Researchers who conducted intensive tissue studies on David, the 12-year-old Houston "Bubble Boy" who spent all but a few days of his life in a plastic isolation unit, say he died of cancer that they believe was caused by a virus acquired through a bone marrow transplant.
The virus, called Epstein-Barr, is the one that causes mononucleosis.
Dr. William T. Shearer, David's physician, said in a telephone interview Wednesday that studies on the youth provide "persuasive evidence" that a viral infection can progress to the point where it becomes malignant.
"That is the powerful lesson that we learned from this patient," said Shearer, who is chief of allergy and immunology at Baylor College of Medicine and Texas Children's Hospital in Houston. "It is the first conclusive evidence of cancer developing in a human being after infection by a virus."
Shearer and 12 other authors speculate in today's issue of the New England Journal of Medicine that David, who died on Feb. 22, 1984, picked up the virus from his 15-year-old sister, who provided the marrow for the transplant.
Like a great majority of Americans, the sister had antibodies to the virus, indicating that she had been exposed to it at some time in the past.
But David, unlike most normal individuals who get mononucleosis, was unable to fend off the virus because he suffered from an immune deficiency that deprived him of a major capacity to fight germs.
Dr. Jeffrey Sklar, an assistant professor of pathology at Stanford University and one of the principal authors of the study, said the findings from David could be significant for the medical management of other patients whose immune system has been suppressed, either by disease similar to David's or because they are transplant patients who are on drugs to prevent organ rejection.
David received the bone marrow transplant in an effort to reconstitute his deficient immune system. Bone marrow contains cells that produce important elements of the body's defenses against viruses and other organisms. The transplant, however, failed to correct David's immune deficiency and he died of lymphatic cancer, known technically as immunoblastic sarcoma, four months later.
Advice to Family
"In the future, we'll have to explain more carefully to family members and to patients that bone marrow transplants may result in cancer," Shearer said.
According to Sklar, such advice is important because persons with a deficient immune system are 40 to 50 times more likely than the general population to develop lymphatic diseases. Previous studies, for example, have shown that 13% of heart transplant patients develop lymph cancer.
Much of the information leading to the cause of David's death was obtained by Sklar and three Stanford colleagues--Drs. Michael Cleary, Roger Wamke and Carl Grumet. They used a variety of molecular techniques to analyze the youth's DNA, or genetic material.
It was by one of these techniques that they found that DNA from some of David's tumor cells contained genetic material from the Epstein-Barr virus. There was no evidence of the presence of any other virus that could have been responsible for the cancer.
They also were able to establish that the cancer arose from David's own cells, rather than from the transplanted bone marrow.
Scientists have long suspected that human cancer can be caused by viruses but, according to Sklar, a debate exists over how the viral infection becomes malignant.
Some researchers believe that the type of lymphatic disease suffered by David is malignant from the start of the viral infection, while others see it as a condition that begins as a viral disease and later, under certain conditions, becomes malignant.
The studies conducted by Sklar's team tend to support the latter view.
They found that some of David's lymph tissues contained malignant cells, while others were benign. Also, the genetic material in some tumor cells suggested that the malignant ones had emerged from the benign ones.
"This provides good indirect evidence that lymphatic tumors can develop gradually over time from an unrestrained viral infection in immune deficient patients, probably caused by the Epstein-Barr virus," Sklar said.