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Dr. Jim Kublin, M.D., M.P.H.

Dr. Jim Kublin is currently Executive Director of the HIV Vaccine Trials Network based at Fred Hutchinson Cancer Research Center.  He is also the Medical Director of the Seattle Malaria Clinical Trials Center, a translational research center established by Fred Hutch and the Center for Infectious Disease Research (CIDR) to test experimental malaria vaccines and drugs in human clinical trials. Jim is also a faculty member in the Department of Global Health at the University of Washington.

Jim has conducted extensive research on HIV and malaria in South America, SE Asia, and Africa, including clinical trials of novel therapies and vaccines. The Gates Foundation awarded Jim a Grand Challenges Exploration award to apply high-throughput system analyses to malaria vaccine development. Before moving to Seattle, Jim was Director, HIV Vaccines – Infectious Diseases, for Merck & Co., Inc where he played a key role in the development and implementation of HIV vaccine studies, overseeing the coordination of clinical assays, site identification and development, government and ethical approvals and providing guidance on vaccine policy issues. Jim completed his B.S. and M.D. at Georgetown University and received his M.P.H. and completed a residency in Preventive Medicine at Johns Hopkins University. Jim continued work in vaccine development and molecular epidemiology while attending the University of Maryland’s School of Medicine for his fellowship in Vaccinology at the Center for Vaccine Development.

 

Article By By Mary Engel

drMany paths led Dr. Jim Kublin to where he is today: executive director of the HIV Vaccine Trials Network (HVTN), based at Fred Hutchinson Cancer Research Center. A good place to start is the 16 days he spent struggling to finish the 1,000-mile Yukon Quest sled-dog race — the lesser known and more demanding cousin to Alaska’s Iditarod.

“You talk about the long haul, and the incredible patience that’s required to really see it through to the finish, and the perseverance,” he said recently.

Kublin was recalling the 1992 race from Fairbanks, Alaska, to Whitehorse, Yukon, when he was 30 years old. But he could have been talking about leading the world’s largest clinical trials network in the marathon quest to develop and test an HIV vaccine. Finding a vaccine can seem less like a race than a slog through blowing snow, sub-zero temperatures and more darkness than daylight.

Kublin’s been there. On average, a third of the mushers who attempt the Yukon Quest scratch. Kublin finished, but for the first half of the race, he was dead last.

With up to 300 miles between checkpoints, he had plenty of time to face — and accept — his vulnerabilities, an experience he described as “enormously humbling.” He used the same words to describe the bond he established with lead dogs Woodrow, Aspen and the rest of his team as he knelt in the snow every couple hours, checking their feet, making sure they rested and ate.

“If I were to say, ‘I can’t do this anymore, these dogs can’t do it, we need help’ — there wasn’t any,” he said. “[The dogs] knew they were entirely dependent on me, and I knew I was entirely dependent on them. And it was just beautiful.”

TURNING POINT

Kublin grew up in a blue-collar iron-ore mining town on Michigan’s harshly beautiful Upper Peninsula. The son of an ophthalmologist (who at age 80 is still practicing), he found both work and role models in the town’s iron-ore mine warehouse and foundry during high school.

“I was surrounded by people who hadn’t had a lot of advantages growing up,” he said. “It just gave me an appreciation of the struggles that many people experience in this country.”

Moving from the sparsely populated, hardscrabble U.P. to Washington D.C.’s Georgetown University added to the Camus-reading teenager’s sense of bridging two worlds. He dropped out after his first two years to accompany a college group going to Nicaragua to do public health work. If growing up in a job-depressed mining town exposed him to disadvantage, Nicaragua showed him true poverty. To this day, he keeps a photo on his bedside table that he took there of a malnourished child.

But Nicaragua in 1981-82, just after the 1979 revolution, was also a place of excitement and idealism. The new government was launching programs to improve literacy, education and health care. Inspired by Liberation Theology’s ideas on social justice and galvanized by his first foray into epidemiology, Kublin, then 20, worked on the country’s malaria eradication campaign — only to come down with the disease himself.

Anyone who knows that curiosity is a vital part of being a scientist will recognize his response to enduring malarial rigors and hallucinating that his reflection in the bathroom mirror was his face in a coffin. “That’s when I first learned about malaria,” he said, “and became fascinated by just the elegance and biology of this parasite life cycle.”

It was to become a lifelong love affair. In addition to his work heading the HVTN network, Kublin is medical director of the Malaria Clinical Trials Center at Seattle Biomed.

Nicaragua proved a turning point. Returning to Georgetown to focus on biology and pre-med, Kublin went from uninspired student to the dean’s list. He did his undergraduate thesis on how parasites attach to the liver cell. Entering medical school, he continued to do malaria research on the side, dissecting the salivary glands of mosquitos to collect the parasite. He was in his first year at Georgetown’s School of Medicine in 1984, the year HIV was found to cause AIDS.

Jim Kublin provides pediatric care as a volunteer medic at a Cambodian refugee camp on the Thai-Khmer border in 1988.

FROM MALARIA TO HIV

Kublin’s internship at New York’s St. Vincent’s Hospital in 1988 put him in the AIDS epidemic’s West Village epicenter. The hospital was filled to capacity, with gurneys in hallways and a cadre of young doctors who felt both energized and besieged by the challenge. Despite their dedication, in the years before antiretroviral therapy, AIDS was essentially a death sentence.

Still, Kublin found a lesson in the madness.

“I learned in that year that some of the most honorable work out there is hospice care,” he said, “and was fortunate myself to do some of that, helping people with their unfinished business, even if it’s just calling somebody they needed to talk to before they die.”

But even that did not prepare him for sub-Saharan Africa. He and his wife, Zara, and their young sons Gus and Henno moved to Malawi in 1998, where he ran a research program and worked as scientific coordinator for an initiative sponsored by the U.S. Centers for Disease Control and the Malawi Ministry of Health and Population. Once there, he found whole villages decimated by HIV, with no one left but elders and orphans.

Antiretroviral treatment, by then resurrecting patients from near death in developed countries, was not yet available in Africa. So Kublin started doing what other U.S. and European workers were doing — getting colleagues back home to send expired but still usable drugs. Then came wrenching decisions on who should get his tiny stash of pills. The drugs were no match for the immensity of HIV in Malawi. The hospital morgue overflowed daily.

Like Nicaragua, Malawi was transformative for Kublin. Having come to work on malaria, he left to help find an HIV vaccine.

STAYING THE COURSE ON THE ROAD TO A VACCINE

In 2004, after a three-year stint working on an HIV vaccine at Merck Research Labs, Kublin was lured by Dr. Larry Corey, a world-renowned virologist and now Fred Hutch’s president and director emeritus, to coordinate operations across the HVTN.

The HVTN conducts all phases of clinical trials, from evaluating experimental vaccines for safety and the ability to stimulate immune responses to testing vaccine efficacy. A model for collaborative global research, its vaccine trial units are located at leading research institutions in more than 30 cities on five continents.

The road to an HIV vaccine has proved challenging. One of the deepest disappointments came in 2007, just before Kublin took over as executive director. A major trial had to be halted when it was found that the vaccine neither prevented HIV infection nor reduced the amount of virus in the blood among vaccine recipients who became infected with HIV. In some cases, it could make the recipient more susceptible to the virus.

The trial was the biggest one in the field at the time, and the vaccine being tested had been considered the best hope. Despite an effort at scientific detachment, the HVTN staff was devastated.

“We designed the trial correctly because it delivered an answer very quickly,” said Niles Eaton, HVTN director of site operations. “But it wasn’t the answer we wanted.”

Kublin too was caught short by how much he had emotionally invested in that vaccine. He was home when the call came, and the news brought him to tears. When he told his children what had happened, his then 9-year-old-son, Gus, after a pause, replied, “But you’re not going to give up, are you? It’s too important.”

The next day, Kublin called the team together and told them what Gus had said.

“He conveyed that to us to keep us going,” said Eaton. “We needed to hear that.”

Kublin takes a dog team, led by Woodrow and Storm, on a run near Skandia, Michigan, in 1994.

RENAISSANCE MAN

For his 50th birthday three years ago, Kublin’s colleagues made a word cloud of phrases used to describe him. Renaissance man topped the list, though “brilliant” and “approachable” — traits not always seen together — were not far behind. So was “steady leadership” and “calm in the storm,” qualities that turn out to be as useful for leading a team of researchers through the ups and downs of vaccine clinical trials as for getting a rookie musher to the finish line.

“In science, an experiment doesn’t fail, it informs us. He reminds us of that,” said HVTN project manager Sue Ferguson, Kublin’s assistant. “There have been rough waters, but he’s a phenomenal leader. He gives you so much room to bring your best every day.”

Last October, the HVTN opened a new, state-of-the-art laboratory in South Africa, which has the highest rates of HIV/AIDS in the world. Next year it will launch a series of clinical trials there. One will test a modified version of a vaccine that prevented about 32 percent of new infections in a six-year trial involving more than 16,000 adult volunteers in Thailand. The study, published in 2009, was the first to show that a safe and effective HIV vaccine is possible.

A vaccine may be the prize at the end of the marathon, but the man described as driven to make a difference savors interim victories as well. The huge effort that goes into setting up trials provides humanitarian benefits that often go unrecognized.

“Large trials require formidable infrastructure and training and raise standards of clinical care—a lasting resource,” he said.

THE LONG HAUL

The first time Kublin got on a sled behind a team of dogs was on May 12, 1990. Yes, he remembers the exact date. A late spring snowfall had dumped 12 inches on the Upper Peninsula, where he had returned after his internship intending to practice medicine, pay off school loans and recover from a tumultuous year. The friend who had invited him along chose six dogs to harness from the dozen spinning, yipping and pleading to go.

Kublin stepped onto the sled runner, and up a hill they flew, like an elevator on speed. The cacophony of the dog yard gave way to the whistle of wind and his friend’s soft “gees” and “haws” directing the dogs left or right around one treefall after another. Kublin was transfixed.

He still is.

View article – http://www.fredhutch.org/en/news/hutch-magazine/2014-06/quest-to-develop-an-HIV-vaccine.html

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