In 2018, nearly 10 million cancer patients worldwide required chemotherapy. As one of the four major classes of cancer treatments, it’s been responsible for protecting and treating patients for over 70 years. But it has actually been around for quite a bit longer than that; it just wasn’t used to treat cancer. Chemotherapy was pioneered well over 100 years ago, in the late 1800s, but back then, it wasn’t the same chemotherapy we use today. When it was first developed, it was intended to treat infectious diseases. There were some instances of it being used on cancer models, but nothing serious. It wasn’t until post-World War II that the field shifted to cancer. But it turns out… it wasn’t even on purpose.

Some of our most famous inventions have actually been accidents — or at least unintentional. The most famous example of this is probably the discovery of penicillin. Penicillin is arguably the most commonly used antibiotic, but it was discovered by accident by Scottish scientist and physician Alexander Fleming. At the time, he was researching bacteria, but left one of his Petri dishes uncovered on a windowsill. It was quickly contaminated with a mould. He noticed that the bacteria on the dish didn’t grow next to the mould colonies, and from this came the discovery of penicillin. There are a handful of other unintentional discoveries or inventions, like the microwave, chocolate chip cookies, X-rays and, in a sense, chemotherapy.

Although chemotherapy was invented intentionally to fight infectious diseases, its use in cancer is rather fortuitous. During World War II, chemical gases, like mustard gas, were used as weapons. In 1943, an Allied harbour in Italy was bombed. One of the ships destroyed was carrying precarious cargo: mustard gas. This led to a cloud of mustard gas being released and troops being accidentally exposed to mustard gas. The scientists and physicians who looked at those exposed to the gas found depleted bone marrow and lymph nodes.

This was the first example of chemotherapy being successfully used to treat cancer patients. So I guess it wasn’t as happy an accident as chocolate chip cookies… it was a not-so-happy accident, but still very useful.

Luckily, no. When it was first introduced, we had very little understanding of how it worked. Many chemotherapies kill cancer by binding to and damaging its DNA in some way. When a cell’s DNA is too damaged, beyond repair, they die. But scientists at the time didn’t know that.

In the early days, chemotherapy was tested on animal tumour models. They took a panel of drugs, without really knowing how they worked, and tried treating the animals. They just happened to find some compounds that were really good at killing cancer. This era of drug innovation was called the “Cytotoxic Era” of drug development. “Cytotoxic” quite literally means toxic to cells - the drugs discovered in this era just killed cells in one way or another.

Because we have more knowledge and more advanced technology, we can use that to our advantage when developing chemotherapies. With mustard gas, there was some testing done with the original compound, but it was far too toxic to use in patients. Because of that, chemists modified the compound to make it less reactive. That made it safe enough to be used in patients to kill cancer, while limiting side effects.

Nowadays, drug development is an entirely different game. Now that we know how chemotherapy works and more about how cancer works, we can design drugs with specific targets. Then, once designed, chemotherapies undergo rigorous testing and examination before they ever touch a person. One of the most powerful advancements that we’ve seen is the combination of treatment approaches. Antibodies fall under biological therapies. They’re molecules, made in our cells, that can recognize and bind specific targets. A major issue with chemotherapeutics is that they’re not specific to cancer, and they unintentionally damage healthy cells. By combining chemotherapy with biological therapies, we can deliver drugs right to cancer’s front door, hopefully avoiding as many side effects as possible. This is still an evolving field, but it’s a promising avenue for more effective drug delivery.

Accidental discoveries have been some of the most important throughout our history. Penicillin has saved countless lives, and chocolate chip cookies probably have too… But not all accidents were as happy. Chemical warfare is a gruesome topic, but it led to the eventual discovery of chemotherapy. And although chemotherapy has roots long before World War II, that’s where it really started to be used to treat cancer. Since then, it has remained a frontline treatment, administered to millions of cancer patients every single year. Luckily, advances in cancer research mean we’re no longer forced to put mustard gas in patients. Instead, we have specifically designed and rigorously tested drugs. A not-so-happy accident turned out to be one of the most influential discoveries for cancer treatment, and we continue to improve on it every single day.

I hope you learned a little something this week, but next week we’re taking a well-deserved rest from therapeutics to discuss the role of sleep in cancer.

See you next week!

If you missed last week’s letter, you can read “Cancer-Killing Power Tools” to learn a little more about molecular jackhammers.