When communications scholar Marshall McLuhan coined the famous phrase “the medium is the message” in the 1960s, he was saying that our understanding of an idea will be shaped by how we receive it — whether it’s conveyed through a book, a lecture, a movie or a song.
Morgridge Institute for Research investigator Jason Cantor has an interesting equivalent for biology researchers: The medium used to grow cells in a lab has a similarly profound impact on the “message” cells receive on how to grow and respond.
This is the concept behind Cantor’s innovation of a new cell culture medium — a biological research tool that since the 1950s has been as ubiquitous in labs as microscopes and pipettes. Notably, Cantor began his postdoctoral training with no prior experience in mammalian cell culture, having completed his PhD in a protein engineering lab where all of his culture work was done in bacterial cells.
Not long into his postdoc, Cantor posed a deceptively basic question: How closely do classic cell culture media reflect biochemical conditions in the human body? The answer: Not too well.
This question ultimately led to the development of Human Plasma-Like Medium (HPLM), a physiologic medium that more closely reflects the metabolic composition of human blood. Cantor reported the design and initial studies using HPLM in 2017 (Cell) while a postdoc in David Sabatini’s laboratory at the Whitehead Institute/MIT in Cambridge. Since that initial publication, HPLM has generated a great deal of interest from biologists across the scientific community.
“We created a kind of miniature media kitchen beginning in David’s lab and then continuing here at Morgridge, and we actually ended up providing batches of HPLM as a free-of-charge service to over 60 labs around the world,” Cantor says. “I think it’s also worth noting that the recipients were not just interested in areas of cancer metabolism and cancer biology. Instead, they really covered the spectrum across most areas of biological research that could involve the use of cultured mammalian cells.”
“It’s exciting to see this go from publication a few years back to now officially bringing a product to market.”Jason Cantor
But now it’s being taken to the next level. Cantor’s laboratory no longer needs to continue its simultaneous role as “kitchen” thanks to a commercialization agreement with Thermo Fisher Scientific. The company announced in March 2021 the wide-scale availability of HPLM for the scientific community.
“It’s exciting to see this go from publication a few years back to now officially bringing a product to market,” Cantor adds. “And it should be pretty exciting to see what others discover with HPLM as well.”
The innovation in cell culture media is a long time coming, as the formulations of these reagents haven’t changed much since Johns Hopkins physician Harry Eagle developed “Minimal Essential Medium” in 1955, opening the floodgates for scientists to culture mammalian cells in synthetic media with less complexity and variability than “natural media” like the biological fluids and tissue extracts from animals.
Cantor notes that the pioneering efforts of Eagle and others indeed allowed for decades of cell culture work and serve as a key milestone in biological research, ultimately leading to countless advances both in our understanding of basic cell biology and in drug discovery and development.
But ultimately, these classic media recipes poorly resemble biochemical conditions in the body, Cantor says. To begin to address this gap, Cantor systematically created what would become HPLM, a physiologic medium that contains more than 60 components at concentrations that reflect average values reported in human blood. Ultimately, by contrast to application-driven goals that had historically guided culture media design, such as supporting rapid cell growth or promoting the production of recombinant biomolecules, the goal was to develop a culture medium that could be used to more faithfully model human cell biology.
Recently, the Cantor lab leveraged HPLM to ask how medium composition may influence “gene essentiality” in cancer cells — in other words, identifying genes that are critical to cell growth and survival. By performing CRISPR-based genetic screens of human cancer cells in either conventional media or HPLM, the Cantor lab together with colleagues at Whitehead Institute reported the profound impact of medium composition on gene essentiality in a study published online in Cell Metabolism in March 2021.
Cantor recalls being posed with a relatively loaded question from a colleague shortly after HPLM was initially reported: “What are you going to do next once everyone else has access to this new physiologic medium”? His response: “What have thousands of labs across the world done over the past half century while mostly using the same small handful of traditional media?”
“The onus is always going to be on the scientist to identify the most interesting questions to ask and the most interesting problems to address,” Cantor adds.