Xconomist of the Week: Evan Snyder—Stem Cell Reality Check

5/25/12Follow @bvbigelow

San Diego Xconomist Evan Snyder has been called a “stem cell revolutionary” and is regarded as a father in the field of stem cell research. When we talked in his office at San Diego’s Sanford-Burnham Medical Research Institute, he told me he isolated the first neural stem cell in the mid-1980s, as well as the first human neural stem cell in 1998. Snyder’s team demonstrated the concept of stem cell pathotropism (the ability of stem cells to home in on injured or diseased regions of the brain) and helped to establish the concept that stem cells can be used to regenerate and repair diseased and damaged tissue.

He arrived in San Diego in 2003 to serve as a professor and director of the Stem Cells and Regenerative Biology Program at the Sanford-Burnham. He also is a scientific leader and researcher at San Diego’s new $127 million Sanford Consortium for Regenerative Medicine. While Snyder is focused primarily on basic research, he talked with me about the prospects for commercial development of stem cell technology—and how the much-publicized regenerative properties of stem cells, while holding tremendous long-term promise, will likely not be the focus of the first market successes. Our conversation, which I’ve condensed and edited, follows here.

Xconomy: My general impression is that much of the early promise and enthusiasm over stem cells has been dissipating.

Evan Snyder: I don’t think I would agree with that. I think there’s an enormous amount of promise.

X: I mean in terms of using stem cells in commercial applications.

ES: What the companies and the public thought was that it wouldn’t take any work, that you’d have a cell and you would sprinkle it with pixie dust and everything would get better. That was certainly unrealistic. It might have been fomented by scientists in the early days who were just totally enamored of the fact that you had cells that could read environmental cues and go down different pathways, and they seemed to do this based on their own intrinsic programming.

But the fine-tuning in the use of stem cells still comes down to really understanding the biology of the cell. That also entails understanding the biology of development, because stem cells really are just a part of fundamental development.

An even more vexing problem has nothing to do with stem cell biology. It has to do with people’s knowledge of the disease state. That’s where probably the biggest obstacle is. It’s with the people studying the disease who don’t know [precisely] what needs to be fixed. As an example, a mother might want us to use stem cells to fix her child’s autism. What’s wrong in autism? What do you want me to fix? I’m ready. I’m here. Just tell me what cell type you want. Tell me what connection you want. Nobody knows.

So I would say the stem cell field is doing really amazingly well, considering how young a field it is. It certainly is if you put it in perspective with other therapies that we now take for granted. For example, everybody does bone marrow transplantation now. We take it for granted. It’s taken us 50 years to be able to make bone marrow transplantation routine. I was an intern in the 1980s, and bone marrow transplantation for kids was still an experimental therapy, and most of the patients died.

X. I guess I was thinking of the enthusiasm surrounding some ventures that were founded to develop gene therapy, where they were using an engineered virus to insert a gene into cells.

ES: There already are ongoing clinical trials that are using stem cells that way. They’re taking a gene and putting it into a stem cell and having it go to areas of injury. There’s a clinical trial to treat brain tumors like that.

When most people think about stem cell research, they think about replacing missing cells—cells that are missing because of a stroke, a spinal cord injury, Parkinson’s, or ALS. You’ve had a heart attack and you want the dead cells replaced. Or you’ve got arthritis and you want your normal joint back.

As a business model, it really depends I suppose on the timeline for the company. It kind of depends on what your VCs are asking of you in terms of how much time you have to get moving and what your target is.

There are some companies that are based on stem cell research that seem to be doing OK. There’s Advanced Cell Technology [in Santa Monica, CA]. They have a clinical trial going for macular degeneration. Stem Cells [based in Newark, CA] has a trial that they’re going to try to do on spinal cord injury, and they started a clinical trial on Batten’s disease.

Again, it has nothing to do with the stem cell field. It has more to do with business and the patient population. Geron, a very well-funded company in the Bay Area, was in the midst of a clinical trial to use stem cell-derived products for repairing spinal cord injury. They had gotten an infusion of money from VCs, they had gotten an infusion of money from CIRM (the California Institute for Regenerative Medicine), and Geron abruptly terminated their trial.

They terminated it after they got a new CEO. What he said was that it had nothing to do with any complications. It had nothing to do with producing the cells. But they did a quick calculation, and saw how much it was going to be to do a full Phase I trial, recognized how much money it would take to do a Phase II and a Phase III trial. And they said there are not enough patients with spinal cord injuries to warrant a return on the investment. So it had nothing to do with stem cells.

A company doesn’t make a decision based on humanitarian indications or intellectual stimulation. They decided to turn the company completely [to focus] on cancer. They decided not to do anything neurologic at all.

Childhood diseases don’t have a chance. These are orphan diseases. Most neurological diseases are not money-makers. The diseases are horrible. The patients suffer. The families suffer, but it’s not a money-maker for companies. Maybe this is the reason you don’t go to the private sector and why the government does need to be involved in these diseases.

People won’t often talk about this, but a company would much rather sell a product that you’re going to need every day than something that’s going to [permanently] cure a disease. When we talk about stem cells, we talk about eradicating a disease. The goal in diabetes is not to continue taking insulin, it’s to give you back your insulin-producing cells so you don’t need anything at all. That’s not a money-maker, unless you’re charging a huge amount of money up front.

X: So what areas of promise do you see for stem cells?

ES: If we were having this discussion 50 years from now, I have no question that we would be talking about replacing circuitry and body parts and cell types and things of that sort. No doubt in my mind.

I rely on my colleagues—the disease biologists—to tell me the areas that they think need to be fixed. So that means using stem cells in transplantation. These cells actually do protect cells and connections and organs that are already there. Using them to detoxify toxic environments. Using them to diminish inflammation. Using them to promote the stem cells that already exist to grow and provide support, so for example using them to help blood vessels grow.

I think using the cells themselves to change a diseased environment so it becomes healthier is there for Lou Gehrig’s disease and Parkinson’s disease and even for some childhood diseases that are caused by rare enzyme deficiencies.

Another area of really low-hanging fruit are stem cells in a dish that model a disease. We call it disease in a dish. They can be used to understand the mechanism of a disease and identify new drug targets in developing a drug to treat the disease. There you have a drug that a company would find interesting and might take it from there

X: Won’t the costs of commercializing this technology decline over time as innovation lowers the cost for everyone in the industry?

ES: I think to an extent everything becomes a little bit easier. But then you hit new challenges. The reality is that it’s expensive no matter what. Research is expensive. What happens in science is that you see the mountain as your obstacle, and you fight, fight, fight to get to the top of the mountain. And then you realize that you just have a better view of the next mountain.

Bruce V. Bigelow is the editor of Xconomy San Diego. You can e-mail him at bbigelow@xconomy.com or call (619) 669-8788 Follow @bvbigelow

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