When Dr. Susan Bullman last year told her husband, Dr. Christopher Johnston, that she wanted to leave her job at Harvard’s Dana-Farber Cancer Institute for a faculty post at Fred Hutchinson Cancer Research Center in Seattle, he was, well, less than enthused.
“We are not moving to Seattle, we’re not leaving Boston. My research is not going to the rain,” was his response, Johnston recalled with a grin, as he chatted with his wife in his new office at Fred Hutch, overlooking Seattle’s Lake Union on a sunny spring morning.
Yes. They both got jobs at the Hutch.
In April, each joined the Fred Hutch faculty, and since then, they have been staffing and stocking their own microbiology labs. With different areas of expertise, each is a leader in research on the microbiota, the trillions of bacteria that inhabit our mouths, our gut and just about every square inch of our bodies.
“I want my work to be meaningful. I want it to be impactful. And I think the Hutch is the place to make that happen,” Johnston said.
They both come from County Cork, in the south of Ireland, and for years their work lives had followed a parallel track.
They met as graduate students at Cork Institute of Technology, but for the first two years, they barely knew one another. As the most studious among their colleagues, eventually they became the only ones left in the lab late into the evenings. “The security guards hated us,” Johnston said. “They were telling us, ‘C’mon, wrap it up and go home.’”
Thus, a romance bloomed.
After graduating, they traveled the route of many European scientists: get a Ph.D. in the home country, and then seek a postdoctoral fellowship in the United States. Johnston called it “getting the BTA” (Been to America), often sought to burnish a newly minted researcher’s credentials.
They both sought fellowships in the Boston area. With so many schools and research labs there, they felt it gave them the best shot at staying together. This was their first experience with what is called in academic circles the “two-body problem.” Because highly educated young people often seek love among those with like interests, couples often face heartbreaking choices when a career takes one of them to a different part of the globe. Good academic jobs are hard enough for one person to find, let alone two.
Boston, of course, came through for Bullman and Johnston. But five years into that chapter, with both holding good jobs, they realized they loved living in the U.S., and their work lives were taking off. But what to do when the next career decision arose? The two-body problem, it seems, is lifelong.
At Dana-Farber and the nearby Broad Institute in Cambridge, Bullman had built a reputation as a rising star for her postdoctoral research on a bacterial species, Fusobacterium nucleatum, known to be linked to colorectal cancer. Her research published in the journal Science showed this bug was concentrated in colon tumors, and was even found in tumors that had spread to the liver.
Early in her East Coast stay, Bullman became acquainted with the Seattle cancer center. At a microbiology conference in Boston, she listened to an address by Hutch’s Dr. Denise Galloway on the role of microbes in cancer. “I was furiously writing down everything she was talking about,” Bullman recalled. "I thought she was amazing.”
Now holder of the Paul Stephanus Endowed Chair at the Hutch, Galloway heads a multidisciplinary, collaborative research program, the Pathogen-Associated Malignancies Integrated Research Center, or PAM-IRC, which focuses Hutch research on cancers caused by bacteria and viruses. So, when the Hutch expressed interest in Bullman’s work, she was eager to join.
Meanwhile, back in 2016, Johnston had set up his own laboratory at the Forsyth Institute, an independent research center in Cambridge affiliated with the Harvard School of Dental Medicine. When the Hutch began recruiting his wife last year, his own lab’s work was well underway. He had already hired staff, set up shop and had won a coveted NIH Directors Transformative Research Award. He specialized in bacteria that inhabit the mouth, and he was gaining notice for an ingenious new way to make bacteria of all kinds easier to modify with genetic engineering tools.
Scientists have been swapping genes in an out of lab mice for decades, a technique that is useful for finding the purpose of a gene by observing what happens when it is changed or missing. But it is still surprisingly more difficult to engineer the genes of simple bacteria. That is because these bugs have evolved, over billions of years, sophisticated barriers against viruses that try to insert their foreign DNA into their bacterial genomes. When a scientist inserts a snippet of new DNA into a bacterium’s genome, it appears just like a virus to the bug and runs directly into these defenses. Such bacteria are known as “genetically intractable.”
There are many strategies around intractability, but Johnston has developed a method that can be likened to Harry Potter’s invisibility cloak. In effect, it blinds the bacterium to the new DNA’s foreign identity, so researchers can more easily slip in a new gene. This lab tool, dubbed SyngenicDNA, is allowing swift and efficient genetic manipulation in previously intractable species.
Johnston was anxious about his wife’s wish to move to Seattle, but he was struck by how positive she was about her prospects. Then came the call from Seattle. This time, it was for him: “Would you mind interviewing for a new opening at the Hutch?”
Johnston admits he was taken with the researchers he met, and with the Seattle environment.
“After one visit, he became just as enthusiastic about the possibility as I was,” Bullman said.
In her new post, Bullman continues to study the role of Fusobacterium nucleatum in colon cancer. “What is important to me is to grow these fastidious bacteria from patient tumors, to tease apart their role in colorectal cancer,” she said. Key to that is her tissue bank of colorectal tumors from which she has isolated more than 120 different Fusobacterium strains, whose genomes she also has sequenced.
One of her research goals is to determine for certain whether the bacterium is causing colorectal cancer or merely turning up in tumors after they form. She wants to learn fully the gene functions and inner workings of this problematic bug — to figure out exactly how it might be causing colorectal tumors, and if possible, how to interfere with that.
To do so, she must overcome a trait that makes it difficult to study: Fusobacterium is one of those genetically intractable bugs.
Not to worry. Just across the street from her new lab, her husband Chris has an app for that.
Sabin Russell is a former staff writer at Fred Hutchinson Cancer Center. For two decades he covered medical science, global health and health care economics for the San Francisco Chronicle, and he wrote extensively about infectious diseases, including HIV/AIDS. He was a Knight Science Journalism Fellow at MIT and a freelance writer for the New York Times and Health Affairs.
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