A brief history of chemo

Chemotherapy drugs, above, were a long time coming.

You have a lot of time to think when you’re going through your first chemo cycle: sprawled on the couch, on the bed, in the chair. One of the things I’ve been thinking about is that if I had been born 100, or even 50, years ago I almost certainly would die of the aggressive little tumor that Dr. Hwang cut out of my left breast two months ago.

Before mammograms were standard and reasonably accurate, I wouldn’t have even known the tumor was there until it was big enough to feel, big enough to be truly dangerous. Only 10 or 20 years ago, it was not really possible to make an educated guess about how likely a tumor might be to spread and recur. So I might not get the aggressive treatment my little tumor turns out to merit.

And yet, today, everyone tells me my prognosis is very good. For that I need to thank the many friends who connected me to doctors, nurses and, not least, my amazing surgeon and oncologist at UCSF. But as I’ve been sitting around trying to be stoic about fatigue and nausea and diarrhea and a flush of cold sores and funny little red dots that seem to be spreading across my chest and belly, I keep coming back to this idea: The main reason that I’m likely to live to see my kid graduate from high school is that today there are systemic ways to treat my cancer: chemotherapy, monoclonal antibodies, hormones. It’s not just about cutting out the tumor any more, medicine has come up with more than 100 ways to seek out and destroy any remaining cancer cells that may still be on the loose in there.

This idea that cancer needs to be treated locally (surgery) and systemically (aforementioned 100 seek-and-destroy drugs) seems pretty obvious today, but it’s an idea that’s barely six decades old.

Old treatments for cancer don’t inspire much confidence. Ancient doctors mostly settled for treating symptoms and reducing pain. Written prescriptions nearly 4,000 years old survive from Sumeria, China, Persia and India. The first recorded incidence of cancer, on an Egyptian papyrus scroll from 2600 BCE, describes using a “fire drill” to treat breast cancer. Imagine pin-cushioning a woman’s breast with a hot poker. And the Egyptians knew this wasn’t a cure, but just a way to slow down the disease. If I was an ancient Egyptian woman, I think I would pass. If you’re going to die anyway, why get tortured first?

The Romans used clover in cancer treatments

The Romans used ginger root to treat skin cancer. That sounds less horrible. Other physicians in classical times also treated tumors with red clover and autumn crocus. The Tibetans and the Chinese prescribed dietary restriction and herbs like licorice and ginseng to treat cancer. But cure or remission? I don’t think those were part of the discussion.

Part of the problem was that doctors really had no earthly idea what caused cancer, a disease that’s really about scrambled DNA that makes cells go haywire. The double helix, of course, did not figure in the philosophy of Hippocrates, who believed the body was made of four “humors;” blood, phlegm, black bile and yellow bile. In the West, the leading theory for more than 1,300 years was that cancer resulted from an excess of black bile.

Paracelcus was one of the first to posit that chemicals could cause, and cure, disease.

It wasn’t until the Renaissance, that doctors began to make some progress. Paracelcus, a student of alchemy, metallurgy and chemistry at the University of Basel in the early 1500s, suggested that chemicals caused many diseases, including cancer, and people could only be restored to health with chemicals. He is credited with introducing many elements and compounds as internal remedies including mercury, lead, sulphur, iron, zinc, copper, arsenic, iodine, and potassium. Alas, his maverick idea that cancer could be cured by chemicals in increasing doses did not gain traction, although metals did begin to be included in cancer remedies.

At about the same time, the religious barriers to autopsy began to fall. Medical autopsies let to greater anatomical understanding as doctors discovered the blood and lymph systems and posited that abnormalities in the lymph system led to cancer. Doctors also wondered if parasites, injury or “chronic irritation” might cause cancer. They also theorized that tumors that hadn’t yet invaded other organs might be treated with surgery.

But again, surgery was like a hail-Mary pass. As late as 1791, Motherby’s Medical Dictionary stated, “If a cancer cannot be cured by the knife, any remaining treatments would only be palliative.” That is, they would only slow the disease or decrease pain, not provide a cure. Some of the various anti-cancer remedies included solutions of alkali such as camphor, chalk, gold, silver, and salts of lead. This was thought to correct the accumulation of malignant acids. One prescription consisted of crab’s eye (1 scruple), red coral (1 scruple), salt of tartar (15 grains), oils of cloves (12 drops), oil of cumin (12 drops), and opium (5 grains). For cancerous ulcers of the womb a woman might be injected with a decoction of hemlock, arsenic, opium, gentian of roses, and carrot. The carrot helped to counteract the nauseating odor of the tumor. My goodness, I’m glad to live in 2010.

Cancer cells as drawn by pathology pioneer Rudolf Virchow

Finally, in the 19th century, scientists began to make some progress that would lay the foundation for chemotherapy. First of all, modern microscopes led to the discovery of the cell. Then, in 1838, Johannes Muller, a German pathologist, demonstrated that cancer was made of cells, not lymph. Muller’s student, Rudolf Virchow, then proved that cancer cells derived from healthy cells, rather than from impurities, parsites or injury. Virchow became known as the father of cellular pathology. At the same time, scientists like Louis Pasteur began to make quantum leaps in understanding bacteriology, leading to the “germ theory of disease,” i.e. that bacteria and viruses can cause illness. This laid the groundwork for the idea of systemic treatments.

The word “chemotherapy” was coined in the early 1900s by the famous German chemist Paul Erlich, who used the term to describe chemical agents that killed disease-causing microbes. Erlich also proved the validity of using animal models to study possible treatments for human diseases. This idea would later be key to developing the first cancer chemotherapy.

Cancer chemotherapy owes its discovery to war. During World War I, doctors noticed that nitrogen mustard gas, the dreaded weapon of that conflict, destroyed lymphatic tissue and bone marrow. Scientists noticed the relationship, but didn’t do much about it. A few researchers observed that topical application of nitrogen mustard, derived from the sulfa mustard used in battle, caused tumors in mice to regress. But again, no one did much about the idea. Devising animal models for human diseases had not yet become the standard.

In 1942, in the heat of World War II, the US government’s Office of Scientific Research and Development engaged several top universities to study chemical weapons. Two young Yale professors of pharmacology, Alfred Gilman and Louis Goodman, began to intensively study the effect of nitrogen mustard on lymphoma, doing more experiments on mice and then on rabbits. The results all showed dramatic regression of the lymphoma. Later that year a Yale professor of surgery referred a 48-year-old silversmith in the terminal stages of lymphosarcoma to the Goodman-Gilman team. Since his case seemed hopeless, the patient was offered experimental therapy with nitrogen mustard.

No one had any idea how much to give him, so beginning in December 1942, the dying man received a tenth of a milligram for every kilogram of body weight, roughly 2.5 times what is now the standard dose. One can only imagine the nausea, vomiting and mouth sores the man endured. But after 10 consecutive doses, the man’s tumors had completely disappeared. Alas, he relapsed a month later, but the results were encouraging enough to merit more testing. Eventually, 67 patients at Yale, University of Chicago and what was then the Sloan-Kettering Institute at Memorial Hospital in New York, would participate in this first clinical trial, which remained a military secret.

Not even caregivers knew of the breakthrough. The orders read, “compound X given intravenously.” By 1943, the team responsible for the first successful clinical trial of cancer chemotherapy had disbanded. Goodman moved to Salt Lake City; Gilman entered the Army.

That same year, the Germans sent a squadron to bomb Bari, Italy. During the attack, explosives hit the SS John Harvey, a ship secretly carrying mustard gas bombs. Because of the horrors of WWI, the Versailles Peace Treaty that ended that war had banned the use of chemical weapons. So when more than 1,000 people died from exposure to a mustard gas spill, it obviously became a state secret.

The army quietly sent doctors to investigate the aftermath. During autopsies of the victims, the medical team observed signs that the mustard gas had severely suppressed the victims’ lymph systems and blood-cell producing bone marrow. Since these types of cells tend to divide quickly, the team suggested that perhaps mustard gas could be used to suppress the division of certain types of cancer cells, also quick-dividing. Cells that don’t divide, die. So this might create a new way to kill cancer cells, the Army report suggested, other than surgery and radiation that were the mainstays of treatment at the time. Again, wartime censorship delayed public knowledge of this insight confirming the Goodman-Gilman work at Yale.

Once the war ended in 1945, medical researchers could publish the results of the first cancer chemotherapy treatments. This created a ferment about how to deliver mustard gas to cancer patients without killing them. Chemotherapy immediately inspired great hopes and great skepticism. The idea that drugs might cure patients with cancer offered a solution to a problem that had stymied doctors for milennia. Yet the reality that remissions were often brief and incomplete gave the doubters data to support their arguments that the approach was not proven and that the horrible side effects were worse than the disease the drugs were supposed to cure. But the work continued and in 1949, the FDA approved the first cancer chemotherapy agent, mechlorethamine, or “Mustargen.” The age of modern chemotherapy had begun.

The chemo comes a drop at a time.

Chemotherapy remains controversial. With the rise of targeted drugs like the Herceptin I’m taking, some posit that chemotherapy may go the way of the buggy whip. This is the argument: Why use chemotherapy which is like a shotgun destroying all in its path, when you could use a “magic bullet” from a finely made, accurate rifle? Others say chemotherapy drugs, of which there are now scores, ARE targeted therapy and will be with us for a long time to come.

As for me, while I’m not thrilled about the nausea and immune system side effects, I’m glad I’ve got chemo.

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About leftbreast

I have had breast cancer. I was diagnosed at 47, and am now 49. I have finished "active treatment," two surgeries, chemo, radiation, monoclonal antibodies. These days, I only take a drug to suppress my uptake of estrogen, since my tumor was highly reactive to that hormone. I have been married to my husband Pete for 21 years. I have a stepdaughter, Maureen, 30, and a daughter, Erin, 10. I've been a freelance magazine journalist for 20-plus years, covering everything from Chinese foreign policy to Catholic nuns to endangered species. I have had a great life. I have lived in Asia and all over the United States. I have spent nights with tree-sitters in Oregon and with astronomers at the Mauna Kea observatory in Hawaii. I've been to a cocktail party on the poopdeck of a British destroyer docked in Shanghai. I've taken the bus to Tibet, and tramped through the cloud forests of Panama with biologists. A magazine sent me on a raft trip down the Colorado through the Grand Canyon; another sent me to cooking school for a week. I have spent time with celebrities, presidents and heroin dealers. I love my work. I have a loving, supportive family and more friends than I probably deserve. I have had the space and time to camp, ski, cycle, garden, cook and spoil my pets (an Australian shepherd, a German shepherd and a tabby cat). If it all ended tomorrow, I would have to say that it has been a really, really good ride. When I was in thick of treatment, I was simply fighting for more time. Now, I'm trying to connect the experience of cancer with the rest of my life, with the time that's been won. I hope the cancer never comes back, but if it does, I'll be ready. That's what this blog is about.
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One Response to A brief history of chemo

  1. As always Heather, this is fascinating. I had no idea of the connection of chemo to the mustard gas of WWI.

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