Scientists Have Been Studying Cancers in a Very Strange Way for Decades

In 1959, an American physician named Harry Eagle mixed up one of the most pivotal cocktails in medical history—a red blend of sugar, salts, vitamins, and amino acids that allowed scientists to efficiently grow the cells of humans and other animals in laboratory beakers. This red elixir, known as Eagle’s minimal essential medium (EMEM), became a bedrock of biological research. Sixty years later, the medium and its variants are still heavily used whenever researchers want to study animal cells, whether to investigate the viruses that infect us, or to work out what goes wrong when cells turn cancerous.

As its name suggests, EMEM was designed to be as simple as possible—it has everything a cell needs to grow and nothing more. And in recent years, scientists have started realizing that such pared-down concoctions might be skewing their results, by warping the ways in which cells process nutrients. It’s as if they had spent decades studying the health of people who had only ever been given rations to eat.

Instead of using generic “culture media” like EMEM (or its more concentrated variant, Dulbecco’s Modified Eagle’s Medium, known as DMEM), it might be better to start creating concoctions that more accurately reflect the chemical profiles of our bodies. That’s what Saverio Tardito did in 2012, when he joined the Cancer Research UK Beatson Institute in Glasgow. “Around 90 percent of the papers in cancer research are using the same two or three commercially available media,” he says. “We researchers are aware that the medium you choose at the beginning of the experiment will affect the output, but it’s too easy to open the door of the fridge and use what’s there. I think we have been all been a bit too lazy.”

Over several years, he fine-tuned a mixture called Plasmax, which contains around 60 nutrients and chemicals at the concentrations usually found in human blood. “It was a side project—just a way of obtaining a better tool to do better research,” Tardito says. “But from the beginning, we noticed that the medium was making a difference.”

“These studies are absolutely a step in the right direction,” says Gina DeNicola of the Moffitt Cancer Center. “For this approach to be applied more broadly, these types of media will need to be commercialized. While it’s possible to make these media in a lab, it’s very costly and time-consuming. Commercial media preparations are also more consistent and higher quality, which will help with reproducibility between labs.” (Indeed, that’s partly why researchers have been so slow to move beyond traditional media like DMEM.)

Commercial preparations would also help Sabatini and Tardito, whose teams have been laboriously making up stocks of their own artisanal media and shipping them to collaborators around the world. “I struggle to keep up with the requests,” Tardito says. Sabatini adds, “We are working with vendors, but it is not easy, as physiological media is more expensive and is likely to have a shorter half-life.”

For researchers looking to understand how cancers gobble up nutrients, “testing one’s finding in a medium such as Plasmax would, without any doubt, add unparalleled rigor, and hopefully become a more widespread practice,” says Natasha Pavlova of the Memorial Sloan Kettering Cancer Center.

But she notes that such media aren’t perfect. They’re still largely missing many important components of blood, including fats and proteins. They don’t capture the different chemical profiles that exist in other tissues and organs. They don’t reflect the chemical wastelands that exist at the heart of tumors, which grow so quickly that their blood supplies can’t provide them with enough nutrients. Just last month, Alexander Muir of the University of Chicago showed that the fluids inside a tumor, which circulate between its cancerous cells, contain different levels of nutrients to those in blood.

Perhaps most important, Pavlova says, many cancer researchers rely on lineages of tumor cells that were created decades ago. These lines have been grown in conventional media like DMEM ever since, and have likely adapted accordingly. If they were now dunked in Plasmax, would that get researchers closer to real-life biology, or further away?  Would researchers have to create entirely new cell lines that are grown in Plasmax from the start?

Tardito acknowledges these issues. “There will never be a perfect medium that mimics the tumor environment beginning to end,” he says. “All we can do is try and minimize those imperfections as much as we can.”

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