David Phillip Vetter (1971–1984)

David Phillip Vetter was born with X-linked severe combined immunodeficiency disorder, or X-SCID, and spent most of his life in an isolated sterile bubble to stay alive. X-SCID is a genetic disorder that causes a deficiency of protective immune cells that fight infections, which increases susceptibility to disease. Vetter’s weakened immune system meant that he would die if he encountered any bacteria, viruses, or other germs, so his doctors placed him in a sterile isolator, a plastic bubble that prevented germs from entering. Vetter was thus a germ-free human, meaning he developed in the absence of germ exposure. He grew up in his sterile isolator, earning him the nickname “Bubble Boy,” and lived there until his death in 1984 at age twelve. Researchers frequently studied Vetter’s development because he was one of the first individuals with X-SCID to survive over a year after birth. As one of the first germ-free humans, Vetter provided an opportunity for researchers to study what happens when a human develops without germs, and his cells helped them determine the genetic cause of X-SCID.

1. Early Life and Diagnosis
2. Life in the Bubble
3. Effects of Isolation
4. An Experimental Treatment
5. Legacy

Early Life and Diagnosis

Vetter was born 21 September 1971 in Houston, Texas, to Carol Ann Demaret and David J. Vetter, Jr. He had an older sister, Katherine Vetter, who was four years his elder. Vetter also had an older brother, David Joseph Vetter, who was born in 1970 and had X-SCID as well. X-SCID patients generally present with few or no T cells, which are immune cells that recognize infectious agents and kill them. The lack of T cells is because X-SCID patients usually have an underdeveloped thymus. The thymus is an organ involved in the maturation and differentiation of T cells. The absence of those immune system components leaves the body defenseless from even simple infections. At the time of Vetter’s and his brother’s diagnoses, most infants with X-SCID did not survive for more than one year because they would already have many life-threatening infections by the time of diagnosis. Vetter’s brother’s case was the family’s first encounter with X-SCID. Due to the absence of protective immune cells and the delay in his diagnosis, Vetter’s brother died in 1970, just a few months after birth, from pneumonia.

When Vetter’s mother became pregnant again in 1971, Raphael Wilson, Jack Montgomery, and Mary Ann South, a trio of doctors at Texas Children’s Hospital in Houston devised a plan in case the infant was also born with X-SCID. The doctors informed Vetter’s parents that if the infant was a boy, he would have a fifty percent chance of having X-SCID. In many chromosomal disorders, like X-SCID, an individual only needs one normal, non-mutated chromosome to avoid getting the disorder. Most people with X-SCID are males because males have only one X chromosome, while females have two, which means that if a male has the X-SCID mutation, he will show symptoms of the disease. If a female has the X-SCID mutation on one X chromosome only, she will usually not present any symptoms because she also has a second non-mutated chromosome.

Prior to working at Texas Children’s Hospital, Wilson isolated and treated twins diagnosed with X-SCID in Germany. He constructed a sterile isolator for the twins so that they would not have any exposure to bacteria and other germs. However, for unknown reasons, the twins’ immune systems developed to the point where they did not need the sterile isolator anymore. Wilson used the same technology for Vetter. The team would deliver Vetter under germ-free conditions, place him in a sterile isolator, and then search for a cure from there. According to Wilson, he did not know if Vetter’s immune system would suddenly develop as the twins’ had, but he knew the technology could keep him alive as his team of doctors researched potential cures.

At the time of Vetter’s birth, bone marrow transplants were one of the only cures for X-SCID. Bone marrow transplants involve the transfer of normal, donor stem cells into the recipient. Stem cells are cells that can turn into various types of cells. In a person with X-SCID, replacing the recipient’s defective stem cells can help create a new immune system. In the 1970s, most bone marrow transplants were between siblings due to their genetic similarity. If the donor and recipient are not compatible for a bone marrow transplant, the recipient’s body rejects the transplant, which could lead to death. Each parent usually has two different sets of genes, or haplotypes, that their child could inherit, so there is a one in four chance that two siblings are compatible for bone marrow transplant. In a Public Broadcasting Service interview aired in 2006, Vetter’s doctors stated that they hoped to use his sister Katherine’s bone marrow for transplant if Vetter did indeed have X-SCID.

In 1971, doctors delivered Vetter using completely sterile techniques. Even though they could not diagnose X-SCID until after birth, the doctors took precautionary measures in case Vetter did have the disorder. The doctors disinfected all surfaces multiple times, sealed the windows, and removed all nonessential equipment from the room to minimize contamination. Additionally, the doctors delivered Vetter via Cesarean section, a surgical procedure in which the surgeon cuts through the abdomen to deliver the infant. During vaginal delivery, the infant comes in contact with bacteria in the mother’s birth canal, and that exposure could be fatal to someone with X-SCID. Thus, Cesarean delivery ensured that Vetter would not encounter any of his mother’s vaginal bacteria. To minimize time spent in the operating room air, which also contained bacteria and other germs, the doctors quickly transferred Vetter to the plastic isolator in under thirty seconds. According to South, who was the immune system specialist on the team, Vetter came out of the womb looking like a healthy infant. Shortly after birth, Wilson, a member of the Catholic Church, baptized Vetter using sterilized holy water.

After Vetter was born, doctors tested him to see if he had X-SCID, and they found that he did have the disorder. They found that Vetter’s number of protective immune cells, such as T cells, was approximately one-tenth of the normal range. Also, the tests showed that the few immune cells he did have were not completely functional and could not respond well to infections. Vetter’s overall immune system was poorly developed, and the doctors subsequently diagnosed him with X-SCID. Additionally, after running several tests on his sister Katherine, the doctors informed Vetter’s parents that she was not a compatible donor match for a bone marrow transplant. Therefore, they decided to keep Vetter in the sterile isolator until either his immune system spontaneously developed on its own, or they found an alternative to the bone marrow transplant.

Life in the Bubble

The sterile isolators that Vetter had to live in resembled plastic bubbles that contained all the basic necessities for life. Engineers from the National Aeronautics and Space Administration, or NASA, originally designed sterile isolators like Vetter’s to isolate moon rocks. The doctors subsequently modified the design to house Vetter at the hospital. The initial living chamber covered an area of five feet by three feet and was encased in polyvinyl chloride film, which is a flexible but durable plastic film. As Vetter grew over time, the doctors increased the size of the isolator to accommodate him. The isolator had a constant stream of filtered air to reduce the possibilities of contamination. The doctors attached a smaller bubble to the isolator that contained supplies such as food, medicine, diapers, and water. Before giving any of those items to Vetter, they sterilized them with peracetic acid, which kills all bacteria and other germs that may be on surfaces, and placed the items inside capsules. There were multiple heavy-duty rubber gloves built into the walls of the isolator, which Vetter’s parents and doctors used to handle and feed him. Vetter had a similar sterile isolator at his suburban home, as well as a sterile transport isolator for travel between his home and the hospital.

While Vetter was in the sterile isolators, researchers would frequently visit him to study the development of his organ systems, both to monitor Vetter’s health and to learn about the development of the human immune system in the absence of bacteria and other germs. The US National Institutes of Health provided $200,000 in research grants each year for Vetter’s care and studies. The primary studies that researchers conducted with Vetter were immunization experiments to monitor the development of his immune system. Because of the protection that the sterile isolator offered him, Vetter was one of the first patients with X-SCID who lived long enough to participate in long-term studies. Nurses took blood samples throughout Vetter’s development to examine the levels of immune cells in his body. Researchers found that, due to his X-SCID condition, Vetter presented with little to no functional T cells throughout his life. In addition, he produced low levels of antibodies, which are proteins that the body makes to neutralize or kill specific foreign invaders. Researchers also studied the development of other organ systems, such as his mental and muscular development. They found that aside from his immunological deficiencies, all other organ systems, overall, developed normally.

In 1975, when Vetter was four years old, doctors convened for a conference at the University of Virginia in Charlottesville, Virginia, to discuss the ethics of Vetter’s case. They talked about the dilemma of how keeping Vetter in an isolator would decrease his quality of life as a human but that removing him would likely kill him. During the conference, a doctor asked Wilson what he would do if Vetter wanted to leave his sterile isolator. Wilson responded that because the isolator was all Vetter had ever known as home, leaving it would be like shedding his own skin.

Also when Vetter was four, he began learning about his own disorder and the implications of his bubble home. One time when a nurse was drawing his blood, he took one of the needles without the nurse knowing. Vetter started poking holes in the isolator, which allowed outside air to come into the sterile environment and contaminate it. Wilson then taught Vetter the risks of his actions, explaining that making holes in the isolator would allow germs to enter and hurt his body. One of Vetter’s therapists noted that as Vetter grew older, he became quieter. When the therapist would visit him, Vetter often had nothing to say and would just rock back and forth on his knees.

Effects of Isolation

In the mid-1970s, Mary Murphy, a child psychologist, began visiting Vetter to help with his feeling of isolation. In an interview, she explained that Vetter had many misunderstandings about the real world. For example, he thought the world was flat. In addition, he described trees as a brown rectangle with green ovals. Murphy stated that when she brought in a tree branch for the first time, Vetter could not believe what it looked like. Murphy also recounted in the interview how she and Vetter would often go on imaginary adventures, such as traveling to other planets, to help him escape the confinement of his isolator. Although Murphy had other children to visit at the hospital, she spent some evenings in Vetter’s room working on her doctoral thesis to keep him company. At the same time, Vetter worked on homework for his elementary school classes, which he attended via telephone.

In 1977, NASA scientists designed a custom space suit for Vetter so that he could venture into the outside world safely. The space suit, referred to as the Mobile Biological Isolation System, was a suit that allowed Vetter to walk outside with filtered, uncontaminated air for one hour at a time. However, according to Murphy, Vetter was afraid of getting into the spacesuit due to the possibility of germs getting in. He told his mother that maybe he should just stay in the bubble, but she encouraged him to step into the suit. In an interview, Vetter’s mother explained that after Vetter began venturing outside of the bubble, he found simple things such as the bathroom faucet fascinating. On his walks outside, Vetter watered the yard and played with his family’s dog. However, because of his fear of the outside world, he refused to leave the isolator again after six outings.

During those years, the original trio of doctors who worked on Vetter’s case left the hospital and new doctors replaced them. Nurse charts from the time documented Vetter’s increase in anxiety due to feelings of abandonment from his doctors leaving him. In 1978, William Shearer, an immunologist, took the lead on Vetter’s case. Unlike the previous doctors, Shearer advised Vetter’s parents to take Vetter out of the isolator and place him on antibiotics and gamma globulin therapy, which are treatments that would artificially help his body fight off infections. Shearer’s case notes showed that his rationale for that decision was to improve Vetter’s deteriorating mental health from confinement in the isolator for so long. However, after consulting with the original trio of doctors on the case, Vetter’s parents refused to remove Vetter from the isolator.

An Experimental Treatment

In the early 1980s, researchers in Boston developed an experimental procedure to transplant bone marrow between noncompatible individuals, such as Vetter and his sister. To perform transplants between noncompatible individuals, doctors almost completely suppress the recipient’s immune cells prior to transplantation to reduce the risk of the recipient rejecting the transplant. In October of 1983, after approval from the Baylor College of Medicine Institutional Review Board, Vetter, who was twelve years old, and Vetter’s parents, doctors performed a bone marrow transplant on Vetter using Katherine’s bone marrow. After the operation, doctors monitored Vetter for signs of rejection and eventually released him to go home in his isolator for the Christmas holiday.

On New Year’s Eve of 1983, just a couple of months after his bone marrow transplant, Vetter had an elevated temperature, leading him to return to the hospital, where his condition worsened and he stayed until his death. Vetter experienced a fever spike of 105 degrees, vomited blood, and had severe abdominal pain. In February of 1984, the doctors could no longer treat Vetter inside the isolator due to limitations from the physical separation, and they had to remove him from the isolator. At the time, the doctors treated him under the impression that he was rejecting Katherine’s transplant. Fifteen days later, Vetter’s condition continued to worsen and he entered a coma. On 22 February 1984, the doctors allowed his parents to enter the room and for the first time in twelve years, Vetter’s mother touched his hand. That night, Vetter died from his illness.

After his death, people from all over the country sent telegrams and flowers to commemorate Vetter, but many also began to debate the ethics of his life circumstances. At the time, Vetter’s story reached national coverage as newspapers broadcasted his unique upbringing. His story also brought forth ethical discussions about whether it was morally acceptable for Vetter to stay in the isolator for his whole life. Montgomery, one of his doctors, claimed that he felt it was right because Vetter leaving the isolator would have caused him to die from infection. However, Raymond Lawrence, a minister who worked at Texas Children’s Hospital, published an article in 1985 criticizing the doctors’ decision to place Vetter in the isolator. In the article, he writes that Vetter never had autonomy in choosing any part of his life. He also questions Vetter’s parents’ and doctors’ choice to carry Vetter to term after finding out the fetus was a male via prenatal tests and knowing that he would have a fifty percent chance of having X-SCID.

By performing an autopsy on Vetter’s body, doctors found that his cause of death was not transplant rejection, but Epstein-Barr virus, or EBV. Katherine’s bone marrow contained a dormant form of EBV that reactivated when transferred to Vetter’s body. EBV is a virus that attacks certain immune cells and increases the risk for other diseases such as cancer. The virus usually becomes inactive in the body after infection, meaning that the virus remains in the body but does not cause any symptoms. However, if reactivation occurs, people with weakened immune systems, like Vetter, are more likely to present with physical symptoms again. The EBV infection in Vetter progressed to lymphoma, cancer that starts from cells part of the lymph system, and doctors found numerous small tumors scattered throughout Vetter’s body during the autopsy. Although researchers discovered EBV almost two decades before Vetter’s death, Vetter’s case was one of the cases that confirmed the hypothesis that the virus caused cancer in humans.

Legacy

The studies researchers conducted on Vetter during his time in the isolator revealed how humans develop under germ-free, or sterile, conditions. Louis Pasteur, a researcher in France who studied microbiology and vaccinations during the late 1800s, hypothesized that organisms cannot survive without germs because of the coexistence of microbes and animals throughout evolutionary history. As of 2024, studies have found that the germs that the body encounters during early life impact the development of body systems such as the immune system. However, as one of the first humans to grow up in a completely sterile environment, Vetter showed mostly normal cognitive development. He displayed an accurate sense of time but had limited spatial awareness. Although researchers had previously grown and maintained germ-free animals, studies on cognition were not possible in nonhuman studies.

In addition, Vetter’s cell lines contributed to researchers finding the genetic cause behind X-SCID. Cell lines are a collection of cells that come from one cell that can continue replicating in a culture over a period of time. In 1993, Masayuki Noguchi, who conducted research at the National Heart, Lung, and Blood Institute in Bethesda, Maryland, used three preserved samples from male children with X-SCID to look at what caused the disorder. He found that in all three samples, one of them being Vetter’s, there was a mutation in a region on the X chromosome that codes for the interleukin-2, or IL-2, receptor. The IL-2 receptor is responsible for the growth and maintenance of T cells in the immune system. Therefore, its mutation led to issues with T cells, and overall immune system development. As a result of that discovery, doctors could conduct prenatal genetic screenings for IL-2 mutations to see if a female carried the mutation and could potentially pass it on to her offspring.

As of 2024, most patients with X-SCID survive because of advancements in bone marrow transplants and other treatments. Bone marrow transplants are a common treatment for most X-SCID patients, and transplantation via genoidentical sibling donors has a survival rate of approximately ninety percent. Another alternative is gene therapy, which is where scientists genetically correct the mutation that causes a disease in a laboratory and then reintroduce the corrected cell without the mutation into the patient’s body.

Although growing up in the sterile isolator took away any semblance of a normal life for Vetter, his life and death answered many scientific questions at the time. Researchers found that, aside from the immune system, humans could develop most physical and cognitive abilities normally even without the presence of microbes. Additionally, Vetter’s case demonstrated that viruses could cause cancer, and his preserved cell lines ultimately led to the determination of X-SCID’s genetic mutation.

Vetter died on 22 February 1984 in Houston.