do with evolution (Prions are so interesting, they may be the subject for their own blog entry). There are so many such examples in science, it would almost be more instructive and fun to come up with out-of-the-mainstream good ideas who took longer than say, a decade or two to become accepted, and trying to figure out why that happened. McClintock’s transposons comes to mind. Any others?

Bill: I wish I knew. Behe certainly should know science, and is an accomplished biochemist, although he has practically ceased publishing since getting involved with ID. You should ask him.

“There are so many such examples in science, it would almost be more instructive and fun to come up with out-of-the-mainstream good ideas who took longer than say, a decade or two to become accepted, and trying to figure out why that happened. McClintock’s transposons comes to mind.”

I think it’s more instructive and fun to see how unorthodox ideas are “quickly” adopted because it shows how eager scientists are to jump on board and explore a new research area. That’s always worth pointing out to the pseudo-scientists : if there were any decent evidence for any of this supernatural stuff, scientists would be all OVER it. I’d certainly stop what I was doing and learn all about ESP if there was any reason to believe that it existed.

The answer to the question re: the slow acceptance of McClintock’s research is two-fold: (1) her discovery was genetics-based and couldn’t be proven until molecular biology passed through its golden age and (2) transposons really aren’t all that interesting, frankly, and there were more fundamental problems to be solved first.

I think one or both of those answers applies to most of the “belated acknowledgement” stories in science. That’s why those stories are, in my opinion, less interesting (at least insofar as they relate to the subject of this weblog).

One last point re: Cairns – his early work on the replication of E. coli is really fascinating. Essentially he “proved” in the late 60s (as I recall) that the E. coli chromosome is circular and replicates as a circle with two replication forks moving in opposite directions. The intermediates in this process have come to be called “Cairns structures” or “theta structures” (because they resemble the greek letter ‘theta’). His initial experiments were electron micrographs of x-ray film that had been laid upon replicating E.coli chromosomes that had been exposed to thymidine, purified and spread out. I am unaware of those experiments ever being repeated and, while they turned out to be correct, they always seemed to me to be too good to be true, given the intensive labor and luck involved.

That’s neither here nor there, except to show that if one is in the right place at the right time and works hard, you can get stuff named after you. ;)

An excellent example of an idea related to evolution that did not take off when first proposed might be continental drift. Alfred Wegener was never really taken too seriously on this idea. After his death, of course, things changed dramatically, and in a very short span of time.

Let me also point out that while CD is important in evolution (and, especially, in biogeography) evolutionary biologists were not really the ones responsible for judging the data.

Chris

A big problem with continental drift is how it was supposed to happen; how do continents plow through oceanic crust? None of the mechanisms proposed by the “drifters” were very convincing.

And the biogeography could be accounted for by the presence of now-sunk land bridges.

Continental drift became accepted after discoveries like seafloor spreading; this meant that continents do not have to plow through oceanic crust, but are instead dragged along.

And although some land bridges, like Beringia (between Alaska and Siberia), could be shown to exist, most others did not.

As Michael Crichton once opined in an editorial in SCIENCE, science fiction has to misrepresent science because science is deadly dull. The tedium of normal research also accounts for the hypnotic appeal of the “genius scientist fighting dogmatic establishment” bit to both intelligent design types and Darwinians. But the ID people win that exchange because so much of the evidence for evolution is utterly routine—think of the warehouses full of geological specimens, the data bases on genes, the taxonomic keys, the maps of strata. Faced with the prospect of delving again into the dusty mass of the confirming evidence, I find myself become sympathetic to Popper out of sheer sloth.

Evolutionary theory is, roughly speaking, simply the truth. For millions, however, it doesn’t make the best movie.

Yes, well, at least Michael Crichton’s variety of science fiction has to misrepresent science.

Others have done better. While they do tend to lean a bit unrealistically toward the Big Breakthrough for storytelling purposes, I have great admiration for some of Gregory Benford’s science-fictional depictions of what scientists do all day, as well as Stanislaw Lem’s (at least, in his straight science fiction; in his comic and satiric work, he tends more to parody the pulp-SF mad-genius tradition).

(Robert J. Sawyer even wrote a novel, “Calculating God”, in which aliens come to Earth and tell a paleontologist that the IDers are right– but God isn’t quite what most of them are imagining. I thought it was pretty good, once I was able to suspend disbelief sufficiently to swallow the premise. It’s not so much about the work of scientists, though.)

I will not grant Michael Crichton any authority at all on whether science is dull or exciting. From what I’ve read of his work, he doesn’t have a clue about how science works.

I think it is true that trying to represent science as a comprehensibly active drama to people who do not understand the language of science is a foredoomed activity. There has been damned little cleavage, gunplay, and hot pursuit in expensive cars in my lab experience, and if people expect that crap in the story, we’re stuck. You get stuff like CSI, with it’s caricature of science.

We just have to concede that science is an abstract and intellectual activity, and while it can be intensely exciting, it’s excitement of a flavor that doesn’t translate well to media for those with short attention spans.

The thing about Michael Crighton is that he has more self-awareness than most of us. I recall that when I first read Jurassic Park, I was astonished that anybody would abuse the notion of chaos theory so outrageously. Turns out that Crighton, who, by the way, is an MD, was perfectly aware of the idiocy of the novel’s premises. The man simply understand what the market will bear, a lesson we should probably absorb.

There’s a fascinating question in itself - to what extent are science fiction writers ethically permitted to distort any underlying science? As Crichton would do, and Arthur Clarke probably would not.

‘From what I’ve read of his work, he doesn’t have a clue about how science works.’

Crichton read physical anthropology at Harvard after deciding majoring in English was too hard (he submitted a piece by Orwell as his own work and got a C IIRC), then went to medical school (at Harvard too). He graduated but did not register as an MD because he could earn a living by writing and much preferred this. He was a visiting lecturer in anthropology at Cambridge University, and got some of his papers on endocrinology published in the New England Journal of Medicine.

PZ: There has been damned little cleavage, gunplay, and hot pursuit in expensive cars in my lab experience, and if people expect that crap in the story, we’re stuck.

That is certainly true, but it must be said that there is actual *sex* in many labs – how do baby lab animals come into existence?

But the sorts of sex that are known to happen … I think I’ll stop here.

Mods, I hope that my previous comment was not too offensive. If you find it offensive, please feel free to censor or delete it.

But back to the main subject. Science fiction varies widely in the sorts of futuristic technologies deployed, from the near-contemporary to bordering on fantasy. A well-known example, Star Trek, sometimes tends closer to the fantasy side. By comparison, Isaac Asimov’s robot stories are more “hard” science fiction, where the technology behaves much like contemporary technology, except that it’s more advanced.

Also, the “point” of science fiction is not to make technological prophecies, but to explore what would happen if various technologies existed – even very unlikely technologies, like psi powers. In effect, science fiction is not about the action, but the reaction. Thus, the point of Asimov’s robot stories is not how the robots’ brains would work, but the sorts of things that the robots would do. Being positronic is not the important thing; the Three Laws of Robotics are what’s important.

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This page contains a single entry by Andrea Bottaro published on April 6, 2004 4:48 PM.

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