This page contains the full text of the following chapter: Athel Cornish-Bowden (2000) "In memoriam: Paul Srere, 1925–1999", pp. 347–349 in Technological and Medical Implications of Metabolic Control Analysis, (ed. Athel Cornish-Bowden and María Luz Cárdenas), Kluwer Academic Publishers, Dordrecht, The Netherlands
I met Paul Srere in Hungary, and chance decided that the last time I saw him would also be in Hungary,
a country that he loved and visited often, so it was appropriate that it should be there that
he made his last presentation to a scientific meeting.
My first encounter with him was at a conference in Debrecen in 1985, long after I first heard of his work.
He started his lecture by saying that many people were unsure how to pronounce his name, and
that the easiest was to remember that it rhymed with dreary
. Useful enough as a mnemonic, perhaps,
but not at all accurate as a description, as it soon became obvious that he was anything but
dreary. On the contrary, his work and ideas have served as the inspiration for many biochemists over
the past 30–40 years, including many who never worked with him. It was during this lecture in
Debrecen that he suggested the use of the term metabolon
to refer to a functional complex of enzymes
in a metabolic sequence (Robinson & Srere, 1986), and since then both the word and the idea have
become closely associated with his name.
Paul’s reputation was built on the firm basis of his extended studies over many years of the biosynthesis of citrate, but he is mainly known to his friends in the field of metabolic control analysis for two more general ideas. He was probably the first to realize that enzyme concentrations in living cells are far higher than they are in a typical enzyme assay, being often as large as or greater than the concentrations of their substrates (Srere, 1967); if he was not the first to realize this he was certainly the first to emphasize that it was potentially important and that many received ideas of how enzymes functioned in the cell would need to be revised to take account of it.
His second general idea followed from the first. If enzymes exist at such high concentrations in the cell that the mean distance between them is of the same order as their molecular diameters then they must be touching one another, or come close to touching one another, most of the time. It follows that we can hardly treat the cell as just a bag of enzymes but that on the contrary we must study how the cell is organized, and how enzyme molecules are arranged in relation to one another. Not surprisingly, therefore, Paul was one of the most vigorous proponents of the idea that cell architecture must be taken seriously, and that biochemists need to come to grips with complexity, however difficult it might be to break with the old notions of reactions in homogeneous solutions.
Paul was also broadminded enough to apply the same rigour to topics rather more remote from his own
immediate activities. He had grown up with and contributed to the studies of feedback
inhibition, allosteric regulation and cooperativity that enriched biochemistry 30 years ago, and he knew how
much these ideas had contributed to the growth of biochemical understanding. At the same
time, however, Paul was able to see that they were not enough, and that to understand a system of enzymes
one must study it as a system. He embraced and encouraged the growth of control analysis with
far more enthusiasm than many others who knew metabolic regulation during its golden age in the 1960s, and
I feel sure that he approved of the words from Henrik Kacser that Douglas Kell and Pedro
Mendes quote at the beginning of this book: But one thing is certain: to understand the whole you must look at the whole.
No one who knew Paul could feel that a description of his scientific achievements gave a complete picture of the
man, with his look of an Old Testament prophet, helpful and kind to everyone even if
they did not share his enthusiasm for channelling, fond of limericks and word play, joking a few weeks before he
died that he was no longer buying green bananas. He had been in poor health for some
time, but he worked actively to the end, and on one of the last occasions when he spoke, at a retirement party
for a colleague, it was to say a few words on the theme of What do you do when your
post-doc retires before you do?
. I was not present on that occasion, but the words fit Paul’s personality
so well that I can easily hear him saying them.
He also liked symbols and ancient history, and it is appropriate to end, therefore, by recalling a remark that he made about Fritz Lipmann:
Before his time the biochemists were like beasts, clothing themselves with phenomenology and feeding on raw data, knowing their biology but not their physical chemistry.
This was in an article (Srere, 1988) about the Emperor Fu Hsi, who died in 2838 BC and who, according to Paul, discovered the Krebs cycle, introduced the squiggle symbol for a high-energy bond, and foresaw the circular chromosome of E. coli. Of him it was said that
Before his time the people were like beasts, clothing themselves in skins and feeding on raw flesh, knowing their mothers but not their fathers.
What can we say of Paul himself? Perhaps that
Before his time the biochemists tried to be modern people, washing abundantly with homogeneous solutions and consuming processed data from cell extracts, knowing their enzymology but forgetting their cell architecture.
However we say it, though, Paul’s departure is a great loss for biochemistry. The number of people with the breadth of knowledge to span biochemistry from the molecular to the physiological levels, enriching all of them, is notably diminished by his death.
I am most grateful to Ron Estabrook for permission to reproduce a photograph of Paul Srere that he took on the 7th May 1999, to Marilú Cárdenas, Jack DeMoss and David Fell for comments on this text, and to Rick Welch for sending me an advance copy of his obituary for Trends in Biochemical Sciences.
Athel Cornish-Bowden