The promise of research with stem cells - Susan Solomon

So embryonic stem cells are really incredible cells. They're our body's own repair kits, and they're pluripotent, which means they can morph into all of the cells in our bodies. Soon, we actually will be able to use stem cells to replace cells that are damaged or diseased. But that's not what I want to talk to you about because right now there are some really extraordinary things that we are doing with stem cells that are completely changing the way we look and model disease, our ability to understand why we get sick, and even develop drugs.

I truly believe that stem cell research is going to allow our children to look at Alzheimer's and diabetes and other major diseases the way we view polio today, which is as a preventable disease. So here we have this incredible field, which has enormous hope for humanity, but much like IVF over 35 years ago until the birth of a healthy baby Louise, this field has been under siege politically and financially. Critical research is being challenged instead of supported, and we saw that it was really essential to have private safe haven laboratories where this work could be advanced without interference.

So in 2005, we started the New York Stem Cell Foundation Laboratory so that we would have a small organization that could do this work and support it. What we saw very quickly is that the world of both medical research and also developing drugs and treatments is dominated by, as you would expect, large organizations. But in a new field, sometimes large organizations really have trouble getting out of their own way, and sometimes they can't ask the right questions.

There is an enormous gap that's just gotten larger between academic research on the one hand and pharmaceutical companies and biotechs that are responsible for delivering all of our drugs and many of our treatments. So we knew that to really accelerate cures and therapies, we were going to have to address this with two things: new technologies and also a new research model. Because if you don't close that gap, you really are exactly where we are today, and that's what I want to focus on.

We spent the last couple of years pondering this, making a list of the different things that we had to do. We developed a new technology—its software and hardware—that actually can generate thousands and thousands of genetically diverse stem cell lines to create a global array, essentially avatars of ourselves. We did this because we think that it's actually going to allow us to realize the potential, the promise of all of the sequencing of the human genome.

But it's going to allow us, in doing that, to actually do clinical trials in a dish with human cells, not animal cells, to generate drugs and treatments that are much more effective, much safer, much faster, and at a much lower cost. So let me put that in perspective for you and give you some context. This is an extremely new field. In 1998, human embryonic stem cells were first identified, and just nine years later, a group of scientists in Japan were able to take skin cells and reprogram them with very powerful viruses to create a kind of pluripotent stem cell called an induced pluripotent stem cell, or what we refer to as an IPS cell.

This was really an extraordinary advance because although these cells are not human embryonic stem cells, which still remain the gold standard, they are terrific to use for modeling disease and potentially for drug discovery. So a few months later, in 2008, one of our scientists built on that research, took skin biopsies this time from people who had a disease, ALS, or as you call it in the UK, motor neuron disease. He turned them into the IPS cells that I've just told you about, and then he turned those IPS cells into the motor neurons that actually were dying in the disease.

So basically, what he did was to take a healthy cell and turn it into a sick cell, and he recapitulated the disease over and over again in the dish. This was extraordinary because it was the first time that we had a model of a disease from a living patient in living human cells. As he watched the disease unfold, he was able to discover that actually the motor neurons were dying in the disease in a different way than the field had previously thought.

There was another kind of cell that actually was sending out a toxin and contributing to the death of these motor neurons, and he simply couldn't see it until you had a human model. So you could really say that researchers trying to understand the cause of disease without being able to have human stem cell models were much like investigators trying to figure out what had gone terribly wrong in a plane crash without having a black box or a flight recorder.

They could hypothesize about what had gone wrong, but they really had no way of knowing what led to the terrible events. Stem cells really have given us the black box for diseases, and it's an unprecedented window. It really is extraordinary because you can recapitulate many diseases in a dish. You can see what begins to go wrong in the cellular conversation well before you would ever see symptoms appear in a patient.

This opens up the ability, which hopefully will become something that is routine in the near term, of using human cells to test for drugs. Right now, the way we test for drugs is pretty problematic. To bring a successful drug to market, it takes, on average, 13 years. That's one drug, with a sunk cost of four billion dollars, and only 1% of the drugs that start down that road are actually going to get there.

You can't imagine other businesses that you would think of going into that have this kind of model; it's a terrible business model. But it is really a worst social model because of, you know, what's involved and the cost to all of us. The way we develop drugs now is by testing promising compounds on cells. We didn't have disease modeling with human cells, so we've been testing them on cells of mice or other creatures, or cells that we engineer, but they don't have the characteristics of the diseases that we're actually trying to cure.

You know, we're not mice, and you can't go into a living person with an illness and just pull out a few brain cells or cardiac cells and then start fooling around in the lab to test for, you know, a promising drug. But what you can do with human stem cells now is actually create avatars, and you can create the cells, whether it's the live motor neurons or the beating cardiac cells or liver cells or other kinds of cells. You can test for drugs, promising compounds, on the actual cells that you're trying to affect.

This is now and it's absolutely extraordinary, and you're going to know at the beginning, the very early stages of doing your assay development and your testing. You're not going to have to wait 13 years until you've brought a drug to market only to find out that actually it doesn't work or, even worse, harms people. But it isn't really enough just to look at the cells from a few people or a small group of people because we have to step back. We've got to look at the big picture.

Look around this room; we are all different. A disease that I might have, if I had Alzheimer's disease or Parkinson's disease, probably would affect me differently than if one of you had that disease. And if we both had Parkinson's disease and we took the same medication, but we had different genetic makeup, we probably would have a different result.

It could well be that a drug that worked wonderfully for me would actually be ineffective for you. Similarly, it could be that a drug that is harmful for you is safe for me. You know, this seems totally obvious, but unfortunately, it is not the way that the pharmaceutical industry has been developing drugs because, until now, it hasn't had the tools.

So we need to move away from this one-size-fits-all model. The way we've been developing drugs is essentially like going into a shoe store; no one asks you what size you are or, you know, if you're going dancing or hiking. They just say, well, you have feet; here are your shoes. It doesn't work with shoes, and our bodies are many times more complicated than just our feet, so we really have to change this.

There was a very sad example of this in the last decade. There's a wonderful drug and a class of drugs, actually, but the particular drug was Vioxx. For people who were suffering from severe arthritis pain, the drug was an absolute lifesaver. But unfortunately, for another subset of those people, they suffered pretty severe heart side effects. For a subset of those people, the side effects were so severe—the cardiac side effects—that they were fatal.

But imagine a different scenario where we could have had an array of genetically diverse cardiac cells, and we could have actually tested that drug Vioxx in Petri dishes and figured out, well, okay, people with this genetic type are going to have cardiac side effects. People with these genetic subgroups or our genetic shoe sizes—about 25,000 of them—are not going to have any problems. The people for whom it was a lifesaver could have still taken their medicine, while the people for whom it was a disaster or fatal would never have been given it.

You can imagine a very different outcome for the company that had to withdraw the drug. So that is terrific, and we thought, all right, as we're trying to solve this problem, clearly we have to think about genetics; we have to think about human testing. But there's a fundamental problem because right now stem cell lines, as extraordinary as they are, are made by hand, one at a time, and it takes a couple of months.

This is not scalable, and also, when you do things by hand, even in the best laboratories, you have variations in techniques. You need to know if you're making a drug that the aspirin you're going to take out of the bottle on Monday is the same as the aspirin that's going to come out of the bottle on Wednesday. So, we looked at this and we thought, okay, artisanal is wonderful in, you know, your clothing and your bread and crafts, but artisanal really isn't going to work in stem cells. So we have to deal with this.

But even with that, there still was another big hurdle, and that actually brings us back to the mapping of the human genome. Because we are all different, we know from the sequencing of the human genome that it's shown us all of the A's, C's, G's, and T's that make up our genetic code. But that code by itself, or DNA, is like looking at the ones and zeros of the computer code without having a computer that can read it. It's like having an app without having a smartphone.

We needed to have a way of bringing the biology to that incredible data, and the way to do that was to find a stand-in, a biological stand-in, that could contain all of the genetic information but have it be arrayed in such a way as it could be read together and actually create this incredible avatar. We need to have stem cells from all the genetic subtypes that represent who we are.

So this is what we've built. It's an automated robotic technology. It has the capacity to produce thousands and thousands of stem cell lines. It's genetically arrayed, has massively parallel processing capability, and it's going to change the way drugs are discovered. We hope and I think eventually what's going to happen is that we're going to want to re-screen drugs on arrays like this that already exist.

All of the drugs that currently exist, and in the future, you're going to be taking drugs and treatments that have been tested for side effects on all of the relevant cells, on brain cells and heart cells and liver cells. It really has brought us to the threshold of personalized medicine. It's here now, and in our family, my son has type 1 diabetes, which is still an incurable disease, and I lost my parents to heart disease and cancer.

But I think that my story probably sounds familiar to you because probably a version of it is your story. At some point in our lives, all of us, or people we care about, become patients, and that's why I think that stem cell research is incredibly important for all of us.