Cancerland

by David Scadden

  It seemed that the country was excited by the prospect of a victory in the war against cancer, with news outlets focusing a great deal of attention on developments occurring after the Nixon announcement. Thanks to articles like “Hope in Chemicals Declared,” which ran in The New York Times, many people came to expect miracles in short order. During the summer after Nixon’s announcement, a press release noting the promise of research into a certain chemical compound led to wide press speculation about a drug found to be “100 percent effective against cancer in animals.” No such drug actually existed, but medical centers were deluged with telephone calls about it. Cancer patients and their families trekked to Oak Ridge, Tennessee, and literally begged to get this compound from a doctor who was mentioned in the press.

  Episodes similar to the one in Oak Ridge would arise with regularity as journalists and the public tried to understand reports on various streams of cancer research. A good example is the term carcinogen, which seeped into the vernacular, but in the struggle to navigate the science, it was easy to get lost. Most forms of radiation and many chemicals are known to cause cancer and are therefore regarded as carcinogens. The compounds in tobacco smoke may be the most well-established carcinogens, and antismoking campaigns have, predictably, helped reduce lung cancer in men almost every year since 1975.

  However, exposure to a carcinogen, even tobacco smoke, does not guarantee that someone will develop cancer. The number of exposures matters in this dynamic, as do factors like a person’s genetic makeup and the strength of his or her immune system. These complicating factors allow for both reasonable doubts and mischief-making by those who might profit from pointing out the fact that cause and effect is extremely hard to establish when you get down to individual cases. How could the general public square the fact that smoking caused cancer with the competing fact that most people who smoked died of something else? Certainly the tobacco companies made much of this disconnect. The industry-sponsored pseudoscientific research distorted the public’s understanding of the health effects of its products and hid research findings connecting smoking to cancer and other illnesses. This disinformation campaign would become the model for future efforts to obscure scientific agreement on many other issues, including climate change. Practitioners of this dark art would prevail.

  In the case of cancer, more confusion would arise as other compounds were linked to various forms of cancer in laboratory animals, and then skeptics pointed out that almost anything would make a lab rat sick if the exposure was great enough. The best-known example of this phenomenon involved the artificial sweetener cyclamate, which was banned as the result of animal studies that were subsequently refuted by more thoroughgoing research. In the mid-1970s, with researchers producing a torrent of new work, Newsweek posed the question “What Causes Cancer?” on its cover. The answer included a host of things, including medications, food, and many chemicals in our environment. Smoking was left out.

  If all the competing reports on the causes of cancer weren’t enough to make people throw up their hands in exasperation, then the ballyhoo that accompanied claims about various cures would be. Worst of all was the disappointment that came as hopes were dashed by those who, for various reasons, promoted, sold, and administered ineffective, unproven, and sometimes dangerous “treatments” to people with cancer. Here the one-word symbol would be a substance called Laetrile, which was derived from apricot pits and used, originally, as a meat preservative.

  Highly toxic (one of its compounds was cyanide), Laetrile had been tried as a cancer treatment in the Soviet Union. In 1972, a U.S. lab reported that it had inhibited secondary tumors in mice that already had cancer. Laetrile did nothing against the existing disease, and this hopeful finding was later proved to be in error. Nevertheless, news reports were enough to spark a huge controversy. Promoters, among them an orthodontist and a professional wrestler, skirted the law to give Laetrile to people with cancer. Their supporters, who believed that a conspiracy was afoot to deprive them of the chemical, lobbied successfully to make this treatment legal in more than two dozen states. A national poll found that despite the overwhelming opposition of physicians and scientists, a huge majority of Americans favored legalizing Laetrile as a cancer treatment.

  No reliable study ever found Laetrile to be effective against any human disease. Thousands of people who were injected with it suffered needlessly before the fad petered out. A New York Times editorial published at the time suggested that unrealistic expectations raised by “the Government’s War on cancer” had set the conditions for both the controversy and a “bitter divorce between the public and physicians.” As the legislators who legalized Laetrile against the overwhelming science demonstrated, trust in medicine had reached a low point. The paper also warned that “because of the continuing intractability of cancer, Laetrile will doubtless be resurrected in a new form” in the future.

  The challenge of understanding cancer, including its intractability, was highly compelling to idealistic young people who noted the attention it was receiving across the social spectrum, from the White House to the press to the families desperate for treatment. I was among them. Although I had headed off to college certain I would study the humanities, my experience in a handful of science classes rekindled my interest in medicine as practiced by Dr. Baldino: a fusion between science and humanism. Raised to believe I had a responsibility to serve others, I imagined working as a small-town physician would be a dream, and so I applied to medical school. There I discovered both the limitations of what medicine could offer to patients and, despite how much I had to learn, how little was really known about the workings of the body. The revolutionary ability to understand the body and diseases at the level of molecules, molecular biology, was just beginning. Figuring out how things work at a fundamental level, such as individual molecules and cells, was just electrifying. I didn’t think I had the ability to contribute at that level, but it was clear medicine would be transformed by it, and I wanted to be a part of making it happen.

  I knocked on the door of Adel Mahmoud, a fabulous physician and scientist, and an inspiring teacher. He was working on how a dreaded parasite, Schistosoma mansoni, could outwit the immune system and cause the devastating liver diseases he had seen growing up in Egypt. He welcomed my clumsy presence in his lab. I spent whatever hours I could steal from my classes and rotations in his lab mostly making a mess but loving the chance to connect with solving a real problem. Nothing was more compelling than discovering for the sake of relieving misery. It drives me to this day. I added nothing to the lab’s effort, I am sure, but it gave me a passion for trying to figure things out. Trying to understand a process to gain some dominion over it so that, just maybe, it could be tamed to help people I knew needed it.

  I left medical school for the postgraduate training program I thought was the most rigorously committed to using science for patient care in the country, the Brigham and Women’s Hospital at Harvard Medical School. It was tough, demanding, and unbelievably rewarding. Nothing was accepted on the basis of “because that is the way we do things.” People, from interns to the most senior faculty, were expected to defend their decisions based on either scientific study or logical deduction from what science could offer. It is now called evidence-based medicine and is a commonplace, but the Brigham stood out then as it does today for baking that into the culture and into every patient care discussion.

  One day, I got a call from my parents. My mother had advanced cancer. I was an intern and pretty frayed by the every-other- or every-third-night-on-call schedule. Thirty-six hours on, twelve off would now be considered torture. I was struggling to keep up with the patients under my care and still tie my shoes. My family was a cushion of comfort and stability I knew I could rely on. That was now gone. Not even the bright light of my mother was without jeopardy. I couldn’t take time off, but a friend told me of the hospital toll-free line so I could check in often. That nearly got me fired: it turns out toll-free was anything but. I finally go
t my mother to have surgery at the Brigham. It was wrenching to be there as family and intern, but at least I could stay close to what was unfolding.

  The paucity of options for my mother made my decision about training for me. I had to go into cancer care. But as I read more and got involved more, it seemed that clinical oncology research was largely focused on mixing and matching different combinations of poisons. There was a paucity of science beyond pharmacology. Hematology and the study of blood cancers were, in contrast, increasingly driven by the emerging field of molecular biology. Indeed, hematologists had almost invented what we now call precision medicine in blood banking and transplantation, where lab analysis of specific blood features could indicate compatibility or danger. In cancer, blood cancers were being recognized as distinctive because of specific genetic abnormalities. It seemed that figuring things out was closest to having an impact on people through the study of the blood, so I chose both hematology and oncology as my subspecialties within internal medicine.

  The choice of specialties was also affected by a sense that when confronting cancer, people are their neediest and their most authentic selves. It is a time when connection to others is intense, but real and simple kindness resonates long. The darkness of the diagnosis dissolves veneers while putting deep values in sharp relief. For patients, their loved ones, and my fellow caregivers, cancer largely sweeps away what distracts us so much of the time and reveals the very essence of what it means to be human. In this state, we are revealed, and in the vast majority of cases, what can be seen is inspiring.

  Given the options of science and medicine, I chose both. The decision led me to a forty-year devotion to the problem of cancer as it presents itself in our lives, in our laboratories, and, given its wider implications, in its social context. In this time, I have marveled at astounding advances in our understanding and felt intensely grateful to be working in this era of discovery. I have also been required, by experience, to accept that today’s promise is often tomorrow’s disappointment and that the processes that produce health and illness are incredibly complex. A telling example can be drawn from my own area of research. Where once we thought it was enough to know that our bone marrow is responsible for the production of blood cells, we now appreciate that the marrow and the adjoining cells engage in a complex dance that enables cell production. The niche that makes up this specialized environment wasn’t widely recognized until about 1980, and we are still learning about how it works.

  The complexity of different body systems helps to explain why laboratory advances and even experimental successes with animals do not necessarily translate into therapies for people with cancer. But we should not be discouraged by the fact that seeming leaps forward turn out to be smaller steps toward understanding. All the science that has gone before has brought us to a place where, as we develop more sophisticated understanding of disease, we can begin to imagine more sophisticated methods of treatment.

  Today’s research efforts bring together more teams comprising different kinds of scientists, including chemists, cell biologists, physicists, and engineers, than were ever seen in laboratories of old. Today, we even include experts in so-called big data analytics and information technology on our teams because these disciplines help us to understand profoundly complex systems and manage knowledge.

  The current state of science and medicine finds us tantalized by possibilities. Cancer therapies that rely on engineered viruses and immune cells improved in the laboratory have been successful in small trials. Research has produced vaccines that can prevent certain kinds of malignancies, such as cervical cancer and liver cancer, by creating immunity against so-called oncoviruses, including human papillomavirus and the hepatitis B virus. Others, which have been approved to treat metastatic prostate cancer and melanoma, appear to be effective against active disease. The genetic variety found in cancers suggests that we may never find a silver-bullet vaccine to stop all malignancies. However, rapid advances in the technology that sequences genes offer hope that custom-made immunotherapies could be within reach.

  More promise is coming from work on stem cells, including some of the projects in my own lab, and from investigations into the naturally occurring immune processes that keep mutations from developing into cancer. These and other developments, including technologies that allow for more precise surgery, radiation therapy, and chemotherapy agents, have yielded big headlines in the press. When a program such as 60 Minutes tells viewers about brain cancer cured with attenuated polio viruses, as it did in 2015, excitement ripples through entire communities of people concerned with cancer.

  Everyone hopes that we have arrived at a point where effective, less-toxic treatments and even cures for a host of cancers are at hand. Huge industries are emerging to support research into the treatments of the future, and the people who run clinical centers stress that they offer the very latest—custom-tailored treatment is the term of art—to patients who come seeking care. No one wants to miss out, and as a consequence, we are beginning to see a flood of advertising by hospitals and companies that make medical technologies. In New York City, you can even tune your radio to hear weekly hour-long broadcasts by a radiation oncologist who pitches his treatments as an effective therapy for patients who have been told by other doctors that they have no options.

  With so much talk about potential breakthroughs and so much publicity touting options for care, a bubble of expectation is ever present. The pressure of this bubble is felt by every person who has an interest in cancer, which means all of us. We live in a time when molecular science is moving at an extraordinary pace, revealing the innermost secrets of how the body works, and our discoveries are giving us good reason to hope. The people, places, and ideas that energize these hopes are exciting to behold. However, we must balance our hope with understanding, lest we become diverted from the course that will serve us best.

  ONE

  DAWN OF THE BIOLOGICAL AGE

  It says something that at many medical schools, a student’s first contact with a patient involves a cadaver in an anatomy lab. For most medical students, the dissection of a human body, one often shared with a partner or two, is a rite of passage that reveals the physical, emotional, and spiritual reality of medicine while shielding them from the more challenging task of facing a living, breathing human being in an examination room. As much as people talk about the challenge of this process, it is far more difficult to work with a patient who can feel the impact of what a physician may say or do.

  It also says something about my medical education, at Case Western Reserve University, that my first encounter with a patient was with a woman expecting a child. All students were introduced to an expectant mother with whom they were to interact and visit in medical settings and on house calls during their education. It was an incredibly powerful affirmation of what medicine is about and spoke legions about what the school valued and why I went there. Although respect and empathy are the expected norm in all cases, the cadaver model impresses a doctor in training with the facts of anatomy and, let’s face it, death. The Case approach, which sent entering med students to visit women at home, take their vital signs, and guide them through the process of obtaining prenatal care, emphasized life.

  My first patient, a woman Yvonne Anderson,1 lived in a tough neighborhood off Euclid Avenue in downtown Cleveland. She was single and younger than I was, but when we met, I was the nervous one. I was twenty-three years old and feeling acutely the extent to which I didn’t know medicine. But Yvonne sensed that she and I were learning the ropes of the medical system together and at least I might help by being inside it—something she certainly didn’t feel as an African American first-time mother. Maybe I could at least help Yvonne navigate the system and get the best care for herself and her soon-to-arrive baby.

  When I made my first home visit to Yvonne’s, it was an epiphany. I knew medicine would stretch my mind about science. I didn’t know how much it would open my eyes to cultures, the stuff for which ther
e was no section of books in the medical library. I was about as white bread as anyone could be and walked down Yvonne’s street for that first visit with my heart in my throat (medical term). All antennae were activated, as the neighborhood was not one I would have walked down even when in Paterson or New York. Shades were drawn on every window in every house, including hers. The doorbell didn’t work, and the lack of response from my knock had me ready to spin around and head for cover. Then the door opened, and Yvonne gave me a stern look and walked me through dark rooms to the kitchen, where I would be expected to perform before her skeptical mother. One ceiling bulb, four mismatched chairs, and a table were the setting for the interrogation. Short-cropped answers from them, too-long, overcomplicated verbiage storms from me, and then we actually had a conversation. I was so relieved when a first laugh seemed to signal détente. By the end, Yvonne was making it clear that it was the two of us who would work together and win over the mom, who knew she would end up taking care of everything anyway. She made clear she knew more about pregnancy and childbirth than I did, and I didn’t mind getting a real-world education from her. It worked out, and I did indeed learn a ton from the Andersons. They taught me that medicine always exists in a human context. That context impacts what people hear. White and black, side by side, hearing the same words from the obstetrician—we often had different interpretations. I wasn’t naive enough to think this wouldn’t happen, but I never expected how extensive it would be and how it could really affect the quality of care and health itself. There was so much suspicion about doctors’ motives and so little ability to pay for the nonprescription part of medical care that it was eye-opening. It was also hard to know without seeing up close the impact of the stress from poverty and the anxieties that come with living in an area that was so rife with crime that everyone kept the shades drawn to confuse would-be burglars. (It took me a while to figure out that safety was the reason that the Johnson home was so dark. In a crime-ridden neighborhood it was best to keep your business, and your posessions, out of view.) My thinking and my way of communicating with patients were forever changed by my experience with Yvonne.