May 2022 Message from the Director

Reasons for stepping down

I’m stepping down as director to rescue a cancer therapy that had spectacular early phase longterm (25 years) results but which wouldn’t get done again without my high priority attention

May 6, 2022

by Irv Weissman

Last year, for our annual meeting with Friends of the Institute, I focused on a potential therapy for patients with metastatic breast cancer, which came out of our Stanford stem cell discoveries in the early 1990s.The concept that led to the trial was pretty simple: increase the dose of chemotherapy combinations substantially, then rescue the blood forming system wiped out by the chemo with the patient’s own cancer-free, highly purified, blood-forming (hematopoietic) stem cells (HSC). People doing bone marrow transplants at that time were trying to do such HSC rescue, except that they were not using purified stem cells. They were rescuing the blood-forming system using mobilized blood from the cancer patient—a source rich in stem cells but also containing cancer cells. The clinicians were extracting a sample of mobilized blood from the patient, giving them chemotherapy to wipe out the cancer, and then rescuing the blood forming system by giving the patient back the mobilized blood, thus also giving patients back their own cancer.

I had formed a company (SyStemix) to purify the HSC away from the cancer cells contaminating the mobilized blood. SyStemix  was purchased by Sandoz/Novartis to develop all kinds of HSC based therapies, but they shut down the entire effort about 10 years later in a business decision. 

Before the program was shut down, we managed to do a small clinical trial, and the data was very promising. I have spent the last 20 years working to bring this approach back. I’ll talk more about the effort in my next – and likely last – Message from the Director. But for now, it’s important to know that after 25 years, the patients rescued with unpurified mobilized blood are all long dead. Half were dead at 2 years. The patients who had the same therapy (CAB1), the same physicians, and the same stage of disease had a much better outcome—33% are now still alive, without cancer, 25 years later. Half died at 10 years, not 2. What I learned in trying to do the trial again is important, and some of the lessons learned will apply to other attempts to bring stem cell therapies to the practice of regenerative medicine. Some lessons are an indictment of how we train physicians, but that is a much longer story. I hope you understand that for me to give up my leadership position, there had to be a very compelling unmet need.

When I informed Dean Minor that it was time for me to step down and for the School to solidify the future of the Institute for Stem Cell Biology and Regenerative Medicine with new leadership, he agreed to the formation of a Scientific Advisory Board made up of the leading stem cell scientists in the US and Canada, and established an equally prominent internal search committee to bring candidates forward. No one on the SAB or the Search Committee could be a candidate. They narrowed the list of potential successors, and gave it to Dean Minor and staff to evaluate the finalists and to consider the resources necessary to accomplish the vision of the final choice.

We have had spectacular support for our building, our institute, our faculty, and our students. We built the first stem cell academic program, and are the first to offer a PhD in stem cell biology and regenerative medicine. Our equipment has allowed us to work at the cutting edge of the institute, now enjoying its 20th year. We were instructed at the inception by then Dean (and now fledgling rabbinical student) Phil Pizzo to make sure that the institute cross all departmental disciplines, bringing the lessons learned by our institute faculty to the entire university and our hospitals, and bringing back what we learned from those other disciplines. To me that meant ending the almost political practice of departments and their disciplines looking always inward for their inspiration and leadership, which led to the exclusion of others in the university community. We ended that practice. Our institute has 8 billeted faculty slots, but we have 31 active faculty within and outside our building, all with the same rights and responsibilities of the billeted faculty. We represent today 14 departments in the University, 5 mainly basic science, and 9 clinical. With the help of the University and our office of development, we’ve found and become close to friends and donors who, along with the California Institute of Regenerative Medicine (CIRM, which was brought into life when the voters of California approved Proposition 71 in 2004 and Proposition 14 in 2020), have raised approximately $500 million to advance our mission since 2003.

I’ve learned that these donors share so much in our vision and in the possibilities of using stem cell biology to understand and treat patients, that they have become friends in every way. For me, they are friends for life.

We now need to make sure that the next director has the resources to move the vision forward even more, and to make sure future patients will benefit from our activities. To that end, we have established a Director’s Fund, toward which we have raised some funding and continue to do so. We are humbled and grateful to those who join us in this effort to expand the stem cell vision pursued in the institute.