You’re listening to Consilience, a podcast from The Scientist. I’m Ben Henry. This month, we’re talking cancer. First, the story of why some people think burnt toast will give you cancer. And second, the man who turned folk medicine into modern cancer treatments.

“It was in September in '97, when they found paralyzed cows...and they found dead fish in the fish culture.”

That’s Margareta Tornqvist. The grim scene she’s describing was discovered near a construction site in Sweden, where a tunnel was being dug for a railroad When railway company executives heard about these mysteriously afflicted animals, they were concerned that they might be to blame.

That’s when they called Tornqvist, a chemist at Stockholm University who studies pollutants.

My colleague Diana Kwon spoke to Tornqvist for a story in the April issue of The Scientist.

“We were contacted, or I was contacted from this railway company—if...

Acrylamide was the chemical that the company thought might have leaked out of the construction site and into the water supply. Here’s what had happened. While they were building the tunnel, water began to trickle in through cracks in the tunnel walls. Workers sealed up those cracks using an industrial-grade sealant, basically, liquid rubber—but one of the key ingredients in that sealant was this chemical, acrylamide.

See “Cooking Up Cancer?

At the time, not a whole lot was known about acrylamide other than that it could be toxic to humans and potentially cause cancer at very high concentrations.

The railway company shut down the project while Tornqvist and her colleagues got to work. They found high levels of acrylamide in the cows and the fish that had been affected. They also found acrylamide in the blood of the tunnel workers. However, since the workers had been exposed for only a short time, Tornqvist concluded they were not at a serious cancer risk.

“That was a message we could give to them, and that calmed down the situation.”

But something else was wrong. In order to figure out how much acrylamide the tunnel workers had been exposed to, Tornqvist compared their blood samples with a control group of healthy people, people who had been nowhere near the tunnel. Those people also had acrylamide in their blood. Not as much as the tunnel workers, but still an unexpectedly high background level of this potentially dangerous chemical.

“We saw that this risk was definitely not acceptable—it was higher than what we judged is acceptable.”

That’s when the focus of her research shifted. Where was all of this background acrylamide coming from, and how dangerous was it?

Earlier studies in rats hinted that one origin of acrylamide could be fried foods. Tornqvist was able to confirm this—particularly, she found acrylamide in foods made from fried potatoes. That includes: potato chips, hash browns, french fries.

“That was very problematic when we had this finding, and what should we do with it?”

Word got out, and the headlines of course wrote themselves. Potato chips cause cancer. In reality, the actual risk posed by low levels of acrylamide was still unclear. But everyone was talking about it now. And the pressure was on for science to come up with some answers.

That’s where Don Mottram came in.

“We came into it right at the beginning, when this article appeared in all the newspapers from the Swedish group, which, of course, took all of us by surprise.”

Mottram, who’s a professor at the University of Reading, would become a leading a researcher in the chemistry of acrylamide. He also spoke with Diana for her story.

“My interests were how is flavor formed during the cooking of food. So immediately I started to think, first of all, why had I never seen this compound, acrylamide, if I had been spending a lot of time looking at what was in food—in cooked foods.”

Turns out, acrylamide is difficult to extract from food samples for laboratory analysis. Most previous studies had just missed it. Nobody really knew what acrylamide was or how it was formed. Until Mottram started working with a chemist named Bronislaw Wedzicha.

“He was examining our degree course at the University of Reading, and he came down for that and we went out for dinner with everybody else who were all the other examiners. We spent the whole evening sat at a table, it was a paper tablecloth, trying to work out where this acrylamide had come from. It bored our colleagues to tears, but we came up pretty quickly with an idea.”

They wanted to make acrylamide, but they had to guess at the ingredients. Imagine trying to bake a pie without a recipe, just a photo of the pie. That evening, the two scientists came up with an educated guess about the ingredients, and decided they would put them together using a chemical reaction that Mottram had been studying.

Those ingredients they had scribbled on the tablecloth at dinner were exactly right. They mixed the amino acid asparagine with sugar in a test tube, and heated it. They got acrylamide.

Here’s what they learned from this breakthrough. The chemical reaction that gives potato chips their toasty, addictive flavor during cooking is the same reaction that makes acrylamide as a byproduct. It’s called the Maillard reaction.

“You see, the Maillard reaction gives us flavor as well as color. Now, if you try and inhibit the Maillard reaction to prevent acrylamide, you’ll also prevent flavor and color.”

The more you cook a potato chip, or nearly any carb-rich toasted food, the more acrylamide you get.

“As an aside, I did say rather flippantly to the potato industry, I can solve your acrylamide problem overnight. Only boil potatoes, don’t fry them or bake them.”

Obviously, that wasn’t going to happen. We’d rather take our chances with acrylamide than live without potato chips. So instead, the industry just decided to fry their potatoes a bit less. Rather than cooking them to a rich brown, potato chip manufacturers left their snacks lightly colored and softer, and they’re still that way today.

“They realized that by varying their processing conditions, they could keep the level of acrylamide low. And there’s good evidence in the literature now to show that this has happened.”

So, mission accomplished. Right? Here’s the thing. Even though acrylamide became a public health scandal, the evidence that it really is harmful at low doses from food—never materialized. Specifically, the claim that acrylamide in food can increase cancer risk was intensely investigated. And so far, the answer seems to be—no.

“There is no direct evidence that acrylamide is carcinogenic to humans.”

Burnt toast, crispy hash browns, crunchy potato chips—they’ve all been wrapped up in what appears to be an urban legend.

Some better studies in the future might turn up a link between acrylamide and cancer. For now, potato chips still aren’t good for you, but it’s not the acrylamide to blame.

The second half of this episode isn’t about what causes cancer, but what cures it. There’s a fundamental problem in cancer research: The disease takes countless forms, so it has countless possible cures.

Even during the early days of cancer research, back in the 1930s, scientists were already thinking up ways to streamline the search for therapies. A man named Jonathan Hartwell had an idea. Hartwell was a chemist, but he was deeply interested in folk medicine—cures and remedies from the eras preceding modern science. What if early forays into treating tumors with natural medicines had been successful? Nobody had ever bothered to do a comprehensive, systematic search to find out.

So that’s what Hartwell did. He and some colleagues spent years poring over archival text for mention of tumor treatments. I spoke to someone who works in this same field one generation after Hartwell, James Graham, an assistant professor at the University of Illinois at Chicago.

“A significant amount of the literature that he’d looked at was what we call the ancient literature of Greek and Rome. . . In Greece we’re talking Plato and Dioscorides. . . You can go even further back into really ancient medicine—so there’s Chinese medicine 2,000, 3,000 years old.”

Hartwell read everything from Vedic scriptures to Renaissance texts.

“So, what he was looking for was indications of some type of cytotoxicity.”

Meaning, some indication that a plant or natural substance kills human cells. That’s the principle behind chemotherapy, to douse tumor cells in a toxic chemical until the tumor is gone.

So, how do you go about extracting scientific information from ancient history?

“I mean, you have to be very careful. . . . Of course, cancer is sort of cryptic, in a way. . . . The person that has the problem with it can feel it, but someone that may be treating them, you can’t see something inside of someone’s stomach. So sort of the symptomatology of cancer itself is a little bit problematic.”

In addition, medical information can be literally lost in translation. Words that refer to a tumor might also refer to other, symptomatically similar ailments.

“A lot of folk cultures have names of diseases that have nothing to do with our concepts.”

So this approach is not just tedious but prone to mistakes, which begs the question: Is it really worth it? After all, Hartwell had all of modern science at his disposal, so why rely on older, less sophisticated therapies? Well, Graham argues we should not underestimate our medical forerunners.

“As researchers, we need to be very honest about the limitations of what we’re undertaking. On the flip side, you have these thousands of years of human experience.”

See “A History of Screening for Natural Products to Fight Cancer

That’s a lot of time for trial and error. Plants with traditional uses were intriguing because somebody at some point thought they were not just safe but useful. Hartwell still needed to put them to the test using modern methods, and that meant acquiring some highly obscure plants.

“It might end up being a really great lead, but if you can’t access the specimen, you’re not going to be able to follow through on it.”

When Hartwell was hired by the US government to study natural products with potential cancer-fighting uses, he circulated a letter to universities around the country. He asked researchers to send him the plant extracts that they had gathered from all around the world. He even brokered a deal with the US Department of Agriculture to acquire specimens from them.

“They were screening thousands upon thousands of specimens.”

Not all those specimens were mentioned in the folk literature, some were just plants that people suspected might have medicinal properties. After a while, people knew that Hartwell was the guy to send your plants to if you wanted them screened for anticancer properties.

Hartwell kept this up for decades, keeping track of everything he knew about each plant on index cards.

The labor-intensive approach led to the development of numerous drugs. Two cancer drugs used today, for example, are synthetic versions of a chemical found in the happy tree—a plant used in traditional Chinese medicine as a tumor treatment—which Hartwell’s group had screened.

Toward the end of his life, Hartwell collected his thousands of index cards and published them in a book called Plants Used Against Cancer. The work was his magnum opus, and remains today one of the single largest repositories of information on medicinal plants.

That work, though, is not over. James Graham runs NAPRALERT, an online database of natural products and their medicinal values. He also works as an ethnobiologist in Peru, documenting the medical knowledge that’s passed between generations by word of mouth. Oral traditions are living entities, not archived texts, rich with knowledge but vulnerable to change. Graham believes we still have much to learn from folkloric medicine, as long as we keep looking.

“If you think about, if it’s not written down, if a person has that knowledge and doesn’t pass it on to another human being, and they die, their knowledge dies with them. . . Unfortunately, the damage has largely already been done. We’re sort of cleaning up what’s left, and trying to sift through these remnants of this traditional knowledge that still remain, and it’s certainly fraught with difficulty.”

That’s it for Consilience this month. This episode was produced and edited by me, Ben Henry, with help from Kerry Grens, Tracy Vence, and Bob Grant. Big thanks to Diana Kwon and Jef Akst, who wrote print versions of these stories in the April issue of The Scientist.

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