A small biotech company launched in the early 1990s with backing from Microsoft co-founders Bill Gates and Paul Allen laid the groundwork for research that would eventually earn two Seattle-area scientists the 2025 Nobel Prize in Physiology or Medicine.

The company, Darwin Molecular, opened its doors in Bothell, Washington in 1992. Two years later, Mary Brunkow and Fred Ramsdell joined the venture, which aimed to clone individual genes during the early days of the Human Genome Project. The startup’s ambitious goals drew skepticism from many in the field, according to Lee Hood, co-founder of Seattle’s Institute for Systems Biology (ISB).

“You had to do it from scratch, and it was an extremely challenging idea,” Hood recalled at an ISB event celebrating Brunkow’s Nobel win. The honoree, now a senior program manager at ISB, remembered being thrilled to start her career in biotech rather than academia.

Working as part of a close-knit team at Darwin Molecular, Brunkow initiated genetic research on mice with a fatal autoimmune condition. Through careful breeding and DNA analysis, she and her colleagues identified a gene they named FOXP3 and pinpointed the mutation causing its dysfunction. Meanwhile, Ramsdell’s group investigated the cell biology and immune system impacts in the affected mice.

The research led to groundbreaking discoveries about regulatory T cells, which act as “security guards” for the immune system. These cells prevent autoimmune responses that can trigger diseases like rheumatoid arthritis, multiple sclerosis, and lupus. The team also found that mutations in the human version of FOXP3 caused IPEX, a rare but severe autoimmune disorder.

“Since that time, this discovery has had an impact in virtually every aspect of human health and disease,” noted Jim Heath, ISB’s president. The findings earned Brunkow and Ramsdell the Nobel Prize, shared with Shimon Sakaguchi of Osaka University.

Darwin Molecular’s independent run was relatively brief – British firm Chiroscience Group acquired it in 1996, later merging with Celltech. The Washington state R&D operations closed in 2004, marking the departure of both Brunkow and Ramsdell. Today, Ramsdell serves as co-founder and scientific advisory board chair at Sonoma
Biotherapeutics, which maintains R&D facilities in Seattle.

Reflecting on her time at Darwin, Brunkow expressed lasting enthusiasm for the groundbreaking project: “I would still be working on that project because it really was an awesome time and an awesome team. And we knew we were doing something really important in the field.”

The small startup’s legacy lives on through this Nobel-winning research that transformed our understanding of immune system regulation and opened new pathways for treating autoimmune conditions.