The Priorities of an Impatient Patient

Avi Kremer doesn’t want your pity. He wants your money. And when patients like him sponsor their own search for a cure, it raises an uncomfortable question: Do some diseases simply deserve more research dollars than others?

Avi Kremer left the doctor’s office at Massachusetts General Hospital thinking he needed to climb to the roof and jump. He was nauseated and overwhelmed with fear; jumping would surely stop it. Somehow, though, Kremer made it home to his apartment near the Harvard Business School. He opened the door and got into bed, and sobbed. He thought about his life and, now, his death, since he knew roughly when it would happen. His diagnosis was amyotrophic lateral sclerosis (ALS), or Lou Gehrig’s disease. The doctor’s advice: Make a will, because there is nothing else to do. Kremer did not get out of bed for three days.

Few people ever seriously contemplate being felled by a monstrous illness. Kremer certainly didn’t. Born in Israel, he’d served four years in his country’s military, rising to captain, then put his computer science degree to work at an Israeli defense technology company. He had come to Harvard Business School in 2004 to become a part of what he called the “money machine,” which he believed could propel him into the CEO chair of whatever Fortune 500 company he chose. He had a beautiful girlfriend. Everything made sense.

ALS erased Kremer’s hubris. The disease causes the body’s motor neurons to degenerate, which means muscles stop receiving orders, atrophy, and finally quit working altogether. ALS patients remain mentally nimble but lose almost every muscle function, one by one, until they cannot speak or even breathe. At 32, Kremer is not yet “a soul suspended inside a completely atrophied and paralyzed vessel,” as he puts it, but he is on his way. His girlfriend left him, and he now relies on friends and his brother to help with once simple tasks. He drinks out of green and purple sippy cups with lids and mangled straws. His hands, crabbed almost into fists, make typing increasingly difficult. Speaking is arduous, particularly in English; Hebrew is easier. Swallow, breath, breath—“I am”—breath, swallow, breath—“much more modest,” Kremer told me in early February. Twenty seconds, five words. This is a good day.

The temptation is to feel pity. I did. I heard it in my voice when I spoke with him, a different tone than I used with the friends who were there to help translate if his slurred voice became too hard to understand. But Kremer doesn’t want to be pitied. This is someone who, as the photo on his desk shows, once stood tall and proud among his men—buzzcut, brown-rimmed glasses, with an expression that looks as if he’s about to burst out laughing; someone who now zooms around Harvard’s campus in an electric wheelchair with a bumper sticker that reads “I ™ Kazakhstan” (only instead of a heart, there’s a picture of Borat’s head).

A week after his diagnosis, Kremer decided to pick a fight with ALS. He could go home, spend time with family, and do all the things he might not otherwise get to do. “But that’s not who I am,” his friend Nate Boaz recalls Kremer saying. Instead, Kremer stayed on at HBS and focused his studies on the business of Lou Gehrig’s. Why wasn’t there a cure? Why hadn’t the life expectancy of three to five years improved since the disease was first identified in 1869? Why was there only one drug that could extend an ALS patient’s life—and by a mere three months, at that?

In June 2006, Kremer and two business school classmates launched Prize4Life. The organization uses cash prizes to spur innovation in ALS research, and it plans to give away about $10 million, of which more than $4.5 million has been raised. The money has come mostly from the HBS community, but also from such Boston notables as Patriots owner Bob Kraft, who took only three minutes to decide to give Kremer $250,000.

I watched one day as Kremer’s physical therapist, Jen, stretched his atrophying muscles. Control is everything to Kremer, and yet he lay on his back, staring at the ceiling, relinquishing it all, muscle by muscle. In that moment, my only thought was that we should throw as much federal funding as necessary at finding a cure. Emotions, though, are rarely a good guide when allocating money: 5,600 people in the United States are diagnosed with ALS each year, whereas 2,400 people die from cardiac disease every day. As heart wrenching as it is to see someone like Kremer cave under the oppressive weight of his illness, you have to ask: Should any one person’s tragedy take money and resources away from other, more prevalent diseases?

The drug development process is not structured to help people with rare diseases. The bulk of federal funding goes toward basic research for illnesses that affect vast swaths of the population, like high cholesterol or cancer, and the academic scientists who receive that money, even those specializing in rare diseases, are committed to enhancing the body of knowledge, not necessarily finding specific cures. On the other side of the equation, pharmaceutical companies have an economic motivation to zero in on drugs with the largest profit potential.

That’s why disease-fighting organizations like the American Heart Association traditionally have focused on raising awareness, lobbying, and funding basic research. Patients, for their part, are meant to be merely cheerleaders—as well as reminders of the reality of the disease—for all those postdocs pulling late nights in the lab. But now some patients and their families, tired of falling through the cracks, are trying to write their own, happier endings. Instead of soliciting second opinions, they are personally getting involved with the research themselves by starting organizations that speed drug development for so-called orphan diseases.

With its surfeit of hospitals, pharmaceutical companies, and universities, the Boston area is at the heart of this movement. Biotech Row in Cambridge is home to a group founded by Jamie Heywood, who lost his brother to ALS, and also a research outfit launched by Parkinson’s sufferer and former Atlantic Trust senior partner Ed Rudman. (Although Parkinson’s is no longer considered a rare disease, drug firms have yet to make great strides toward a cure.) The Progeria Research Foundation, started by Leslie Gordon—whose 10-year-old son, Sam, is one of 42 children worldwide afflicted with the disease, which causes rapid aging and tends to kill its victims before they turn 13—is based in Peabody. And though Kremer’s family still lives in Israel, and his Prize4Life colleagues work in New York, Atlanta, and elsewhere, he has decided to pursue his work here as well. “I had to choose the place where I could have the most impact, and Boston is definitely it,” he says.

As the number of patient-driven foundations grows, though, some researchers and medical ethicists are raising questions about this kind of hands-on advocacy. No, you can’t blame patients like Kremer for trying to find a cure. But what if organizations like Prize4Life siphon money away from research on more-common diseases, inadvertently holding up a vital breakthrough on, say, breast cancer? The Progeria Research Foundation has, over the past eight years, raised more than $4.3 million to research an illness that affects fewer than 50 children. These are kids who engender compassion in everyone they meet. But the cold reality is that smart research decisions can’t be made based on who’s got the saddest stories. “The most rational way to allocate research monies,” says Dan Brock, head of the Division of Medical Ethics at Harvard Medical School, “isn’t based on which disease has the most effective lobbying group, the most vocal group, or the most-sympathetic patients.”

Another concern is whether terminally ill patients can dispassionately evaluate medical treatments. Internet ALS forums, for example, are awash in speculation about a possible link between ALS and Lyme disease, with some of the posters seeking therapies intended only for Lyme in the desperate hope that should they work, it’ll prove they don’t have ALS. But the consensus among scientists, according to John McCarty of Jamie Heywood’s ALS Therapy Development Institute, is that there’s little overlap between the two diseases. (McCarty knows of only one case in which there appeared to be a misdiagnosis.) And taking Lyme disease drugs can actually ravage ALS patients’ bodies and may even accelerate their muscle deterioration.

Finally, you have to wonder whether patients’ fear might lead them to make the wrong decisions in their research work. Prize4Life is a case in point: Kremer modeled his organization on the Ansari X Prize competition, which in 2004 granted a $10 million award to the team that realized the long-held goal of private space flight, and last month announced a similar bounty for developing a car that can get 100 miles per gallon. Kremer admired the prize’s ability to stimulate innovation—but pay only for results—in a field that had seemed stagnant; maybe, he thought, prizes could “revolutionize” ALS research in the same way.

So successfully did Prize4Life imitate the X Prize model that Kremer’s people eventually began to talk with its leaders last year about turning his organization into an X Prize for ALS. By joining forces, Prize4Life would have access to more money (the minimum award would be $10 million) and a bigger, better-established operation. Much like Warren Buffett’s giving $36 billion to the Gates Foundation, it appeared to be a natural fit.

The X Prize Foundation was receptive. But its representatives felt strongly that to capture the public’s interest, and that of the very best scientists, the prize had to be linked to breakthroughs in neurodegenerative diseases as a whole. Upon hearing their terms, Kremer declined. He was worried that Prize4Life’s funding and previous work might ultimately go toward research that had no benefit to ALS. Determined to maintain his foundation’s tight focus, he opted to go it alone.

If Prize4Life were subject to a Harvard Business School case study, many students would have urged Kremer to “find synergies” and merge with the X Prize Foundation. But when it’s your life hanging in the balance, your tolerance for risk is greater. After all, for Kremer, what’s there to lose?

Avi Kremer woke up one day in February and could speak again. Not the way he could before he had ALS, but the way he had in December, when I first met him. “I feel like I could talk forever,” Kremer told me. He had no idea why it had happened—his doctor said it was unheard of—and could only hope it would last.

Solving the mystery of Kremer’s improved speech might be possible if doctors could follow the progression of ALS inside the body. For many diseases, scientists have identified what is known as a biomarker, which allows them to measure the advancement of the disorder. Biomarkers come in many forms: With AIDS, doctors track CD4 cells; with multiple sclerosis, they look for brain lesions with an MRI scan. There is no similar way to assess the effect ALS is having on the body, or how well a certain drug treatment is working. Lacking such a precise tool, Kremer’s physicians monitor his condition by observing physical indicators, such as muscle control. Researchers, meanwhile, have to measure a potential ALS drug’s effectiveness by charting how long sufferers survive, a drawn-out and costly process.

Prize4Life’s first award is for identifying a biomarker that would make it possible to evaluate how well a prospective ALS treatment works. Its second is for a laboratory mechanism that would quickly screen potential drugs. There’s a reason Kremer has set up such explicit targets: Medical research often suffers from a lack of concentrated effort—every scientist is working on something different. Prizes are one of the few ways to focus researchers’ attention on a single idea that could significantly advance drug development. (In the software realm, the vaunted breakthrough of open-source software came only after many talented programmers coordinated their efforts.) “We see the prize as a lighthouse that directs researchers toward the most necessary links between academia and the private sector,” Kremer says.

Indeed, Kremer often describes Prize4Life as a “dating agency.” The idea is to reward cutting-edge work in the academic sector or elsewhere (New cell-biology technology measures progression of ALS, seeks research partner for clinical trials), then take that work—if the prizewinners lack the capacity to do it themselves—and deliver it to those in the industry who have the resources to bring it to the market (Drug company seeks advanced research, nearly riskless, to take on study dates and potentially sell, if all goes well).

If Prize4Life succeeds in finding a biomarker, that discovery would “fill in the pieces of the puzzle that will make drug development for ALS easier and quicker,” says David Meeker, a president at Genzyme, the Cambridge-based company that has proved rare disease research and treatment can be highly profitable. But on the big question of whether prizes like Kremer’s can fundamentally alter the drug research landscape, there’s precious little consensus. The corporate-sponsored teams that competed for the Ansari X Prize, for example, collectively spent $100 million and nearly 10 years researching private space flight in order to try to win $10 million—a total that something as obscure as an ALS biomarker would have a hard time generating. “People don’t invest in medicine on speculation,” says Dr. Jeffrey Rothstein, who heads the Robert Packard Center for ALS Research at Johns Hopkins. “It just doesn’t work that way.”

So far, Prize4Life has attracted close to 50 entries for the first part of its competition, which will award five prizes of $15,000 to those with the best theoretical proposition for an ALS biomarker. (Among the contestants: a dentist who thinks he might have a way to measure the disease’s progression via saliva and a researcher who thinks it’s as simple as monitoring changes to the skin, both ideas that never would have made it through a traditional grant-making process.) Kremer expects even more interest in the second part of the contest, which will award $1 million next year to the team that creates the best usable biomarker. Well aware that he might not be here to hand out those prizes, Kremer, along with the all–volunteer team that runs Prize4Life, is hiring a full-time chief operating officer to run the foundation when Kremer no longer can.

The ultimate evidence of Prize4Life’s potential may be Leslie Gordon’s Progeria Research Foundation, which since its inception has identified the progeria gene shared by all the children who have the disease, and launched a $2 million clinical trial on a new drug with Children’s Hospital in Boston. Ed Rudman’s Link Medicine is gearing up for clinical trials on a Parkinson’s treatment. And by evaluating more than 800 different possible treatments and testing 120 on mice—and finding that none are effective—Jamie Heywood has allowed the ALS community to cross those off the list and move on to new avenues of research. This is a bigger accomplishment than it sounds: Science is an additive process—failures and success contribute to the end result, sometimes equally.

Indeed, the incremental efforts of these groups may be just the thing to speed up drug development for orphan diseases. Nine years ago the Cystic Fibrosis Foundation changed its approach from one focused on basic research and advocacy to one targeting specific treatments. Struck by the same epiphany as Kremer and others in Boston, the foundation began backing drug development directly. It has spent $300 million on that effort, of which $200 million goes directly to companies, a majority of them in the Boston area. The efforts of the foundation have brought four drugs to market. And those drugs have helped increase the life expectancy of cystic fibrosis patients by four years.

Four extra years would grant Kremer the chance to award his prizes, and see some of his work come to fruition. But for now, he is content just to be able to talk. “My speech fluctuates, but even at its worst it is a bit better than a month ago. Yay!” he told me in an uncharacteristically chatty e-mail in March. Mammoth effort went into typing those extra three letters with his crumpled hands, but his elation over his speech made the exertion worth it.

Some days, Kremer will admit that no matter how much he thinks about ALS or how many people he meets with, Prize4Life will never move fast enough to help him. On other days, especially when his voice is back, he’s more optimistic. “If and when my condition gets to a point where I need 24-hour supervision,” he says, “I will probably go back to my family in Israel.” When I ask if he still thinks there is an “if,” he smiles and shrugs. “Miracles happen,” he says.