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By Keith Collins May 4, 2013

This is a story about ups and downs. Sitting on a plastic bed in the in-patient/out-patient wing of the Weinberg Cancer Center at Johns Hopkins with an IV connected to a catheter that had been implanted in my chest, things were looking up. It was 2008 and I was 28 years old, and due to a recent battery of high-dose chemotherapy that had left me with maybe one white blood cell, which I’d named Melvin, I had to wear one of those surgeon’s masks at all times to keep the world’s germs out of my face. Here I was, if you can imagine, bald and eyebrowless, with a paper mask over my mouth, a tube coming out of my chest, the picture of cancer, and things were looking up. Scans showed that the cancer (along with just about every other cell in my body) was disappearing.

Months earlier, oncologists at the University of Pennsylvania and Memorial Sloan-Kettering had urged me to undergo a bone marrow transplant. This is the standard treatment for someone in the position I was in, they said; this is what people with advanced Hodgkin’s lymphoma do when the first line of treatment fails, when the cancer returns after a brief remission. Despite the damage a bone marrow transplant can do to a body, this is the method that has worked for many who came before me. They take stem cells out of your body, put them in a freezer, fill you up with chemotherapy, then put the stem cells back in. What I can tell you about the procedure to access your bone marrow is that someone cranks a thick needle—literally cranks it—into your bone at the back of your hip. The first time they dug into mine for a biopsy, I screamed and cursed for half an hour.

And so my mother Googled. For days on end, she didn’t eat or sleep. She Googled in pursuit of something better, more advanced, more indicative of a civilization that refuses to let sons die. The leaps and bounds in medical research that hit the front pages of newspapers every week seem to elude you when you actually need them. Eventually, my mother found someone at MD Anderson who was conducting a clinical trial and got the doctor on the phone. She told my mother the trial was over, though, and to just go forward with the transplant. My mother pushed until the woman relented and said, almost in a whisper, to look into Johns Hopkins. My mother said she felt like she was doing a drug deal. In fact, she was.

There was more Googling, I believe, my mother becoming an expert in my condition, reading scientific research papers, reading everything coming out of Johns Hopkins oncology. At the bottom of one paper, she found a name and an email address. A week later, we were in Baltimore, and a doctor was drawing a diagram of a B-cell on a piece of notebook paper. He had just finished recruiting for a clinical trial that involved high doses of chemotherapy, a sort of cancer vaccine, and something called monoclonal antibodies–a form of immunotherapy. He was willing to take me into the clinical trial even though they had finished recruiting.

He said: Half the time, bone marrow transplants don’t work.

He said: If the first transplant fails, you have to get bone marrow from a donor and try again.

He said: If the second transplant fails, treatment options become very limited.

If I did the trial and it didn’t work, I’d be back to where I started, with a 50 percent chance of living and two potential transplants ahead. If I opted to go directly to the transplant and it didn’t work, I’d have less than a 50 percent chance of surviving and only one treatment option remaining. The doctor pointed at the cancerous B-cell he’d drawn and explained how monoclonal antibodies would attack it. B-cells are a type of white blood cell that happen to become malignant in my type of lymphoma. The antibodies would find and latch onto the proteins that cover B-cells; the presence of the monoclonals would signal other cells in my immune system to attack. This approach would be combined with a chemo carpet bomb. The idea was to find every microscopic bit of cancer in me and kill, kill, kill.

The choice was clear.

Now, as I sat on a plastic bed at Johns Hopkins, a liquid monoclonal antibody army hovered beside me in a plastic bag. A line led from the bag to my chest and into an artery, allowing the army to enter. It was an army that was built over a century of research, of breakthrough insights and false steps, of ups and downs. It started in Berlin in 1890 when a physiologist named Emil Behring injected a mouse with the blood of a guinea pig.

Behring was doing this work in search of a way to fight infections, not cancer. The guinea pig he’d taken the blood from had just recovered from diphtheria, an infectious disease caused by bacteria. He infected the mouse with diphtheria, then gave it the guinea pig’s blood, and the mouse was cured. In fact, the mouse was now immune to the disease.

In 1975, two immunologists at the Medical Research Council in Cambridge, England, developed the first method to produce monoclonal antibodies. You inject a mouse with an antigen, something its immune system will interpret as a danger. The immune system produces an antibody. You isolate the antibody. You fuse it with constantly replicating cells. You inject it into humans.

In the 1980s, monoclonal antibodies were going to be the “magic bullet” that could cure cancer. In trials on mice, it killed cancer time and time again. But the treatment failed in clinical trials, and people got even sicker. It was because the antibodies themselves were of mice—the human immune system saw them as enemies and reacted badly. Most scientists abandoned monoclonal research. All but a few. It wasn’t until 1988 that progress was made: a biochemist named Greg Winter at the Medical Research Council developed methods to humanize monoclonal antibodies, making them more compatible with human biology. This led to the invention of rituximab–the monoclonal antibody that would be used in my clinical trial. It was approved by the Food and Drug Administration in 1997.

This cycle of hype and abandonment isn’t uncommon in experimental cancer treatments. Someone cures cancer in mice, enthusiasm builds, but then the treatment fails in human trials. Everyone cuts their losses and moves on to something else. A decade before the ebb and flow of monoclonal antibodies, another immunotherapy drug called interferon went through its own cycle. This was a drug that was made from proteins released by white blood cells. There was big hype around it all through the seventies—interferon was that decade’s magic bullet. It, too, shrank tumors in mice. And it, too, produced poor results human trials.

So when a doctor named James Allison began pursuing immunotherapy research in the late ’70s and early ’80s, people reportedly told him to stop. After interferon, interest in the idea that the immune system alone could be used to attack cancer cells was in decline; Allison had entered this field of research in its period of abandonment. I called him recently to ask why this pattern continues to emerge, why the ups and downs are so stark and so frequent.

“That’s the nature of science,” he said. “It’s not a linear progression; it’s like a tree, and most limbs snap off.”

Allison’s focus was on T-cells, which are another type of white blood cell. But unlike B-cells, T-cells don’t become malignant. Instead, they simply fail to recognize that cancer is present around them, and largely go about their business as if their host were not dying. Allison’s aim was to manipulate the T-cells—to get them to recognize cancer as a threat and start attacking. In the mid 1990s, Allison’s lab at the University of Texas discovered antibodies that could manipulate the T-cells and prompt them to act. They began testing it on mice, and the treatment was shrinking tumors left and right. In 2004, two drug companies agreed to fund a clinical trial.

The patients treated with the T-cell approach were evaluated after 12 weeks. For the most part, their tumors had only gotten bigger.

The first phase of my clinical trial at Johns Hopkins was ICE chemotherapy. ICE is a combination of three chemo drugs: ifosfamide, carboplatin, etoposide. The first time I walked into the chemo lounge at the hospital, the head nurse, Jane, told me to go ahead and pick a recliner or day bed. The recliners were scattered around the large room; the day beds were by the windows. I was used to the cancer center at the University of Pennsylvania, where I had been treated a year earlier before going into my brief remission. At Penn, I got a private room for my chemo treatments. Now, as Jane asked me to pick a place to get my poison, I looked around the open room and froze. I just froze.

“I hate it here,” I said.

“Well, you can leave,” Jane replied. “You can get treated wherever you want.”

And I loved her instantly. The world needs to know about nurses who deal in chemotherapy. The depth of their compassion extends beyond understanding; they know the sick better than they know themselves. They know the patients who come in on sympathy overload, or the ones who feign a positive attitude, or the ones who have made peace with their fate. They know the powerlessness of the man who walks into their cathedral and says that he hates it.

I chose a day bed.

For nine weeks I came to this place, once every three weeks for three days at a time. They’d insert the IV needle into my hand or my arm, and I’d sit back and take it in. Compared with what would come, ICE was pretty tolerable. It came with a bit of queasiness, and a bit of what we call “chemo brain,” where books and television become too difficult to process.

After the nine weeks of ICE, I went into another remission, but my treatment wasn’t finished. Now it was time to kill, kill, kill. I was soon given my first dose of rituximab. I felt nothing as a result. It might as well have been aspirin. But then there was the cytoxan—the most potent and toxic chemotherapy drug I’d ever take on. Cytoxan is a fucking chemical weapon. They pumped it into me for 12 hours a day, five days straight. When I try to access the memory of that week, all I see is grey. My mother tells me I slept most of the time and refused food. When I had to eat, I cringed with every bite.

Let me tell you about how mustard gas became the cancer treatment we call chemotherapy. In 1943, President Roosevelt had ordered mass production of chemical weapons after being led to believe that the Axis was doing the same. The idea was to assure mutual destruction in the event that it was used, of course. And so when a U.S. merchant ship was attacked and destroyed in the Adriatic Sea near Bari, Italy, it happened to be carrying 100 tons of mustard gas. It spilled into the harbor and into the town.

Just about everyone on the ship died in the attack, including everyone who knew what the ship’s cargo was. A chemical warfare expert named Stewart Alexander was sent to investigate what happened in Bari, and quickly figured out it was mustard gas. He did autopsies of hundreds of victims, noticed that their white blood cells were all but gone, wondered if nitrogen mustard could have the same effect on cancer cells, and you can guess at the rest.

A year prior to all of this, two Yale pharmacologists who were working in secrecy for the War Department treated lymphoma-riddled mice with Mustargen, and also found that it targeted rapidly-dividing cells. This, combined with Alexander’s findings, led to the use of nitrogen mustard to treat cancer. Mustargen itself was still part of the standard treatment of Hodgkin’s just a few years before I was diagnosed.

Cytoxan is a nitrogen mustard alkylating agent.

It was a few weeks after the cytoxan that I sat on the bed at the in-patient/out-patient wing of the Weinberg Cancer Center at Johns Hopkins with an IV connected to a catheter that had been implanted in my chest, and things were looking up. Much of me was gone, including my hair and my immune system, but things were looking up because I saw those who’d gone through the bone marrow transplant I’d avoided. Their bodies had been ravaged in ways that mine had not. Among the ones who’d received the last line of treatment — the donor transplant — some contracted graft-versus-host disease. It’s a wretched condition in which the immune system sees the rest of the body’s cells as foreign and begins to attack. The body destroys itself from within.

Things were looking up for me because, over the past century, researchers had risked their careers to find new ways to treat cancer. A drug that began as mustard gas may have been the reason I lived, sure, but a drug that began as mouse blood gave me an extra option. And neither would exist if scientists hadn’t pursued wild ideas, and I’d be sitting in a hospital with less than a 50 percent chance of living and only one possible treatment remaining.

Several months after Dr. James Allison’s T-cell trial had failed, something happened. The tumors within the patients treated in the trial stopped growing and, in some cases, began to shrink. Allison’s antibody, the one that manipulates the T-cells into action, was approved to treat melanoma by the FDA in 2011. Nature published a positive review of the drug that year, and Dr. Jerome Groopman wrote about Allison’s success in an article for The New Yorker in 2012. Allison had brought the immune system approach out of its period of abandonment and into resurgence.

“When you evaluate things, you’ve got to be careful to understand their mechanism,” he said when we spoke. “So if you’re evaluating a drug that’s supposed to directly kill tumor cells, there can’t be any tumors that get bigger because if they do, that means the drug’s not working.”

That is, in order to test immunotherapy, you have to understand immunotherapy.

“With drugs that target the immune system,” Allison continued, “they don’t do anything with the tumor cells. They’re trying to regulate and keep the immune response from stopping. The bottom line is, that can take some time. If you use the same standards that were used for cytotoxic to evaluate immune therapies, you miss a lot of people that have benefited. So if you don’t pay attention to that, you’ll kill the drug, because the trials weren’t designed with enough insight into the mechanisms. Things can fail for the wrong reasons.”

James Allison is now the chair of the Department of Immunology at MD Anderson.

At the beginning of 2013, four years after going back into remission, I made my annual trip to Johns Hopkins for a checkup. I was there to see if my remission had persisted. I went into phlebotomy to have some blood drawn, and I saw Jane, the nurse who had told me I could leave chemotherapy if I wanted to. We hugged and caught up, and she made fun of me for my behavior when we first met, as she always does. Then I went for a CT scan, then waited in a checkup room to see my doctor. At the four-year mark, having no signs of cancer would be a very good sign. After five years of remission from Hodgkin’s lymphoma, patients are considered cured.

My doctor – the same one who had drawn me a picture of a B-cell four years earlier – walked in and told me I was all clear. I asked him a question I’d been considering all day. If I had done the ICE and the cytoxan without any rituximab, would we have gotten the same results?

“You know, we just don’t know,” he said. He also told me that the clinical trial was successful, which I took to mean that the majority of participants have remained in remission. In the very specific case of treating patients like me – who have relapsed with advanced Hodgkin’s lymphoma – doctors are still learning about the effects of rituximab. However, the drug has become a standard treatment in early stage non-Hodgkin lymphoma.

I told my doctor that I was writing this story, and he told me about a drug called thalidomide. In the 1950s, it was used as anti-nausea medication for pregnant women. It was withdrawn from the market in 1962, after it was discovered that it caused birth defects. Later, in 1964, a biologist named Jacob Sheskin was treating a patient who was critically ill with leprosy. Looking for something to get the patient through the night, Sheskin found some thalidomide.

“He wasn’t even supposed to have it,” my doctor told me.

Sheskin administered the drug anyway and found that it did more for the patient than relieve his nausea—it improved his other symptoms as well. The drug soon went into clinical trials for leprosy and produced favorable results. Then, in 1994, a doctor named Robert D’Amato at Boston Children’s Hospital discovered that thalidomide could actually shrink tumors. Today, it’s commonly used to treat multiple myeloma.

“And it actually works,” my doctor said. “It’s one of the hottest cancer treatments out there right now.”