Francis Crick 享年 88
Francis Crick, Co-Discoverer of DNA, Dies at 88
The New York Times
July 30, 2004
By NICHOLAS WADE
Francis H. C. Crick, co-discoverer of the structure of DNA, the genet-
ic blueprint for life, and the leading molecular biologist of his age,
died on Wednesday night in a hospital in San Diego. He was 88.
He died after a long battle with colon cancer, said Andrew Porterfie-
ld, a spokesman for the Salk Institute, where he worked.
Dr. Crick laid the foundations of molecular biology in a sustained
burst of creativity that began in 1953 with the discovery of the structu-
re of DNA, the hereditary material, in Cambridge, England, and ended
about 13 years later with the subject's primary problems solved, most of
them either by Dr. Crick or by scientists in his circle.
The discovery of the structure of DNA resolved longstanding question-
s about the nature of the hereditary material and the manner in which it
is copied as one generation succeeds another. The proposal for the struc-
ture, almost immediately accepted, was electrifying to scientists not
only because of its inherent elegance but also because it showed how
biology, evolution and the nature of life itself could ultimately be
explained in terms of physics and chemistry. Indeed, the desire to repla-
ce religious with rational explanations of life was a principal motivati-
on of Dr. Crick's career.
So central is DNA to biology that the names of Francis H. C. Crick
and James D.
Watson, his American colleague in the discovery, may be remembered as
long as those of Darwin and Mendel, the architects of the two pillars of
modern biology, the theory of evolution and the laws of genetics.
Some consequences of understanding the structure of DNA are already
familiar, from linking suspects to crime scene evidence to manipulating
it to make genetically engineered crops. But these are just foretastes
of a gene-based medical revolution that is expected to unfold in the
years ahead now that the human genome - about three billion units of DNA
, encoding all the biological information needed to generate and maintai-
n a living person - has been deciphered.
Dr. Crick was a scientist with a thirst to understand and a talent
for productive friendships. It was his two-year collaboration with Dr.
Watson that made possible the discovery of the structure of DNA, a feat
that each has said he would not have accomplished without the other.
After Dr. Watson returned to the United States, Dr. Crick's close collab-
orator for many years was Sydney Brenner, with whom he solved the nature
of the genetic code.
Dr. Crick occupied a rarely paralleled position of intellectual
leadership in the early years of molecular biology. In intense efforts
to explore beyond the door opened by the discovery of DNA, biologists
from Paris to Pasadena, were drawn into a pursuit that at every stage
was shaped by Francis Crick.
"By brain, wit, vigor of personality, strength of voice, intellectua-
l charm and scorn, a lot of travel, and ceaseless letter-writing, Crick
coordinated the research of many other biologists, disciplined their
thinking, arbitrated their conflicts, communicated and explained their
results," the historian Horace Freeland Judson wrote in "The Eighth Day
of Creation."
The French biologist Jacques Monod told Mr. Judson: "No one man
discovered or created molecular biology. But one man dominates intellect-
ually the whole field, because he knows the most and understands the
most. Francis Crick."
A unforgettable portrait of Francis Crick was drawn by Dr. Watson in
"The Double Helix," his best-selling account of their discovery. Mr.
Crick was unknown at the time, pursuing his Ph.D. at the advanced age of
35. But the lack of this credential did not diminish his confidence in
his own abilities.
"I have never seen Francis Crick in a modest mood," Dr. Watson wrote
in the first sentence of his book.
He described Mr. Crick's animated conversation, his manic laughter,
his habit, infuriating to colleagues, of pumping them for their data and
showing them what it meant.
"Conversation with Crick," Dr. Watson wrote, "frequently upset Sir
Lawrence Bragg," the director of the Cavendish Laboratory in Cambridge,
where Mr. Crick then worked, "and the sound of his voice was often suffi-
cient to make Bragg move to a safer room."
Yet Dr. Watson's vivid portrait held elements of caricature. Mr.
Crick's immodesty did not extend beyond the realm of intellectual argume-
nt.
"Rather than believe that Watson and Crick made the DNA structure, I
would rather stress that the structure made Watson and Crick," Dr. Crick
wrote diffidently in a memoir, "What Mad Pursuit."
On the day of the discovery, Dr. Watson asserted, "Francis winged
into the Eagle," the dingy Cambridge pub where they lunched every day, "
to tell everyone within hearing distance that we had found the secret of
life."
Dr. Crick did not remember that incident, he has written, but he did
recall going home and telling his wife, Odile, that he seemed to have
made a big discovery. Years later, he continued, Odile told him that she
had not believed a word of it, saying, "'You were always coming home and
saying things like that, so naturally I thought nothing of it."
Rejected Tenured Position
Francis Harry Compton Crick was born on June 8, 1916, in Northampton
, England, where his father and uncle ran a boot and shoe factory founde-
d by their father.
He studied physics at University College, London, and after a short
period researching the viscosity of water under high pressure (in his
view "the dullest problem imaginable"), he was drawn by World War II
into military research, working on the design of magnetic and acoustic
mines. He did so well at this job that after the war, Dr. R. V. Jones,
the head of Britain's wartime scientific intelligence, wanted Mr. Crick
to succeed him. But Mr. Crick chose research.
"Looking back, it was absurd because I had a tenured job," he said
in a recent interview. Finding himself at loose ends after the war, he
decided the most interesting research problem lay in trying to understan-
d the physical basis of life, the division between the living and the
nonliving. The choice eventually drew him to the Cavendish Laboratory in
Cambridge, one of the world's leading centers for studying the structure
of proteins by X-ray analysis. At 35, he started working for his Ph.D.
on the structure of proteins.
Proteins were already understood to be the cell's working parts, and
Mr. Crick began with studying the structure of hemoglobin, the oxygen-ca-
rrying pigment of the blood. He worked in a branch of the Cavendish, the
Medical Research Council unit, headed by Dr. Max F. Perutz. Well before
his thesis was finished, however, he realized that a far more interestin-
g problem was the structure of deoxyribonucleic acid, or DNA. A classic
experiment of 1944 had pointed to DNA as the genetic material. But biolo-
gists had made almost no progress since then in understanding how DNA
might store hereditary information and few were actively working on the
problem.
Mr. Crick's life was changed one day in October 1951 when a Dr.
Watson, a 23-year old American biologist, walked into his life. Dr.
Watson also understood that the structure of DNA was the key to everythi-
ng. Neither was supposed to be working on DNA, but they at once fell
into discussing how the problem might be approached, in conversations so
sustained that the pair were given their own small office at the Cavendi-
sh laboratory so their voices would not disturb everyone else.
"Jim and I hit it off immediately," Dr. Crick later wrote, "partly
because our interests were astonishingly similar and partly, I suspect,
because a certain youthful arrogance, a ruthlessness and an impatience
with sloppy thinking came naturally to both of us."
Their approach, copied from the great chemist Linus Pauling, then at
the California Institute of Technology, was to build exact scale models
of the DNA that would be compatible with the limited information availab-
le from X-ray crystallography, a method of probing a chemical's structur-
e with X-rays. A political difficulty was that the problem of DNA's
structure had been assigned to another scientist, Maurice H. F. Wilkins
of King's College, London. Under the etiquette of British science, to Dr
. Watson's amazement, no one else was supposed to muscle in on it.
But Dr. Wilkins, a wartime friend of Mr. Crick's, said he did not
object to his trying a model. Dr. Watson and Mr. Crick soon had one
ready. It was based, in part, on X-ray data about DNA obtained by Dr.
Wilkins's colleague, Dr. Rosalind Franklin. Dr. Watson had heard Dr.
Franklin describe these data in a public lecture but had misunderstood
them.
For their model, Mr. Crick and Dr. Watson constructed the backbone
of the DNA molecule in the form of a spiral, or helix, with the winding
chains held together in the middle by metal ions. The bases, the four
chemical subunits that spell out the genetic information, pointed outwar-
d from the chains because the two researchers could see no way that the
necessarily irregular sequence of bases would match together neatly if
they pointed inward.
With the model completed, Mr. Crick invited Dr. Wilkins and Dr.
Franklin to Cambridge to inspect their progress. Dr. Franklin instantly
recognized a glaring error, and a few days later Dr. Bragg, embarrassed
by the debacle, ordered Mr. Crick to do no more work on DNA.
Nonetheless, Mr. Crick and Dr. Watson kept thinking about the proble-
m and a few months later were able to reverse Dr. Bragg's prohibition.
The precipitating event was the announcement by Linus Pauling, who was
Dr. Bragg's peer and rival, that he had found the solution to the struct-
ure of DNA. Mr. Crick and Dr. Watson knew that Pauling's solution was
wrong, but believed it might be only days before Pauling realized his
error and seized on the solution.
In their second attempt, Mr. Crick and Dr. Watson picked up several
important clues. As part of a reporting system designed to share informa-
tion among laboratories supported by the British Medical Research Counci-
l, Mr. Crick came to see a correct version of the X-ray data that Dr.
Franklin had reported at the lecture attended by Dr. Watson. Although Dr
. Franklin had insisted that these data proved DNA could not be a helix,
Mr. Crick understood that they proved the opposite and that the two
chains were antiparallel, in other words that the head of one was always
laid against the tail of the other.
The two biologists had also belatedly learned of Chargaff's rules,
named for Erwin Chargaff, a longtime student of DNA at Columbia Universi-
ty. The four bases that occur in DNA are known as adenine, guanine,
thymine and cytosine, or A, G, T and C for short. Chargaff had discovere-
d that from whatever organism DNA was isolated, A and T were found in
roughly equal quantities, as were G and C.
Ingredients in Place
From Jerry Donohue, an experienced American chemist who happened
then to be sharing their office, Mr. Crick and Dr. Watson also learned
the true chemical structures of the DNA bases and the fact that the
structures shown in current textbooks were incorrect.
The ingredients for the discovery were now all in place. With the
right structures in hand, Dr. Watson was one day playing with cardboard
cutouts of the four bases when he noticed that an A-T pair on his small
desk was identical in shape with a G-C pair. He immediately perceived
how the bases could point inward, holding the spiral staircase together
with steps of always equal width, provided that adenine always paired
with thymine, and guanine with cytosine.
The pairing rule at once explained the equivalences of Chargaff's
rules and, more critically, how one DNA chain could serve as the templat-
e for building another, the essential requirement for any molecule that
embodied hereditary information.
"That morning," Mr. Judson wrote in "The Eighth Day of Creation,'' "
Watson and Crick knew, although still in mind only, the entire structure
: it had emerged from the shadow of billions of years, absolute and
simple, and was seen and understood for the first time."
In his memoir, Dr. Crick said: "It's true that by blundering about
we stumbled on gold, but the fact remains that we were looking for gold.
Both of us had decided, quite independently of each other, that the
central problem in molecular biology was the chemical structure of the
gene." No other scientists were pursuing the structure with such single-
mindedness.
It took only a few days to build the model dictated by their new
concepts. This time it convinced everyone because it explained everythin-
g.
"It has not escaped our notice," Mr. Crick wrote in a lapidary concl-
usion to their report of April 25, 1953, in the journal Nature, "that
the specific pairing we have postulated immediately suggests a possible
copying mechanism for the genetic material."
After making the discovery and completing the requirements for his
Ph.D., Dr. Crick plunged into the problems now made accessible by the
new structure. How did the sequence of bases in DNA determine the sequen-
ce of amino acids in the ribbon-like structure of each protein molecule?
How was the information copied from DNA and transferred to the cell's
protein-synthesizing centers?
Though many scientists played important roles in solving this array
of problems, the guiding intelligence at almost all points was Dr. Crick
's. It was he, for example, who first realized there could be only a
specific number of amino acids, the building blocks of proteins. Scannin-
g the confused biochemical literature, he drew up the canonical list of
the 20 acids.
With his colleague Sydney Brenner, Dr. Crick eventually proved, in
an experiment of remarkable elegance, that the genetic code was a comma-
less, triplet code in which a set of three bases determines an amino
acid unit and a string of triplets thereby specifies the full sequence
of amino acids in a protein chain. The Crick-Brenner experiment essentia-
lly consisted of deleting bases, one by one, in the DNA of bacteria and
showing that only after three bases had been eliminated in close proximi-
ty did the DNA-transcribing system come back into correct phase.
In a conversation in 1960 with the French biologist Francois Jacob,
Dr. Crick and Dr. Brenner recognized the long-puzzling identity of the
messenger chemical, now known as messenger RNA, that distributes copies
of the genetic information in the cell's nucleus to the protein-making
apparatus in the cell's periphery.
In another insight of remarkable power, Dr. Crick in his "adaptor
hypothesis," divined that there must exist both a class of carrier molec-
ules that recognize triplets of bases on the messenger and adaptor enzym-
es that link each kind of amino acid to its appropriate carrier. Biochem-
ists ridiculed the idea, saying that if the adaptor enzymes existed,
they would already have found them. But both the transfer RNA's and the
adaptor enzymes proved to exist, as Dr. Crick had predicted.
Dr. Crick derived several sweeping theories that have stood the test
of time. He assumed from the start that the genetic code was universal
to all forms of life, as indeed with trivial exceptions it has proved to
be. His "central dogma" formulated the view that once genetic informatio-
n had passed into protein, it could not get out again. The dogma meant
that the genetic message was impenetrable by information from outside
the cell, thus excluding the Lamarckian thesis that acquired characteris-
tics could be inherited.
Nobel Prizes for Three
In 1962, Dr. Crick, Dr. Watson and Maurice Wilkins received the
Nobel Prize in medicine for their work on DNA. Dr. Wilkins and Dr. Frank-
lin had contributed the X-ray data that suggested and confirmed the
structure of DNA, but Dr. Franklin died of leukemia in 1958.
The discovery of DNA brought unwelcome attention, too. In 1967 Dr.
Crick read a draft of Dr. Watson's account of their discovery, "The
Double Helix." The memoir, which then bore the working title "Honest Jim
,'' was a startling departure from the usual staid accounts of laborator-
y life. After its opening declaration about Dr. Crick's lack of modesty
it adroitly portrayed the participants' feelings as the helter-skelter
pursuit of DNA wound to its resolution. Dr. Crick viewed the gossipy
narrative as a betrayal of their friendship, a violation of his privacy
and a distortion of their methods and motives. He was unsuccessful in
efforts to prevent the book's publication.
Dr. Crick later came to terms with his colleague's account.
"In those days there was a different convention, at least in Britain
, about writing about your friends," he said in an interview in 2003.
"But I came out of the book quite well, apart from the first sentence.
As Peter Medawar said, the person who comes out worst is Jim."
One of the problems caused by the book was Dr. Watson's implication
that the pair of them had obtained Dr. Franklin's data on DNA surreptiti-
ously and hence had deprived her of due credit for the DNA discovery. Dr
. Crick believed he obtained the data fairly since she had presented it
at a public lecture, to which he had been invited. Though Dr. Watson had
misreported a vital figure from the lecture, a correct version reached
Dr. Crick through the Medical Research Council report. If Dr. Franklin
felt Dr. Crick had treated her unfairly, she never gave any sign of it.
She became friends with both Dr. Crick and Dr. Watson and spent her last
remission from cancer in Dr. Crick's house.
Dr. Crick gave his younger colleague no equivalent cause for complai-
nt. Dr. Watson acknowledged the selflessness of Dr. Crick's motives.
"Francis was always so kind to me," he said in an interview in 1998.
"He never tried to promote himself. He was just interested in solving
problems."
By 1966, the first era of biology at the molecular level was complet-
e. Though many details of enormous interest remained to be discovered,
the foundations had been well and truly laid. Dr. Crick and Dr. Brenner
decided to move on to another vast field of biology, the manner in which
a whole organism develops from the fertilized egg.
In 1977 Dr. Crick left Cambridge, and his well-known house on Portug-
al Place, with its golden helix above the front door, where he and Odile
had held many high-spirited parties. The Cricks moved to the Salk Instit-
ute in San Diego. There he took on another challenging unsolved problem
of biology: the nature of consciousness.
He had little expectation of producing any radically new ideas at
age 72, he wrote in 1988, "but at my time of life I had a right to do
things for my own amusement." Never one to let his mind lie fallow, Dr.
Crick produced a stream of papers about aspects of the brain and a well-
regarded popular book in 1994, "The Astonishing Hypothesis," which summa-
rized his ideas.
Another diversion that Dr. Crick allowed himself was a bold speculat-
ion about the origin of life. Only the most eminent and secure of scient-
ists would dare flirt with the idea that earth may have been seeded with
life by a rocket ship from another planet. But that possibility, a thesi-
s Dr. Crick termed "Directed Panspermia," was aired in an article he
published in the journal Icarus (1973) with his Salk Institute colleague
Leslie E. Orgel and in a popular book by Dr. Crick alone, "Life Itself"
(1981).
Dr. Crick in no way rejected the orthodox scientific thesis that
life evolved in some way, yet to be specified, from the chemicals presen-
t on the early earth.
But he was impressed by the unexplained universality of the genetic code
and uncomfortable with the narrow window of time between the date the
earth cooled enough to be habitable and the first appearance of life in
the fossil record. With "Directed Panspermia," he prepared, in effect,
an intellectual escape hatch, an alternative explanation for life should
scientists in fact find it too hard to account plausibly for the remarka-
bly rapid emergence of earth's first life forms.
Dr. Crick's style of practicing science was unusual. Most biologists
do experiments; he did so very rarely, being one of biology's few theore-
ticians. He did not take graduate students, preferring instead to work
with a single colleague. His scientific interlocutors were, after Dr.
Watson, Dr. Brenner during the Golden Age of molecular biology, and Dr.
Christof Koch, for his work on the brain.
"Francis essentially works alone but likes to have a colleague to
play against, so to speak," Dr. Brenner said recently.
Dr. Crick wrote little about his own life and, despite his fame,
remained a surprisingly private person. His first marriage, to Ruth
Doreen Dodd, ended in divorce in 1947. He is survived by his wife, the
former Odile Speed, an artist; a son from his first marriage, Michael F.
C. Crick of Seattle; and by two daughters from his second marriage,
Gabrielle A. Crick and Jacqueline M-T Crick Nichols, both of England;
and four grandchildren.
What is the nature of scientific genius? Dr. Crick was perhaps offer-
ing an answer in his response to a different question, that of whether
he enjoyed his life.
"I cannot do better," he said, than to quote from a lecture by the
painter John Minton "in which he said of his own artistic creations,
'The important thing is to be there when the picture is painted.' And
this, it seems to me, is partly a matter of luck and partly good judgment,
inspiration and persistent application."
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