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<h2 class="header">The Origins of Enzymology</h2>
<p class="header">This page contains the complete text of
the following article: Athel Cornish-Bowden (1999) "The
Origins of Enzymology,"
<cite>The Biochemist</cite> <strong>19(2),</strong> 36–38</p>
<p><strong>It would be an exaggeration to say that the
centenary of Eduard Buchner’s discovery of cell-free
fermentation<sup>1</sup> passed completely unremarked by
today’s biochemists; Arthur Kornberg<sup>2</sup>, 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
book<sup>3</sup> 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.</strong>
<div class="centred">
<h4><img src="images/menten.jpg" width="212"
height="268" alt="Maud Menten as a young woman">
</h4></div>
<p class="legend">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.)</p>
<p>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 complex<sup>4</sup>
<p>Foresighted though Brown’s model was, it was not very
thoroughly worked out, and Victor Henri<sup>5,6</sup>
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.
<div class="centred">
<h4><img src="images/manass.jpg" width="164"
height="210" alt="Maria Manasseina"></h4></div>
<p class="legend">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) <cite>V. A. Manasseina:
Her Life and Work,</cite> State Publishing House, Moscow</p>
<p>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 Buchner<sup>7</sup>. He himself was
dismissive of these claims<sup>8</sup>, 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
Lagnado<sup>9</sup> has pointed out inconsistencies in his
treatment of her, and has suggested that she deserves more
credit than she has usually received.<br>
<div class="centred">
<h4><img src="images/fulhame.gif" width="288"
height="501" alt="Title page of Fulhame (1794)">
</h4></div>
<p class="legend">FIG. 3. The title page of Elizabeth
Fulhame’s book</p>
<p>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 catalysis<sup>10</sup>. This is usually credited to
Jöns
Jacob Berzelius<sup>11</sup>, 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 <cite>An
Essay on Combustion</cite>
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
review<sup>12</sup>: 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.<br>
<p>There are good reasons for remembering the origins of
our subject, and Kornberg<sup>2</sup> 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
<q>reduced</q> to chemistry. The centenary year itself saw
the publication of a widely acclaimed
<a href="http://bip.cnrs-mrs.fr/bip10/rose.htm">book by Steven Rose</a>
attacking the reductionist approach and claiming that life
in general and biochemistry in particular are too
complicated to be amenable to analysis by it<sup>13</sup>.
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
simple chemistry.
<p>Kornberg<sup>2</sup> 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.
<p>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
Menten<sup>14</sup>, 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 concept<sup>15</sup>, 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.
<p>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.
<h3 class="framed">References</h3>
<ol>
<li>Buchner, E. (1897) <cite><abbr
title="Berichte der deutschen chemischen Gesellschaft">Ber. dt. Chem. Ges.</abbr></cite>
<strong>30,</strong> 117–124 (reprinted as pp. 17–24 of ref. 3,
and in an English translation by H. Friedmann as pp. 25–31
of ref. 3)
<li>Kornberg, A. (1998) <cite><abbr title="Trends in Biochemical Sciences">Trends Biochem. Sci.</abbr></cite>
<strong>22,</strong> 282–283 (reprinted as pp. 61–65 of ref. 3)
<li>Cornish-Bowden, A, ed. (1997) <cite><a
href="buchner.htm">New Beer in an Old Bottle: Eduard
Buchner and the Growth of Biochemical Knowledge,</a></cite>
University of Valencia
<li>Brown A. J. (1892) <cite><abbr title="Journal of the Chemical Society (Transactions)">J. Chem Soc. (Trans.)</abbr></cite>
<strong>61,</strong> 369–385
<li>Henri, V. (1902)
<cite><abbr title="Comptes rendus hebdomadaires des Séances de l’Académie des Sciences de Paris">C. r. hebd. Acad. Sci.
Paris</abbr></cite>
<strong>135,</strong> 916–919
<li>Henri, V. (1903) <cite>Lois Générales de l'Action des
Diastases,</cite> Hermann, Paris
<li>Manasseina, M. (1872) <cite><abbr title="Berichte der deutschen chemischen Gesellschaft">Ber. dt. Chem. Ges.</abbr></cite>
<strong>30,</strong> 3061–3062
<li>Buchner, E., and Rapp, R. (1898) <cite><abbr title="Berichte der deutschen chemischen Gesellschaft">Ber. dt. Chem. Ges.</abbr></cite> <strong>30,</strong> 209–217
<li>Lagnado, J. (1992) <cite>The Biochemist</cite>
<strong>14(5),</strong> 21–22
<li>Fulhame, E. (1794) <cite>An Essay on Combustion, with a
View to a New Art of Dying and Painting, wherein the
Phlogistic and Antiphlogistic Hypotheses are Proved
Erroneous,</cite> published by the author, London
<li>Berzelius, J. J. (1836) <cite><abbr title="Jahresberichte">Jahresber.</abbr></cite>
<strong>15,</strong> 237–245
<li>Coindet, J. F. (1798) <cite><abbr title="Annales de Chimie">Ann. Chim.</abbr></cite>
<strong>26,</strong> 58–85
<li>Rose, S. (1997) <cite><a href="http://bip.cnrs-mrs.fr/bip10/rose.htm">Lifelines:
Biology, Freedom, Determinism,</a></cite> Allen Lane, London
<li>Michaelis L. and Menten, M. L. (1913) <cite><abbr title="Biochemisches Zeitschrift">Biochem. Z.</abbr></cite> <strong>49,</strong> 333–369
<li>Sørensen, S. P. L. (1909) <cite><abbr title="Comptes rendus des Travaux du Laboratoire Carlsberg">C. R. Trav. Lab.
Carlsberg</abbr></cite> <strong>8,</strong> 1–168
</ol>
<div class="centred">
<h4>
<img src="images/athel.jpg" width="108" height="140"
alt="Author"></h4></div>
<p class="legend">Athel Cornish-Bowden
(athel@ibsm.cnrs-mrs.fr) is Directeur de Recherche in the
<abbr title="Centre National de la Recherche Scientifique">CNRS</abbr>
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. </p>
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Page created on 9 June 1999<br>
Last update: 22 December 2008<br>
Last significant update: 7 April 2006<br>
<em>Comments to <a href="mailto:acornish@ifr88.cnrs-mrs.fr">Athel Cornish-Bowden</a></em><br>
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