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SALK INSTITUTE FOR BIOLOGICAL STUDIES/MARC LIEBERMAN
FRANCIS CRICK
8 june 1916 . 28 july 2004
PROCEEDINGS OF THE AMERICAN PHILOSOPHICAL SOCIETY
VOL. 150, NO. 3, SEPTEMBER 2006
biographical memoirs
F
RANCIS CRICK, on whose behalf it would not be unreasonable to claim that he was the greatest and most influential theoretician of biology since Charles Darwin, died of colon cancer
in La Jolla, California, on 28 July 2004, at the age of eighty-eight. My
declaring that Crick was a “theoretician of biology” is not meant to
imply that his main scientific interest concerned the working out of the
quantitative relations that govern the behavior of complex biological
systems. Rather, by calling him a “theoretician” I want to indicate that,
like Darwin’s main scientific interests, Crick’s also lay in developing novel
qualitative concepts that can account for previously unfathomed aspects
of life.
Crick was born in Northampton, England, on 8 June 1916. On completing his secondary education at Northampton Grammar School he
went to University College, London, where he received a B.Sc. in 1937.
He stayed on to do graduate work for a Ph.D. in physics. However, in
1939 his studies at University College were interrupted by the outbreak
of war. During the war, Crick worked at the British Admiralty in London, devising detonators for magnetic and acoustic mines. Very likely,
all that time a hapless German Anti-Crick sat at the Kriegsmarineamt
in Wilhelmshaven, locked in a battle of wits with the future greatest
theoretician of biology since Darwin in the design of ever more sophisticated mines able to discriminate between the approach of real enemy
ships and dummy decoys.
The DNA Double Helix
Crick left London and the Admiralty in 1947 and went up to Cambridge for graduate studies in biology at the Strangeways Laboratory.
He was not thrilled, however, by the research project assigned to him
there—a study of the viscosity of the cytoplasm. So he moved to the
Cavendish Laboratory, the renowned Cambridge center for the determination of molecular structures by X-ray crystallography. At the Cavendish, Crick joined the research group headed by Max Perutz and
John Kendrew and began an X-ray crystallographic study of protein
structure for his Ph.D. thesis.
A crucial event in Crick’s career occurred in 1951, when James
Watson, a young American postdoctoral student trained in the formal
genetics of viruses and bacteria but hitherto a stranger to X-ray crystallography, turned up at the Cavendish. Watson was bent on determining
the structure of the DNA molecule, in which the genetic information
carried in the chromosomes of living creatures had recently been found
to be encoded. Chemical analysis of DNA had shown it to consist of
long chains of nucleotides, each nucleotide consisting of the five-carbon
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sugar deoxyribose, to which one of two kinds of purine bases—adenine
and guanine—or one of two kinds of pyrimidine bases—thymine and
cytosine—is attached. The nucleotides are linked via phosphate diester
bonds, which join many consecutive deoxyribose moieties, thus forming a polynucleotide chain.
Watson and Crick undertook a collaborative X-ray crystallographic
study of DNA at the Cavendish, which, by the spring of 1953, had culminated in their discovery that the DNA molecule is a double helix,
composed of two intertwined polynucleotide chains, held together by
hydrogen bonds formed between an adenine and a thymine, or between
a guanine and a cytosine, on opposite sides of the double helix.
The Central Dogma
At first sight, Watson and Crick’s discovery of the double helical structure of the DNA molecule resembled Linus Pauling’s—by then twoyear-old—discovery of the helical structure of protein molecules, in that
the formation of intramolecular hydrogen bonds also has an important
role in shaping Pauling’s protein helix. At second sight, however, the
discovery of the DNA double helix emerged as an event with much
greater heuristic consequences. It opened up enormous vistas for the
imagination and led Watson and Crick to their formulation of what
came to be known as the “central dogma of molecular biology.” The
central dogma provided a coherent account of the mechanisms by which
the parental DNA molecule achieves its two principal functions. One
of them is its self-replication, that is to say, its provision of the genetic
material for its offspring. The other is its expression, that is to say, its
direction of the synthesis of protein molecules whose chemical structure (that is to say their amino acid sequence) is encoded in one of the
two paired parental DNA polynucleotide chains.
According to the central dogma, DNA self-replication is a one-stage
process, in which, upon their unwinding, both of the pair of intertwined
polynucleotide chains of the parental DNA molecule serve directly as
templates for the assembly of a pair of replica DNA polynucleotide chains.
DNA expression is a two-stage process, however. At its first stage, one
of the two intertwined polynucleotide chains of the DNA molecule (the
“coding strand”) serves as a template for the synthesis of a single chain
of another type of nucleic acid, namely ribonucleic acid (RNA).
The basic chemical structure of RNA is similar to that of DNA, in
that RNA too is composed of long chains of nucleotides, with each
nucleotide consisting of a five-carbon sugar (ribose rather than deoxyribose, as in DNA), to each of which one purine base (adenine or guanine) or one pyrimidine base (cytosine or the thymine-analog uracil) is
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attached. Just as in DNA, so also in RNA are the nucleotides linked via
phosphate diester bonds, which join many consecutive ribose moieties,
thus forming a DNA-like polynucleotide chain.
At the second stage of the process of protein synthesis the nascent
RNA transcript is translated into protein molecules with the DNAspecified sequence of amino acids. This feature of Watson and Crick’s
central dogma implied that there must exist a genetic code that relates
the nucleotide sequences of the DNA’s “coding strand” to the amino acid
sequence of the encoded species of protein molecules. A simple consideration quickly revealed that this code could be no simpler than one
involving the specification of each amino acid by at least three successive nucleotides in the DNA’s coding strand. For the four kinds of nucleotides taken three at a time can provide 4 4 4 64 different kinds
of code words, or codons. Thus each of the twenty kinds of protein
amino acids of which natural protein molecules are composed can be represented in the genetic code by one such triplet codon. Moreover, because
the number of available kinds of codons is greater than the number of
kinds of protein amino acids to be specified, it seemed that some codons
are synonyms, i.e., that they encode the same kind of amino acid.
That the genetic code really does involve a language in which three
successive nucleotides in the DNA polynucleotide chain are read threeby-three in the protein translation process was proved experimentally
by Crick and Sydney Brenner in 1961.
Another example of Crick’s brilliant formulation of a novel qualitative concept, which he cut from whole cloth, was his conjecture in
1958 that the “transfer RNA” molecules, then recently identified in the
cytoplasm of all living cells, provide a set of nucleotide adaptors for
protein synthesis. Crick proposed correctly that it is by means of these
adaptors that messenger RNA recognizes the nucleotide triplet codon
representing a particular one of the twenty different kinds of protein
amino acids for its programmed, site-specific incorporation into a nascent
polypeptide chain.
In recognition of their seminal role in laying the foundations of
molecular biology, Watson and Crick shared the 1960 Lasker Award
and the 1962 Nobel Prize in Physiology or Medicine.
The Origin of Life
It so happens, however, that some other, less well known aspects of Crick’s
work, namely, his failures, provide clues for the future of biological
research. Inasmuch as I consider Crick the greatest theoretical biologist
since Darwin, I suspect that the problems he addressed but failed to
solve are probably insoluble: If Crick couldn’t solve them, nobody can.
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One of these great, unsolved biological problems is the origin of
life. Not only does it still remain unsolved, but it even lacks a credible,
molecular-biologically coherent proposal for its solution. Furthermore,
despite the obvious scientific importance of the origin of life problem
(and the virtual certainty of the award of a Nobel Prize for its solution), few biologists seem to be working on it any longer these days.
Some solutions for the origin of life enigma have been put forward
from time to time, but none have the feeling of “Eureka!” that Watson
and Crick’s discovery of the DNA double helix and their promulgation
of the central dogma evoked in the mid-twentieth century.
In 1981 Crick published a book-length essay entitled Life Itself: Its
Origins and Nature, in which he presented a theory about the origin of
terrestrial life. His main idea was what he called “directed panspermia,”
namely, the possibility that terrestrial life might not have originated on
Earth at all. Instead, extraterrestrial intelligences, or ETIs, living on a
planet outside of our solar system about four billion years ago, might
have known of our (as yet lifeless) planet Earth, with its mild climate,
salubrious atmosphere, and oceans of nutritious primeval soup. So, they
sent a rocket Earthward, loaded with living ET microbes. On impact
with planet Earth, the rocket discharged its microbial cargo into our as
yet sterile terrestrial oceans, and the rest is Darwinian history.
On first sight, Crick’s directed panspermia theory seemed little
more than science fiction, hardly worthy of the greatest theoretician of
biology since Darwin. On second sight, however, it turned out to be a
fiendish idea. For if it really had been the case that terrestrial life is
descended from microbes deliberately sent here a few billion years ago
by ETIs, then there is no reason to suppose that our kind of life actually had a natural origin. An ET Doctor Frankenstein might have fabricated our microbial ancestors from scratch in his lab, while his own ET
kind of life involved neither our proteins, nor our nucleic acids, nor our
genetic code. Hence, far from being science fiction (or a mere hocuspocus transfer of the real problem of the origin of life from one venue
to another), Crick’s directed panspermia hypothesis implies that the
problem of the actual origin of life may be insoluble in principle. For
if the only kind of life known to us did not have a natural origin and if
the ET life that did arise naturally is known to us only via the laboratory artifact it created (namely, our own ancestors), then the roots of
life itself would be lost forever in cosmic space.
Consciousness
Suppose that—as improbable as it may seem at present—the origin of
life did happen to be worked out one of these days. Then there would
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still remain another deep, unsolved biological problem, namely the consciousness provided to us TIs by our brain. Of all the remaining unsolved
biological problems, consciousness is one of the most difficult, as well
as one of the most fascinating.
The search for a resolution of the enigma of consciousness became
very popular lately among the romantic types of scientists who, in the
mid-twentieth century, had laid the conceptual foundation for the latterday discipline of molecular biology. These romantics included Crick, who
had left Cambridge in 1977 and moved to the Salk Institute for Biological Studies in La Jolla, California, where he remained until his death. His
main working hypothesis about consciousness was that there exists a special neural ensemble, which he designated “neural correlates of consciousness,” or NCC. They convert the subliminal, or unaware, sensory input
received by our sensory organs into conscious (i.e., aware) experience of
it in the parts of our cerebral cortex dedicated to sensory perception.
Crick’s postulation of the NCC was particularly relevant for the
pathological phenomenon neurologists call “performance without awareness,” which offers very promising experimental approaches to the enigma
of consciousness. An opportunity for studying this phenomenon is provided by a rather rare category of persons who have sustained some
slight damage to a restricted area of the brain dedicated to the processing of sensory input. They suffer from what appears to be a paradoxical impairment of their perception of one or another kind of sensory
stimuli.
A striking example of performance without awareness is provided
by the condition that has been given the oxymoronic name of blindsight. It is manifest in some persons who have suffered a brain lesion—
usually due to a cerebral stroke or a head injury. Blindsighted subjects
report that they are unable to see anything at all, or at least are unable
to see anything in some substantial part of their normal visual field. Yet
carefully designed tests reveal that these subjects are, in fact, able to
locate the spatial position of “unseen” visual stimuli. In other words,
although the blindsighted subjects do see the stimuli after all, they are
not consciously aware of having seen them.
Thus the abnormal exclusion of a particular piece of sensory input
from consciousness, i.e., of the existence of subliminal knowledge,
holds out the promise of identifying the normal neural pathways that
lead from subliminal sensation to conscious experience.
Crick’s specific conjecture that the NCC consist of ensembles of
cerebral nerve cells, which display a synchronous impulse rhythm at a
frequency of 40Hz, did not work out. But Crick’s concept of the NCC
has proved useful in the attempt to fathom the blindsight phenomenon.
In his last years, Crick formulated a neurological explanation of blind-
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sight in terms of two separate neural pathways along which the visual
input is processed and passed on to the motor cortex for execution of
appropriate body movements. One of these pathways passes through
the parts of the brain dedicated to the production of conscious awareness, i.e., Crick’s postulated NCC on its way to the motor cortex.
Hence if there is a lesion in that pathway the visual input may remain
subliminal.
The other pathway bypasses the cortical areas dedicated to the production of conscious awareness of the visual input and reaches the motor
cortex via a more direct route. Thus blindsighted persons can respond
to visual input with appropriate body movements in the absence of its
awareness because their motor cortex does know of the visual scene
subliminally.
In his book-length essay, The Mysterious Flame, the philosopher Colin
McGinn claimed that the problem of consciousness is insoluble in principle, not only from the biological but also from the philosophical
point of view. Other philosophers interested in understanding the brain
have branded McGinn as a “mysterian.” Yet despite having wrestled with
the problem of consciousness for the last fifteen or so years of his life,
even Francis Crick did not come up with any profound new insights
into consciousness, other than his speculations about the NCC. Thus
Crick’s failure to solve the problem of consciousness provides strong
support for McGinn’s proposition that it is insoluble.
Crick and God
Crick’s attitude toward religion was uncompromisingly hostile. So at
first sight it seemed surprising that he prefaced his anti-vitalist John
Danz Lecture entitled On the Nature of Vitalism (Seattle and London:
University of Washington Press, 1966) with this quotation from Salvador Dali: “And now the announcement of Watson and Crick about
DNA. This is for me the real proof of the existence of God.”
As readers of James Watson’s autobiography, The Double Helix,
know, Watson wrote that he had never seen Francis in a modest mood.
But not even Watson would have claimed that Crick really believed
that they delivered the real proof of the existence of God. No, Crick
considered Dali’s statement a tremendous joke, and although Dali’s
intent was surely serious, Crick was making fun of Dali by according
him a place of honor under the masthead of an anti-religious tract.
In my opinion, however, Dali had sized up the situation quite correctly: The achievements of molecular biology did furnish proof for the
existence of God (or for its atheistic synonym, “Nature”), the single
principle that, according to Plato, makes science conceptually possible
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in the first place. Crick evidently subscribed to this Platonic doctrine
as well, because in his Danz Lecture he pointed out that “though the
three-dimensional conformation of proteins can, in principle, be worked
out from the structure of their component amino acids, the necessary
computations are almost prohibitively long. But proteins find their conformations all the same because Nature’s (read ‘God’s’) own computer—
the system itself—works so fantastically fast. Also she (read ‘He’) knows
the rules more precisely than we do. But we still hope that, if not to
beat her (read ‘Him’) at her (read ‘His’) game, we can at least understand her (read ‘Him’).”
Albert Einstein affirmed his unwillingness to accept the epistemological implications of Werner Heisenberg’s uncertainty principle by
asserting that “God does not play at dice.” By their statements both
Crick and Einstein reveal their allegiance to the Platonic doctrine, and
Crick probably made the verbal substitution of a personified “Nature”
for “God” only to avoid giving the impression that (God forbid!) he
was a Christian. Crick may not have known that Niels Bohr suggested
a theological solution to Heisenberg’s uncertainty principle, namely,
that there IS no God but He DOES play at dice.
Elected 1972
Gunther S. Stent
Professor of Neurobiology, Emeritus
University of California, Berkeley