The Imaginations of Unreasonable Men (24 page)

Epstein would be easy to underestimate. She’s small and slim, and she walks with a brittle gait because of an old back injury. When she got out of her van, I was surprised to find her in uniform: khakis, well-shined black patent leather dress shoes, and a black sweater with three gold stripes on each shoulder. As she got out of the car, she fitted a khaki garrison cap over a thick knot of black hair pinned up on the top of her head. Her demeanor was serious. Though she was friendly and open, I don’t think I ever saw her smile.

We headed over to Building 141, the headquarters for the Center for Clinical Trials. An old whitewashed building from the 1940s or 1950s, it contained offices, conference rooms, and examining rooms. Epstein, who had an office in
the back, introduced me to several other investigators, including a nurse and a doctor. The corridors were quiet. Some of the staff was in another building, busy copying 20,000 pages needed for an Institutional Review Board.

Judy came late to the malaria community—and even to science and medicine. Her father was a doctor, her mother a painter whose first husband was Will Barnet, an artist best known for his enigmatic portraits of women and girls. Notwithstanding childhood dreams of being a marine biologist or working on the
Hope
hospital ship, she left college after one year for ballet and joined the company of legendary choreographer Agnes de Mille. When the revival of
Oklahoma
opened at the Palace Theater on Broadway on December 13, 1979, she was in the cast.

It was the combination of her own back injury and de Mille’s stroke that led Judy to leave dancing and become de Mille’s caretaker. She grew more interested in health issues and considered becoming a physical therapist. At the age of twenty-eight she returned to Columbia University and “kind of locked myself away for three to four years.” After graduating she took another year off because her father was battling colon cancer, and from there it was off to Harvard Medical School.

Interested in both parasitology and pediatrics, Epstein did a residency at Children’s Hospital in Philadelphia and was then awarded a four-year research grant. In 1998, the last year of her fellowship, an adviser recommended that she join the navy, and she was given a billet in the dengue program. “Then I saw Steve Hoffman’s papers and asked to
meet him,” she told me. “As soon as I met him I said, ‘I have to work for him.’” She found a way to work
with
him instead, as principal investigator running the clinical trials that began in September 2009.

The trial had two critical phases: the immunization, and the challenge. The threshold question for immunization was not the efficacy of the vaccine, but its safety. Would there be “breakthrough infections”? That is, might the vaccine be so strong that it not only triggers the immune system but goes so far as to make sick the person one is attempting to immunize?

Hoffman’s wife, Kim Lee, oversaw the immunizations each day. At 6:00 A.M., she’d start the process of extracting the vaccine from the liquid nitrogen and then diluting it. It would be injected intradermally or subcutaneously, and then the volunteers would be observed for thirty minutes. There were four cohorts of about twenty people each.

Although every aspect of a clinical trial is planned out with great care, the human factor can play havoc with any effort to even approach choreography. Trials use volunteers, and though carefully screened, volunteers can still be unpredictable. For example, one man came down with fever, chills, and joint and muscle pains, which could have been a reaction to the vaccine that would stop the trial. But ten days of intensive diagnostic efforts showed that it was instead
Lyme disease. Low, medium, and high doses are administered, the high doses twice, and many things can go wrong. But two weeks later, Hoffman told me that “the headline is ‘no breakthroughs’”—in other words, no infections.

But then Steve explained how, the day before they were to challenge the third group—“the day I’d been waiting for for seven years”—he

When I asked Hoffman how typical it was that a mistake like this would happen, he explained that, “of the 1,000 things that could result in a vaccine trial being suspended, this is one that I would never have imagined or seen coming.”

In early 2010 Hoffman tried again, but by May he had more disappointing news to share: “There’s a lot we don’t know about how the mosquito delivers the parasites when it bites. In any case, what we learned is that our dose was
way too low, more than tenfold too low. But that’s what you do in a Phase I.”

The results were illuminating, but a potential problem in terms of future funding: “We gave 80 volunteers one dose, 66 volunteers four doses, and 17 volunteers 6 doses,” Hoffman told me:

Sanaria’s main funder, the PATH Malaria Vaccine Initiative, he explained, “said we hadn’t met their go-no go criteria and that, at least in the short run, there would be no more funds, despite the fact that more than $50 million had already been invested in this approach. . . . They wanted the clinical trials to show not only safety but effectiveness. So did I! But often that’s not how science works. That’s not what the first phase of clinical trials is for.”

After all the years of preparing for that moment, all of the lab results, all of the papers, conferences, and collaborations,
when it came to administering the vaccine Hoffman was left to make an educated guess. Trying intradermal and subcutaneous injections was a huge “maybe,” and when the trial results finally came back, nature had answered “maybe not.”

“This trial was what I’d been waiting for and working toward for almost a decade,” Steve told me:

After about two weeks, Hoffman finally pulled himself together and went to New York to see Ruth Nussenzweig. It was like journeying to Delphi to touch base with the oracle. “You know what she said?” he asked me. “She said, ‘So you’re no magician.’ And she’s right. I’m no magician. That’s life. Who was I to think that on the first try I’d have the vaccine? That it would be easy for me and for me alone. In my head, I knew that you can’t get that from Phase I. Still, I’d hoped.”

He also went to see Tony Fauci at NIH, who said, “You must keep going!” And then he got a call from his son Seth
at Cornell, who said, “Dad, it would be totally immoral and unethical to stop now, no matter how disappointed you are.”

“Look. Bed nets aren’t going to solve this problem,” Steve said to me. People were dying, including Americans. He cited a Stanford student who had been traveling in Ghana, an American traveling in India, and a Seabee (a member of the Construction Battalion, or CB) from the U.S. Navy, all of whom had contracted malaria in recent months and died. “If I see you on the first or second day that you’ve been infected I can cure you for sure,” Steve said. “The medicines work.” But there are many who do not receive treatment until it is too late, if at all. At this point Hoffman pulled out a recent
Lancet
editorial arguing that a vaccine is the only thing that has ever been effective in eliminating a disease.
¹²

Hoffman had raised $63 million and spent almost all of it. Current funds would keep him going for another twelve months. “So now I’ve got to make the case again that we’ve got a business plan and economics that make sense for investors. So I don’t have to keep begging for money only from foundations,” he said. “There is actually a multibilliondollar market for travelers and the military. And a vaccine can be a lot cheaper than taking Malerone (the current antimalarial of choice) for extended periods.”

Some people are as energized by defeat as by victory. Their competitive juices flow stronger when they’ve picked themselves up off the mat than before they were knocked down. Depending on how long they were down and out, whether they crawled away or were carried, or walked off on
their own power, they may be wiser as well. I could sense that Hoffman had bounced back, was undeterred, but I wasn’t prepared for what he said next: “So we’re going to go forward and do a trial in which the vaccine is administered intravenously. Probably in about four months if we can raise the millions we need. If you can draw blood from someone, as doctors do in offices around the world every day, you can immunize them through an IV inoculation. There is no difference. We’re going to prove that the vaccine works and we’re going to prove that people can be immunized with IV’s.”

It would be hard to imagine that the creator of what many consider the most impractical vaccine ever manufactured could actually make its delivery equally impractical, but Hoffman may do just that by using the IV delivery route. Hoffman is not only undeterred, but more enthusiastic than ever. Because while he’s not sure how to administer the vaccine, he knows it’s still the only one that provides high levels of protection, the only one that can save the lives of a million kids a year and be used to eliminate
Plasmodium falciparum
. The clinical trial helped take at least one option off the table. In the spirit of Thomas Edison, who once said, “I have not failed. I’ve just found 10,000 ways that won’t work,” for Steve that means one of the remaining possibilities is all the more likely to be the right one.
¹³

A malaria vaccine has protected a significant percentage of children against uncomplicated malaria, infection, and even severe forms of the disease for at least six months, according to a proof-of-concept study published today in
The Lancet
. . . .

—Barbara K. Hecht, Ph.D., and Frederick Hecht, M.D.,
“Malaria Vaccine Battle Has Been WON,”
MedicineNet.com
, October 14, 2004

 

 

 

T
HE ECONOMIST
SAID IN 2007 that “there is much talk nowadays of a new golden age of philanthropy dawning.”
¹
It is an era that has indeed been marked by a huge infusion of capital, thanks to economic growth and a technology industry that made many tech-savvy entrepreneurs wealthy at a young age. A greater intergenerational transfer of wealth is
anticipated than at any time in our nation’s history. It is projected to reach $41 trillion by 2052, according to the Center on Wealth and Philanthropy at Boston College. Even in the face of the recession of 2009-2010, there is excitement about philanthropy’s potential, not just because of the amount of money involved but because of new thinking about how it should be deployed.

Indeed, it is an era of tremendous intellectual ferment about the role of philanthropy and how it can have the greatest impact, an era accompanied by experimentation, with each new major philanthropy testing out its own signature style. Organizations such as the NonProfit Finance Fund, which provides growth capital strategies to nonprofits; Venture Philanthropy Partners, which uses venture capital practices in philanthropic investing; and Community Wealth Ventures, which designs earned-income strategies, strive to demonstrate the merits of their approaches.

Perhaps what has changed most significantly is philanthropy’s ambition. In philanthropy’s earliest days, the wealthy felt an obligation to “give something back,” and charitable organizations were the vehicle that enabled them to do so. As social consciousness spread and philanthropy became more grassroots, many simply wanted to genuinely contribute to the aid of others, ensuring that the poor were clothed and fed, that widows and orphans were cared for rather than neglected, that the homeless were sheltered. Others returned wealth to the organizations from which
they had personally benefited, such as universities or cultural institutions.

But over the past twenty-five years, and especially in the past ten, the ambition of much philanthropy has shifted from seeing “doing good” as good enough to instead wanting to actually solve complex social problems. It is now not uncommon to have a foundation fund the planning process for solving a problem and to then, in effect, subcontract out the necessary actions to nonprofit grant partners. The Gates Foundation very much acts like the general contractor responsible for eradicating malaria, using a wide variety of subcontractors who specialize in vaccines, drugs, diagnostic techniques, and public health systems. On a smaller scale, the Eli and Edythe Broad Foundation aspires to do the same in transforming public education, as does George Soros’s Open Society Institute when it comes to strengthening civil society.