I assure you that I did not plan to do this. I wanted to write a little story about proteins and cancer, nuclear magnetic imaging and a scientist turned entrepeneur of billion-dollar biotechs. Maybe a touch on communist East Germany. A sprinkle on her (what I assumed had been) past life as a world-class athlete. I did not — would not — plan on writing a story about someone succeeding “on-the-court and off-the-court,” a story held together by what I assumed would have to be forced parallels between basketball and science.
And then I spoke to Dorothee Kern, and the first thing she told me to explain her work was a basketball analogy, one about her own game. And when I followed up, asking about any connection between basketball and why she got into biotech, her second response is: “I want to win and cure patients … there’s this competitive spirit, but you want to win the championship, you have to get drugs on the market.”
The first response was about an analogy between the proteins she watches being in motion and she herself being in constant motion. “Shooting for the win” was also mentioned.
“There’s a reason they call me the protein dynamics lady!” she said.
Basketball is indeed about as fundamental to Kern as her science. She calls the sport “her ATP” — and she has a lot of ATP, her frame built like an athlete and her words spoken with the frenetic energy befitting of someone who goes by “Doro.”
The competition, I learned, never actually became a thing of the past. This summer she had planned to return with the German team to the FIMBA Maxibasketball European Championship to defend their title. Covid-19 ended that, so for excitement, Kern, a professor of biochemistry at Brandeis University, will have to settle for the launch of her second biotech: MOMA Therapeutics, which emerged this week out of Third Rock with an $86 million Series A and a focus on a versatile class of proteins called molecular machines. Her first biotech, founded in 2016, had emerged with a $57 million Series A and later attracted a $400 million Softbank-led Series C.
The new one, she said, will be even bigger. Or at least the science will be.
“I compare these molecular machines and MOMA to a power of 3 to what has been done so far,” Kern said. “Nobody has done this. It’s on a whole different scale.”
Dorothee Kern driving up the court
Kern grew up in communist East Germany, the daughter of two high-minded biochemists who considered biochemistry a dinner-table topic of choice and who refused to cooperate with the communists or their secret police, the Stasi. That rectitude would cost her father a promotion and her mother her job and, with high school reserved for party loyalists, could have cost Kern her education. Except that Kern had just made the junior national basketball team. Her parents convinced the government that was a public service, one worthy of an exception.
Basketball provided a way into the system. Science, Kern said, provided a refuge from that system, from a dictatorial government that wrote the textbooks to suit whatever version of events they thought expedient. For a naturally curious student, it was the only field that looked like it could provide real answers.
“Everything was twisted, there was no truth being told in all the other subjects: history, economics and business, the humanities,” Kern said. “The one thing they couldn’t twist was 2+2=4.”
One day in 1987, future Noble Prize winner Kurt Wüthrich gave a lecture at the Leopoldina, a centuries-year old learned society where East German scientists could still hear visiting lectures from the West. At the time, X-ray crystallography — the same technique that led to the discovery of the double helix — had become the hottest thing in biochemistry, with journal after journal plastering their front pages with new images of molecules, black-and-white still lifes of the chemical world. This was exciting but it also struck Kern as fundamentally lacking.
“The whole beauty of enzymes is that they actually move,” Kern said. “And if they don’t move they are dead. There’s a reason life doesn’t exist below 180 kelvin.”
In a brief aside, Wüthrich mentioned nuclear magnetic resonance spectroscopy, a different technique he had developed to take pictures of atoms. Sitting in the audience, Kern realized she could use the same techniques to take pictures of molecules and specifically proteins in motions, what she calls “real-time movies.”
East Germany, though, lacked the tools needed for these experiments. They were like kids’ toys, she said, in comparison to Western equipment, and early on she could only study substrates, little shards off the overall whole. Then the Berlin Wall fell. She became a fellow in Sweden, a post-doc in Berkeley. She began to make her movies, illuminating invisible particles that moved on millisecond scales.
“It was a dream come true,” she said. She compared it to going from pickup basketball to the world championships.
(Kern, meanwhile, had never given up basketball, playing on the German national team until she left and continuing to school guys half her age in Boston five days a week. I asked her if she ever had thought about choosing one or the other, pointing out that the time commitments of being a graduate student or scientist and a national basketball player. “Absolutely not,” she said. “I get bored quickly. I love multi-tasking.”)
Her motion work would bring accolades and a professorship at Brandeis. Eventually, between 2012 and 2014, she started to learn how to link those proteins’ movement with their function. She began to study allosteric sites — spots of a protein away from the binding site (where most drugs are targeted) that can nonetheless affect the overall function of the molecule. It was the kind of how-things-work understanding her entire career had been building to.
It was also the kind of information that could be used to build drugs. Kern, who had always been too concerned with discovering how things work to go into biotech, booked a meeting with Third Rock Ventures.
Before a dozen executives, she pulled out her laptop and played Lady Gaga’s “Just Dance” while the little dots in a protein diagram pulsed to the beat. She offered no financial or revenue projections. Nevertheless, she proposed a biotech that would channel her 30 years of research on protein motion into treatments for cancer and neurodegenerative diseases. “Dance,” she called it, after her ‘dancing’ proteins.
“Yes,” Third Rock said. And then, with Justin Timberlake-from-The Social Network flair: “Just change the name.”
Relay Therapeutics now says they are on the verge of the clinic, although they have not revealed any targets or drug candidates and no “pipeline” is listed on their site. Working there changed Kern. She still cared deeply about fundamental discoveries, she said, but the potential to help patients was “eye-opening.”
The newest venture, MOMA, was a Third Rock idea. Kern acknowledges that of the founding team of her, Timur Yuzusafi, Eva Nogales and Johannes Walter, she has the least direct experience with the science at the biotech’s center, but in many ways it builds off work she has done for decades. The new biotech focuses on molecular machines — proteins that are unique in their size and their degree of movement, shape-shifting over and over again to carry out their tasks.
That size and nimbleness also makes them difficult to study. Never mind crystallography, that old technique that came in vogue as Kern was an undergrad. Many of these proteins don’t crystallize. How to build, screen and inhibit them are still open questions.
Those aspects are also what make them so exciting. They do so much, and that opens up a world of potential drugs.
“Where they are involved is just mind-boggling,” Kern said. “You could build a large pharma company around this going forward.”