9 M e m b r a n e Biol.

91, 193-197 (1986) The Journal of

Membrane Biology
9 Springer-Vedag New York Inc. 1986

In Memory of

Albert Lester Lehninger

Albert Lester Lehninger

1917-1986

With the death of Albert Lester Lehningcr on and from then on the mechanisms of energy capture
March 4, 1986, the field of biochemistry lost a tow- and transduction in cells became the central themes
ering figure. During his career of 40 years he helped of his scientific life.
to shape the new discipline of bioenergetics and the In 1945 Lehninger moved from Wisconsin to
scientific lives of many of its leaders. He was a the University of Chicago where he assumed the
renowned teacher and the author of BiochemislO', titles of both Assistant Professor of Biochemistry
perhaps the single most influential and successful and Assistant Professor of Surgery. The latter title
textbook of biochemistry ever written. He was a signified his close association with the laboratory of
member of the Board of Editors of The J o , r , al of Charles Huggins (Nobel Prize in Physiology and
Membrane Biology since its beginning. The Journal Medicine, 1966) which later became known as the
owes much to his foresight and wisdom. It has lost Ben May Laboratory for Cancer Research. Al-
one of its pillars. though they never published jointly, Huggins pro-
Albert Lehninger was born on February 17, foundly influenced Lehninger's scientific career.
1917, in Bridgeport, Connecticut. In 1935 he en- Following their first meeting, Huggins summarized
tered nearby Wesleyan University as an English his impressions succinctly to one of the writers:
major and devoted himself to the writing of stories "He looks like a racehorse to me." And a racehorse
and poetry, a talent he was later to exploit in sci- he was! During the ensuing six years at Chicago,
ence. At Wesleyan his interests soon changed to Albert Lehninger and his first students, Eugene P.
chemistry, where he was introduced to the exciting Kennedy (now Hamilton Kuhn Professor of Biolog-
developments then occurring in the new field of bio- ical Chemistry at Harvard Medical School) and
chemistry. Lehninger was inspired by the monu- Morris E. Friedkin (now Professor of Biology at
mental work of Otto Warburg in Berlin on the University of California, San Diego), provided two
"Wasserstoffubertragende Fermente" (hydrogen- of the most fundamental and significant generaliza-
transporting enzymes) and the equally exciting tions of contemporary biochemistry. Lehninger and
work of Hans Krebs in Sheffield on the tricarboxy- Kennedy made the landmark discovery that mito-
lic acid cycle. This interest led him to embark upon chondria contained virtually all of the organized ox-
a combined career in Medicine and Biochemistry at idative activity of the cell. They demonstrated that
the University of Wisconsin, where he received the these subcellular particles had the capacity to cata-
Doctor of Philosophy degree in the Department of lyze the complete oxidation of fatty acids to CO:
Physiological Chemistry. His dissertation research and H20, and thus possessed all of the enzymatic
under Edgar J. Witzemann was concerned with the components for the/3-oxidation of fatty acids, the
metabolism of acetoacetate and the oxidation of tricarboxylic acid cycle, and the electron transport
fatty acids by disrupted liver preparations. He aban- system. Lehninger and Friedkin showed that elec-
doned the medical studies and then joined the war- tron transport from NADH to oxygen is an immedi-
time research effort of the Plasma Protein Fraction- ate and direct energy source for oxidative phos-
ation Program master-minded by E.J. Cohn. At this phorylation.
time he became aware of the early papers on oxida- His imaginative work on fatty acid oxidation
tive phosphorylation, which appeared in the early and oxidative phosphorylation attracted world-wide
1940's. These discoveries seized his imagination attention, and in 1952 Lehninger was invited to as-
196 Albert Lester Lehninger

sume the DeLamar Professorship and Directorship chondrial vesicles. He and his colleague, Carlo S.
of the Department of Physiological Chemistry (now Rossi (now Professor of Biological Chemistry at the
Biological Chemistry) at the Johns Hopkins Univer- University of Padua), carried out a classical study
sity School of Medicine at the early age of 35. He of the stoichiometric relationship betwecn the num-
served as Director of the department until 1978 ber of Ca 2+ ions transported into the mitochondrial
when he was honored by appointment as University matrix and the number of electrons flowing from
Professor of Medical Science at Johns Hopkins, a substrate to oxygen. The capacity for stoichio-
position which was especially created for him. At metric coupling between electron transport and ion
Johns Hopkins he built up a distinguished faculty, transport so demonstrated gave much impetus to
and innovative teaching and graduate programs. In the chemiosmotic coupling hypothesis of Mitchell,
1958 the first NIH training grant specifically desig- which was proposed in 1961 but not given much
nated for graduate study was awarded to the Johns serious consideration until the mid 1960's, when ion
Hopkins School of Medicine with Albert Lehninger transport became widely accepted as an important
as its Program Director. Lehninger's perception of mitochondrial activity.
the important issues of high caliber medical and In 1963 Lehninger observed that accumulation
graduate education enabled him to play a leading of Ca 2+ and phosphate by isolated milochondria
role in the academic affairs of the Johns Hopkins leads to formulation of electron-dense insoluble de-
University. posits in the mitochondrial matrix. These amor-
Lehninger's most important scientific contribu- phous deposits of calcium phosphate were postu-
tions centered on two themes: (I) discovery of the lated by Lehninger to be involved in biological
major role of the mitochondrion in respiratory me- calcification processes. Based upon these and other
tabolism and in compartmentation of metabolism in lines of evidence he formulated a general hypothe-
the cell, and (2) discovery of some of the main fea- sis of biological calcification,
tures of oxidative phosphorylation and other en- Albert Lehninger's more recent work l-bcused
ergy-coupling mechanisms associated with the elec- on the number of H + ions ejected by electron trans-
tron transport chain. His career began with the port during mitochondrial respiration. Whereas the
basic observations that led to the discovery in 1948 chemiosmotic hypothesis postulated two H ~ ions
that the entire complex of enzymes catalyzing the ejected per pair of electrons per energy-conserving
Krebs tricarboxylic acid cycle, electron transport site, Lehninger and his colleagues, with more re-
and oxidative phosphorylation, and oxidation of fined methods, established that each energy-con-
fatty acids are localized in the mitochondria. He serving site ejects 4 H + ions to the medium. These
was the first to show that oxidative phosphorylation experiments, together with stoichiometric data on
of ADP is coupled to the flow of electrons along the H + ion movements during ATP synthesis and mem-
respiratory chain from NADH to oxygen. Although brane transport processes gave important insights
thermodynamic analysis had predicted this to be the into the role of H + ion transport in oxidative phos-
case as early as 1939, it was not until 1951 that phorylation and in ATP-dependent reversal of elec-
Lehninger proved it experimentally with the recog- tron flow.
nition that oxidative phosphorylation takes place During his long career Lehninger received
within the mitochondria and that the membrane many honors which included membership in the
presents a permeability barrier to the entry of National Academy of Sciences, the American Phil-
NADH and other reduced coenzymes. His discov- osophical Society, and the American Academy of
ery that NADH cannot pass through the membrane Arts and Sciences. He held honorary Doctor of Sci-
of intact mitochondria established that NADH ence degrees from Wesleyan University, University
formed by glycolysis does not directly enter the mi- of Notre Dame, Acadia University (Nova Scotia),
tochondria and indicated that some other pathway Memorial University of Newfoundland, University
was required, one that would necessarily be of cru- of Paris Val de Marne, Catholic University of Lou-
cial importance in the integration and regulation of vain, and an honorary Doctor of Medicine degree
glycolysis and respiration. This work ushered in a from the University of Padua. He delivered numer-
new era in our understanding of cell metabolism and ous distinguished lectureships and received the
later led to the recognition that many other metabo- Paul-Lewis Award in Enzyme Chemistry in 1948,
lites, such as tricarboxylic acid cycle intermediates, the Remsen Award of the American Chemical Soci-
and coenzymes, such as ATP and Coenzyme A, are ety in 1969, the Premio La Madonnina of the City of
compartmented into separate pools. Milan, Italy, in 1976, and the Passano Foundation
Lehninger was among the first to consider ion Award in 1986.
transport as an important means of energy conser- He was frequently called upon to serve on im-
vation by mitochondria. Early work in his labora- portant decision-making bodies at the national
tory revealed a very rapid incorporation of K + and level. He served on the Councils of the National
Ca :+ ions into respiring mitochondria and submito- Academy of Science and the Institute of Medicine,
Albert Lester Lehninger 197

He was appointed in 1975 by President Ford to the chemistry worldwide. It may well represent the last
President's Panel on Biomedical Research man- time that a single author can successfully write a
dated by an act of Congress. He served as president comprehensive account of general biochemistry
of the American Society of Biological Chemistry in suitable for undergraduates, medical students, and
1972-3 and was a member of the Scientific Advisory graduate students. Lehninger was the author of two
Committee of the Massachusetts General Hospital. other excellent monographs of major importance:
In 1975 he was elected vice-president of the Ameri- The Mitochondria (1964) and Bioenergetics (1965,
can Philosophical Society. He was also a member of 1971). All of these books have been translated into
the Editorial Boards of many important journals, many foreign languages.
including the Journal of Biological Chemistry, In many ways Albert Lehninger was a very pri-
Physiological Reviews, Journal of Biophysical and vate person, but where science was concerned
Biochenlical Cytology, Biochemistw, and the ,lore'- there were no boundaries in sharing from the depth
hal of Membrane Biology. and breadth of his scientific insight. He was a gen-
Among Lehninger's most widely-known tleman; he was a gentle man.
achievements was the writing of a comprehensive
biochemistry text, which was first published in 1970
with the second edition appearing in 1975. This M. Daniel Lane
book, a monumental accomplishment, was gener- Paul Talalay
ally recognized as the outstanding textbook of bio- Baltimore, Maryland