Tay

Book Review Supplement

 

Experimenta
iucijera

Erwin Chargaff

 

 

The Professor, The Institute and
DNA, By R. J. Dubos. Pp. 238.
(Rockefeller University: New York,

1976.) $14.50.

 

In the late 1930s, during my carly days
at Columbix University, [ had frequent
occasion to visit the Rockefeller Insti-
tute for Medical Research, as it was
then called. The uninviting structures
on Avenue A near the East River were
not easy of approach. True to its cha-
racter of a citadel of learning, the door
of the Institute was fortified by gruff-
ness; and after passing inspection by
Cerberus or Cerbera, the visitor had to
be accompanied to his destination by a
special young man. In my case this des-
tination usually was the laboratory of
the organic chemist Max Bergmann,
much admired by me. I had known
Bergmann when he directed a Kaiser
Wilhelm Institute in Dresden; here in
New York he shared the uneasy fate
of his generation of German emi-
grants. On seeing me, he would ex*
claim: ‘“‘Zuerst rauchen wir eine
Friedenspfeifet” producing a large
glass jar in which a package of cig-
arettes was kept in a controlled habitat.
Occasionally, he conducted me after-
wards to another laboratory, that of P.
A. Levene or D. D. van Slyke; and
sometimes J would come upon the
light-brown shadow of an_ elderly
mouse-like figure tripping along the
corridor walls. This, I was told, was Dr
Avery, a name not unknown to me as
that of the greatest expert on the
pneumococcus, although at that time I
could not have known how important
his name would become to me a few
years later.

These reminiscences were brought
on by an uncommon book about an
unusual man, Oswald T. Avery (1877-
1955). It is, in my opinion, a very good
book, and I enjoyed reading it. As the
title indicates, this is not merely a Sci-
entific biography. The book operates
on several intercommunicating levels,
taking into account the man, the time,
and the place; and painting, with extra-
ordinary competence, the ever-
changing human and scientific back-
drops. This competence is not entirely
surprising: René Dubos, apart from
being a very good writer, was a mem-
ber of Avery’s department from 1927
to 1941, and the warmth of personal
contact and observation is felt through-
out the narrative,

Born to English parents in Haltfax,
Nova Scotia, Avery was taken to New
York City at the age of ten, when his
father, who was a Baptist clergyman,
was invited to be pastor of the Marin-
ers’ Temple on the lower Eastside,
even at that time a pretty horrible part
of the city. But five years later, the
father was dead, and the three sons
were brought up by the mother who
must have been an energetic lady.
Oswald Avery, aside from becoming
an accomplished cornetist, got a good
education: first something called,
soberly, the New York Male Gram-
mar School, then Colgate Academy,
Colgate University, and finally, be-
tween 1900 and 1904, the College of
Physicians and Surgeons of Columbia
University, which was then one of the
best finishing schools for clinicians.
The latter seems to have finished him
in more than one sense: in went a
lively, communicative young man,
majoring in the humanities, excelling in
oratorical contests, playing the cornet,
leading the Colgate University band,
and clearly not particularly attracted to
the natural sciences; out came what I
would term, perhaps with some exag-
geration, a scientific recluse. This
shock of confrontation is not a very
rare event: I have noticed it often in
several generations of medical stu-
dents, when I taught at the same medi-
cal school; only few of those affected,
I am sure, turned into other Averys;
mostly they became psychiatrists or
even psychoanalysts.

Scientists in general lead uneventful
lives, with the exception of the few
who, for instance, are guillotined
during the French Revolution or killed
by highway robbers in Southern
France. What counts is their inner his-
tory to which their published papers
afford only precarious access, for the
history of ideas, and especially of
scientific ideas, is a slippery discipline.
But in the present instance, Dubos has
succeeded in producing as multi-
dimensional an image as is possible.

With the exception of a very short
period, after graduation, in medical
practice, Avery devoted his entire life
to research in bacteriology and im-
munology, first in a now extinct pri-
vate institution, the Hoagland Labora-
tory in Brooklyn, and since 1913 in
the Rockefeller Institute, where he re-
mained until he was 71. The last few
years of his life were spent, let us hope
serenely, in the South. Or as Dubos
puts it: “In 1948, he decided that he
had shot his bolt; as he no longer felt
able to function effectively in the
scientific arena, he retired to Nash-
ville, Tennessee”. Each of the verbs in
the preceding sentence could lend it-
self to a philosophical analysis which
J shall not attempt here, except to

Nature Vol. 266 28 April 1977

wonder why society seems to reserve
circus acrobatics and science for the
very young, assuming that these occu-
pations require muscular vigour rather
than wisdom. Why had, for instance,
Telemann not yet “‘shot his bolt,”
when at the age of 81 he wrote what is
widely considered as his greatest work,
the oratorio Der Tag des Gerichts?
The multiplicity of possible answers
shows that we have not yet found the
corecf one.

The major part of the book is de-
voted to a detailed and lucid discus-
sion of the problems investigated by
Avery during his 35 years at the
Rockefeller Institute. This is done in
five chapters the titles of which will
indicate the areas under study: ‘The
Lure of Antiblastic Immunity and the
Chemistry of the Host’: ‘The Chemi-
cal Basis of Biological Specificity’;
‘The Complexities of Virulence’; ‘Bac-
terial Variability’; and ‘Heredity and
DNA.’ It will be recognised that
Avery was one of the early micro-
biologists who understood the dominat-
ing role that chemistry was to play in
biology. This was, incidentally, quite in
harmony with the genius loci of the
Rockefeller Institute, which in this re-
spect, as in many others, was a most
remarkable place. Dubos does full jus-
tice also to this side of his story; and
the Institute, with its members, semi-
nars, conferences, and, especially, . its
memorable capitalistico-monastic lunch
room, is one of the indispensable cle-
ments of his account.

Avery was comparatively late in
starting, but he lasted: his most im-
portant work was published when he
was past sixty-six. The pneumococcus
was his microcosm; he showed that
general principles of great import can
be derived from little things if it is
given to the researcher to join pene-
tration to perseverance, and bold de-
duction to honest induction. As always,
what counts is the balance, the mix-
ture; but has anybody in science suc-
ceeded in mixing himself, in filling his
own recipe?

Avery became interested in the
pneumococcus because one of the
principal projects studied at the Rocke-
feller Hospital was the development of
a serum therapy for lobar pneumonia.
I do not believe the practical results
of his research ought to be stressed,
but out of this work there emerged
a new understanding of the chemical
basis of antigenicity, and, even more
suprisingly, the recognition that genes
were made of DNA. These glories
may be taken to demonstrate the
stupidity of our era of target-directed
research. Actually, science has never
operated entirely without goals; but the
goals were chosen by a few reasonable
men, not by frightened politicians or
bureaucrats, and were enforced with
Avery’s Department, 1932.

Nature Vol. 260

Seated (left to right): T. Francis, Jr, Avery, W. F. Gochel

tact and imagination. The directors of
the Institute and the Hospital were
wise enough to leave such a man as
Avery in peace. They had trust in him;
something that no ‘peer group’ with
its silly priorities can afford or ac-
complish. The absence of frenzy is one
of the main impressions I get from
Dubos’ description of Avery’s labora-
tory.

The existence of many immunologic-
ally different pneumococcus types had
been known for some time. In 1916,
Avery’s intimate friend, Alphonse

Book Review Supplement

  

course, to the work on the biological

activity of DNA. In view of the
witches’ brew now being stirred all
over the world, with “recombinant
DNA” as its main ingredient, I can
only hope that the title of this essay
will not have to be changed to experi-
menta Luciferi; although the Devil
hardly needs experiments to make his
point.

Less than sixteen years—1928 to
1944~-were required for the first fun-
damental observation to lead to the
definite proof that DNA was the in-

Dochez—-I knew him very well during %strument of genetic specificity. That it

his years as a Columbia professor-—
discovered that type-specific soluble
material was released into the culture
fluids by the organisms. These observa-
tions, extended and refined in the
course of several years, finally led to
Avery’s collaboration with Michael
Heidelberger, and later also. with
Walther Goebel, and to the identifica-
tion of a host of type-specific bacterial
polysaccharides as the basis of the im-
munological specificity of the various
strains. It is not too much to say that
this work had a profound influence on
the growth of immunochemistry and on
later concepts of “the chemical aspects
of biological specificity.” This was the
title of the series of Jesup lectures that
IT gave at Columbia University four
years after Avery’s death. His name
was mentioned more often than any-
body else’s, with the exception, of
course, of my own.

Leaving aside a large number of
interesting and important investigations
by Avery and his collahorators-—
almost all within the confines of his
“‘pneumocosm’-—I should like to move
rapidly to what most of us will consider
the most illuminating, the lucifer-
rimum, of his many experimenta
lucifera. (Dubos quotes Francis Bacon’s
distinction, in his Fastauratio Magna,
between “experiments of light” and
“experiments of fruit.) I refer, of

actually took much more time before
this proof was accepted generally, was
due to obtuseness, malevolence, and
the desire to protect various vested in-
terests. I remember the names of both
the heroes and the villains in this story,
but only a few of the first will be men-
tioned here. When the transformation
of pneumococcal types in vivo was dis-
covered in 1928 by F. Griffith, there
were no loud objections, perhaps owing
to the rapid confirmation of his find-
ings in other laboratories or because
most bacteriologists at that time were
Lamarckians. But for some reason the
observations were filed away and, had
it not been for Avery, they might have
slumbered a long time. It was in
Avery’s laboratory that Dawson and
Sia achieved transformation in vitro
and that Alloway described the isola-
tion of a crude transforming factor.
All this was accomplished before 1933;
and Dubos takes great pains to explain
why more than ten years clapsed be-
fore the next, and in every respect
final, publication. Such explanations
are really not necessary: before World
War IT, science was not yet an achieve-
ment sport; speed records formed no
part of the accomplishments of a scien-
tist as they do now. Griffith and Avery
are both quoted as deprecating hurry;
and Duhos tells us that Avery liked to
recall “the words of an old black

- Hy Babers

Standing: E. E. Terrell, K. Goodner, Dubos,

731

patient who watched, with amused sur-
prise, the young doctars rushing: about
the wards of The Johns Hopkins Hos-
pital: ‘What’s your hurry, Doc? By
rushing that way, you passes by much
more than you catches up with!’”,

When in 1944 the epochal paper by
Avery together with Colin M. MacLeod
and Maclyn McCarty appeared, it cer-
tainly was something worth waiting for.
The stages leading up to this publica-
tion and the all-in-all shabby reception
granted it by the experts are well docu-
mented in the book, althougi more
could, and probably will, be said even-
tually. As to the effect that the identi-
fication of the transforming principle
as a form of DNA had on me and on
the direction of my subsequent work, I
have described it before. Avery him-
self obviously realised the implications
of his discovery much more profoundly
than he was willing to put inte print.
The letter he wrote to his brother
Roy on 26 May, 1943, is particularly
instructive in this respect. His entire
character as a scientist—relentless per-
severance, courageous imagination,
extreme caution—can he developed
from this document.

Many readers will, I am sure, find
one chapter especially moving—
namely, chapter twelve, entitled “As T
Remember Him.’ { have never seen
this done before in the biography of
a scientist. To the limited extent that
a scientific investigator is also a human
being, the carving of the private bust
calls for an unusually tactful and sen-
sitive observer; and this René Dubos
must have been in the many years he
spent with or near Avery. Neverthe-
less, Avery was an extremely private
person, and there must have been a
wall around him, not of his own build-
ing—a wall that constrained him ag it
testrained access to him. I am not sure
that we can ever understand another
man so as to resurrect him on paper.
The reason why figures invented by
great novelists strike us as so alive is
that they are invented. At any rate,
what T got out of reading about this
shy, puritanical, disciplined, and cau-
tious man was a renewed awareness of
the poverty of greatness,

As I said at the beginning, this is
an interesting book. Tt is also very well
produced, with 2? illustrations, some
quite fascinating, and with a good
index. It should be read by all who
consider themselves part of the ‘hio-
medical community’, and molecular
biologists should read it twice. Even
philosophers and historians of science,
if they can spare a few moments from
their contemplation of the dark side
of the Reverend Moon, will find the
book profitable. O

 

Erwin Chargaff is Emeritus Professor of
Biochemistry at Columbia Jniverstty,
New York, New York