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Getting away with
By Andrea Bottaro
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
"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 .
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 . 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
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 . 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 .
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 . 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 . 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 .
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 .
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
I'll let Dr. Cairns have the last
[Scientific] truth is quite unlike
the verdict of a court of law, because it does not depend on advocacy. 
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.
 S. E. Luria and M. Delbruck (1943). Mutations
of bacteria from virus sensitivity to virus resistance. Genetics 28:491-511
 Cairns J, Overbaugh J, Miller S (1988). The origin of mutants. Nature 335:
 Stahl FW (1988) Bacterial genetics. A unicorn in the garden. Nature
 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).
 Cairns J. (1998) Mutation and cancer:
the antecedents to our studies of adaptive mutation. Genetics 148: 1433-40.
 Foster PL (1998). Adaptive mutation:
has the unicorn landed? Genetics 148: 1453-9.
 Hall BG (1992). Selection-induced mutations. Curr. Opin. Genet. Dev.
 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.
 A good review is found in: Rosenberg SM (2001). Evolving responsively:
adaptive mutation. Nat Rev Genet. 2: 504-15.
 Cairns J (1991) Nature 352, 101. From a letter regarding the Imanishi-Kari
scientific fraud allegations (later proven unfounded).
Originally posted at The Panda's Thumb.