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Establishing a link.

About 13 yeara ago, a baby in Texas was born without a functioning immune system. Faced with what was, back then, a fatal situation, doctors placed the boy in a completely sterile environment. They were buying time until they could figure out what to do, and beginning a unique scientific experiment.

That experiment ended last year when David, the "bubble boy," died after a gallant fight and despite the heroic efforts of his team of doctors (SN: 3/3/84, p. 133). In his death, though, he provided a clear link between Epstein-Barr virus and cancer.

It is likely that more was known about David's health history than that of anyone else who has ever lived. With no "compatible" relatives to provide him with immune-cell-producing bone marrow, David had to wait for the technology to rid donated marrow of the cells that would attack his own. After David spent 12 years in a bubble, doctors hoped the technology was ready, and the boy received treated marrow from his sister.

Eighty days after the transplant and still in a germ-free environment, David developed some of the clinical signs of mononucleosis, a condition caused by Epstein-Barr virus. As his health slipped away, doctors brought him out of isolation fro easier treatment, hoping his sister's marrow cells had taken hold and would protect him from the microbes the rest of us encounter every day. Her cells hadn't esablished themselves, and David died about four months after the transplant.

What killed him was not the immediate failure of the transplant but cancer. His own B cells had run amok--a proliferation induced by Epstein-Barr virus. The autopsy revealed small, whitish-pink cancer nodules throughout his body, and closer study showed that these cells all contained Epstein-Barr virus--a virus he could only have gotten through his sister's bone marrow.

"We're certain [the cancer] came from the transplant itself," says William T. Shearer of Baylor College of Medicine in Houston, who was the lead physician on David's case. David had a B cell cancer of a type similar to Burkitt's lymphoma, and while Shearer can't absolutely say the two types of cancer are kicked off in the same way, "it seems likely that some of these same processes occur."

David's case has also shed light on what was until recently a serious problem for transplant recipients. People who receive hearts, kidneys or other organs are given drugs to bring them closer to the immune-suppressed state that David was born into, so they won't reject their new organs. Many of them have then been beset by cancer, most commonly lymphoma.

At one time, says Jeffrey Sklar of Stanford University, who with Shearer and others authored a paper in the May 2 NEW ENGLAND JOURNAL OF MEDICINE detailing David's death, 13 percent of heart transplant patients died of lymphomas 100 to 200 days after the transplant. (With the refinement of immunosuppressive therapy, he notes, cancer following transplantation is no longer a problem.) Epstein-Barr virus had been suspected in such cases; David's case, says Sklar, "confirms our suspicions about Epstein-Barr virus being an inducer of cancer in immunosuppresed individuals."

Because of the peculiarities of David's situation, the time sequence -- how quickly Epstein-Barr virus can induce cell transformation--is now known. "We can now without any doubt describe the very clear progression from infection to the development of cancer," says Shearer.

"This is a very clear demonstration of a virus causing a cancer," says Sklar. "It's also clear as to how the tumors evolved." First, David's B cells were activated by the Epstein-Barr virus, and began dividing. Then a handfull of cells took hold, with some of the cancer nodules arising from single cells and others apparently arising from several different cells.

One of the requisites for proving viral transmission of a disease is to infect a test subject with the virus and see if the disease occurs. "Inadvertently this is what happened," says Sklar.

David had been germ free--there's no way he could have come into contact with Epstein-Barr virus before the transplant. "In a way you have a documented transmission of virus followed by development of tumor," says Sklar.

Says Shearer, "I think this study documents that this common virus produced this cancer." While there's a tragic human story behind the finding, it resulted in an important advance in knowledge, he says. "This will be the beginning of many studies to come."
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Title Annotation:between Epstein-Barr virus and cancer
Author:Silberner, Joanne
Publication:Science News
Article Type:Biography
Date:Jun 1, 1985
Previous Article:Cancer virus redux; viruses were once a hot subject of cancer research; after a decade out of the limelight, they're back again.
Next Article:The sound of data.

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