class="bi x0 y0 w0 h1"
 W andering in the gardens of the mind
John Prebble
Bruce Weber
Foreword by Sir Tom Blundell
W
andering in the
1
2003
peter mitchell
and
the making of glynn
Gardens of the Mind
1
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Library of Congress Cataloging-in-Publication Data
Prebble, John, 1944–
Wandering in the gardens of the mind :

hardt, Kalckar, Ochoa, and others first described the process of oxida-
tive phosphorylation, whereby metabolic energy of oxidation is con-
served as ATP (adenosine triphosphate), the energy currency of the cell.
There are other reasons for writing a biography of Mitchell. Apart
from developing the chemiosmotic theory, which solved a long-stand-
ing problem, he engaged in other creative activities. Endowed with
family money, he set out to prove that it was still possible to set up and
run a small independent research institute, the Glynn Research Insti-
tute. This he did with his lifelong associate, Jennifer Moyle. The award
of the Nobel Prize in Chemistry to Mitchell in 1978 not only provided
recognition of his contribution to biochemistry but also, at least in his
eyes, justified the existence of the institute. To date, there have been two
biographies of Mitchell: a short authoritative Royal Society biographical
memoir by Bill Slater and a short unpublished manuscript by Milton
Saier.
Essentially, Mitchell is that rare breed of scientist, a theoretical biolo-
gist. He believed in thinking about science almost as an activity in its own
right, and, unlike his older contemporary Hans Krebs, Mitchell proposed
complex theories before proceeding to test them. The words of our title ap-
pear on a plaque in the garden of remembrance created by Helen Mitchell
and reflect the spirit with which Peter Mitchell approached biology.
All of these aspects of Mitchell’s life, and many others, are why we
feel a life of Peter Mitchell is needed. The history of the remarkable
achievements of twentieth-century biochemistry is only beginning to be
written, with but a few biographies so far published. It is our intention
that this biography of Peter Mitchell will tell one important story of this
stream of human endeavor.
One of us (J. P.) first heard Peter Mitchell lecture in 1956 and was
fascinated by his approach to biological thinking. Although he heard
him lecture many times over the years, he did not get to know Mitchell

we are aware that some of his contemporaries will have different
views.
Mitchell left relatively few laboratory notes, and the ones we found
are almost exclusively from the Edinburgh period (1956–1963). He did
not keep good records of his experiments, and those that have survived
are sketchy; they can be interpreted only with difficulty and some un-
certainty. They were originally housed in binders, but by the time we
saw them in the last days of the Glynn Research Institute, they were al-
most all loose and mostly undated. During the Glynn period, the labo-
ratory notes were probably kept exclusively by Jennifer Moyle, who, re-
grettably, has forbidden access during her lifetime.
There are special problems about writing a scientific biography of a
twentieth-century scientist, which relate to the nature of the science.
While the central reason for writing about Mitchell is the achievement
of his science, the essential character of that science itself is not easily
conveyed to the reader because of its extremely technical nature. We
have endeavored to simplify the biochemistry but realize that, to bio-
chemists, we will be seen to have glossed over, and on occasions mis-
represented, important details of Mitchell’s and also other scientists’
work. We also appreciate that our attempts to eliminate the technical
detail may not have gone far enough for some readers, and, to give
some assistance to them, we have added an appendix on the theories of
oxidative phosphorylation.
We would like to acknowledge the help of Dr. Peter Rich, who suc-
ceeded Peter Mitchell as director of the Glynn Research Institute and
who gave us access to Mitchell’s papers before they were transferred
to Cambridge. The many others who have given us their time, advice,
and support are listed in the acknowledgments. Their generosity and
friendship are greatly appreciated. We are indebted to our editor, Kirk
Jensen, and his colleagues at Oxford University Press for their help.

David Green
Edward F. Hartree
Y. Hatefi
Julia Heffer (née Mitchell)
Peter Hinkle
Eva Ibbotson
Baz Jackson
André Jagendorf
Hermann Kalckar
Douglas Kell
Sir John Kendrew
Arnost Kleinzeller
Margot Kogut
C. P. Lee
Albert Lehninger
Alan Maddy
Aubry Manning
Vanessa Martin
Eileen McNeil (formerly
Eileen Mitchell)
Helen Mitchell
Jeremy Mitchell
Peter Mitchell
Murdoch Mitchison
Harold Morowitz
Jennifer Moyle
Don Northcote
Sam Perry
Max Perutz
Lord George Porter

xii
Fred Sanger
Vladimir Skulachev
Bill (E. C.) Slater
Jui Wang
Ian West
Mårten Wikström
Bob Williams
John Wrigglesworth
Contents 
Foreword, by Sir Tom Blundell xv
Chronology xix
1 Prologue: Who Was Peter Mitchell? 3
2 Early Years and Education: 1920–1939 10
3 The Early Cambridge Years: 1939–1947 24
4 Research at Cambridge: 1947–1955 44
5 Edinburgh: 1955–1963 64
6 The Creation of Glynn: 1962–1965 96
7 Testing the Theory: 1965–1968 115
8 Exploring the Implications of the Theory: 1969–1973 146
9 Getting the Arithmetic Right: 1974–1976 170
10 From Review to Nobel Prize: 1977–1978 195
11 The Cytochrome Oxidase Controversy: 1977–1986 222
12 Science for Humanity: 1985–1992 248
13 Epilogue: Mitchell and Glynn 269
Appendix: Theories of Oxidative Phosphorylation 278
Notes 285
Index 307
Foreword 
The popular image of science bears little relationship to what most in-

stinct he was nonideological; he despised what he characterized as the
hothouse atmosphere of Marxism that he found in the department of
biochemistry in Cambridge. Those who knew him in Cambridge at that
time found that he had an assurance and ruthlessness found amongst
the rich. He dressed flamboyantly and wore his hair long, looking like
Beethoven. His natural independence of mind was reinforced by the
confidence of his class.
But Mitchell did not have things all his own way. His undergradu-
ate exams were not a success; he gained only a third-class pass in his
first year at Cambridge University. His Ph.D. dissertation was a mixture
of theory and somewhat unrelated experiment; he was asked to resub-
mit by his examiners. Indeed, even at this early stage in his career, his
main interest was to establish a theoretical framework, devising experi-
ments only thereafter. Whereas this approach was accepted as neces-
sary in some areas of theoretical physics and astronomy, where experi-
ments are difficult and expensive, it was certainly unconventional in the
life sciences. For a community that was used to devising experiments in
a series of careful steps, each arising out of the previous, this approach
raised eyebrows. It also led to the appearance, and probably to the prac-
tice, that experiments needed as controls had not been done appropri-
ately. Indeed, this was the view of Hans Krebs, another Nobel Prize
winner, on listening to one of Mitchell’s early talks.
Biochemistry in Cambridge is now a large department with over
four hundred researchers. In the 1940s, when Mitchell started his re-
search, it was known as the Dunn Institute of Biochemistry and was
much smaller. It occupied less than a quarter of the present space, but
with a cabin annex and space made available in the neighboring
Molteno Institute. It had been established twenty years earlier by Fred-
erick Gowland Hopkins, who won the Nobel Prize for his work on vita-
mins and who advised the U.K. government on nutrition during the

Mitchell had a very focused approach to supervision of research.
He was reprimanded early in his career at Cambridge for setting goals
that were too well defined for the research student whose work he was
supervising. One wonders whether his approach was appropriate for
research training. But his interaction with Jennifer Moyle through sev-
eral decades of collaboration was remarkably successful. He was also
appreciated by his technical staff at Glynn. And of course it worked: he
developed a new area of science, with a relatively small team, and with-
out much of the infrastructure on which other institutions depended.
In reading this biography, I found myself often asking whether
Mitchell needed to be so uncompromising about his science. Perhaps it
was necessary to sustain his more holistic approach in terms of the strong
theoretical framework of the chemiosmotic theory. But perhaps it was
more his nervousness about having his theory diluted and his ideas lost
in the process. I still find his treatment of the debate with Bob Williams,
the very imaginative and original Oxford chemist, quite extraordinary.
An open publication of their extensive correspondence in the 1960s, to-
gether with a recognition that it had taken place, would have allowed a
more balanced assessment of the development of the theory and would
have been a fair response to Williams’s generosity in discussing his ideas
earlier. Mitchell’s reactions to the conformational model of Paul Boyer
are also difficult to understand, especially with the advantage of the sub-
foreword
xvii
sequent work of Boyer, John Walker, and others. It is clear that conforma-
tional change does play a major role in coupling transport and me-
tabolism and in many of the concepts complementary to those of the
chemiosmotic theory. But then it does take an extraordinary person to se-
cure a paradigm shift in scientific thinking. This biography makes it clear
that Peter Mitchell was such an extraordinary person.

1981 Awarded the Copley Medal of the Royal Society
1983 Retirement of Jennifer Moyle
1985 Glynn Research Ltd. renamed Glynn Research Foundation Ltd
1986 Conclusion of the disputes on the arithmetic of proton
translocation
1987 Mitchell retired
1990 Celebration of Glynn’s silver jubilee
1992 Death of Peter Mitchell
1996 Glynn Research Institute closed
1998 Glynn Laboratory of Bioenergetics opened at University College,
London
chronology
xx
 W andering in the gardens of the mind
3
1 
Prologue
Who Was Peter Mitchell?
The life of Peter Dennis Mitchell (1920–1992), like that of most people, is
characterized by complexities, contradictions, and paradoxes. Biogra-
phers, to the extent that they succeed, can capture only partially the
richness of the phenomenon of another human being and his or her ac-
tion in the world. Our knowledge is limited, no matter how much de-
tailed information is available. Thus this biography inevitably repre-
sents an interpretation of Mitchell’s life from several of the numerous
perspectives possible. This problem is compounded by the fact that the
subject was a scientist, and much of Mitchell’s creativity and passion
were engaged in activities that required both a technical and a specialist
knowledge. Hence, there is a need to balance the personal and the sci-
entific, as well as to endeavor to make the science as accessible as pos-

major contribution—the theory for which he is most remembered, the
chemiosmotic theory—was not formulated until 1961 and was not prop-
erly understood in the field until the 1970s. It was in this latter decade
that the bioenergetic community finally felt the full force of his ideas.
 Mitchell’s Achievement, Contributions,
and Controversies
Mitchell’s two major contributions to biology, well documented in con-
temporary textbooks of biochemistry, concern the link between the oxi-
dation of foodstuffs by oxygen and the conservation of energy as ATP
(adenosine triphosphate). ATP is the energy currency of the cell and is
formed in the small particles (organelles) in the cell that are known as
mitochondria. The link between ATP formation and the oxidation of
foodstuffs had been a mystery that puzzled biochemists for some thirty
years. To try to solve the puzzle, a hypothetical chemical intermediate
had been proposed, but despite enormous effort and expenditure of
money, particularly in Europe and North America, such intermediates
could not be found. One philosopher regarded the field as having
reached a state little short of crisis. It was against this background that
Mitchell proposed his chemiosmotic theory in 1961, his first major con-
tribution, which described the link between oxidation (cellular respira-
tion) and ATP synthesis (phosphorylation) as a gradient of protons
wandering in the gardens of the mind
4
(with an accompanying electrical potential) across a biological mem-
brane. Oxidation (respiration) would create the gradient; the gradient
would be used to drive ATP synthesis. Therefore, while his contempo-
raries saw the link as a chemical substance, Mitchell saw it as a gradient
of protons (with an accompanying electrical potential). Such a funda-
mental change in thinking was not easily accepted, and it took at least a
further fifteen years for most of the field to accept Mitchell’s proposals,

that emerged in the mid-1970s concerned the quantitative aspects of his
proposals and lasted for a further decade. They involved both the de-
tailed mechanisms for moving protons across membranes, as proposed
prologue
5
by Mitchell, and the quantitative results obtained in Mitchell’s and
other laboratories. This second round of controversies mostly went
against Mitchell.
Mitchell’s last years were spent reformulating aspects of his theory
to bring it into accord with experimental findings and attempting to se-
cure funding and a stable future for the Glynn Research Institute as an
independent entity. Glynn did survive Mitchell’s death in 1992, but
only for a few years.
Mitchell is regarded as one of the “superstars” of biochemistry. His
picture is included in many contemporary textbooks of biochemistry,
where the basic insights of his chemiosmotic theory are presented as a
central and unifying conceptual framework, tying together what had
previously appeared to be disparate phenomena. Indeed, Mitchell was
featured in a millennium essay in Nature, where his contribution was
compared with that of Darwin and Einstein.
1
This echoed earlier ap-
praisals that likened Mitchell’s contribution in cell bioenergetics to a
paradigm change comparable to the Copernican,
2
although it is too
early to know whether such views are justified.
 Mitchell the Man
Anyone who met and interacted with Peter Mitchell was impressed by
the originality and force of his intellect and personality. They usually

He was a colorful and somewhat eccentric dresser. There was a
flamboyant aspect to Mitchell, certainly in his younger days, when he
wore vibrant coats and pants; later, after he received the Nobel Prize, he
sported an earring. The choice of the fine Georgian house at Glynn, in
which he accommodated his family and the institute, was consistent
with this aspect of Mitchell’s self-image. Through the formality of the
institute’s founding and management, he sought to give his institute an
administration comparable to that of much larger bodies.
Mitchell’s confidence, creativity, and love of independent action
shaped his approach to science and to much else. He had no hesitation
in extensively remodeling the first two homes he owned, and, moving
on from that experience, he enthusiastically undertook the two-year
restoration of Glynn House by directing the work. Subsequently, he re-
stored a number of ancient buildings in Cornwall. Mitchell, a city boy
and academic, took on running a dairy farm that was initially part of
the Glynn House complex of buildings, and he won awards for the
quality of the cream. He also engaged in various quixotic activities such
as minting his own silver “Glynn pieces”; he initiated schemes, which
did not come to fruition, for bottling and selling spring water from the
estate, and he designed a windmill for electricity generation.
 Mitchell the Scientist
Much of Mitchell’s approach to science can be understood in terms of
his personality. He had a passionate, creative, confident, and imagina-
tive engagement in his research. His strength lay more in the develop-
ment of theory rather than in the life and work of the laboratory. His
prologue
7