The biotech sector is increasingly being shaped by synthetic drugs and pressure from investors to move quickly and demonstrate commercial viability. Nobel Laureate Fred Ramsdell took a different approach – one built on cell-based therapies, philanthropy and patient investing.
That approach began at Darwin Molecular, a biotech startup in Bothell, Wash., launched in 1992 with the backing of Bill Gates and Paul Allen. Microsoft’s founders weren’t in a rush to recover quickly, Ramsdell said, and that freedom attracted dedicated researchers.
“People bought that because you are trying to do something that will make a difference,” he said. “It wasn’t a one-drug company. It wasn’t too focused on something specific. It was trying to figure out how we could affect change in patients.”
That tradition of mission driving became fertile ground. Ramsdell’s work on Darwin eventually led to the Nobel Prize in Physiology or Medicine, which was awarded in October and shared with Darwin’s colleague Mary Brunkow and Shimon Sakaguchi of Osaka University in Japan. The three have been credited with fundamental work on regulatory T cells, or Tregs — the so-called “guardians of the immune system.”
The discovery of Tregs revolutionized therapies by showing that the immune system has a built-in brake mechanism that can be developed to treat autoimmune disease, transplant rejection and graft-versus-host disease, or blocked to improve cancer immunotherapy.
Ramsdell recounted his journey at the annual Life Science Washington conference in Seattle on Tuesday, tracing the discovery’s unlikely origins back to the Cold War.
Darwin’s group studied a line of mice came down to post-Manhattan Project research on the effects of radiation on living things. In 1949, the program produced a mouse from a naturally occurring, non-radioactive mutation, later named “scurfy.”
Half of the male mice were sickly and lived only a few weeks. “They had all the autoimmune diseases in one animal,” Ramsdell said — diabetes, Crohn’s disease, psoriasis, myocarditis and more.
That suffering referred to something important. The scurvy mice carried a mutation that Darwin scientists identified and named Foxp3 – a gene that is important in keeping the immune system from attacking healthy immune cells. The mouse gene has a human counterpart, FOXP3.
“We saw the power of these cells,” Ramsdell said. Introducing healthy Tregs into people with an autoimmune disease could potentially cure the condition – but the scientific tools to make that a reality have yet to be found.
Darwin was acquired in 1996 by the London-based Chiroscience Group, which merged with the British company Celltech. When the company closed its Washington state R&D operation in 2004, Ramsdell and Brunkow moved on.
Ramsdell finally arrived at the Parker Institute for Cancer Immunotherapy, which he helped found in 2016. A nonprofit research center presented another unique opportunity. Founded with a $250 million grant from tech entrepreneur Sean Parker, it operates as a network of seven major US cancer centers, applying immunotherapy to cancer in ways that existing centers cannot.
The secret ingredient, Ramsdell said, is trust — intentionally built through Parker Institute retreats that bring scientists and their families together.
“The ability to build trust and cooperation, true collaboration, and inclusion [research] that couldn’t be put together, it was incredibly exciting for me,” she said.
Today, Ramsdell serves as a scientific advisor to the Parker Institute and Sonoma Biotherapeutics, a Seattle- and South San Francisco-based startup he co-founded that focuses on Treg cells. The company has a partnership with Regeneron to develop cell therapies for Crohn’s disease, ulcerative colitis and other conditions — a direct line from scurvy mice in the 1940s to the clinic.
Even in advisory roles, Ramsdell keeps coming back to big-picture biological questions. He is currently fascinated by people who carry genes for diseases that never happened – and what that might reveal about the hidden code in their DNA that delays illness.
If you look at this condition in a large population, scientists can test these genetic factors, he said, “and that will open a lot of doors.”
