Seattle Biotech’s Research Helped Shape Nobel-Winning Discovery

Long before two scientists were recognized with the Nobel Prize in Physiology or Medicine, their groundbreaking research began at a little-known biotech startup in the Seattle area that received early backing from Microsoft co-founders Bill Gates and Paul Allen.

That company was Darwin Molecular, a Bothell, Washington-based biotechnology startup founded in 1992. Among the researchers who joined the company in 1994 were Mary Brunkow and Fred Ramsdell, whose pioneering work on the immune system would eventually contribute to one of the most significant medical discoveries of recent decades.

Earlier this week, Brunkow and Ramsdell were awarded the Nobel Prize in Physiology or Medicine, alongside Shimon Sakaguchi of Osaka University, for helping identify regulatory T cells, often described as the immune system’s “security guards.”

Their research laid the foundation for a deeper understanding of how the immune system prevents itself from attacking healthy tissues, opening new possibilities for treating autoimmune diseases.

Darwin Molecular emerged during the early days of the Human Genome Project, when scientists were only beginning to map the complete human genetic code. The company’s ambitious goal was to clone individual genes even before a full genome sequence was available.

Speaking during a celebration at the Institute for Systems Biology (ISB) in Seattle, renowned biologist and ISB co-founder Lee Hood reflected on how difficult the task seemed at the time.

“When the company started, there was no complete genome to work from,” Hood said. “You had to do it from scratch, and it was an extremely challenging idea. And there was enormous skepticism.”

For Brunkow, joining Darwin Molecular instead of pursuing an academic career proved to be a defining decision.

She recalled the excitement of working in a small startup where researchers had the freedom to test bold scientific ideas.

“We made a great team at this small startup company where we were given the freedom to try different things,” Brunkow said. “And it was a really exciting time.”

Her research centered on a fatal autoimmune disease found in mice. She launched a genetics program to breed affected mice, identify the mutation responsible, and isolate the defective gene.

After carefully analyzing DNA sequences, Brunkow and her colleagues discovered the FOXP3 gene and identified the genetic mutation responsible for causing the disease.

At the same time, Ramsdell’s team focused on understanding how immune cells behaved in the mutant mice, helping explain the biological role of the newly identified gene.

Together, the discoveries revealed how FOXP3 controls regulatory T cells, specialized immune cells responsible for preventing excessive immune responses.

The scientists later demonstrated that mutations in the human version of the FOXP3 gene cause IPEX, a rare but life-threatening autoimmune disorder.

According to Jim Heath, president of the Institute for Systems Biology, FOXP3 has become the defining marker of regulatory T cells, making the discovery one of the most influential advances in immunology.

“Since that time, this discovery has had an impact in virtually every aspect of human health and disease,” Heath said.

Today, the findings continue to influence research into autoimmune disorders including rheumatoid arthritis, multiple sclerosis, lupus, and numerous other immune-related conditions.

Ramsdell currently serves as co-founder and chair of the scientific advisory board at Sonoma Biotherapeutics, which operates research and development facilities in Seattle.

Darwin Molecular itself had a relatively short corporate lifespan. In 1996, the startup was acquired by the London-based Chiroscience Group. Three years later, Chiroscience merged with British biotechnology company Celltech. The Washington research operations eventually closed in 2004, prompting both Brunkow and Ramsdell to leave the company.

Looking back on those early years, Brunkow said the experience remains one of the highlights of her career.

“I would still be working on that project because it really was an awesome time and an awesome team,” she said. “And we knew we were doing something really important in the field.”

Although Darwin Molecular no longer exists, the company’s research legacy lives on through discoveries that have transformed modern immunology and ultimately earned one of science’s highest honors.

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