Interview with the World's Most Celebrated Virus Hunter: Ian Lipkin

part 1

When Ian Lipkin chose a career in infectious diseases, he envisioned hunting for pathogens in daring treks around the world. Though disappointed to learn that modern-day virus hunters work largely from the lab, he still wound up a pioneer. At the Scripps Research Institute in La Jolla, then at the University of California, Irvine, and since 2001 as director of the Center for Infection and Immunity at Columbia University’s Mailman School of Public Health, Lipkin has developed groundbreaking techniques that have helped a new generation of disease detectives sleuth out the infectious roots of mystery ills, chronic disease, and neuropsychiatric disorders like autism and OCD. Lipkin’s signature invention is a technology called Mass Tag PCR, which searches through large numbers of known viral and bacterial genomes to identify a culprit in a few hours. He often complements this test with others, including microbial detection microchips (GreeneChips) and gene sequencers that can complete an exhaustive search for known and unknown pathogens within a tissue sample in less than a day.

When DISCOVER features editor Pamela Weintraub interviewed Lipkin last year, he had to cut his workday short because his dog, Koprowski””a gift from Polish virologist Hilary Koprowski””was desperately sick. Lipkin had a treatment plan: not an antiviral drug or chemotherapy, but red meat. “It has antibiotics, it has growth hormone, it has everything. Koprowski’s my best friend in the world,”‌ he explained before descending into the subway and heading home.

You were in the first class of men at Sarah Lawrence, where you studied anthropology, even shamanism. Yet you are known for hunting pathogens. How did that come about?

”©I felt that if I went straight into cultural anthropology after college I’d be a parasite. I’d go someplace, take information about myths and ritual, and have nothing to offer. So I decided to become a medical anthropologist and try to bring back traditional medicines. Suddenly I found myself in medical school.

But you didn’t become a medical anthropologist. Instead you studied neurological disease and infection. Why?

By 1977 I had gotten a fellowship at the Institute for Neurology in London, where a professor named John Newsom-Davis was working on myasthenia gravis, a neuromuscular disorder characterized by weakness often so profound that people lose their ability to breathe. Back then, nobody really understood what the disorder was. John was trying something new, treating it with plasmapheresis.

What is plasmapheresis, and why did Davis think it would help his patients?

Plasmapheresis is a method where you take the blood, put it into a centrifuge, and as you spin it the components separate out. You have white cells and platelets in one area, red cells in another. And then you have plasma, which contains antibodies. You introduce what amounts to a straw to suck up the plasma. You replace plasma with albumin to maintain the blood volume, but now the antibodies are gone. With the antibodies gone, the symptoms are relieved.

With antibodies at the root of symptoms, you knew that a pathogen could be the precipitating cause. How did you end up linking infection and diseases of the nervous system and brain?

I took a residency in neuroscience at the University of California, San Francisco (UCSF). It was 1981 when I drove into San Francisco on Gay Pride Day in a Ryder truck right up Castro Street. It was the apex of freedom and joy in the gay community, but we soon started seeing HIV, and I was one of the only people willing to see the patients who were both sick and had neurological disease. One thing I found that was interesting and important was that a lot of people with grid had idiopathic thrombocytopenic purpura, a bleeding disorder. It’s idiopathic, meaning nobody knows what causes it. Thrombocytopenia means you don’t have platelets, so the blood doesn’t clot properly. Purpura refers to the fact that you get these blotches on your skin where blood vessels break. Their platelets were getting chewed up by their antibodies.

HIV was turning the patients’ bodies against themselves, the hallmark of an autoimmune disease. But you found that their immune systems were attacking not just their blood but their nervous systems as well. How did that finding come about?

I discovered this because we then had the only MRI scanner in the world at UCSF. As a result, a colleague asked me to see a patient of his, a ski instructor from Vail, Colorado. The man was thought to have MS, multiple sclerosis. So this fellow arrived at my clinic early one morning, and I did a very detailed neurological exam. As I left him and came back to him over the course of an hour, his symptoms changed. He was becoming quite fatigued, because the testing is arduous. So I gave him a break of 15 minutes. And he came back in to see me and now both sides of his face were so weak he couldn’t smile. He had numbness and tingling and then, right there in my office, his face became so weak he couldn’t close one eye. Then he couldn’t close the other eye.

It was clear this wasn’t MS, and I thought of a couple of causes for what I saw. One was exposure to some kind of toxin. So I checked the man’s spinal fluid for the presence of protein indicating inflammation. His protein was orders of magnitude higher than anything I’d ever seen, and the spinal fluid came out like glue. My colleagues asked what I wanted to do, and I said, I want to do plasmapheresis.

Why did you go back to that technique? Because you wanted to remove the antibodies that you felt were driving his symptoms?”

That way I wouldn’t be adding a drug that I couldn’t remove. I’m just reducing the number of antibodies that might be causing this disease. So I talked with the renal dialysis people who had the machinery required to do this, and they said, this guy’s gay, so he has this GRID, right? And he has elevated liver enzymes, so he possibly has non-A, non-B hepatitis. And you want us to contaminate our machines with this guy’s blood? I don’t think so.

What did you do then? I know you couldn’t abandon him. ”

After the first treatment he modestly improved””and he was better yet after the second treatment. I treated him on and off for two years. He started skiing again but eventually progressed to AIDS and died. While he was getting this treatment, though, it helped him function. After that I decided to study infectious disease.

San Francisco in the early 1980s””that would have been a logical time to continue your study of AIDS. But that’s not what happened.”

I flew down to the Scripps Research Institute in La Jolla to meet with neuroimmunologist Michael Oldstone. I told him I had all these nerves from AIDS patients and all this brain material. But he says to me, AIDS is a flash in the pan. There’s a vaccine around the corner. You’re going to work on the Rosetta stone of immunobiology: lymphocytic choriomeningitis virus, or LCMV.

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