Remembrance of pathogens past: a physician ponders suggestive evidence that periodic infections are needed to foster a normal immune system

Natural History, Feb, 2002 by T.V. Rajan

I was sitting downstairs having quiet cup of tea when I heard screaming from one of the bedrooms above. It was my daughter Tara. Between shrieks were occasional bursts of words: "Omigod, omigod! Daddy!" she was yelling in the signature diction of a turn-of-the-twenty-first-century American teenager. "Come here! This is so gross!" Rushing upstairs wondering if a rabid raccoon had somehow made its way into her bedroom, I found my daughter cowering in a corner. She pointed to her bed. There, silently crawling over pristine white bed linens, was a dark spider, no more than a quarter inch long. "Omigod, Daddy, please get rid of it! Eeeewww!" Half relieved, half annoyed, I picked up the errant arachnid with a piece of paper and carried it out.

I couldn't help comparing the circumstances in which my daughter is growing up with those of my own childhood in India. In our house in Madras (now officially known as Chennai), we ended many a searingly hot day by sitting out on an open veranda, trying to cool off in the ocean breeze. After sunset, when the house lights came on, the veranda's whitewashed walls would gradually darken to near black, transformed by the countless insects attracted to the lamps. And with the insects came the geckos that stalked them and swallowed them whole. I don't believe we ever paid particular attention to this nightly panorama; it was just part of our lives. Only now, when I go back to Madras and stay with my parents, do I notice the contrast between my dirt-free, animal-free Connecticut home and my boyhood home, which teemed with untidy, unruly life.

Along with the household cleanliness in Connecticut comes a kind of internal bodily sterility as well. My own childhood in India was characterized by what seems, in retrospect, to have been an interminable series of infections. My cousins and I were always getting diarrhea, colds, and fevers of unknown origin. In a country where potable water and sewage are barely separated at the best of times, a minor inclemency sent by the weather gods can blur the distinction even further, making one family's effluent another's sustenance. Add to that the ubiquitous puddles of water that breed every conceivable species of mosquito, and the result is an environment in which waterborne pathogens compete with those carried by arthropods for a foothold in every available human. Life is so different in suburban America. My own children go through long periods when they are well, truly well. It is difficult to appreciate the wonders of modern sanitation and sewage control if one has never been exposed to the realities experienced by most of the world's population. And of all the accomplishments of modern science, the conquest of childhood illnesses must surely rank among the greatest.

It is in this context that I have become particularly fascinated by two reports about ethnically South Asian children growing up in Canada and the United Kingdom. For many years, physicians had informally observed that such children are more likely than others in those countries to suffer from ulcerative colitis, an inflammatory bowel disease (IBD) of unknown etiology. IBD patients suffer from attacks of bloody diarrhea and have an increased risk of colon cancer. Following up on physicians' anecdotal reports, Scott M. Montgomery, scientific research fellow at London's Royal Free and University College Medical School, and others recently published a careful analysis of the cumulative incidence of IBD in a group of children born in the United Kingdom during a specific week in 1970. People of Indian, Pakistani, and Bangladeshi backgrounds, Montgomery's team found, were indeed significantly more likely than any others in the group studied to develop IBD (which includes both ulcerative colitis and a similar disorder, Crohn's disease) by the age of twenty-six. The second study, by H.J. Freeman and N. B. Hershfield, of the University of British Columbia, showed that Indo-Canadian children also have a significantly increased risk of developing IBD and that the onset of disease was earlier for Indo-Canadians than for Canadians of other ethnic groups.

Both studies are even more striking because they indicate that the rates of IBD in the United Kingdom and Canada are actually higher than the rate in India. Although the data from India are sparse, they do suggest that, in general, the disease is relatively milder there and has a later onset. Also quite fascinating is the well-documented inverse relationship between infant and early-childhood mortality rates and the incidence of IBD. India, with one of the world's higher rates of infant and child mortality, has one of the lower rates of inflammatory bowel disease.

The authors of the Canadian and U.K. studies reasonably conclude that ethnic Indians (and presumably others of South Asian ancestry) have a genetic predisposition for these bowel disorders that expresses itself in combination with an environmental factor. But what might the environmental factor be? To answer that question, an illuminating comparison can be made between the situation of ethnic Indian children in the United Kingdom and Canada and that of a strain of laboratory animal known as the non-obese diabetic (NOD) mouse.