Louis Pasteur’s tomb in Paris. Late last year Charlie Mills traveled across Europe, explaining his research on macrophages to scientists and medical researchers.

Around the world, medical scientists are revising their understanding of the immune system, how it functions at the cellular level and how we might enhance immune responses to treat ailments from allergies to cancer. 

Although the ideas behind immunotherapy have been around for more than a century, the research behind those ideas didn’t always lead to success in practice. 

But a scientific breakthrough made by Marine’s Charles Mills more than a decade ago (and reported on by the Messenger Sept. 17, 2014) seems to have provided a missing link.  And international interest in Mills’ research recently took him on a tour across Europe to share his ideas with scientists and medical researchers from England to Italy. 

“What I discovered some time ago,” said Mills, “almost 15 years ago now, were two new cells. They’re white cells in the immune system that do polar opposite things. There’s one that kills and one that heals.”

Prior to Mills’ discovery, scientists had been somewhat stumped by what they called the macrophage, or “big eater.” 

“They couldn’t figure out how one cell would help things grow and kill,” said Mills, whose research unveiled that macrophages can take on different functional roles, adapting to the body’s need to fend off disease, then repair damage.

He termed the macrophages “M1” and “M2” — M1 macrophages kill and M2s heal. It’s a simplification, he says, but it gets his point across.

One implication of Mills’ discovery was that macrophages are responsible for a lot more immune activity than previously thought. For decades, T and B cells were given most of the credit for fighting disease. 

But without macrophages acting as the body’s sentinels, said Mills, alerting T and B cells to disease and keeping it in check until the fighter cells arrive on the scene, the body would be quickly overcome by infections.

These discoveries are especially relevant in the emerging field of immunotherapy, which uses the body’s natural defenses to heal. 

“The immune system needs to make decisions and going in different directions,” Mills explained. “Sometimes it needs to kill, sometimes it needs to heal. Wounds and cancer seem different, but they’re similar. Healing is a constructive process. …. With cancer, the immune system thinks it’s healing.”

In other words, cancer requires the presence of M2 macrophages — they’re essential to tumor growth — but if they could be turned into killer macrophages, M1s, the body could destroy the tumor without chemotherapy or other invasive treatments.

And those medications are being developed, said Mills.

“It’s not pie in the sky,” he noted. “I’m not saying (this medication) will be available next week, but it’s a reality.”

Since he was profiled in the Messenger in Sept. 2014, Mills has written another 10 articles about macrophages and was invited to write a review about cancer immunotherapy, which he calls “the next breakthrough.”

“Breakthrough” is not a word he uses lightly. And it applies to more than cancer, he said. The same ideas can help find new treatments for allergies, rheumatoid arthritis and angiosclerosis.

“Many things in science are slow to change,” he said. “But interest in this topic has exploded and I’m extremely grateful to be a part of that.”

Late last year, Mills was invited to explain his discoveries and their potential applications to scientists across Europe.

“On the trip people were saying, I never understood this, but you made me understand it,’” Mills recalled, smiling with satisfaction.

Part of his mission is helping everyone understand the immune system better, from fellow scientists to locals at the coffee shop. 

“Seeing simplicity among complexities is often how science advances,” he explained.

After speaking in London and Bristol, Mills presented at the Louis Pasteur Institute in Paris.

“Louis Pasteur is probably one of the most well known scientists ever, so that was an honor,” said Mills. “I arrived there about two weeks after the Paris bombings so the Pasteur Museum was closed, but they set up a private tour for me. I saw Pasteur’s tomb, he’s in black marble, with mosaics on the wall. It really took my breath away.”

He spoke in Stockholm, Sweden, Mannes, Germany and Naples, Italy, spending about three days in each place. Not only was the food tremendous, he said, but he was very well received.

“I was honored to be invited,” said Mills, “but they were at least as honored to have me. The most remarkable thing (was realizing that) people in Europe admire Americans. … There is probably a small minority of Americans who go over there and act like they own everything. But even the French like us.”

During each hour-long seminar, Mills spoke to a mix of young scientists and medical professors, making an effort to incorporate humor and the history of the city he was speaking in. 

“Each place had scientific advancements that had happened,” he said. 

Science is built on such advances, each one contributing to the next. Mills’ discoveries were enabled by previous advances, and where they lead remains to be seen.

“This is not being overhyped,” he said of recent advances in immunotherapy. “You’re going to keep seeing it. And that’s good.”

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