As far as love stories go, Heiko Jessen and Andrew’s story was passionate. Their four years together had forged the kind of love that even an HIV diagnosis couldn’t break. As Jessen’s fears became ratcheted up by the lack of any acceptable therapy capable of treating the virus, his desperation turned into action. He reached out to every scientist to whom he had even the slightest connection. He was desperate for new drugs, clinical trials, anything that might save Andrew. He still perceived the illness as Andrew’s alone. He hadn’t tested himself or even admitted his own stark risk for the disease he regularly counseled others to treat early.
One of the phone calls he made was to Robert Gallo, the prominent American scientist, the codiscoverer of HIV. Jessen had spent a few months training with Gallo’s group at the NIH. He had seen Gallo speak many times. At these lectures, he had been his usual engaging self, asking many questions and loving the enthralling discussion of scientists. For Gallo, Jessen stood out. Decades later, he still remembers the amiable, blond young man whom he would see at all his talks. He remembers Jessen tenderly, calling him a “little angel.” Jessen, to Gallo, was a man “you just had to like.” So when Gallo got a call from him, desperate for new HIV drugs, he wanted to help. He put Jessen in touch with Franco Lori, a physician Gallo worked closely with, especially during the early development of AZT.
Lori, in turn, passed the question along to his colleague and close friend Julianna Lisziewicz. She had known Jessen during his brief stint of training at NIH. She was happy to help. Unfortunately, Lisziewicz didn’t have much to offer. She had no magic drug. She didn’t have data from a clinical trial. All she had to offer was an idea. Lisziewicz spoke to Jessen about a drug that she and Lori thought might have potential: hydroxyurea. It had been around for quite a while. It was, like the underpinnings of AZT, a cancer drug. Developed in Germany in 1896, hydroxyurea was approved by the FDA in 1967 for a specified group of cancers. The drug works by blocking a specific enzyme that’s needed to form the single units of DNA, called deoxyribonucleotides. By blocking this one enzyme, the drug has been effective in battling cancer, psoriasis, and sickle-cell disease. The idea about HIV was that hydroxyurea would work similarly to AZT. By cutting off the ability to form new DNA, the drug was essentially cutting off HIV’s technique of replicating itself.
Hydroxyurea also freezes the cell. Hydroxyurea keeps the cell from dividing, and HIV can’t replicate in a cell that isn’t dividing. With the virus frozen in place, other antiviral drugs can come in and attack. The beauty of using a drug that targets the cell instead of the virus is that the virus can’t outsmart it. If given early in infection, the drug had the potential to keep the virus from getting a foothold in the body. At least that’s what Lisziewicz and Lori hypothesized.
Even though the new drug hadn’t been tested in an HIV patient, Jessen was desperate to try it. Lisziewicz had tested the drug only in cell culture, in vitro, in Robert Gallo’s lab. They had yet to publish any results on hydroxyurea. There was no particular reason to think it would be effective in humans; many drugs that are promising in dishes warmed by an incubator fail when exposed to the delicate complexity of the human body.
When the chance of death is high enough, though, physicians will try anything. HIV was considered fatal. Under “compassionate use” exemptions, physicians were allowed to try other drugs, licensed for diseases other than HIV. Any drug could be repurposed to treat the virus. This approach favors the family-doctor style of medicine, often called cradle-to-grave medicine. Family physicians typically know their patients well. They are there for all their patients’ firsts; they may know their patients’ habits and quirks. They know if their patients can handle both the responsibilities and consequences of experimental drugs. Unfortunately, family doctors are in short supply. In an era when medical school tuition is soaring and interest rates for student loans are high, graduating physicians in the United States are drawn to higher-paid specialties, leaving a need for primary care doctors in nearly every state. In the early 1990s, 40 percent of medical school graduates chose to specialize in family medicine; today that number hovers around 8 percent.
A clinical trial involves a large team of researchers, statisticians, and administrators. Many people are surprised to learn that clinicians, those who directly treat patients, are often left out of clinical trial design. Instead, the initial spark for a clinical trial typically comes from a research lab where promising experiments are performed by PhDs, not MDs. These experiments are replicated, undergo peer review, are published, and then move into animal studies. The trial is designed to feed a statistical model. A clinical trial answers the big question: Can this drug work for the group that needs it? A family doctor answers the small question: Can this drug work for you? We need both systems and, perhaps, more cross-talk between the two. What works in a clinical trial will not always work for an individual and vice versa. Both fields inform each other, and ultimately, no matter how we get there, they both share the same goal.
Jessen, empowered by the international compassionate use provision, decided to give Andrew an experimental cancer drug never before tested in a patient with HIV. In doing so, he was taking a huge risk. He was risking his reputation as a doctor, his relationship with his patients, and, most of all, his relationship with the man he loved. The essential component of the doctor–patient relationship is trust. Patients, particularly those with life-threatening diseases, often put blind faith in their doctors, questioning little of their impending therapy. “You can convince a patient to agree to anything,” says a candid physician at Massachusetts General Hospital before adding, “We have to impose our own ethical standards to make sure we don’t ask too much of our patients.” Informed consent by this measure often relies on the ethical standards of the physician. How much is explained to a patient, and how much they agree to, is defined only by the boundaries of a single doctor or researcher. It’s a risky way to practice both medicine and science.
It was a risk that couldn’t be taken lightly. Jessen decided he would leave Berlin to treat Andrew with the experimental regimen. He wanted seclusion. They found a house to rent on the beach in the North Frisian Islands off the northern coast of Germany. It was a seven-hour drive to Berlin; no one knew them there. Jessen feared that other doctors would find what he was doing absolutely crazy as well as unethical. Every day, Jessen rode a ferry to the mainland, flashed his ID, and picked up the experimental drug. On a strict timetable, he took Andrew to the mainland hospital himself, explaining that he was “sick” and needed a blood cell count. In their peculiar isolation, Jessen fought to maintain his composure. Andrew couldn’t stand it and found every day of their two-month stay painful.
Andrew would occasionally ask, “What about you? Shouldn’t you get tested?” Jessen was able to deflect the attention away from himself. It was a time, as he would later say, “when everyone died. . . . The only important thing was saving Andrew.”