biochemistry

biochemistry The science of biochemistry, nowadays regarded as one of the fundamental pillars upon which the study of medicine rests, is something of a newcomer. It has its origins almost equally in chemistry and physiology, and indeed what we would today call biochemistry was commonly referred to as physiological chemistry a hundred years ago. Looking further back we can trace early ideas about the make-up of living things to the birth of organic chemistry, the scope of which seems originally to have been a good deal wider than would be admitted today. In 1806 Berzelius referred to organic chemistry as ‘the part of physiology which describes the composition of living bodies, and the chemical processes which occur in them. In the early nineteenth century there was a good deal of debate as to whether the chemical substances found in living things were fundamentally different in character from the ‘inorganic’ constituents of inanimate matter, and the issue was only resolved (in favour of no difference) with the chemical synthesis of urea by Wöhler in 1828 and by subsequent syntheses of molecules hitherto only associated with living organisms. Thereafter organic chemistry became confined to the study of carbon compounds, and knowledge of the transformations undergone by such compounds in the course of metabolism was left to be re-born as biochemistry decades later. A major influence in that re-birth was the concept of catalysis and the realization that catalysts must play a vital part in living processes. Here the studies of Pasteur and his contemporaries in the mid nineteenth century played an indispensable part, and led to the broad unifying concept that the nature of life processes must be very similar in disparate organisms, including man, and that catalytic enzymes (the word literally means ‘in yeast’) are responsible for directing and controlling chemical transformations in the living cell.

Given the acceptance of the concept of oxidation, and the demise of the phlogiston theory, thanks to the work of Lavoisier in the late 1700s, it was natural that the early study of metabolism should be preoccupied with understanding the processes of respiration, breakdown of sugars, and energy generation. There was also much interest in nutrition and the chemical processes underlying the digestion of food. The identification of enzymes as proteins arose naturally from these efforts and spawned the science of enzymology, which remains a major division of biochemistry to the present day. The question of how enzymes work engaged the attention of many of the finest biochemical brains in the 1990s and will continue to do so for the foreseeable future. Moreover, the day is not far away when enzymologists will astonish us all by creating more or less de novo enzymes endowed with hitherto-unknown catalytic properties. Already ‘catalytic antibodies’ have been described, that bind small molecules with exquisite specificity, producing chemical change, and as knowledge of fundamental mechanisms of catalysis emerges from the efforts of physical organic chemists, the practical applications of that knowledge will not be far behind.

It was with the arrival of the twentieth century that biochemistry came of age, so to speak, and made such a major impact on medicine that it was recognized as a formidable science indispensable to the understanding of the human body. Those were the days of vitamin and hormone research. The pioneering work of Sir Frederick Gowland Hopkins (1861–1947) and his colleagues, which led to the discovery of vitamins, had a lasting influence on generations of biochemists and underpinned the unravelling of intermediary metabolism. The isolation, identification, and eventual production of hormones in sufficient quantity for therapeutic use likewise illuminated some of the most perplexing medical problems, and transformed endocrinology into an important branch of clinical science.

Biochemistry has long boasted of its roots in exact physical sciences and has never been afraid to divert the attentions of practitioners of those sciences to the study of life. By that route some of the most spectacular advances of knowledge in the twentieth century have been achieved, perhaps none more so than the birth of the enfant terrible, molecular biology, which nowadays dominates the subject. Molecular biology, rooted in structural studies on proteins and nucleic acids, owes much to the contributions of far-sighted crystallographers and geneticists (aided and abetted by a cohort of physicists and even mathematicians) who built upon the bed-rock of biochemistry to produce a veritable revolution in biology that is still evolving apace. It is sometimes hard to imagine how abstract the concept of a gene was prior to the discovery of the structure of DNA by Watson and Crick in 1953, since nowadays the precise identification of genes and expectations of their manipulation (for good or ill) can be read about in newspapers intended for the man in the street. Biochemistry is no longer the academic tool of medical researchers but, having embraced its sister disciplines in the physical as well as biological sciences, has taken on new meaning as the huge promise of biotechnology looms before us.

Never has it been more evident how the pace of scientific discovery is driven by technical advances in experimentation, the invention of new techniques, and the application of ideas imported from cognate disciplines. The twin sciences of molecular and cell biology have adapted the foundations laid by the painstaking ‘bucket’ experiments of the early biochemists to illuminate the marvels and mysteries of molecules and cells in a fashion which can only be described as spectacular. Even philosophers and theologians can no longer ignore the prospects of bio-revolution introduced into our daily lives: genetically engineered foodstuffs; super-athletes; new approaches to treating infertility; eradication of diseases. How many more triumphs (or horrors) attributable to the application of biochemically-based technology await us? And how are we going to cope with them?

M. J. Waring