Discovering Cisplatin: The Penicillin of Cancer Drugs

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Discovering Cisplatin: The Penicillin of Cancer Drugs

Finding the cure for cancer is the holy grail of scientific research. Of life, really. Everyone is looking for it.

Discovering the elusive remedy has captivated and tormented scientists for generations.

So, when Dr. Barnett Rosenberg emerged from his lab in the old biochemistry building at Michigan State University in 1965 and proclaimed to a group of grad students, “I’ve just cured cancer!” it got their attention.

What Rosenberg and his research partner, microbiologist Loretta Van Camp, discovered were the first glimpses of cisplatin — what would later be referred to as the “penicillin of cancer drugs.”

The chemical compound cisplatinum interferes with the growth of cancer cells, slowing their advance in the body. It prevents DNA from replicating, confusing the cancer cells and causing them to die. The drug cisplatin is used to treat many types of cancer, but it’s most widely prescribed for testicular, ovarian, bladder, lung and stomach cancers. It has become the gold standard to which many new cancer medicines are compared.

Among those witnesses that day in 1965 was James Trosko, then a grad student studying genetics, now a professor emeritus of pediatrics and human development researching the mechanisms of carcinogenesis and mutagenesis in genes.

“We didn’t know what was going on, but in his mind, Barney had cured cancer,” Trosko said. “He yelled out, ‘Eureka!’ He believed he had discovered a way to block cell division in tumors.”

Rosenberg had, though he hadn’t exactly discovered it yet. The path to the answer would take several more years.

This year marks the 40th anniversary of the FDA’s approval of cisplatin as an anti-cancer drug – an event not only of incredible significance in medicine, but to Michigan State University and the future of all research done on its campus.

That’s because a portion of patent and licensing royalties from cisplatin headed to the MSU Foundation, fueling investments in research and economic development initiatives through the commercialization of cutting-edge technologies invented by MSU faculty, staff, and students.

Four decades later, cisplatin is making new discoveries possible every day at Michigan State University.

A series of aha moments

But back to that aha moment.

It’s easy to look back and pinpoint the moment everything shifted in Rosenberg and Van Camp’s work, but the reality is it was a series of moments, years of work and a lot of creative thinking that paved the road to cisplatin’s discovery.

That first moment, though, when Rosenberg and Van Camp knew they were onto something, came when they discovered something they were working on was causing cancer cells to elongate but not divide.

“They knew exactly what that meant,” said James Hoeschele, who later worked with the team on the discovery of carboplatin, an updated, less-toxic form of cisplatin. Rosenberg and Van Camp understood that this elongation interfered with DNA replication, killing the fastest-proliferating cells, which in theory are carcinogenic.

But the process wasn’t smooth sailing from there.

When it came time for the independent replication of their results, the experiment failed. But Van Camp noticed the stock solutions used to host the bacteria were being bleached by the sunlight entering the windows of the new lab setting, thus causing the solution to become more concentrated. Something as simple as the existence of windows where none had been previously changed the outcome of the experiment.

“It was a serendipitous moment,” Hoeschele said. “Loretta’s observation skills were exceptional.”

They recreated the environment from their original lab and the experiment worked.

The team, which by then included graduate student Thomas Krigas – credited as the third co-inventor of cisplatin – spent the next five years injecting every possible variable that could affect bacterial growth into the experiment. They altered the physical conditions – voltage, current, temperatures – as well as every possible variable they could think of to determine the causative agent before settling upon the precise compound.

The rest is cancer-fighting history.