Rest in Peace, Happy Physicist

Image Courtesy of Ben Harris

Image Courtesy of Ben Harris

Ben Harris grew up in a “chaotic” and “rough-and-tumble” household (descriptions proffered by his older brothers Mike and Dan). There were six siblings—first Mike, then Dan, then Kathy, Amy, Ben, and finally Jason—and often each would have two or three friends over. But the constant party didn’t seem to bother anyone. Some even used the popularity to their advantage. Dan was lucky enough to have acquired an Atari 400 computer, but to play any games, he and Ben would copy the code, line by line, from the Atari magazine using a membrane keyboard. Five hundred lines of code; it took hours. Then they thought of a better way: get the neighborhood kids to do it. If you typed for one hour, you could play for three, that was the deal. Their friends jumped on it, and before long they were all taking turns gunning down rudimentary rocket ships.

Ben excelled in the classroom, even convincing his parents to send him to a selective prep school so he could get into a good college. It worked: he went to Columbia, then to the University of California at Riverside for graduate school. He met and married his wife, Beccy, and comfortably settled into his dream career, which he also excelled at. Recruited by a company called ProCure, Ben would travel the country helping install and maintain proton radiation facilities in US hospitals and cancer treatment centers. He had a son, Rawden, who inherited his father’s intelligence, choosing to engage it as a member of the school’s chess club. Beccy helped organize the chess tournaments; Ben ran a program that randomly paired up the students for matches. Life was good, damn near perfect, and he knew it, rarely losing the perspective that comes with true appreciation. Unfortunately, Ben didn’t get to enjoy his good life as long as he may have liked.

Ben Harris, aka AmazoBen or just plain Amazo, passed away last fall, victim of a disease that he had spent his final years trying to help solve. His friends and family all cite his intellect among his defining characteristics, with many implicitly or explicitly admitting inferiority to Ben in that regard. They also emphasize his kind and supportive nature: never did he make them feel any less intelligent than he; if anything, they felt smarter when they spoke with Ben.

I had the pleasure of meeting Ben last April, four months before his death. He shared with me his personal story, as well as some of his radical ideas on the public sharing of patient data, the clinical trial system, and role of government regulation in end-of-life medical decisions. With a masters in philosophy in addition to his more practical degree in physics (which pragmatic Mike had gently talked him into), Ben liked to push the boundaries of traditional thinking. And while drug development and regulation may seem delicate areas to question the status quo, Ben is certainly not alone in his belief that something needs to change.

As he neared the end of his life, Ben navigated the final descent as gracefully as he’d handled the entire journey. The family trickled through Ben’s Bloomington, Indiana home, enjoying the last months, weeks, and days with their beloved Amazo. In early August, Ben made the decision to stop eating. He had always said that, as soon as he was unable to care for himself, he would let the disease take him. He didn’t want to live that way. More importantly, he didn’t want his family to live that way. He wanted his wife and son to remember him as he was, and to celebrate that memory as they continued their lives without him.

Ben was a dedicated researcher of ALS and a willing experimentalist, trying various unproven treatments on himself, sometimes and sometimes not in the context of an FDA-sanctioned clinical trial. Most of the time I think he was more hopeful that his detailed and open records of his own experiences could yield some insight into the still-mysterious disease, than he was hopeful that any of the treatments would really help him. He was a vocal advocate for compassionate use programs that gave patients access to therapies still making their way through clinical testing and a strong believer in the legalization of assisted suicide. But to me, more than any of these valiant causes, the thing that struck me most about this dying man was that he was happy.

He’d be the first to admit it. He had always been happy. Despite the unfortunate luck he’d had with his health, everything else in life had gone just right. Even when ALS had done its worst—robbing Ben of his ability to control his own body and killing him in less than three years—he never lost his gratitude for the life that he had. He was happy, he said, and he would do it all over again in a heartbeat.

The Rise of the FDA

ElixirSulfClip

FDA HISTORY OFFICE

As my last post suggested, I’ve taken an interest in the history of the FDA. One of the more interesting anecdotes I came across in my research is the Elixir Sulfanilamide tragedy, in which 105 people died after taking a drug whose solvent was toxic. At the time, the FDA enforced “truth-telling” in the food and medicine industries—that is, companies had to be honest about the ingredients of their products or they could be reprimanded by the agency. But the FDA did not have the authority to oversee food and drug safety. Following the widespread deaths linked to the Elixir, however, Congress passed the 1938 Food, Drug, and Cosmetics Act, which turned the FDA into the consumer watchdog we know today. (It would be another quarter century, however, before the agency began to oversee drug efficacy.)

In any case, I wrote about this particular story for this month’s issue of The Scientist. Check it out!

The Loss of Gentlemanly Honor

Until recently, when I read the story of how American trade became institutionalized in the 19th century, changing both physical and economic landscapes, I had never given much thought to the culture of the pre-business world. When commerce was done face-to-face, there was no need for government oversight: men were simply bound by an inherent moral code. But as business owners became more and more removed from their customers, deceit and greed were allowed to creep in.

NY skyline

Panorama of Lower NY City in the late 1800s
Wikimedia, New York Public Library

Harvey Wiley, an early champion of government regulation, was stunned by the accepted nature with which businesses would cut corners to make cheaper products, and then lie about doing so. Many companies had started synthetically manufacturing glucose and calling it sugar, for example, despite the fact that it lacked the flavors that true plant-derived sugars contained. Other examples, particularly of adulterated medicines, are more egregious.

In a thus-far excellent book I’ve just started reading, Protecting America’s Health, author Phillip Hilts writes, “The corporations were developing a reputation not only for lack of accountability, but also for ruthlessness in competition and hardness toward their workers. There was a fear that the money-centered values of the great combines [corporations] and their owners would soon displace personal decency and honor.”

So began, in earnest, the discussion of government regulation over business. Corporations, and those that stood to gain from their success, not surprisingly opposed the idea. But those who favored regulation called for government enforcement of honorability and fairness. They believed that “. . . business had shown in the nineteenth century it could not well serve two masters—it could not seek profit with a single-minded energy and at the same time take care that citizens were protected from the injustices and injures that its actions or products might cause,” Hilts writes. “The new kind of business could not, in other words, honestly police itself.”

*  *  *

The FDA—founded by the 1906 Pure Food and Drug Act as the Bureau of Chemistry, with Harvey Wiley as its chief chemist—was a direct result of the national uproar against the rampant sale of adulterated foods and drugs. The agency has gained more power over the years—often in response to tragedy—and has grown to some 14,000 employees around the country. But that’s still a relatively small agency, with an even weaker budget, to oversee some 95,000 businesses selling about $1 trillion of goods each year.

Hilts’s conclusion is that, especially in light of its limited resources, the FDA has done a damn good job of keeping the populace safe. But more and more, the agency is feeling the pressure to bring drugs to market sooner.

“They are in a tough spot and that is our fault,” says medical physicist and ALS patient Ben Harris. “They are damned if they do and if they don’t.” Indeed, if the end goal of the FDA is to save lives, the agency must consider the patients who die before a life-saving drug gains approval. On the flip side, approving a drug too soon risks inflicting harm. Furthermore, one failed product can devastate other drugs in development, if the company is unable to sustain the loss, stalling or halting programs that might well have been successful. Clearly, the equation is not simple.

*  *  *

While the business community of the early 20th century fought the creation of a government regulatory body, today’s industry embraces the FDA. Companies rely on the agency to keep them in good standing with the public—particularly after something goes wrong, like the discovery of some adulterated products. By performing regular screens, the FDA reassures consumers of the products’ safety and purity.

In the biomedical world, companies are hesitant to allow their experimental drugs to be used before they can be ushered through the appropriate trials to gain market approval. More people using a drug increases the chances that an adverse effect will arise—stalling or even derailing a drug development program. With hundreds of millions, often billions of dollars invested, companies understandably want to reduce those risks until they can start to recoup some of their losses.

The FDA is similarly wary of condoning more widespread access to drugs that have yet to complete the full battery of clinical tests required for marketing approval, and while the agency continues to create expedited pathways to market, it still follows an overwhelmingly precautionary approach.

So what’s the solution? Should terminally ill patients be granted early access to experimental treatments? Who should make those decisions?

Some think that the DIY model of clinical research, while extremely new and unproven, could be one answer. By going outside of the regulatory system, DIY trials are not subject to the lengthy FDA review process. And by yielding results in a fraction of the time, the approach could save both lives and money. “I don’t think the FDA model will ever go away,” says Harris—“DIY will not replace it.” But he believes the online environment serves as “a form of oversight,” he says. “[The patient community on the internet] seems to me to be very good at self-regulating.”

Institutionalizing DIY

Image Courtesy of Ben Harris

Image Courtesy of Ben Harris

“I would argue it should be mandatory that the patient’s medical record be public,” said medical physicist and ALS patient Ben Harris. “Privacy kills.”

Thus far, I have focused the story of do-it-yourself medicine on patients working entirely on their own, coordinating their efforts online to test new treatments for an incurable disease. But all of these patients have doctors, many of whom support their DIY efforts. Ben envisions a reformation of existing health-care system and clinical research protocols—supported by patient activism and data sharing.

He envisions physicians of terminally ill patients having the authority “to prescribe any drug to their patient”—even those not yet approved for the disease being treated—“with the agreement that their data is made available publicly,” he told me earlier this month in his home in Bloomington, Indiana. The information generated, he said, could help guide drug development, flagging promising candidates to enter formalized clinical trials, while weeding out the bad eggs. “We should already know if a substance works before we go to a clinical trial,” Ben said. “[To] find out if it works with a clinical trial, it takes too long and is too costly.”

Currently, however, FDA regulations limit patient use of experimental treatments, and even those programs designed to grant early access are often resisted by drug companies and manufacturers concerned that an adverse event could stall or derail the drug’s path to the clinic. Furthermore, even for drugs that are on the market, liability and other legal issues dissuade many physicians from prescribing drugs off-label (for an indication other than the one for which it has been approved).

But Ben thinks that regulations could be put in place to supply patients with experimental drugs and give doctors the freedom to make decisions about the drugs’ use on a patient-to-patient basis, just as they already do for cases in which multiple treatment options are available. “If a trial drug hurts me, I can’t sue anyone. Drug companies are protected,” he said, communicating by typing on the family’s flat-panel television because ALS has completely taken his voice. “Why couldn’t we protect physicians in a similar way?”

Of course, one of the leading criticisms of DIY medicine is safety. Patients may have incomplete information, and physicians may not be qualified to decide whether a patient should take a drug that hasn’t been approved to treat his disease. But when I raised these concerns with Ben, he simply reiterated that he was advocating specifically for terminally ill patients, who need the leeway to go outside of the clinical research system to try new treatments before it’s too late.

“All I am saying is allow those with terminal illness to take big risks,” he said. “I find it fascinating that we as a country were perfectly willing to send 4,000 young men and women to their death overseas but I am forbidden to risk my life with a risky treatment, even though I will die soon anyway.”

Crowd regulation

Among the many safety risks of trying experimental drugs outside the context of a formalized clinical trial is the potential for predatory salesmen to take advantage by peddling unproven or even dangerous remedies for profit. That was the overriding problem that the US Food and Drug administration was founded to resolve, and while the agency has taken great strides toward preventing the deception that was rampant at the turn of the 19th century, such maleficence still exists.

But Ben, who has taken part in both FDA-sanctioned and DIY clinical efforts, argues that the online patient community is “very good at self-regulating.” “I see internet-based sharing is a form of oversight,” he said. “Scams depend on secrecy.” He recalled animated discussions in online patient forums about a stem-cell procedure being offered in China. Some patients were really touting its effectiveness, but when fellow ALS patient Rob Tison took a closer look at the data they were reporting, he found that the treatment was not having any benefit. “It was a bloody fight online, but the truth did prevail,” Ben said—“the procedure was useless.”

He added that the online model he proposes would work most readily for drugs that are already on the market. “Most of the drugs that go through safety testing have been shown to be safe already,” he said. Other treatments, such as sodium chlorite, while not approved as a drug for any medical use, has been tested extensively for safety because it is used to purify drinking water. And besides, he added, there is no reason to believe that the risk is any greater than in an FDA-sanctioned trial. Indeed, several experimental treatments for ALS have actually caused harm, accelerating disease progression in many patients. “The risk is there anyway,” he said.

Furthermore, Ben argued that the risk associated with a formal clinical trial may be more obscure. “When you hand a consent form to an uneducated person, the vast majority do not understand what they are reading.” But in the online model, the ones taking the risk are the ones running the experiment, he said. “If the ‘trial’ is organized by the individuals [partaking], consent takes a different meaning. You don’t have a business entity asking you to swallow a chemical; you are doing it on your own and sharing your experience.”

Ben’s ideas rest on the ability of patients with terminal, incurable diseases to participate in their own risk-benefit assessments and help make decisions about their care—something that many bioethicists will question. But it’s something that Ben has done from the start. “I don’t think you can be overly protective of people,” he said. “It is up to the person what level of risk they are willing to take.”

His thought experiment could be considered radical, but as the Facebook generation ages, he argues, the pressure for such a change is only going to grow. “Twenty years from now, the majority of terminally ill patients will seek outlets for sharing their medical information. If there are a couple success stories with this model, it will probably move the government to formalize it.”

What do you think? Ben welcomes your responses below—the good, the bad, and the ugly! “I love debating so don’t hold back,” he said. “I have an MS in philosophy so I can talk until the cows come home (only limited by my weak hands).”

A Personal Trial

Today premiers an article I reported for The Scientist magazine, where I have worked for almost 4 years. It describes a new movement in medicine in which ALS patients are taking a larger role in their own medical care, even going so far as to organize their own unofficial clinical trials to test experimental drugs. The story is grossly over-researched for a 3,000-word magazine feature, and condensing more than 9 months of reporting, 50 hours of interviews, and 200-some pages of notes into what I hope is a cohesive story was as hard as it sounds. Still, I’ve only just scratched the surface.

Eric Valor

Eric Valor
© ELIOT DRAKE

My interest in these patient-driven efforts started with an April 2012 Wall Street Journal article about a group of ALS patients who were taking a homemade mixture of sodium chlorite, which they hoped would mimic a chlorite-based drug currently in development. That month, my editor at The Scientist tasked me with writing a short piece on the sodium chlorite “trial” for the magazine. My article, published in July, recounts the story of three patients—Eric Valor, Ben Harris, and Rob Tison—who spearheaded the effort to gather patient results online as ALS patients started ingesting sodium chlorite on their own at home. But it was clear that 700 words could not do it justice. This story is years in the making—from the creation of the US Food and Drug Administration to protect patients from predatory drug salesmen, to patients’ circumvention of the agency’s clinical trial process to test drugs on their own.

Today, FDA administrators are under constant pressure to give dying patients access to experimental treatments earlier and earlier in the drug development process, before it is convinced of a drug’s safety and efficacy. The agency is understandably conflicted. Regulators cannot in good conscience put a drug on the market that they aren’t 100% sure is safe enough to warrant the benefits it could yield. But what is “safe enough?” How are those calculations made? Don’t they depend on circumstance? Surely a patient losing control of his own body and facing imminent death has a different risk-to-benefit calculation than someone much earlier in his disease. And surely they should have a right to partake in decisions regarding their own care.

Eric2

Eric uses an infrared camera to control the various technology in his room.
© ELIOT DRAKE

Today’s article centers on the story of Eric Valor, an active member of the ALS patient community. Eric was diagnosed with ALS in 2005, and his body has nearly completely succumbed to the disease. His mind, however, is as strong and motivated as ever. I have come to know ALS as one of the worst diseases to afflict humankind, leaving its victims paralyzed and bed-ridden in less than 2 years, and usually taking their lives shortly thereafter. But it leaves the mind untouched—which can be a blessing or a curse depending on how you look at it. Eric has decided this is a blessing, and equipped with modern eye-gaze computer technology, he makes full use of his days (or more accurately, his nights, as his average day runs from about 1pm to 3am) researching ALS and advocating for early access to experimental drugs.

In 2011, Eric started taking sodium chlorite and helped organized the patient effort to collect data on the treatment. While wholly patient-organized trials like this are uncommon, and largely limited to the ALS community, patients across the board are becoming more involved in their own health care. Doctors, the FDA, and drug companies all have their concerns about this trend. At the same time, patient involvement is creating a veritable deluge of data, which researchers are only just beginning to take full advantage of.

So, nearly a year into this, I feel like my work has only just begun. There are innumerable stories of inspiring patients, fascinating tales of the successes and failures in the drug development and regulatory world, and countless questions left to be answered. I have aspirations to write a book on this topic someday, but for now, I plan to bring you updates here, in my new blog. I welcome any and all feedback as I go along. Thanks for reading!