Self & Other
11. When the System Is Quiet
On September 21, 1971, in Houston, Texas, a baby was born and immediately placed inside a sterile plastic chamber. He was named David Vetter. He had a brother who had died ten months earlier, at seven months old, from an infection that no one his age should have died from. The doctors had told David’s parents that any future son they had would have a fifty-percent chance of having the same condition, and that the only way to find out was for the baby to be born and tested. The plastic chamber was a precaution. If David turned out to have what his brother had, the chamber was the only thing that could keep him alive.
David did have it. He spent the first twelve years of his life inside a series of plastic enclosures, never touching another human being directly until shortly before his death. The disease was called severe combined immunodeficiency, or SCID. The press called him the boy in the bubble. He died in 1984, at twelve, after a bone marrow transplant from his sister failed.
This is not a chapter about David Vetter. This is a chapter about the children who came after him.
Today, in the United States and many other wealthy countries, every newborn baby has a small amount of blood drawn from a heel prick within the first day or two of life. The blood is tested for a panel of conditions, and one of the things on that panel — added in most U.S. states between 2008 and 2018 — is a marker for SCID. A baby with SCID, identified at birth, can be isolated until the immune system is reconstituted by bone marrow transplant or, increasingly, by gene therapy. The survival rate, with early diagnosis and modern treatment, is now well over ninety percent. Most of these children grow up indistinguishable from any other children. They go to school. They get colds. They live whole lives. The screening test exists, in part, because of what David Vetter’s life and death revealed.
The previous chapter was about an immune system that attacks too much. This chapter is about an immune system that attacks too little. The two are biological mirror images. The people they happen to are not less deserving of careful attention than the people in the previous chapter. They have just been, in many cases, less visible.
What SCID Actually Is
SCID is not one disease. It is a family of diseases, all of which share a single basic feature: the adaptive immune system fails to develop. T cells do not form, or do not function. B cells, often, do not function either. The newborn enters the world with no defense against the kinds of infections that the adaptive system handles. Common viruses, the ones that other babies fight off in a few days, can kill within weeks.
There are at least two dozen different genetic causes of SCID. Some involve mutations in the V(D)J recombination machinery we met in Chapter 3 — the very genes that allow B and T cells to generate their random receptors. Without working V(D)J, no functional B or T cells can be made. Other forms involve mutations in receptors for cytokines essential to early immune cell development. The most common form, X-linked SCID, involves a single gene on the X chromosome and almost exclusively affects boys. Another form, ADA deficiency, involves a missing enzyme that normal immune cells need to survive their own metabolism.
Without treatment, SCID is uniformly fatal in the first year or two of life. With treatment — either a bone marrow transplant from a matched donor, or, for some forms, gene therapy that delivers a working copy of the missing gene to the patient’s own bone marrow cells — the prognosis has been transformed. Bone marrow transplant for SCID has been done since the 1960s and has been refined enormously since. Gene therapy is newer and, in some forms, dramatic. In 2016, the European Medicines Agency approved a gene therapy product called Strimvelis for ADA-SCID; it was the first ex-vivo gene therapy ever approved for any disease. The treated children, given the missing enzyme by way of their own corrected cells, are now growing up.
Ashanthi DeSilva was four years old in September 1990 when she became the first person ever treated with gene therapy. She had ADA deficiency. The procedure was experimental and the results, in her case, were partial — she still required other treatments alongside the gene therapy, and gene therapy for ADA-SCID has been substantially improved in the decades since. But Ashanthi lived. She is now in her late thirties. The child who in 1990 had no immune system worth speaking of has had a normal adult life: school, work, marriage. She is not a footnote. She is a person, and the medicine that gave her a life is now treating other children every year.
HIV, and What It Did
In June 1981, the Centers for Disease Control in Atlanta published a short bulletin describing five young men in Los Angeles who had developed a rare lung infection that had previously been seen almost exclusively in patients with severely suppressed immune systems. The men were all otherwise healthy. None of them had any obvious reason to have suppressed immunity. One of them was already dead by the time the bulletin appeared. The others would all be dead within a year.