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Plagues - Investigating Disease Patterns
July 19, 1996

The many fascinating stories in Plagues: Their Origins, History and Future are all to do with diseases that have been known to spread rapidly and cause epidemic or pandemic disasters. They have been carefully chosen by Christopher Wills to illustrate some of the ideas he shares with biologists who have made a special study of molecular or population genetics, and to show the place plagues and endemic diseases have in a world of incessant battles between unicellular and multicellular organisms.

Thus, there are stories to show how these battles are constantly driving both parties towards further genetic diversity - by having recognition and destruction of foreign proteins as the principal methods of defence and attack - and stories to show how micro-organisms are constantly adapting to new situations. There is also a visit to an Amazonian rainforest to remind readers that ecologists now believe that "pest pressure is the inevitable, ubiquitous factor in evolution which makes for an apparently pointless multiplicity of species in all areas where there has been time for this to operate".

In the section dealing with bubonic plague, we learn about three widely spaced epidemics of this greatly dreaded disease: the one that spread from Constantinople to Ireland and finally destroyed the Roman Empire; the Black Death that eight centuries later again decimated the European population; and the epidemic that swept through China in 1896 and gave Alexandre Yensin his opportunity to identify the plague bacillus (Y. Pestis). This discovery showed that plague is a flea-borne disease that damages the vector as well as the host, but also has temporary effects on the fleas that help the bacilli to be such successful killers of human beings. We also learn why Wills suspects that "no ecological relationship in which all the interacting members are behaving abnormally is likely to persist for long".

As examples of water-borne diseases we are offered cholera, which is caused by Vibrio cholerae, and typhoid, which is caused by Salmonella typhi. Evidently only one strain of vibrio cholera carries a gene cluster that is harmful to man. But this modification of an otherwise harmless organism is liable to happen whenever the arrival of large numbers of humans in the vicinity of an estuary adds unusually rich nutrients to slightly salty and often warm water. Whenever the dangerous variant of vibrio cholera has arrived on the scene, the effects have been so devastating that, as with bubonic plague, cholera epidemics have threatened the very existence of the human race. S. typhi has never had such horrendous effects, but supplying cities with clean water has always been less successful in eradicating typhoid than cholera. The exceptional tenacity of S. typhi is clearly the result of this organism finding a safe haven in the gall bladders of patients, and thus circumventing the clean water problem by creating a pool of human carriers of typhoid.

The protozoal causes of malaria, which affect all warm-blooded animals including birds, find it much harder to cope with cold and dry than hot and wet climates. But they, too, have special ways of surviving in uncongenial environments. For example, although the causes of the human disease (Plasmodia vivax, malariae and falciparum) normally spend their lives being pumped in and out of blood corpuscles by Anopheles mosquitoes, they can adapt to life in the human liver and thus cause recrudescence of the disease in cold as well as hot climates. An added danger comes from the Anopheles mosquito also breeding in cold as well as hot swamps and, until 1850, malaria was a scourge in low-lying parts of England and Denmark. In the tropics the malarial parasites have defeated all attempts at eradication, but when farms in England and Denmark acquired cowsheds and pigsties, the mosquitoes moved in with the warm-blooded animals and soon lost their parasites. This change marked the disappearance of malaria from the northern half of Europe and is gleefully described by Wills as "a public health problem that disappeared before anyone ever knew that it was a public health problem".

As examples of micro-organisms that can cause different diseases although they look exactly alike and have the same genes and antigens, Wills has chosen two members of the treponemes family: T. pallidum and T. pertenue. These spirochaetes can only survive in human tissues, but there they cause three distinct diseases with different geographical distributions and different modes of transmission. Thus, as a cause of syphilis, T. pallidum has become a worldwide menace by taking advantage of the warm, moist conditions of the human sex act. As a cause of bejel, which mainly affects Bedouin children, T pallidum has taken advantage of the fact that these youngsters huddle together in tents, have communal clothes and never wash. Finally, as a cause of yaws, which is not a venereal disease although it resembles syphilis, T. pertenue has not stirred outside the tropics.

From diseases caused by unicellular organisms that can only survive in human tissues it is a short step to Aids, which comes from two variants of the human immunodeficiency virus, and is defeating all attempts at cure and prevention. HIV-1 and HIV-2 are retroviruses or fragments of genetic material that "inhabit a twilight world between life and nonlife" and get passed to new hosts while furiously producing replicas of themselves by a curious budding process. Why this mode of transmission has suddenly become so successful, and why each new victim dies from the effects of gradual destruction of essential parts of the immune system, remains a mystery. But possibly "retrovirus formation" is a regular accompaniment of the complex process of cell division that often leads to fragments of genetic material being lodged in plants and animals.

Finally, Wills, who has made a special study of herd immunity - the phenomenon that allows a resistant majority in a herd of animals to protect a susceptible minority - has found "that species herd-immunity really is operating in the rainforest". This has convinced him that preservation of any complex ecosystem requires preservation of pathogens as well as hosts, and that without such systems there would be a greatly increased risk of epidemics and pandemics. Hence this final message to his readers: we are now living in an artificial self-made environment where even bubonic plague can no longer hold numbers in check. But unfortunately we are driving other species to extinction and thus simplifying many otherwise complex ecosystems. Therefore, what the future holds may depend less on human diseases than on the plagues of more vulnerable animals and plants.

Though the stated purpose of Investigating Disease Patterns: The Science of Epidemiology is to convey "some of the excitement, importance and challenge" of "an under-appreciated branch of medical science", this book has none of the sparkle of Plagues. It even fails to justify the second half of its title and, at one point, confuses epidemiologists with clinicians or pathologists by saying that one of their primary activities is "the description and classification of diseases".

The lack of systematic information about the science of epidemiology in the book is the result of Paul Stolley and Tamar Lasky packing it with stories about scientists from other disciplines (notably clinical medicine, public health and pathology) who have, on odd occasions, borrowed some of the simpler tools of epidemiology to solve a one-off problem. They seem to have forgotten that, as an academic discipline, epidemiology owes its existence to the fact that in most countries there are now vast collections of official vital statistics - or statistics of immediate relevance to the health of nations - that are waiting to be integrated with comparable data from specially designed surveys. The subject naturally has strong links with public health - but the idea that the closest thing to a whole-time practitioner of epidemiology is a public health official is quite wrong and is tantamount to confusing people who are developing a new technology with the principlal users of their new inventions. Like scientists in other disciplines, epidemiologists are experts at collecting and analysing relevant data; and, like other sciences that are dealing with intangible and unalterable situations (for example, astronomy and demography), epidemiology is a branch of applied mathematics.

Though readers of Investigating Disease Patterns are quite likely to come away with the idea that epidemiology is a collection of useful tools rather than a subject in its own right, and though Stolley and Lasky have missed a good opportunity to show how recent advances in biostatistics and computer science are revolutionising the scope and power of human surveys, the book has several good features. For example, in addition to a plentiful supply of diagrams and other illustrations, it has much of interest to say about the causes of cancers and obscure infections and the effects of dangerous occupations, drugs or habits. And it certainly highlights the importance to medicine of the epidemiological standpoint.

Alice Stewart is senior research fellow, department of epidemiology, University of Birmingham.

Plagues: Their Origin, History and Future

Author - Christopher Wills
ISBN - 0 00 255611 1
Publisher - HarperCollins
Price - £20.00
Pages - 324

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