When people ask me what I do at CIRM I sometimes half-jokingly tell them that I’m the official translator: I take complex science and turn it into everyday English. That’s important. The taxpayers of California have a right to know how their money is being spent and how it might benefit them. But that message can be even more effective when it comes from the scientists themselves.
Recently we asked some of the scientists we are funding to do research into COVID-19 to record what’s called an “elevator pitch”. This is where they prepare an explanation of their work that is in ordinary English and is quite short, short enough to say it to someone as you ride in an elevator. Hence the name.
It sounds easy enough. But it’s not. When you are used to talking in the language of science day in and day out, suddenly switching codes to talk about your work in plain English can take some practice. Also, you have spent years, often decades, on this work and to have to explain it in around one minute is no easy thing.
But our researchers rose to the challenge. Here’s some examples of just how well they did.
There are some people who, when you think of them, always bring a smile to your face. Dr. Bert Lubin was one of those people. Sadly, we lost Bert to brain cancer two days ago. But the impact he had, not just as an advocate for stem cell research but as a pioneer in sickle cell disease research and a champion for children’s health, will live on.
Bert had a number of official titles but probably the one he was most proud of was President & CEO of Children’s Hospital Oakland (now UCSF Benioff Children’s Hospital Oakland). But it wasn’t the title that he cared about, it was the opportunity it gave him to make a difference in the life of children in Oakland, to create a program to find new treatments and cures for a life-threatening disease. And he has made a difference.
As I started to write this tribute to Bert, I thought about who I should ask for a quote. And then I realized I had the perfect person. Bert himself. I was fortunate enough to interview him in December 2018, when he decided to step down after eight years on the CIRM Board. As always, he had his own positive spin on that, saying: “I don’t see myself leaving. I’m just repurposing what is my role in CIRM. I’m recycling and reinventing.”
And Bert was always full of invention.
He grew up in Bellevue, a small town outside Pittsburgh, PA. His parents ran a fruit and vegetable market there and, growing up, Bert often worked in the store. It wasn’t something he enjoyed but he said he learned some valuable lessons.
“I think what happened in my childhood is that I learned how to sell. I am a salesman. I hated working in that store, I hated it, but I liked the communication with people, they trusted me, I could sell things and they were good things. Like Christmas. I’m Jewish, we were the only Jews in that community, and at Christmas we sold Christmas trees, but the trees were sometimes crooked and they were $2.99 a tree so I convinced families that I could go to their house and set the tree so it looked straight and I helped them decorate it and they loved it.”
He said, thinking back on his life it’s almost as if there were a plan, even if he wasn’t aware of it.
“I started thinking about that more recently, I started wondering how did this even happen? I’m not a religious person but it’s almost like there’s some fate. How did I get there? It’s not that I planned it that way and it’s certainly not that my parents planned it because I was the first in my family to go to high school let alone college. My parents, when I went to medical school and then decided I wanted to spend more time in an academic direction, they were upset. They wanted me to go into practice in a community that I grew up in and be economically secure and not be on the fringe in what an academic life is like.”
And then, fate stepped in and brought him to the San Francisco Bay Area.
“What happened was, I was at the University of Pennsylvania having trained at Boston Children’s and Philadelphia Children’s, where I had started a sickle cell disease program, and was asked to look at a job in southern California to start a sickle cell program there. So, I flew to San Francisco because a lot of people I’d studied with were now working at UCSF and I thought it would be fun to see them before going down to southern California. They took me out to dinner and showed me around and I said this place is beautiful, I can play tennis out here all year round, there’s lots of music – I love jazz – and they said ‘you know Bert, have you looked at Oakland Children’s hospital? We want to start a sickle cell program center, but the patients are all in Oakland and the patient population that would be served is in Oakland. But if you came out to the Bay Area we could partner with you to start that program.
“So, when I walked in the door here (at Oakland) and said ‘I want to create this northern California sickle cell center with UC’ the staff that was here said ‘you know we’re not a research hospital, we are a community based hospital’. I said, ‘I’m not saying you shouldn’t be that but I’m trying to create an opportunity here’ and they said to me ‘as long as you don’t ask for any money you can go and do whatever you want’.
‘They recognized that I had this fire in me to really create something that was novel. And the warmth and community commitment from this place is something that attracted me and then allowed me to build on that.
“For example, when I became the director of the research program we had $500,000 in NIH grants and when I left we had $60 million. We just grew. Why did we grow? Because we cared about the faculty and the community. We had a lovely facility, which was actually the home of the Black Panther party. It was the Black Panthers who started screening for sickle cell on street corners here in Oakland, and they were the start of the national sickle cell act so there’s a history here and I like that history.
“Then I got a sense of the opportunities that stem cell therapies would have for a variety of things, certainly including sickle cell disease, and I thought if there’s a chance to be on the CIRM Board, as an advocate for that sickle cell community, I think I’d be a good spokesperson. So, I applied. I just thought this was an exciting opportunity.
“I thought it was a natural fit for me to add some value, I only want to be on something where I think I add value.”
Bert added value to everything he did. And everyone he met felt valued by him. He was a mentor to so many people, young physicians and nurses, students starting out on their careers. And he was a friend to those in need.
He was an extraordinary man and we are grateful that we were able to call him a colleague, and a friend, for as long as we did.
When Burt stepped down from Children’s his colleagues put together this video about his life and times. It seems appropriate to share it again and remind ourselves of the gift that he was to everyone fortunate enough to know him.
Rich Lajara, the first patient treated in a CIRM-funded clinical trial
May 4th, 2011 marked a landmark moment for the California Institute for Regenerative Medicine (CIRM). On that day the Stem Cell Agency’s Board voted to invest in its first ever clinical trial, which was also the first clinical trial to use cells derived from embryonic stem cells. Today the Stem Cell Agency reached another landmark, with the Board voting to approve its 50th clinical trial.
“We have come a long way in the past seven and a half years, helping advance the field from its early days to a much more mature space today, one capable of producing new treatments and even cures,” says Jonathan Thomas, JD, PhD, Chair of the CIRM Board. “But we feel that in many ways we are just getting started, and we intend funding as many additional clinical trials as we can for as long as we can.”
The project approved today awards almost $6.2 million to Angiocrine Bioscience Inc. to see if genetically engineered cells, derived from cord blood, can help alleviate or accelerate recovery from the toxic side effects of chemotherapy for people undergoing treatment for lymphoma and other aggressive cancers of the blood or lymph system.
“This is a project that CIRM has supported from an earlier stage of research, highlighting our commitment to moving the most promising research out of the lab and into people,” says Maria T. Millan, MD, President & CEO of CIRM. “Lymphoma is the most common blood cancer and the 6th most commonly diagnosed cancer in California. Despite advances in therapy many patients still suffer severe complications from the chemotherapy, so any treatment that can reduce those complications can not only improve quality of life but also, we hope, improve long term health outcomes for patients.”
The first clinical trial CIRM funded was with Geron, targeting spinal cord injury. While Geron halted the trial for business reasons (and returned the money, with interest) the mantle was later picked up by Asterias Biotherapeutics, which has now treated 25 patients with no serious side effects and some encouraging results.
Rich Lajara was part of the Geron trial, the first patient ever treated in a CIRM-funded clinical trial. He came to the CIRM Board meeting to tell his story saying when he was injured “I knew immediately I was paralyzed. I thought this was the end, little did I know this was just the beginning. I call it being in the wrong place at the right time.”
When he learned about the Geron clinical trial he asked how many people had been treated with stem cells. “Close to none” he was told. Nonetheless he went ahead with it. He says he has never regretted that decision, knowing it helped inform the research that has since helped others.
Since that first trial the Stem Cell Agency has funded a wide range of projects targeting heart disease and stroke, cancer, diabetes, HIV/AIDS and several rare diseases. You can see the full list on the Clinical Trials Dashboard page on our website.
Rich ended by saying: “CIRM has proven how much can be achieved if we invest in cutting-edge medical research. As most of you here probably know, CIRM’s funding from Proposition 71 is about to run out. If I had just one message I wanted people to leave with today it would be this, I will do everything I can to make sure the agency gets refunded and I hope that all of you will join me in that fight. I’m excited for the world of stem cells, particularly in California and can’t wait to see what’s on the horizon.”
The CIRM Board also took time today to honor Dr. Bert Lubin, who is stepping down after serving almost eight years on the Board.
When he joined the Board in February, 2011 Dr. Lubin said: “I hope to use my position on this committee to advocate for stem cell research that translates into benefits for children and adults, not only in California but throughout the world.”
Over the years he certainly lived up to that goal. As a CIRM Board member he has supported research for a broad range of unmet medical needs, and specifically for curative treatments for children born with a rare life-threatening conditions such as Sickle Cell Disease and Severe Combined Immunodeficiency (SCID) as well as treatments to help people battling vision destroying diseases.
As the President & CEO of Children’s Hospital Oakland (now UCSF Benioff Children’s Hospital Oakland) Dr. Lubin was a leader in helping advance research into new treatments for sickle cell disease and addressing health disparities in diseases such as asthma, diabetes and obesity.
Senator Art Torres said he has known Dr. Lubin since the 1970’s and in all that time has been impressed by his devotion to patients, and his humility, and that all Californians should be grateful to him for his service, and his leadership.
Dr. Lubin said he was “Really grateful to be on the Board and I consider it an honor to be part of a group that benefits patients.”
He said he may be stepping down from the CIRM Board but that was all: “I am going to retire the word retirement. I think it’s a mistake to stop doing work that you find stimulating. I’m going to repurpose the rest of my life, and work to make sure the treatments we’ve helped develop are available to everyone. I am so proud to be part of this. I am stepping down, but I am devoted to doing all I can to ensure that you get the resources you need to sustain this work for the future.”
The five-year survival rate for people diagnosed with the most advanced stage of non-small cell lung cancer (NSCLC) is pretty grim, only between one and 10 percent. To address this devastating condition, the Board of the California Institute for Regenerative Medicine (CIRM) today voted to invest almost $12 million in a team from UCLA that is pioneering a combination therapy for NSCLC.
The team is using the patient’s own immune system where their dendritic cells – key cells in our immune system – are genetically modified to boost their ability to stimulate their native T cells – a type of white blood cell – to destroy cancer cells. The investigators will combine this cell therapy with the FDA-approved therapy pembrolizumab (better known as Keytruda) a therapeutic that renders cancer cells more susceptible to clearance by the immune system.
“Lung cancer is a leading cause of cancer death for men and women, leading to 150,000 deaths each year and there is clearly a need for new and more effective treatments,” says Maria T. Millan, M.D., the President and CEO of CIRM. “We are pleased to support this program that is exploring a combination immunotherapy with gene modified cell and antibody for one of the most extreme forms of lung cancer.”
The CIRM Board also approved investing $14.15 million in four projects under its Translation Research Program. The goal of these awards is to support promising stem cell research and help it move out of the laboratory and into clinical trials in people.
Researchers at Stanford were awarded almost $6 million to help develop a treatment for urinary incontinence (UI). Despite being one of the most common indications for surgery in women, one third of elderly women continue to suffer from debilitating urinary incontinence because they are not candidates for surgery or because surgery fails to address their condition.
The Stanford team is developing an approach using the patient’s own cells to create smooth muscle cells that can replace those lost in UI. If this approach is successful, it provides a proof of concept for replacement of smooth muscle cells that could potentially address other conditions in the urinary tract and in the digestive tract.
Max BioPharma Inc. was awarded almost $1.7 million to test a therapy that targets stem cells in the skeleton, creating new bone forming cells and blocking the destruction of bone cells caused by osteoporosis.
In its application the company stressed the benefit this could have for California’s diverse population stating: “Our program has the potential to have a significant positive impact on the lives of patients with osteoporosis, especially in California where its unique demographics make it particularly vulnerable. Latinos are 31% more likely to have osteoporosis than Caucasians, and California has the largest Latino population in the US, accounting for 39% of its population.”
Autologous iPSC-derived smooth muscle cell therapy for treatment of urinary incontinence
Development of a noninvasive prenatal test for beta-hemoglobinopathies for earlier stem cell therapeutic interventions
Children’s Hospital Oakland Research Institute
Therapeutic development of an oxysterol with bone anabolic and anti-resorptive properties for intervention in osteoporosis
MAX BioPharma Inc.
Morphological and functional integration of stem cell derived retina organoid sheets into degenerating retina models
CIRM funds research trying to solve the Alzheimer’s puzzle
In science, there are a lot of terms that could easily mystify people without a research background; “translational” is not one of them. Translational research simply means to take findings from basic research and advance them into something that is ready to be tested in people in a clinical trial.
Yesterday our Governing Board approved $15 million in funding for four projects as part of our Translational Awards program, giving them the funding and support that we hope will ultimately result in them being tested in people.
Those projects use a variety of different approaches in tackling some very different diseases. For example, researchers at the Gladstone Institutes in San Francisco received $5.9 million to develop a new way to help the more than five million Americans battling Alzheimer’s disease. They want to generate brain cells to replace those damaged by Alzheimer’s, using induced pluripotent stem cells (iPSCs) – an adult cell that has been changed or reprogrammed so that it can then be changed into virtually any other cell in the body.
CIRM’s mission is to accelerate stem cell treatments to patients with unmet medical needs and Alzheimer’s – which has no cure and no effective long-term treatments – clearly represents an unmet medical need.
Another project approved by the Board is run by a team at Children’s Hospital Oakland Research Institute (CHORI). They got almost $4.5 million for their research helping people with sickle cell anemia, an inherited blood disorder that causes intense pain, and can result in strokes and organ damage. Sickle cell affects around 100,000 people in the US, mostly African Americans.
The CHORI team wants to use a new gene-editing tool called CRISPR-Cas9 to develop a method of editing the defective gene that causes Sickle Cell, creating a healthy, sickle-free blood supply for patients.
Right now, the only effective long-term treatment for sickle cell disease is a bone marrow transplant, but that requires a patient to have a matched donor – something that is hard to find. Even with a perfect donor the procedure can be risky, carrying with it potentially life-threatening complications. Using the patient’s own blood stem cells to create a therapy would remove those complications and even make it possible to talk about curing the disease.
While damaged cartilage isn’t life-threatening it does have huge quality of life implications for millions of people. Untreated cartilage damage can, over time lead to the degeneration of the joint, arthritis and chronic pain. Researchers at the University of Southern California (USC) were awarded $2.5 million to develop an off-the-shelf stem cell product that could be used to repair the damage.
The fourth and final award ($2.09 million) went to Ankasa Regenerative Therapeutics, which hopes to create a stem cell therapy for osteonecrosis. This is a painful, progressive disease caused by insufficient blood flow to the bones. Eventually the bones start to rot and die.
As Jonathan Thomas, Chair of the CIRM Board, said in a news release, we are hoping this is just the next step for these programs on their way to helping patients:
“These Translational Awards highlight our goal of creating a pipeline of projects, moving through different stages of research with an ultimate goal of a successful treatment. We are hopeful these projects will be able to use our newly created Stem Cell Center to speed up their progress and pave the way for approval by the FDA for a clinical trial in the next few years.”
Yesterday Dr. Lubin visited CIRM headquarters to talk about sickle cell disease (SCD). SCD is a group of inherited disorders caused by unhealthy, sickle-shaped red blood cells. People with SCD have abnormal hemoglobin, an important protein in red blood cells used to transport oxygen from the lungs to organs and tissues throughout the body.
The What, Why and Who of SCD
A mutation in the globlin gene leads to sickled red blood cells that clog up blood vessels
Genetic mutations in the hemoglobin genes lead to changes in the hemoglobin protein that cause normal, healthy disc-shaped red blood cells to take on a crescent, sickle shape. These sickle cells are a big problem because they stick to each other and to the walls of blood vessels, causing blockage and impeding blood flow. This leads to a plethora of clinical complications that we will touch on later in this blog.
Dr. Lubin shared some shocking facts including that 2 million African Americans are carriers of SCD mutations and 100,000 Americans have the disease. In the US, 1000 babies are born with SCD each year, but this number pales in comparison to the 1000 African babies that are born with SCD each day.
“So anything we do here with CIRM has a direct impact on sickle cell disease,” Lubin explained. “It’s something we should consider because it could have a global impact on SCD.”
SCD Affects Every Organ in the Body
Dr. Bertram Lubin
Dr. Lubin next discussed a laundry list of clinical manifestations associated with SCD, making it clear that SCD is not just a blood disorder, it affects every organ and tissue in the body. Examples he gave included infection, enlarged spleen, stroke, bone disease, retinopathy, and gastro-intestinal complications. And these were only a handful of the symptoms he discussed that SCD patients deal with.
However, Dr. Lubin emphasized that early detection of SCD in babies can drastically improve the quality and length of life of SCD patients. He proudly explained how California was the first state to screen every newborn baby for SCD (a procedure that is now done in every state) and that CHORI’s Center for Sickle Cell Disease and Thalassemia is one of the major SCD programs in the world. Their center “strives to improve public awareness of these diseases, expand the current knowledge base, and ultimately, to provide innovative treatment, care – and cures.”
Dr. Lubin also commented on the importance of knowing if patients who go to the ER or doctor have SCD:
Dr. Bertram Lubin
“With new born screening before we identified who had sickle cell disease, an African American child could come to the emergency room with a 103 F temperature. And they would say, well this is a virus, go home, and half of those kids would die by the next day. Because those with pneumococcal sepsis [a bacterial infection that SCD patients have an increased risk for] don’t last very long. Now when someone comes into the emergency room with a 103 F temperature and we know they have sickle cell, they get antibiotics right away. That told us there is a different way to do it and that really showed how genetics and public health can have an impact on the overall health of the population.”
Treatments and Hope for SCD
Dr. Lubin ended his talk by discussing the current management and treatment strategies for SCD patients. Early identification through universal newborn screening and family education are essential as well as preventative measures like penicillin and immunization to avoid infection.
As for therapeutic interventions, he mentioned blood transfusions, hydroxyurea treatments (which boosts the levels of healthy hemoglobin in blood cells), and bone marrow stem cell transplants. He said while bone marrow transplants have successfully treated some SCD patients, there are still many barriers to this form of treatment. Only 14% of families of SCD patients have an HLA-identical sibling donor and only 19% have an unrelated HLA-matched donor. Additionally, some doctors avoid recommending bone marrow transplants to SCD patients because of the risks for transplant rejection (graft vs. host disease) and death.
However, Dr. Lubin is hopeful that recent advances in stem cell research and genome engineering will one day make stem cell transplants the go-to treatment for SCD patients.
He ended with:
“The future of curative therapies that will have broad availability for SCD might follow advances in genomic correction of sickle mutation in hematopoietic [bone marrow] stem cells.”