Surveying a monumental landscape from the shoulders of giants

Proteins, Enzymes, Genes

January 5, 2001

Like Euclidean geometry, science forms a pyramidal edifice of knowledge. Today's discoveries are made because we are standing on the shoulders of the giants of previous generations. Unlike Euclidean geometry, however, the structures lower in the pyramid of science are largely hidden. Some, though well founded, are imperfect and others have crumbled away. The strength at our level of the pyramid is continually tested by appeal to experiment, and if the results are satisfactory, we may feel no need to probe too deeply into the foundations.

At this moment, the flowering of the basic life sciences makes this particularly evident in biochemistry, cell biology and genetics. Many life scientists know very little about the history of their subject. The lecturer, hard pressed to squeeze in the new insights since the course was taught last year, throws out all non-essentials and tries to teach the ideas in a sequence that is readily assimilated. This rarely accords with the path of history.

The exponential growth of scientific literature exacerbates the situation. Few libraries have room for primary literature more than about 30 years old. To access earlier literature is inconvenient and time consuming. It is not so easy for the graduate to read the 60-year-old head of department's early work.

For an overview of history, we all know books by those professional scientific authors who are so good at writing fascinating bestsellers about the great themes of scientific progress, but who must avoid bogging down their readers in detail. Equally, textbooks of the history of science tend to concentrate on the great figures of the past, but omit the detail. Biographical works are too often obsessed with personality, attitudes and social behaviour, to the exclusion of the great scientific themes of the day. Autobiographies have a well-understood lack of objectivity. Our knowledge remains a sketchy cartoon of the truth. Take enzymology, for instance: Louis Pasteur must surely have started the subject; Emil Fischer was the great figure towards the end of the 19th century; Leonor Michaelis constructed a kinetic theory, built on by J. B. S. Haldane; while Frederick Gowland Hopkins followed Felix Hoppe-Seyler in identifying the first enzymatic pathways; and James Sumner got into trouble because he crystallised an enzyme, but nobody believed that his crystals were the enzyme. What else was there before 1930?

Joe Fruton's book is a wonderful antidote to all this simplification. The first thing to be said is that it is breathtakingly broad in perspective, staggeringly erudite, but (for the most part) easy to read and enjoy.

My cartoon view of history is shattered. I must admit with shame that I did not know that Pasteur's famous demonstration in 1861-62, showing that fermentation could be prevented by heating and sealing the sample or even by ensuring that nothing could fall into the sterile sample, was mostly a neater presentation of experiments already done by Heinrich Schroeder and Theodor van Dusch seven years before. Nor did I know that Lavoisier had published, in 1789, a paper showing that the fermentation of sugar using yeast gave alcohol and carbonate in appropriate quantities to demonstrate conservation of matter. Gay Lussac obtained more accurate figures in 1815 to confirm the correct molar proportions of products. Huge efforts and controversies, throughout the 19th century, many of them carried on by the great chemists of the time, painstakingly established the basic facts that one takes for granted today.

This is straightforward scientific history, based on intimate knowledge of the subject, making no concessions to social dogmas or political attitudes. Fruton writes: "I have eschewed generalisations such as those relating to 'paradigms', 'gestaltswitches' or 'creativity'. I do not find it necessary to invoke the concept of material culture in referring to the instruments, chemicals, or organisms used in particular researches, nor do I use the term moral economy in writing about the social relations amongst scientific investigators", but "I dissent from the opinions of those of my scientific colleagues whose biographical writings incline toward hagiography, and side with those historians who, in admiring the scientific achievements of famous men ...have provided insights into the frailties which attend scientific genius."

Fruton is widely recognised as a leading biochemist of his era, but is less known for his consuming interest in the history of his subject. He has a wonderful facility for extracting a quotation from a classic or infamous paper that not only states the essence of the argument, but gives the flavour of the author's attitude. For example, these three quotations from others set the scene for a chapter on the chemistry of heredity. "That the fundamental aspects of heredity should have turned out to be extraordinarily simple supports us in the hope that nature may, after all, be entirely approachable. Her much-advertised inscrutability has once more been found to be an illusion due to our ignorance. This is encouraging, for if the world in which we live were as complicated as some of our friends would have us believe, we might well despair that biology could ever become an exact science" (Thomas Morgan 1919). "I started with genetics, not because I realised in 1932 the key role this subject was destined to play, but at least in part because it is a field congenial to one trained in mathematics" (Warren Weaver, 1970). Finally, around 1960, "geneticists tended to think in formal rather than in biochemical or molecular terms. DNA was a physical structure which could mutate and recombine and it was not necessary to worry at this stage about the underlying biochemistry" (Robin Holliday, 1990).

Fruton's total mastery of this huge literature is almost overwhelming. The book's 500 pages of text are supplemented by 250 pages of notes and references. These are extremely well organised, leading painlessly to more information if you want it, but easily ignored if you do not. The book provides not only a detailed historical insight into the steps that resolved the grand themes of biochemistry and molecular biology, but is also ideal for dipping into so as to find the background to some point of interest.

One of the difficulties of writing modern history is knowing when to stop. Without stating a definite cut-off, Fruton follows through each strand of research to 1970 or so, occasionally into the 1980s. This means that many of his readers will have first-hand experience of the scientific work described, putting the historian into a vulnerable situation. In the particular cases where I have personal know-ledge, I was not able to identify an error of fact. In some cases, the emphasis and judgement were different from my interpretation, but this is an author's privilege.

The first 100 pages are the weakest part of the book. The author feels a need to justify himself in taking a historian's role, and that dominates the introduction and leads into the first chapter. This chapter mainly discusses the names given to branches of biological science at different times, and the attitudes underlying the nomenclature. Fruton must believe it is essential to sort this out, but I felt a sense of strain.

The second chapter was written to deal with the difficulty of organising the material. We are introduced to hundreds of scientists' names, many from the 19th century, but few of us have any idea about who worked where and with whom, how one school was nurtured from another, and how opinions were polarised. This long chapter is useful and important in explaining these points but, standing at the beginning of the book, it creates a barrier that readers must surmount before reaching the material they want. It was a difficult chapter to write, and sometimes degenerates into lists of names. It could function well as an appendix.

Then there is a brief third chapter on philosophy and science.

My advice to readers is to skip to chapter four after the introduction. Here Fruton embarks on his real historical theme, the writing gets back into its stride, and you will be drawn into a thrilling series of stories of human achievement interwoven with human error and confusion.

The author's credentials as a historian, with encyclopedic knowledge of his material, are obvious. He had no need to justify himself so laboriously. The fact that he can also deliver authoritative judgements about the scientific arguments must make this book unique. It will be a standard work of reference for many years to come.

David Blow is senior research fellow, Imperial College, University of London.

Proteins, Enzymes, Genes: The Interplay of Chemistry and Biology

Author - Joseph S. Fruton
ISBN - 0 300 07608 8
Publisher - Yale University Press
Price - £30.00
Pages - 783

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