Correction: An earlier version of a caption on a photo of Steven M. Holland that accompanies this article on clinical trials incorrectly said that Holland, chief of the Laboratory of Clinical Infectious Diseases at the National Institutes of Health, had placed patient Samantha Seinfeld in a trial. The patient was Erin Hudlow, as the article reported. The caption has been corrected.
Scientists at the National Institutes of Health know Samantha Seinfeld’s body down to its cellular makeup. Every few months, she shows up at NIH’s leafy Bethesda campus to get a CT scan and be injected with an experimental vaccine. Made from a live fowlpox virus pumped up with genes, the vaccine is intended to boost Seinfeld’s immune system. Later, at home, she gives herself injections of a drug that stimulates the growth of white blood cells. Seinfeld, a 35-year-old former solar energy marketer, endures this in the hopes of staving off a recurrence of Stage IV breast cancer — but she is also contributing to scientific research. For three years Seinfeld has been a participant in one of NIH’s clinical trials, or medical studies conducted on humans. This one is testing whether a vaccine called PANVAC and its follow-up boosters will keep breast cancer, which first showed up in Seinfeld’s breastbone five years ago, from coming back. It’s risky, uncertain and exhausting at times — and not necessarily foolproof.
Despite all that, Seinfeld is extremely grateful. “Clinical trials are not for everyone,” she said. “My faith has been in science. I find it more comforting to look at numbers, statistics and research. Cancer is not a death sentence in this day and age. So much is being done in research.” Seinfeld, who no longer works, devotes much of her day to learning everything she can about her disease.
NIH is conducting nearly 1,500 trials at its Clinical Center and is budgeted to spend about $10 billion on clinical research this year, with about $3 billion of that specifically for trials. The center is the largest hospital in the world dedicated to these human studies. Their topics range from obesity to rare blood diseases to cerebral palsy, and they represent only a small fraction of the trials conducted in the United States. Still, they are unique because many of the diseases being studied are too rare, or the treatment is too much of a gamble, for pharmaceutical companies, biotech firms or universities to pursue.
“It is the only way to know if a new drug or device will work,” said John Gallin, director of NIH’s Clinical Center. “As such, [a clinical trial] is the future of medicine.”
A new drug or device cannot get the okay from the Food and Drug Administration unless it has gone through three phases of clinical trials. It was here that scientists discovered that fluoride can prevent cavities, that lithium can bring relief to people with bipolar disorders, that AZT can prolong the life of people with AIDS and that an MRI scan can assess the risk of a heart attack in patients with chest pain.
The government created the Clinical Center in 1953. Initially NIH scientists relied on word of mouth among doctors around the country to find patients to participate in research. Today, many people learn about trials through the Internet at Clinicaltrials.gov and the center’s own site, and the numbers hoping to get into a trial has ballooned.
About 400,000 patients have participated in NIH-sponsored clinical trials, and they come for a variety of reasons: a last-ditch effort at a cure; a rare disease no one else understands or can treat further; a new approach to a disease; or a desire to further medical knowledge.
The care is free, Gallin said. “We have never sent a bill. We will pay for travel for patients who need travel support. No one is denied access because of socioeconomic reasons. Often people come here when everyone else has given up.”
Before they participate, patients get a consent form outlining the risks involved with human trials, which they discuss with the study team, including the possibility that a drug or procedure being tested could have potentially life-threatening side effects. “But what is the gap between reading and understanding?” asked Ezekiel J. Emanuel, director of the Department of Bioethics at the Clinical Center. “We are interested in [whether] people even read the documents. In our view, the most important issue is risk. Most people don’t realize how risky research is.”
Yet for many, the risk is worth it.
Eight years ago, when Erin Hudlow’s doctor in Atlanta couldn’t figure out why she had a low white blood count and abnormal chromosomes, she sent the girl, then 16 years old, to NIH. Hudlow received a diagnosis of trisomy 8, a rare chromosomal condition, and myelodysplasia, a dysfunction in blood cell production in the bone marrow. An NIH hematologist, Elaine Sloand, enrolled Hudlow in a trial to further study the natural history of these diseases.
Hudlow began visiting NIH every three months for a checkup and every six months for a bone marrow biopsy. But in June 2009 her health took a turn for the worse. “I had low white blood cell counts, my platelets dropped, also my hemoglobin and my red blood cells. I was admitted into the hospital [in Atlanta,] and they found I had bacteria in my blood,” Hudlow recalled.
Hudlow’s doctor determined she had an infection caused by a mycobacterium, an organism related to tuberculosis.
Steven M. Holland, chief of the Laboratory of Clinical Infectious Diseases at NIH, put her in a trial that he runs, this one following the natural history and treatment of mycobacterial infections.
It also turned out that Hudlow has a rare genetic disorder in which some blood cells are missing and patients get unusual infections called MonoMAC. Hudlow entered her third clinic trial, this one focused on bone marrow transplants.
“There are 21 patients with this disease here,” Holland said. “And I know of at least 10 more throughout the world. Why do we study this? We study this particular disease because it is at the confluence of cancer and infection susceptibility.”
Last summer Hudlow had a bone marrow transplant at NIH. She is taking antibiotics and regaining her strength. “I hope to live a normal life,” Hudlow said by phone from her home in Atlanta.
Just a few weeks ago, Holland’s lab found a gene “that caused [Hudlow’s] problems, confirming that she had had this all her life, and [it] was noticed [only] when it began to cause problems,” Holland said. Through the clinical trials “we learned about a gene that controls susceptibility to cancer [i.e., leukemia] and to infection [mycobacteria], as well as a few other things all wrapped into one small stretch of DNA.”
For Seinfeld, the vaccine she receives offers a novel approach and a chance to stay alive. When she developed breast cancer in 2006, she was as fit as she ever had been, running 10 to 15 miles a day, and living with the love of her life in Tiburon, Calif.
Her OB/GYN shrugged off a bump on her breastbone that Seinfeld pointed out at her yearly exam, saying she was too young for cancer. But the bump made Seinfeld nervous, and a few weeks later she had it checked out by another doctor. Before long, she was in the midst of full-blown cancer treatment, with a lumpectomy, a removal of her ovaries and chemo, followed by the removal of part of her liver when her surgeon found the cancer had matastasized there.
In 2008, Seinfeld entered a trial of an experimental vaccine for cancer patients at the University of Washington in Seattle, commuting there for treatment from California. Six months into it, her breast cancer returned.
“The cancer had metastasized to my chest cavity. . . . That is when I went to NIH,” Seinfeld said. She found out about the trial on the Internet and asked the clinical trial director in Seattle for advice about it and for the encouragement to join the trial.
“She said the vaccines are looking really good,” Seinfeld said. “The fact that it was another vaccine trial could work in tandem with the vaccines I had received over the six-month period in Seattle. Nothing is scientifically proven; it is pure theory, but it was enough for me. I flew out to Bethesda from California.”
That was three years ago. She’s been in the Washington area more or less ever since, leaving her job and her boyfriend.
Now, Seinfeld is the last participant in her study, which originally included 12 other patients with breast cancer and 14 with ovarian cancer. “Some of the others have died from their cancer and in all of the others [except Seinfeld] the cancer eventually got worse,” said James Gulley, director of the Clinical Trials Group in the Laboratory of Tumor Immunology and Biology at the National Cancer Institute.
Seinfeld, on the other hand, has “no evidence” of cancer anywhere in her body, Gulley said. He added that he doesn’t know why that is but three things may have played a role: Seinfeld had “less disease” than others when she entered the trial, had had a longer break from chemotherapy and had the previous anti-tumor vaccine. “That we couldn’t even see it any more is quite remarkable,” he said.
Seinfeld hopes to continue her treatment as long as possible. “I do think, ‘Why me? Why did I get cancer?’ ” she said. “Why am I so responsive to a drug and why am I so well when others are not?”
Gulley, meanwhile, says Seinfeld’s trial may yield a significant advance in how doctors treat cancer. “If we can train the immune system to kill — to take apart a tumor — with limited side effects, we can set in motion a dynamic, self-perpetuating anti-cancer response,” Gulley said. And perhaps change the course of medicine.
Hambleton is a writer and documentary filmmaker who lives in Chevy Chase.