Biased Sampling: Listening to Edith Boyd

The following historical incident offers a vivid illustration of the dangers of biased sampling. In this case, failing to identify a representative sample ultimately led to the death of thousands of people who were otherwise totally heathy.

A second lesson from this history is how women researchers tend to be ignored. If people had paid attention to the research of a single woman scientist (Edith Boyd, way back in 1927) thousands of lives would have been saved. The prejudices we develop in our ordinary lives carry over into our research.

Crib Death (SIDS)

For nearly two centuries, pediatricians have been aware of the seemingly random phenomenon of crib death. A perfectly healthy baby is put to bed, and the next morning is tragically found to have died. Today, the phenomenon is know as sudden infant death syndrome (SIDS). Modern parents are terrified when they hear stories of these apparently haphazard deaths. In recent decades, some progress has been made in identify the cause of SIDS. In late pregnancy, a developing fetus may sometimes suffers an oxygen deficit that damages cells in the middle and lower brain stem. These cells regulate respiration. After birth, this preexisting brain damage predisposes the infant to sudden respiratory arrest, leading to death (Paterson, et al., 2006).

Until the 1990s, however, pediatricians and medical researchers had no idea what was causing SIDS. Parents were frantic to understand (and prevent) this enigmatic and horrible death.

Toward the end of the nineteenth century, an Austrian pathologist named Richard Paltauf made a sustained effort to unravel the mystery. Paltauf carried out meticulous detailed autopsies of infants who had died from SIDS. He systematically compared these autopsies with autopsies of infants who had not died of SIDS. It didn’t take him long before he discovered a smoking gun. In nearly every case of SIDS, Paltauf found that the thymus glands of SIDS infants were much larger than those for the non-SIDS infants.

The thymus glands are located on either side of the trachea or windpipe. Paltauf theorized that the enlarged thymus glands were pressing against the windpipe, reducing the airflow, and endangering the infant’s breathing. SIDS infants were dying, he proposed, because of suffocation induced from excessively large thymuses. A few years later, Escherich (n.d.) gave the proposed syndrome the name status thymico-lymphaticus.

Paltauf’s theory of SIDS was quickly adopted and the search was on for an effective treatment. If a physician detects an enlarged thymus, what can be done? An exciting new medical technology available in the early 20th century was the X-ray machine. At the time, it was well-known that exposure to X-rays would often cause tissues to shrink—and indeed, this was the case with the thymus. Mainstream pediatric textbooks prescribed a standard preventive treatment: in order to prevent SIDS, an infant’s thymus should be shrunk by irradiating the throat with X-rays (Lucas, 1927). This preventive treatment became widespread and continued into the 1950s.

Of course, X-rays are also dangerous. They can cause cell mutation, leading to cancer. The thyroid gland (also located in the throat) is especially sensitive to X-rays. Over the decades, what was intended to be a preventive treatment led to tens of thousands of cases of thyroid cancer, and ultimately led to thousands of premature deaths. In the end, the treatment proved worse than the disease.

But what then of Paltauf’s theory of the enlarged thymuses? Recall that Paltauf compared autopsies of SIDS infants with autopsies on infants who had died from other causes. As you might imagine, not all parents agree to have their infant autopsied after death. Throughout history, anatomists have had difficulty accessing bodies to study. If your infant died under mysterious circumstances, you might well agree to permit an autopsy. But what if your infant died for perfectly obvious reasons? Many parents would be much less likely to agree to an autopsy.

An exception happens in the case of poor people. If a medical researcher offers to pay for the cost of a funeral (and perhaps other costs), poor parents are much more likely to permit an autopsy. This means that most of the autopsies and anatomical studies that are carried out are done on people from impoverished backgrounds. As it turns out, poor people are also likely to be less healthy, and to suffer more from various forms of stress.

When Paltauf carried out his autopsies, he didn’t realize that there was a confound between the SIDS infants and the non-SIDS infants. Non-SIDS infants were more likely to come from impoverished families. Most of these non-SIDS infants had died from chronic illnesses that had caused a certain degree of “wasting.” One of the consequences of chronic stress is that the thymus glands tend to shrink. By contrast, the SIDS infants had died suddenly—rather than following a prolonged illness. When Paltauf examined the SIDS infants, he was one of the first pathologists to observe normal infant anatomy. It was not the case that the thymuses of SIDS infants were enlarged. Instead, the thymuses of non-SIDS infants were smaller than normal. In other words, it was not the case the SIDS infants had larger than normal thymuses. Rather, the stressed infants from impoverished backgrounds had abnormally small thymuses.

This unfortunate history could have turned out differently if researchers had paid attention to a 1927 publication by pathologist Edith Boyd. Boyd had also carried out a number of autopsies of infants who died under a number of circumstances. Boyd found that infants suffering from malnutrition had small thymuses. By comparison, she found that infants who died due to accidents had large thymuses. She reasoned that the thymuses of infants who died due to accidents were likely to be normal in size. To Boyd, it didn’t make sense to suppose all of the children who died in automobile accidents (for example) were also “suffering” from status thymicolymphaticus. She suggested that Paltauf’s theory of SIDS was wrong, and that the difference in the sizes of the thymuses was an artifact of thinking that impoverished infants had normal thymuses. Alas, the medical community paid no attention to Boyd’s work. It wasn’t until 1945 that a pediatric textbook (Nelson, 1945) repudiated Paltauf’s theory, and admitted that treatment by irradition had been a tragic mistake. Even then, X-ray treatments continued into the 1950s.

References:

Edith Boyd (1927). Growth of the thymus, Its relation to Status Thymicolymphaticus and Thymic Symptoms. American Journal of Diseases of Children, Vol. 33, pp. 867.

T. Escherich (n.d.). Status thymico-lymphaticus, Berlin klin,” Woeschesucher, no. 29.

W. Lucas (1927). Modern Practise of Pediatrics. New York: Macmillan.

W. Nelson (1945). Nelson’s Texbook of Pediatrics, 4th ed. Philadelphia: Saunders.

Paterson, D.S., Trachtenberg, F.L., Thompson, E.G., et al. (2006). Multiple serotonergic brainstem abnormalities in sudden infant death syndrome. Journal of the American Medical Association, Vol. 296, No. 17, pp. 2124-32.

A. Paltauf (n.d.). Plotzlicher Thymus Tod, Wiener klin. Woeschesucher (Berlin), nos. 46 and 9.

Robert Saplosky (1997). “Poverty’s Remains” Reprinted in Saplosky’s The Trouble with Testosterone New York: Touchstone, 1997.