How to Live with a

A DNA pioneer takes another look at his seminal discovery

The discovery of the structure of DNA has been de-
scribed in print several times already, not only by
Jim Watson in that rather breathless fragment of his
autobiography he called The Double Helix (perhaps
Lucky fim would have been a better title), but also, in
a more sober, detailed and scholarly way, by Bob
Olby (The Path to the Double Helix). At least one TV
documentary has been made about it. Leaving more
ephemeral effusions, whether girlish or soured, on
one side, we have an excellent account by Horace
Judson. His book, The Eighth Day of Creation (Simon
and Schuster, 1979), covers not only the discovery of
the double helix, but also the search for the genetic
code and the three-dimensional structure of pro-
teins. Very well researched, scientifically accurate
and written in a lively and readable style, it reveals
more about the way molecular biology was done and
about the people who did it than any other account I
know.

  What more can I add? Before the whole thing
gets out of hand and becomes an academic cottage
industry, I think a dose of cold water could do no
harm. No doubt it is fascinating to read just how a
scientific discovery is made; the misleading experi-
mental data, the false starts, the long hours spent
chewing the cud, the darkest hour before the dawn,
and then the moment of illumination, followed by
the final run down the home straight to the winning
post.

  And what a cast of characters! The Brash
Young Man from the Middle West, the Englishman
who talks too much (and therefore must be a genius
since geniuses either talk all the time or say nothing
at all), the older generation, replete with Nobel
Prizes, and best of all, a Liberated Woman who ap-
pears to be unfairly treated. And in addition, what
bliss, some of the characters actually quarrel, in fact
almost come to blows. The reader is delighted to
learn that after all, in spite of science being so im-
possibly difficult to understand, SCIENTISTS ARE
HUMAN, even though the word "human" more ac-

6   THE SCIENCES   SEPTEMBER 1979

curately describes the behavior of mammals rather
than anything peculiar to our own species, such as
mathematics. Surely the script must have been writ-
ten, not in heaven, but in Hollywood.

  Unfortunately a closer study shows that real life
is not always exactly like a soap opera. Not every-
body was competing madly, with one eye on Stock-
holm. In actua1 fact there was a considerable


amount of cooperation mixed in with the inevitable
competition. The major opposition Rosalind Frank-
lin had to cope with was not from her scientific col-
leagues, nor even from King's College, London (an
Anglican foundation, it should be noted, and there-
fore inherently biased against women), but from her
affluent, educated and sympathetic family who felt
that scientific research was not the proper thing for
a normal girl. Rosalind's difficulties and her failures
were mainly of her own making. Underneath her
brisk manner she was oversensitive and, ironically,
too determined to be scientifically sound and to
avoid shortcuts. She was rather too set on succeed-
ing all by herself and rather too stubborn to accept
advice easily from others when it ran counter to her
own ideas. She was proffered help but she would not
take it.

  The soap opera has many other distortions and
simplifications. I need not elaborate further. The
plain fact that science is largely an intellectual pur-
suit, that it involves an enormous amount of hard,
often grinding, work (both theoretical and experi-
mental), that it is based upon an immense body of
closely interlocking facts and theories, much of
which must be thoroughly mastered before any pro-
gress at all can be made-all this tends to be sub-
merged in the popular mind beneath those personal
aspects which ordinary people relate to more easily.
It is certainly an excellent idea to kill the stereotype
of the cold, impersonal scientist in the white coat-
such people do exist but they are as dull in science as
they are in life-but we must not let the public think
that because they understand some of our motives
they thereby understand what science is about. The
most surprising characteristic of modern Western
society is that in spite of its being largely based on
science and technology, the average citizen under-
stands so little about the scientific enterprise. It is
not only that elementary scientific facts are not
known (the shape of H,O, for example) but there is
an almost complete lack of any scientific overview, a
lack of any description, even in outline, of what is
well established, what we still have to discover, and
how we hope to go about discovering it.

  I think what needs to be emphasized about the
discovery of the double helix is that the path to the
discovery was, scientifically speaking, fairly com-
monplace. What was important was not the way it

Francis Crick shared the Nobel Prize in physiology or medicine
in 1962 with James Watson and Maurice Wilkins for their dis-
covery of thaw molecular structure of DNA. He is presently Kieck-
hefez Research Professor at the Salk Instittie in San Diego. This
article is based on the Lynen Lecture delivered at the Eleventh
Miami Winter Symposium earlier this year. The Symposium
was entitled: "From Gene to Protein: Information Transfer in
No4 and Abnormal Cells." The proceedings of the Symposi-
um, including the full text of Dr. Crick's lecture, will be pub-
lished by Academic Press, Inc., New York, in the fall.

was discovered but the object discovered-the struc-
ture of DNA itself. One can see this by comparing it
with almost any other scientific discovery. Mislead-
ing data, false ideas, problems of personal interrela-
tionships occur in much if not all scientific work.
Consider, for example, the discovery of the basic
structure of collagen. It will be found to have all
these elements. The characters are just as colorful
and diverse. The facts were just as confused and the
false solutions just as misleading. Competition and
friendliness also played a part in the story. Yet no-
body has written even one book about "The Race for
the Triple Helix." This is surely because, in a very
real sense, collagen is not as important a molecule as
DNA.

  Of course this probably depends upon what you
consider important. Before Alex Rich and I worked
(quite by accident, incidentally) on collagen we tend-
ed to be rather patronizing about it. "After all," we
said, "there's no collagen in plants." After we got in-
terested in the molecule we found ourselves saying,
"Do you realize that one-third of all the protein in
your body is collagen?" kut however you look at it,
DNA is more important than collagen, more central
to biology, and more significant for further re-
search. So, as I have said before: it is the molecule
which has the glamour, not the scientists.

Looking for Gold

What then do Jim Watson and I deserve credit for,
if anything? There are certain technical points
which are sometimes overlooked. It took courage
(or rashness, according to your point of view) and a
degree of technical expertise to put firmly on one
side the difficult problem of unwinding the double
helix and to reject a side-by-side structure. Such a
model was suggested by George Gamow, not long
after ours was published, and it has been suggested
again more recently by two other groups of authors.
It is less well known that in 1953 we very briefly con-
sidered a four-stranded model--the structure even-
tually published by Stewart McGavin-and had the
good sense to reject that also. But these are small
points. If we deserve any credit at all it is for persist-
ence and the willingness to discard ideas when they
became untenable. One reviewer thought that we
can't have been very clever because we went on so
many false trails, but that is the way discoveries are
usually made. Most attempts fail not because of lack
of brains but because the investigator gets stuck in a
cul-de-sac or gives up too soon. We have also been
criticized because we had not perfectly mastered all
the very diverse fields of knowledge needed to guess
the double helix but at least we were trying to master
them all, which is more than can be said for some of
our critics.

However, I don't believe all this amounts to

THE SCIENCES   sEPTEMsERI979 7


much. The major credit I think Jim and I deserve,
considering how early we were in our research ca-
reers, is for selecting the right problem and sticking
to it. 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 indepen-
dently of each other, that the central problem in
molecular biology was the chemical structure of the
gene. Hermann Muller had pointed this out as long
ago as the early twenties and many others had done
so since then. What both Jim and I sensed was that
there might be a shortcut to the answer, that things
might not be quite as complicated as they seemed.
Curiously enough this was partly because I had ac-
quired a very detailed grasp of the current knowl-
edge of proteins. We could not at all see what the an-
swer was, but we considered it so important that we
were determined to think about it long and hard,
from any relevant point of view. Practically nobody
else was prepared to make such an intellectual in-
vestment, since it involved not only studying genet-
ics, biochemistry, chemistry and physical chemistry
(including x-ray diffraction-and who was prepared
to learn that?) but also sorting out the essential alloy
from the dross. Such discussions, since they tend to
go on interminably, are very demanding and some-
times intellectually exhausting. Nobody could sus-
tain them without an overwhelming interest in the
problem.

  And yet history of other theoretical discoveries
often shows exactly the same pattern. In the broad
perspective of the exact sciences we were not think-
ing very hard but we were thinking a lot harder than
most people in that comer of biology, since in those
days, with the exception of geneticists and possibly
the people in the phage group, most of biology was
not thought of as having a highly structured logic.

  Of course it is obvious now that nucleic acid is
the main if not the only genetic material, but in the
late forties and early fifties this was far from clear.
Everybody knew of the work on the transforming
principle by Oswald Avery and his colleagues. Even
the conservative Royal Society gave Avery a pres-
tigious medal for the discovery as early as 1945. The
citation shows clearly that they understood its genet-
ic implications but not everybody else was convinced
so easily. Alfred Mirsky in particular thought for
some time that the effect was due to contaminating
protein but I do not think that was the main stum-
bling block. The real difficulty was to decide wheth-
er transformation was of general significance or
whether it was a freak. Initially it had been found
only in pneumococcus-and it was not even known
whether that organism had genes in the ordinary
Mendelian sense. Moreover, it appeared to affect
only one character, the nature of the coat. A little
later the very careful work of Rollin Hotchkiss

8   THE SCIENCES   SEPTEMBER 1979

showed that other charticters could be tr&sformed.
He also made the idea of a proiein impurity highly
unlikely. But transformation still remained an al-
most isolated case. Moreover, one could always
argue that the experiments fitted equally well the
idea that a gene contained two essential and specific
components, nucleic acid and protein, The impor-
tance of the Hershey-Chase experiment on phage
T4 was that it provided a second quite separate in-
stance of the genetic specificity of DNA, even
though, by comparison, the ,experiments were far
dirtier than those of Avery and Hotchkiss. Her-
shey's results made a deep impression on Jim and
myself, even though many people couldn't see what
the fuss was all about. From then on we had few re-
servations that DNA was biologically important.
Whether its structure would tell us anything inter-
esting we could only guess-and hope for the best.

  Looking back I can see that it is also important
not to be too clever. Consider the following argu-
ment: DNA fibers show a iery good x-ray diffraction
pattern, implying that the microcrystalline structure
which produced the many spots is very regular. But
for a genetic material to have any interest it must
necessarily be somewhat irregular. Therefore noth-
ing of interest is likely to come from studying dif-
fraction patterns of DNA. A similar argument could
be used about its base composition. Only an imper-
ceptive person could possibly spend time measuring
the exact amounts of the four bases in DNA since
how could that possibly reveal anything of genetic
interest? Fortunately neither of these arguments
influenced us at the time. We can see now that ihey
are wrong because of the overwhelming importance
of base-pairing and because one base-pair looks very
like another in shape and, at that resolution, to the
x-rays. The important thing is not to be deflected
too muc,h by negative -arguments of this general
type, even though they may indeed turn otit to be
correct and one's labors to have been in vain. The
much stronger rule is that if something is of great
scientific importance one can hardly learn too much
about it, even by what, at first sight, may seem raiher
pedestrian methods. Of course, not everybody may
be equipped to appreciate the significance of some
rather simple observation (why the stars come out at
night, for example) as the history of the double helix
shows rather clearly.

The Secret_ of Life

But what was it like to live with the double helix? I
think we realized almost immediately that we had
stumbled onto something important. According to
Jim, I went into the Eagle, the pub across the road
where we lunched every day, and told everyone that
we'd discovered the secret of life. Of that i have no
recollection, but I do recall going home and telling


my wife Odile that we seemed to have made a big
discovery. Years later she told me that she hadn't be-
lieved a word of it. "You were always coming home
and saying things like that," she said, "so naturally I
thought nothing of it." W.L. Bragg, Cavendish pro-
fessor, was in bed with `flu at the time, but as soon
as he saw the model and grasped the basic idea he
was immediately enthusiastic. All past differences
were forgiven and he became one of our strongest
supporters. We had a constant stream of visitors, a
contingent from Oxford which included Sydney
Brenner among them, so that Jim soon began to tire
of my repetitious enthusiasm. In fact at times he had
cold feet, thinking that perhaps it was all a pipe
dream, but the experimental data from King's Col-
lege, when we finally saw them, were a great encour-
agement. By the summer, most of our doubts had
vanished and we were able to take a long cool look at
the structure, sorting out its accidental features
(which were somewhat inaccurate) from its really
fundamental properties, which time has shown to be
correct.

  For a number of years after that, things were
fairly quiet. I named our house in Portugal Place
"The Golden Helix" and eventually erected a simple
brass helix on the front of it, though it was a single
helix rather than a double one. It was supposed to
symbolize not DNA but the basic idea of a helix. I
called it golden in the same way that Apuleius called
his story "The Golden Ass," meaning beautiful. Peo-
ple have often asked me whether I intend to gild it.
So far we've got no further than painting it yellow.

Gradually DNA became better known. Paul
Doty told me that shortly after lapel buttons came in
he was in New York and to his astonishment saw one

with "DNA" written on it. Thinking it must refer to
something else he asked the vendor what it meant.
"Get with it, bud," the man replied in a strong New
York accent, "dat's the gene."

  Nowadays most people know what DNA is, or if
they don't, they know it must be a dirty word, like
"chemical" or "synthetic." Fortunately people who
do recall that there are two characters called Watson
and Crick are often not sure which is which. Many's
the time I've been told by an enthusiastic admirer
how much they enjoyed my book-meaning, of
course, Jim's By now I've learned that it's better not
to try to explain. An even odder incident happened
when Jim came back to work at Cambridge in 1955.
I was going into the Cavendish one day and found
myself walking with Neville Mott, the new Caven-
dish professor (Bragg had gone on to the Royal In-
stitution in London). "I'd like to introduce you to
Watson," I said, "since he's working in your lab." He
looked at me in surprise. "Watson?" he said, "Wat-
son? I thought your name was Watson-Crick."

The First

The double helix is indeed a remarkable molecule.
Modern man is perhaps 50,000 years old, civiliza-
tion has existed for scarcely 10,000 years, and the
United States for only just over 200 years; but DNA
and RNA have been around for at least a billion
years, if not longer. All that time the double helix
has been there, and active, and yet we are the first
creatures on Earth to become aware of its existence.

  There was in the early fifties a small, somewhat
exclusive biophysics club at Cambridge, called the
Hardy Club, named after a Cambridge zoologist of a
previous generation who had turned physical chem-
ist. The list of those early members now has an illus-
trious ring, replete with Nobel laureates and Fellows
of the Royal Society, but in those days we were all
fairly young and most of us not particularly well-
known. We boasted only one F.R.S.-Alan Hodg-
kin-and one member of the House of Lords-Vic-
tor Rothschild. Jim was asked to give an evening talk
to this select gathering. The speaker was customarily
given dinner first at Peterhouse. The food there was
always good but the speaker was also plied with
sherry before dinner, wine with it, and, if he was so
rash as to accept it, drinks after dinner as well. I
have seen more than one speaker struggling to find
his way into his topic through a haze of alcohol. Jim
was no exception. In spite of it all he managed to
give a fairly adequate description of the main points
of the structure and the evidence supporting it, but
when he came to sum up he was quite overcome and
at a loss for words. He gazed at the model, slightly
bleary-eyed. All he could manage to say was, "It's so
beautiful, you see, so beautiful!" But then, of course,
it was.                               Cl

TwsxNcEs   !3EPTEMsER1979 9