The stem cellsman: Lawrence Goldstein
When it comes to regenerative research, UCSD neuroscientist no dummy
BY SCOTT LAFEE, UNION-TRIBUNE STAFF WRITER
MONDAY, MARCH 22, 2010 AT 12:03 A.M.
JOHN GIBBINS / UNION-TRIBUNE
UCSD neurologist Lawrence Goldstein, a leading stem cell expert, co-authored the book "Stem Cells for Dummies."
Derived from human embryonic stem cells, precursor neural cells grow in a lab dish and generate mature neurons (red) and glial cells (green), in the lab of University of Wisconsin-Madison neurodevelopmental biologist Su-Chun Zhang.
Lawrence Goldstein may not be the face of stem cell research, but the professor of cellular and molecular medicine at the University of California San Diego is certainly among its most vocal and staunchest advocates — and a leading researcher in the field.
He helped write Proposition 71, the unprecedented 2004 proposal to create a $3 billion funding organization in California to support stem cell research. The proposition passed with almost 60 percent of the vote. Goldstein’s lab, meanwhile, is using stem cell technologies to investigate a diverse range of human diseases, from cancer to Alzheimer’s.
This month, Goldstein and co-author Meg Schneider, a writer, published “Stem Cells for Dummies.”
QUESTION: Why write a “Stem Cells for Dummies” book?
ANSWER: We live in an increasingly technological and science-driven society, and people who are not scientists need easy access to information that will help them understand what’s going on inside all of our university labs, because at the end of the day, they’re the ones who are paying with their tax dollars for all of the research we do.
With stem cells in particular, it’s important that people are able to form opinions and make decisions — ethical, scientific, financial — based on accurate, objective, up-to-date information. There’s not a lot of that out there.
It’s a funny thing about the Dummies books. As a professional academician, I guess I could worry about them being sort of insulting to the average person and maybe not suitably dignified for an ivory-tower resident. On the other hand, they have a long and honorable history. Everybody has a couple on their shelves. They know these are books in which they’re going to get reasonable content, sensibly written in a way they can understand.
I respect people who are not scientists. I don’t assume scientists are simply smarter than everybody else. They just know and understand a specific language and set of ideas or concepts. Some scientists are pretty damn smart, but some nonscientists are pretty damn smart, too.
QUESTION: Stem cell research isn’t new, but it’s only in recent years that the public has really become aware of it and embraced the possibilities. Are these the glory days of stem cell research?
ANSWER: No, I think we’re just now picking up speed. I would turn the question around, and ask what are the problems to be resolved? We’re talking about questions of pure science and then how to apply that knowledge to human disease. We’re asking how stem cells can help solve human disease. That’s a question of huge magnitude. We spend hundreds of billions in treatment for hundreds of diseases, often with poor results. We have expensive therapies that don’t change the course of diseases like Alzheimer’s or Parkinson’s. They may improve symptoms, but they don’t address why the disease is raging. I look at it that way and I think that, as a nation, we’re wildly under-invested in medical research, as we are in a lot of areas of science and technology.
The thing that is new and different now is that basically for the last 50 years of biomedical research, we’ve worked only on nonhuman systems: yeast, fruit flies, worms, mice. Stem cells are a tool that can be applied to human systems. We’re at the beginning of a process that will truly crack open human cell biology and physiology.
QUESTION: There is a lot of talk about stem cells leading to possible treatments, even cures, for many difficult diseases and conditions. Does such talk concern you? Is it hyperbole? Are people’s expectations too great?
ANSWER: Of course, I’m worried about it. No scientist wants to make unrealistic projections. On other hand, you can’t look at stem cells and not see the enormous potential. I think what’s lost is not the potential, but the sense of time.
Things are changing fast. Some of the things we do now were science fiction when I was an undergrad at UCSD 30 years ago. But it’s still progress measured in terms of years and decades. There’s a kind of disconnect in expectations. How long does it take to achieve a real breakthrough? To actually solve a disease? There’s no way to make that prediction. Research is about discovering what you don’t know. You can discover something that makes the research go faster or something that makes it go slower. Breakthroughs and setbacks happen constantly. If you look across the whole spectrum of effort, there is some pretty amazing progress happening almost every day, but it isn’t always happening where you most want it.
QUESTION: When people discuss or debate stem cell research, often they’re talking about human embryonic stem cells (ESC), which are controversial for some because they are derived from early-stage human embryos. ESCs have the ability to become many different kinds of cell. Does that make them the gold standard? Can they be replaced by other kinds of stem cells?
ANSWER: I don’t think anybody knows yet. Again, it’s an issue of research: We’ve got to do the work and figure it out. But the question can be addressed another way. Imagine for a moment that there were no ethical issues raised regarding embryonic stem cells. If there weren’t, they would simply be an important tool in the toolbox, but not the only tool.
Right now, they are clearly much better understood than other kinds of cells. People have been looking at them longer. And they definitely have special, unique properties. But whether this will be true three years from now, who knows.
QUESTION: Do you have pet peeves regarding how the public perceives stem cell research?
ANSWER: I have a few.
The first is the myth that human embryonic stem cells come from aborted fetuses. This is nonsense. It’s just not true. These stem cells come from frozen blastocysts (a very early embryo consisting of 150-300 cells) not used in in-vitro fertilization procedures. These cells are going to be discarded, no matter what. End of story. There’s no abortion involved.
Second, people sometimes think stem cell research is just one thing. In fact, the research covers lots of different kinds of stem cells with different properties related to different diseases. No one kind of stem cell can substitute for another. What makes ESCs so special is they can make many kinds of stem cells that we can’t otherwise get in reasonable qualities.
Third, there’s the oft-repeated myth that adult stem cells can do everything. This is completely undocumented and misleading. People have to remember that a collection of press releases doesn’t establish a fact. Just because one or two scientists think something may be true doesn’t necessarily define it as an independently reproducible, consistent, useful finding that forms a correct foundation.
Fourth and most dangerous are the pronouncements by some people that adult stem cells can cure any disease. This has resulted in a proliferation of clinics across the border and around the world that will, for a price, offer unproven therapies. People go to them for help without enough information necessarily to know what they’re getting. These clinics are unregulated. There’s no accountability to make sure they tell the truth. The treatments are so hyped that people are putting their lives at risk. We’re seeing cases of people who have gone to these clinics and come back with real damage.
QUESTION: If the ethical debate over ESCs could be resolved, would it be full-speed ahead?
ANSWER: If that debate went away, then the big issue becomes determining the appropriate level of social investment in the science. That’s a much bigger issue than people realize. We need to train many more scientists. We need to invent the things we will need to progress. All of that takes money, and it’s something private companies cannot do. In this, society really is the only deep pocket, the only thing with any durability.
QUESTION: Stem cell therapies have proved effective in treating some blood disorders. Where do you see the next big, sustained advance?
ANSWER: You’re never going to pin me down on that one because just one experiment can reveal something that either completely derails an avenue of research or brings it to fruition twice as fast.
QUESTION: What about cancer? Are stem cells a possible magic bullet there?
ANSWER: I think we’ve made some pretty significant strides in cancer treatments without stem cells. The notion of a magic bullet for most diseases is misleading. Even when you have one, it usually only works for while. Medicine is like a war. It’s one foot in front of the other. It’s incremental progress as you gradually push back a disease, turning what was once lethal to chronic. Take HIV. That diagnosis used to be a death sentence, often in less than a year. And it was an ugly death.
But some folks figured out how to put together individual drugs that ultimately lead to cocktail therapies. There’s still a long way to go, but HIV is now mostly a chronic disease, something people can live with for a long time.
In the future, we’ll have new treatments, and there’s plenty of precedent to expect they will make a big difference. I’m a little uncomfortable with the notion of cures. It’s pretty hard to see how we can cure certain disorders, but I can see big advances for many diseases like HIV or diabetes.
QUESTION: What about neurological conditions?
ANSWER: This is where I think we have the most potential for benefit, if only because our current approaches are so bad. If you get Lou Gehrig’s disease (Amyotrophic lateral sclerosis), there’s not much we can do right now. Same with Alzheimer’s disease. We can provide some symptomatic relief, but these treatments don’t really change the course of the disease.
The picture has been so bleak that some pretty minor improvements will make a big difference.
QUESTION: But you see possibilities — cracks in the black box that is the human brain — where stem cell research might really help?
ANSWER: Absolutely. It’s just a question of how long it will take. We will eventually figure out the human brain, and stem cells will make a huge difference. They accelerate the process of discovery. Embryonic stem cells and reprogrammed cells are great sources of neurons for study, for testing of drugs. We didn’t have these tools 10 years ago. All you could get were brains after people had died. Or you worked on the brains of mice or fruit flies. Those are great model systems. We have learned a lot from them. The principals of neurological function work similar across many species, but the parts aren’t interchangeable. A human brain is different from other brains in important ways. And neurons from human stem cells allow us to work directly upon human pathologies. That’s revolutionary. It’s a paradigm breaker.
QUESTION: If you could resolve any one mystery about stem cells or make a singular, profound advance in your lab, what would it be?
ANSWER: I want to crack what’s gone wrong with the brain in Alzheimer’s disease. I want to know why those neurons get sick and die. I think stem cell science is the technology to do it.
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