This page contains the complete text of the following article: Athel Cornish-Bowden (1999) "The Origins of Enzymology," The Biochemist 19(2), 36–38
It would be an exaggeration to say that the centenary of Eduard Buchner’s discovery of cell-free fermentation1 passed completely unremarked by today’s biochemists; Arthur Kornberg2, for example, wrote an interesting article on the occasion of the International Congress of Biochemistry and Molecular Biology in San Francisco, and this was later reprinted in a book3 that set out to trace the roots of modern studies of multi-enzyme kinetics in Buchner’s pioneering work. On the other hand it could hardly be claimed that this centenary was the main talking point of 1997, most of us being too busy pushing back the frontiers to have much time for looking back to see where we came from.
FIG. 1. Maud Menten some years before her collaboration with Michaelis. (Reproduced with permission from a leaflet prepared by D. B. Smith and H. B. Stewart to commemorate the unweiling of a plaque at the University of Toronto during the XIth International Congress of Biochemistry in 1979. The original photograph was supplied to Dr Smith by Mrs Dorothy C. Craig, Maud Menten’s niece.)
This was brought home forcibly to me some 20 years ago, when I was teaching a graduate course on kinetics at a university in Canada: I mentioned that Maud Menten (Figure 1) was both one of the first women and one of the first Canadians to make her mark in biochemistry, but it was clear from the blank looks on the faces of the students that none of them could see any reason to introduce information that was unlikely to be needed for the examination. In the same period, when I lectured in the Biochemistry Department at Birmingham, which has an Adrian Brown Chair, few students seemed much interested in knowing who Adrian Brown had been or what he had done: in fact his work foreshadowed that of Michaelis and Menten, and he was probably the first to suggest that the tendency of enzymes to show substrate saturation was a consequence of a mechanism involving an enzyme–substrate complex4
Foresighted though Brown’s model was, it was not very thoroughly worked out, and Victor Henri5,6 criticized it for assuming a fixed lifetime for the enzyme–substrate complex. His own work clearly prepared the way for Michaelis and Menten as well, and some authors suggest that he should be given partial credit for the equation associated with their names. This is a mistake, however, because Henri (like most workers at that time) was not trying to derive an equation for the initial rate of a reaction but for the whole time course, and although with hindsight it may seem an obvious step to introduce the initial-rate condition into his algebra this was not a step that he took.
FIG. 2. Maria Manasseina (1843–1903) shortly before her departure from St Petersburg to join Professor J. Wiesner’s laboratory at the Polytechnic Institute in Vienna, where she carried out her research on alcoholic fermentation in yeast first published in 1872. Reproduced from G. Arsenyev (1951) V. A. Manasseina: Her Life and Work, State Publishing House, Moscow
Whether or not Menten was the first Canadian biochemist,
she was certainly not the first woman biochemist. Her
predecessor, the Russian Maria Manasseina (Figure 2),
claimed to have discovered cell-free fermentation a
generation earlier than Buchner7. He himself was
dismissive of these claims8, pointing out that
the supposedly sterile sugar solutions that she used were
almost certainly contaminated with micrococci. Most writers
have accepted his view without looking any deeper, but John
Lagnado9 has pointed out inconsistencies in his
treatment of her, and has suggested that she deserves more
credit than she has usually received.
FIG. 3. The title page of Elizabeth Fulhame’s book
Much earlier still, as remote indeed from Buchner as he
is from us, another remarkable woman, Elizabeth Fulhame,
was doing experiments that laid the foundations of the idea
of catalysis10. This is usually credited to
Jacob Berzelius11, but Fulhame’s work was much
earlier, and, emphasizing the catalytic role of water, it
is more relevant to modern explanations of enzyme action
than the studies of platinum and the other heavy metals
that formed the focus of most 19th Century work on
catalysis. Virtually all that we know of her work or her
life is what is contained in her book, entitled An
Essay on Combustion
and published on Guy Fawkes Day in 1794 (Figure 3). This
book is now virtually unobtainable — I have a photocopy,
but do not know who has the original from which it was
made. Much easier to track down is Coindet’s 28-page
review12: regarded as a review this is almost
wholly without interest, but it has the merit of providing
a blow-by-blow account of the book.
There are good reasons for remembering the origins of
our subject, and Kornberg2 emphasized what is
perhaps the most important: the battle against vitalism may
have seemed to have been won a century ago, but in reality
it is still with us, because vitalist ideas threaten
whenever we forget the arguments that led scientific
biochemistry to be born out of the marriage of physiology
and chemistry. Vitalism is by no means eradicated even now,
and can spring up again at any time, whenever someone claims
that this phenomenon or that is too complicated to be
reduced to chemistry. The centenary year itself saw
the publication of a widely acclaimed
book by Steven Rose
attacking the reductionist approach and claiming that life
in general and biochemistry in particular are too
complicated to be amenable to analysis by it13.
Much of the book is no more than a campaign against
oversimplification, but there are parts that come close to
a plea for vitalism, such as the denial that the
oxygen-carrying function of haemoglobin can be reduced to
Kornberg2 called Buchner’s discovery the birth of modern biochemistry: before Buchner there was no serious possibility of studying metabolism, and without metabolism there was little possibility of taking enzymology beyond the fragmentary study of a few extracellular enzymes.
It is no coincidence, therefore, that the development of enzymology was greatly stimulated by Buchner’s discovery, and the first decades of the 20th Century saw the groundwork laid for the study of the kinetics and mechanisms of enzyme action, most notably by Leonor Michaelis and his collaborators. Although we mainly remember him now for his paper of 1913 with Maud Menten14, he was a tremendously productive researcher, even if judged by the standards of today, and he contributed greatly to the development of several aspects of enzyme action, including inhibition and pH effects — having been close to the idea of pH when Søren Sørensen introduced the concept15, he was among the first to build upon it, and the five years from 1910 to 1914 saw nearly one hundred publications, including five books. After 1914 his output dropped somewhat, for obvious reasons, but he continued to publish important work for the rest of his life.
In first three-quarters of the century after Buchner’s work the science of biochemistry was created and consolidated. In his day little or nothing was known about metabolic pathways or enzyme catalysis; in ours, if we believe some commentators, everything worth knowing about metabolism and enzymology is now known, and only people unable to keep up with the changes of fashion are still interested in them. If this is true at all, however, it is only true if we keep the two subjects largely separate. Once we start to ask how enzymes interact with one another in the cell and how the properties of metabolic pathways depend on the properties of the enzymes that they contain, we realize that the work is only now beginning, and that a great deal remains to be done during the second century.
Athel Cornish-Bowden (email@example.com) is Directeur de Recherche in the CNRS Laboratoire de Chimie Bactérienne in Marseilles. For most of his career he has been interested in the kinetic behaviour of enzymes, in recent years especially when considered as components of metabolic pathways rather than one at a time.