Catching on to What's Catching

Natural History, Feb, 1999 by Paul W. Ewald, Gregory Cochran

Some infections are slow to be recognized.

Applying Darwinina thinking to the study of disease refocuses our attention on bacteria, viruses, and other pathogens.

The year 1972 saw the publication of the last edition of the classic Natural History of Infectious Disease, by Nobel laureate Macfarlane Burnet and David White. Like two climbers reaching a summit, Burnet and White surveyed the impressive accomplishments of a century of germ-theory science. In their eyes, the triad of vaccination, antibiotics, and improved hygiene had virtually ended the threat of infectious disease in wealthy countries and was on its way to doing so in poorer countries as well. "The most likely forecast about the future of infectious disease," they concluded, "is that it will be very dull."

Predicting the future is, of course, a tricky business. But had Burnet and White trained their eyes more closely on the horizon, they could have discerned a range of formidable peaks. Intransigent, antibiotic-resistant infections, for example, had been circulating in hospitals--ominous harbingers of the outbreaks that would plague these institutions during the 1980s and 1990s.

Burnet and White failed in another way to glimpse the future. The list--the very category--of what they called infectious disease would soon expand. In the past three decades, research has increasingly implicated infection as a cause of diseases that many still think of as produced solely by lifestyle factors (stress, diet, lack of exercise), environmental pollution, or genetic inheritance. Between 15 and 20 percent of all human cancers are now attributed to infection. A bacterium--Helicobacterpylori--has been implicated as the cause of peptic ulcers and is also connected to stomach cancer. In heart disease, evidence that the stage is set by the bacterium Chlamydia pneumoniae looks stronger and stronger every month. In short, we seem to be in the middle, not at the end, of our effort to comprehend the scope of infectious disease.

Whether out of convenience or ignorance, medical historians often imply that our understanding of infectious disease causation began with the establishment of the germ theory at the end of the nineteenth century. But comprehension of the problem began before that. Some medical textbooks of the mid-nineteenth century described chicken pox, scarlet fever, measles, and smallpox as contagious and sometimes even as infectious. Breakthroughs in the 1870s and 1880s---such as Robert Koch's discovery of the bacilli that cause anthrax, tuberculosis, and cholera--cemented earlier understanding of the concept of infection.

Some infectious illnesses were (and are) slow to be recognized, however. If we scan modern medical history a few decades at a time, we can see a pattern that is still evident today: the more obscure (or "cryptic") the chain of infection, the more slowly the medical community comes to recognize a disease as infectious.

In some cases, transmission from person to person is easily observed. Take chickenpox: Johnny was playing with Susie the day that Johnny came down with chickenpox; two weeks after that, Susie got it; and two weeks after that, Susie's little brother got it. It is no surprise that diseases with overt signs and symptoms--like chickenpox, with its red lesions and fever--were recognized as infectious decades and even centuries before the causative agents were identified.

Where the chain of infection is difficult to trace, the story has been different. When yellow fever broke out in Barcelona in 1822, Nicholas Chervin led a study to determine whether the disease was contagious. He demonstrated that yellow fever in a sample population occurred in localized flare-ups rather than as a spreading grass fire--something he expected to see if it was being communicated from one victim to another. Chervin concluded, quite reasonably, that yellow fever was not communicable. It took another half century for Cuban epidemiologist Carlos Finlay to propose the missing link in the chain of infection: mosquitoes. Likewise, the seemingly discontinuous outbreaks of cholera in London in the 1840s and 1850s were not understood until the careful studies of John Snow (an English physician) implicated indirect transmission of a then unknown infectious agent through a contaminated water supply.

Sometimes social factors obscured the links, as was the case with gonorrhea in eras when unsanctioned sexual contact was kept secret. In the nineteenth century, if Henry had gonorrhea's symptomatic "drip," it was probably unknown to everyone except himself. A sexual relationship between Henry and Martha might also have gone unnoticed. Thus, although gonorrhea was known to be contagious under certain conditions, and although the gonococcus that causes the disease was described by the German dermatologist Albert Neisser in 1879, its infectiousness was not generally accepted until years later--well after the nature of acute respiratory infections had become understood.

By the end of the first quarter of the twentieth century, careful study and experimentation had unmasked most of these moderately cryptic links between pathogens and disease. But further discoveries would require recognition of the more obscure links. One difficult puzzle was rheumatic fever, an illness that causes inflammation of the tissues of the heart and joints. Researchers long suspected an infectious cause, but rheumatic fever was not easily connected with its necessary predecessor: an untreated throat infection. Lacking the discovery of a pathogen at the damage site, and with a variable lag time between the infection and the onset of heart or joint symptoms (not to mention the relatively low odds that the initial throat infection would lead to a secondary disease), it took thirty years before antibiotic trials conclusively identified the culprit: group-A streptococcus.