Budgeting for the future of the stem cell agency

ICOC_DEC17-24

The CIRM Board discusses the future of the Stem Cell Agency

Budgets are very rarely exciting things; but they are important. For example, it’s useful for a family to know when they go shopping exactly how much money they have so they know how much they can afford to spend. Stem cell agencies face the same constraints; you can’t spend more than you have. Last week the CIRM Board looked at what we have in the bank, and set us on a course to be able to do as many of the things we want to, with the money we have left.

First some context. Last year CIRM spent a shade over $306 million on a wide range of research from Discovery, the earliest stage, through Translational and into Clinical trials. We estimate that is going to leave us with approximately $335 million to spend in the coming years.

A couple of years ago our Board approved a 5 year Strategic Plan that laid out some pretty ambitious goals for us to achieve – such as funding 50 new clinical trials. At the time, that many clinical trials definitely felt like a stretch and we questioned if it would be possible. We’re proving that it is. In just two years we have funded 26 new clinical trials, so we are halfway to our goal, which is terrific. But it also means we are in danger of using up all our money faster than anticipated, and not having the time to meet all our goals.

Doing the math

So, for the last couple of months our Leadership Team has been crunching the numbers and looking for ways to use the money in the most effective and efficient way. Last week they presented their plan to the Board.

It boiled down to a few options.

  • Keep funding at the current rate and run out of money by 2019
  • Limit funding just to clinical trials, which would mean we could hit our 50 clinical trial goal by 2020 but would not have enough to fund Discovery and Translational level research
  • Place caps on how much we fund each clinical trial, enabling us to fund more clinical trials while having enough left over for Discovery and Translational awards

The Board went for the third option for some good reasons. The plan is consistent with the goals laid out in our Strategic Plan and it supports Discovery and Translational research, which are important elements in our drive to develop new therapies for patients.

Finding the right size cap

Here’s a look at the size of the caps on clinical trial funding. You’ll see that in the case of late stage pre-clinical work and Phase 1 clinical trials, the caps are still larger than the average amount we funded those stages last year. For Phase 2 the cap is almost the same as the average. For Phase 3 the cap is half the amount from last year, but we think at this stage Phase 3 trials should be better able to attract funding from other sources, such as industry or private investors.

cap awards

Another important reason why the Board chose option three – and here you’ll have to forgive me for being rather selfish – is that it means the Administration Budget (which pays the salaries of the CIRM team, including yours truly) will be enough to cover the cost of running this research plan until 2020.

The bottom line is that for 2018 we’ll be able to spend $130 million on clinical stage research, $30 million for Translational stage, and $10 million for Discovery. The impact the new funding caps will have on clinical stage projects is likely to be small (you can see the whole presentation and details of our plan here) but the freedom it gives us to support the broad range of our work is huge.

And here is where to go if you are interested in seeing the different funding opportunities at CIRM.

Creativity sparks a bright future for science

When some people want to see the future they use a crystal ball. Others use tarot cards or runes. But when anyone at CIRM wants to see the future all we have to do is look into the faces of the students in our Creativity program.

Creativity students 2015 with program director Dr. Mani Vessal (front & center with tie)

Creativity students 2015 with program director Dr. Mani Vessal (front & center with tie)

Over the past three years the Creativity program has given some 220 California high school students a chance to spend the summer working in a world-class stem cell research facility. And when I say work, I mean work. They are required to attend lectures, grow their own stem cells, and do experiments. In short, they are expected to do what all the other scientists in the lab do. In return they get a great experience, and a modest stipend for their effort. At the end they produce papers on their work with titles like:

  • Notch Signaling as a Possible Regulator of Mesenchymal Stromal Cell Differentiation in the Hematopoietic Stem Cell Niche
  • RNA Splicing Factor ZRSR2 in Human Erythroleukemia and Stem Cells

We also ask the students to either write a blog or create a video about their experiences over the summer. Many do both. We’ll come back to the video portion later this week. The blogs make for a great read because they chart the students as they progress from knowing little if anything about stem cells, to being quite proficient at working with them. And all in just 8 weeks. One of the hardest parts of our job is choosing the best blog. For example Alice Lin, part of the City of Hope program, got an honorable mention for her blog that was a “diary” written by an embryonic stem cell. Here’s a small sample of her approach:

‘Also, this is NOT YOUR TYPICAL LAB JOURNAL ENTRY. It’s an autobiography chronicling my life. That way, when the stem cell controversy cools down, the general public can get a FIRST HAND ACCOUNT of what we do. This blog is going to rack up some serious views someday. Until then, I’m attached to my colony and the plate.’

Ryan Hale, part of the Scripps team, wrote about how the experience taught him to think like a scientist:

‘One day, after performing an experiment, our mentor asked us the reason behind our experiment. He wasn’t asking us about the experimental procedure or quizzing us on the pre-reading packet, he wanted us to understand the thought process a researcher would go through to actually think up such an experiment… Our mentor stressed how important it is to be creative, inquisitive, and critical if one wants to become a successful researcher.’

Selena Zhang

Selena Zhang

The winner was Selena Zhang, also part of the City of Hope team. She writes about her experiences in the lab, learning the ropes, getting to understand the technology and language of science. But it’s her closing paragraph that sealed the deal for us. In a few short sentences she manages to capture the romance, the mystery and the magic of science. And we’re also happy to say that this program is coming back next year, and the year after that, for five more years. Our Board has just approved renewed funding. The name of the program is changing, it will be called SPARK, but the essence will remain the same. Giving young students a glimpse at a future in science. You don’t need a crystal ball to know that with these students the future is bright. Here’s Selena’s winning blog:

My very own lab coat. It was a lot to live up to, my freshly laundered lab coat with the City of Hope logo. Looking around the lab, I was nervous and excited to start my very first day. There were papers to read and meetings with my mentor to hear about my project. I was starstruck, as I learned that I would be working with induced pluripotent stem cells, Alzheimer’s disease, and CRISPR. Terms that seemed to only exist in textbooks and science magazines that I lovingly read at the library were suddenly alive to me. Although, embarrassingly enough, the only thing that came to mind when my mentor mentioned CRISPR was a salad crisper. Fairly certain that she was a) speaking about something else and b) that I needed to eat more for breakfast, I asked her what that was. It turned out that CRISPR was a new genome editing tool we could use to create isogenic lines to study the independent effects of each allele of the APOE gene that is the most significant risk factor for Alzheimer’s. We would do this by converting a patient and wild-type fibroblast into induced pluripotent stem cells. From this, we would edit a normal allele into the patient’s cell for rescue and the mutated allele in the wild-type cell for insertion, respectively. We would eventually differentiate these cells into neurons and astrocytes to study how the change of this allele can impact neural interaction. This was real science in progress, not enshrined in a textbook, but free, fluid, and vibrant. I slowly grew into my own independence around the lab. I found myself more confident and emotionally invested with each experiment, every immunostaining and PCR. Science, for all of its realism, had always seemed like the unimaginable fantasy to me. Through this opportunity, science has become more tangible, grounded in unglamorous details: hard work and deadlines, mistakes and mishaps, long lab meetings and missed lunches. Yet, that has only made me more confident that I want to pursue science. Now, I’m embracing a reality, one that gives me something worth striving for. In fact, I am very fortunate that my project has encountered numerous obstacles. My initial response to these problems was and still is a lot less Zen and a lot more panic-driven. But I’ve slowly come to realize the beauty of the troubleshooting process for progress. My project has been an emotional rollercoaster, as our rescue cell line met success, but couldn’t advance to the next stage. Our insertion cell line appeared to have incorporated the mutation, but it turned out it only incorporated one allele. It’s been a process of finding the balance between defending our ideas and accepting new ones, the border between defending and defensiveness. My curiosity and drive to improve, to understand, to conquer the unknown is learning to coexist with the need for patience and flexibility No matter how solid our theory should have been, reality is fickle and all the more interesting for it. I thought science was all about doubt and skepticism, questioning everything. Through this internship, I’ve learned that there’s also a surprising amount of faith, the faith to accept any setbacks as part of the discovery process. I thought I loved science before because I loved how enough facts could help me make sense of things. But through this internship in the lab, I’m learning to love a larger part of science, which is not only loving knowledge, but also loving not knowing, loving discovery for all of its uncertainty and perfect imperfections. I’m learning to grow into my lab coat, and hopefully, to find my place in the field of science.

Sonic Hedgehog provides pathway to fight blood cancers

Dr. Catriona Jamieson: Photo courtesy Moores Cancer Center, UCSD

Dr. Catriona Jamieson:
Photo courtesy Moores Cancer Center, UCSD

For a lot of people Sonic Hedgehog is a video game. But for stem cell researcher Dr. Catriona Jamieson it is a signaling pathway in the body that offers a way to tackle and defeat some deadly blood cancers.

Dr. Jamieson – a researcher at the University of California, San Diego (UCSD) – has a paper published online today in The Lancet Haematology that highlights the safety and dosing levels for a new drug to treat a variety of blood cancers. CIRM funding helped Dr. Jamieson develop this work.

The drug targets cancer stem cells, the kind of cell that is believed to be able to lie dormant and evade anti-cancer therapies before springing back into action, causing a recurrence of the cancer. The drug coaxes the cancer stem cells out of their hiding space in the bone marrow and gets them to move into the blood stream where they can be destroyed by chemotherapy.

In a news release Dr. Jamieson says the drug – known by the catchy name of PF-04449913 – uses the sonic Hedgehog signaling pathway, an important regulator of the way we develop, to attack the cancer:

“This drug gets that unwanted house guest to leave and never come back. It’s a significant step forward in treating people with refractory or resistant myeloid leukemia, myelodysplastic syndrome and myelofibrosis. It’s a bonus that the drug can be administered as easily as an aspirin, in a single, daily oral tablet.”

The goal of this first-in-human study was to test the drug for safety; so 47 adults with blood and marrow cancer were given daily doses of the drug for up to 28 days. Those who were able to tolerate the dosage, without experiencing any serious side effects, were then given a higher dose for the next 28 days. Those who experienced problems were taken off the therapy.

Of the 47 people who started the trial in 2010, 28 experienced side effects. However, only three of those were severe. The drug showed signs of clinical activity – meaning it seemed to have an impact on the disease – in 23 people, almost half of those enrolled in the study.

Because of that initial promise it is now being tested in five different Phase 2 clinical trials. Dr. Jamieson says three of those trials are at UCSD:

“Our hope is that this drug will enable more effective treatment to begin earlier and that with earlier intervention, we can alter the course of disease and remove the need for, or improve the chances of success with, bone marrow transplantation. It’s all about reducing the burden of disease by intervening early.”

New tech tool speeds up stem cell research

It’s hard to do a good job if you don’t have the right tools. Now researchers have access to a great new tool that could really help them accelerate their work, a tool its developers say “will revolutionize the way cell biologists develop” stem cell models to test in the lab.

Fluidigm's Castillo system

Fluidigm’s Callisto system

The device is called Callisto™. It was created by Fluidigm thanks to two grants from CIRM. The goal was to develop a device that would allow researchers more control and precision in the ways that they could turn stem cells into different kinds of cell. This is often a long, labor-intensive process requiring round-the-clock maintenance of the cells to get them to make the desired transformation.

Callisto changes that. The device has 32 chambers, giving researchers more control over the conditions that cells are stored in, even allowing them to create different environmental conditions for different groups of cells. All with much less human intervention.

Lila Collins, Ph.D., the CIRM Science Officer who has worked closely with Fluidigm on this project over the years, says this system has some big advantages over the past:

“Creating the optimal conditions for reprogramming, stem cell culture and stem cells has historically been a tedious and manually laborious task. This system allows a user to more efficiently test a variety of cellular stimuli at various times without having to stay tied to the bench. Once the chip is set up in the instrument, the user can go off and do other things.”

Having a machine that is faster and easier to use is not the only advantage Callisto offers, it also gives researchers the ability to systematically and simultaneously test different combinations of factors, to see which ones are most effective at changing stem cells into different kinds of cell. And once they know which combinations work best they can use Callisto to reproduce them time after time. That consistency means researchers in different parts of the world can create cells under exactly the same conditions, so that results from one study will more readily support and reflect results from another.

In a news release about Callisto,  Fluidigm’s President and CEO Gajus Worthington, says this could be tremendously useful in developing new therapies:

“Fluidigm aims to enable important research that would otherwise be impractical. The Callisto system incorporates some of our finest microfluidic technology to date, and will allow researchers to quickly and easily create complex cell culture environments. This in turn can help reveal how stems cells make fate decisions. Callisto makes challenging applications, such as cellular reprogramming and analysis, more accessible to a wide range of scientists. We believe this will move biological discovery forward significantly.”

And as Collins points out, Callisto doesn’t just do this on a bulk level, working with millions of cells at a time, the way the current methods do:

“Using a bulk method it’s possible that one might miss an important event in the mixture. The technology in this system allows the user to stimulate and study individual cells. In this way, one could measure changes in small sub-populations and find ways to increase or decrease them.”

Having the right tools doesn’t always mean you are going to succeed, but it certainly makes it a lot easier.