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Science Talk

Shocking Research: Electroshock Therapy and Stem Cells

In this episode, journalist Larry Tye talks about his new book, SHOCK, written with electroshock patient Kitty Dukakis, wife of former governor and presidential candidate Michael Dukakis. Following Tye, Charles Welch, director of the Massachusetts General Hospital electroconvulsive therapy program, discusses the treatments knowns and unknowns. Then Scientific American editor Christine Soares shares some insights about an unusual stem cell research conference held last week in New York City. Plus we'll test your knowledge of some recent science in the news. Websites mentioned on this episode include www.egrandslam.com; www.sciam.com/news; blog.sciam.com.

Science Talk November 1, 2006 -- Electroshock Therapy; Stem Cell Research

Welcome to Science Talk, the weekly podcast of Scientific American for the seven days starting November 1st. I am Steve Mirsky. This week on the podcast, a couple of controversial subjects, electroshock therapy and stem cell research. Plus, we will test your knowledge about some recent science in the news. Scientific American editor Christine Soares attended a stem cell symposium last week and we will hear from her later. First up though, electroshock. A few weeks back I went to a session at the Massachusetts General Hospital featuring Kitty Dukakis and Larry Tye, the coauthors of a new book called simply Shock, as well as Dr. Charles Welch, the head of the hospital's ECT program. Dukakis is the wife of former governor and presidential candidate Michael Dukakis, and she says electroshock—more technically called electroconvulsive therapy—saved her life. Larry Tye is a veteran journalist and I spoke to him for a few minutes after the formal presentation.

Steve: Larry, good to talk to you.

Larry: Nice to talk to you.

Steve: Tell me about the things that surprised you as you were doing a research for this book.

Larry: There were several things that surprised me. One is I thought as a long time medical reporter that I understood a lot of the trends in psychiatry and medicine and I had no idea that ECT—that electric shock treatment—A, was still around and B, was as widely used as it is today. There were as many as a 100,000 people getting it each year in America, more than a million worldwide, and yet most of the public assumes this treatment went out with the cuckoo's nest.

Steve: How much damage did that movie do to the potential for people being treated with this modality?

Larry: I think it did lasting damage. The unfortunate thing is that it did its damage with an inaccurate portrayal of ECT at the time that Ken Kesey wrote his book, One flew Over the Cuckoo's Nest. At that time, ECT was being done with anesthesia, with muscle relaxant, and with oxygen, and it did not look like the torturous treatment that he described. ECT does have risks. People ought to know about those, but they shouldn't think it looks like The Cuckoo’s Nest because it doesn't.

Steve: Some of the risks are?

Larry: There are two kinds of risks: One is the medical risk and that is a risk that, it is a medical procedure and you need anesthesia and the risk medically is mainly the risk of the anesthesia itself. The risks in terms of side effects of the treatment are mainly memory loss. For most people, they are short-term memory loss surrounding the period of treatment. For some people, they are longer lasting and going back to a deeper period of memories and for some people they are devastating. For most people that I talked to—and I interviewed more than 100 people who had the treatment—they feel the risks meaning this memory loss is worth a benefit meaning keeping them alive and digging them out of this deep hole of depression.

Steve: Any other things that jumped out [as]of you as being unexpected while you were doing the research?

Larry: Yes; one thing that was quite surprising to me is ECT's effectiveness. Generally, for antidepressants if you are talking about them individually or as a cocktail, we talk about a 60 or more percent effectiveness rate. 60 percent of the people will positively experience the antidepressants in terms of reducing their depression. With ECT, the average is about a 75 percent effectiveness rate, which means that ECT is about the most effective treatment—one [that] has been weighed in scientific studies against the alternatives—about the most effective treatments out there.

Steve: So, it sounds like this is a treatment that has been stigmatized out of use.

Larry: Yes. In addition to people of having mental illness facing the stigma because of the mental illness, ECT is what Kitty Dukakis and I call the whisper treatment—that there is a double stigma; one is the stigma of the illness, the other is the stigma associated with the treatment. And I am not saying ECT is right for everybody, I am not saying that lots of people won't have side effects with it, I am saying that one of those side effects should not be the stigma of having had a treatment.

Steve: You mentioned in your prepared remarks earlier an interesting generation gap in the description; it's not clear what the mechanism of action is for ECT when you talked about how various people of different ages describe what it seems to do.

Larry: Yes, scientists have lots of wonderfully technical ways of describing what it's doing. Some people say it sort of mimics an effect of these SSRI antidepressants. Others say it might have actually an anticonvulsant effect and that's where the benefits come from. The descriptions I prefer are the metaphors that people who have had ECT themselves used. For people under 50, the active metaphor is it's like rebooting your computer. You are not sure why the rebooting produces magical effects, but very often it does. For people over 50, they prefer the metaphor of going by and kicking a TV set that has a fuzzy screen and sometimes the screen goes right; and again what they are expressing is that they don't really care [what] the mechanism [is] by which it works; they care [about] the fact that it has worked for them.

Steve: By that analogy, the brain is a PC and not a Mac.

Larry: Absolutely, and by that analogy the brain is really still too much of a black box. We are not sure why antidepressants that work, why they work, and we are not sure why ECT works.

Steve: Larry, thank you very much.

Larry: Thank you.

Steve: I also had a chance to talk to Dr. Welch, who runs Massachusetts General’s ECT program. Dr. Welch, thanks very much for talking to me today.

Welch: My pleasure.

Steve: Tell me about ECT in terms of our lack of real understanding and[of] how it works.

Welch: Although the mechanism of action of ECT is not known, there are some interesting clues to this question. We know for instance that the seizure is the effective component of the treatment. A grand mal seizure is an extraordinary event. It's sort of like if every light bulb in New York City was flashing on and off in exact synchrony three times per second. For some reason, this event resets brain chemistry in ways that we don't understand. It looks as though the things that are getting reset are the precisely regulated chemical pathways that modulate thought and affect in the brain. We think that the seizure in some way causes a reset of these very precisely regulated chemical pathways and which ones, well that's anybody's guess. My own favorite is that we are resetting ion channels. The sodium channel and the chloride channel really wear it out in terms of generating and regulating neurological impulses in the brain. Both of these channels have a number of receptors on them. This may be utterly too simplistic, but my favorite hunch is that by forcing the brain to shut off a seizure, we force the brain to mobilize stabilizing chemical pathways such as GABA—Gamma-aminobutyric acid—which then strike the chloride channel and force chloride into the cell, thereby increasing the electrical gradient across the cell membrane. The higher the gradient, the more stable that membrane is. Viewed this way, if this hypotheses were correct, it would mean that depression is basically an inability to maintain electrical stability in the brain, presumably mainly because of an inherited vulnerability and inherited weakness in the ability to maintain these electrochemical gradients on the cell membrane.

Steve: You want to talk for a moment about the challenges of doing research in a field like this where you have both ethical considerations and funding issues.

Welch: One of the problems with funding in ECT is that it is mainly government funded and there is no private entity that has any financial incentive to fund this research, unlike antidepressant drugs where there is invariably at least one pharmaceutical company that has a financial incentive to fund research. So, ECT research is underfunded in this country. A lot of the best research is coming out of institutions that have their own funding such as the New York State Psychiatric Institute, which has independent funding, or the Medical Research Counsel in Britain, which is an independent entity. So, that's one hurdle. The second hurdle is the obvious reality that the brain is a difficult research tissue. With other tissue, we can usually take a little slice or we can insert things into it to measure the physiologic function in[at] either at the macro level or the micro level. Even the slightest invasive technique in the brain raises some serious ethical problems, and so this is not a tissue that is readily available for research. Animal studies with brain tissue are, by and large, fairly frustrating because there is such an enormous difference between animal physiology and human physiology around the kinds of issues that we are dealing with.

Steve: And when I was talking about ethical considerations, people might have though I meant the ethics of zapping somebody with voltage, but in fact I am talking about the ethics of doing experiments with say a placebo treatment when you know that the actual treatment works so well.

Welch: ECT is clearly the most effective treatment for depression and the response rates in people who have failed antidepressants are reported as somewhere between 70 and 90 percent, i.e., 70 to 90 percent of people who have failed antidepressants will have a full remission of their disease with ECT. In that situation, it's pretty difficult to make a case for a placebo control trial.

Steve: What do you get by understanding the mechanism of action that you don't have now by knowing that it works?

Welch: What we all hope for is that someday we will have a way of inducing the chemical changes that ECT induces without having to put someone through the process of this treatment. It would be great if we could have ways of giving someone a medication or inducing some reset of these chemical pathways in another way with electrical fields or magnetic fields, some really reliable way of resetting the physiology of the brain that didn't involve undergoing a grand mal seizure, and so that would be the big payoff. If we can figure out the pathophysiology of depression, then I think it opens the door to creating a better treatment than ECT, but for now, I think ECT is here to stay for the foreseeable future. It's the only treatment we have that can reliably induce a full remission of depression or bipolar disorder in a majority of patients who have it.

Steve: Dr. Welch, thanks very much. We appreciate it.

Welch: My pleasure. Thanks for asking.

Steve: Again, the name of the book is Shock by Kitty Dukakis and Larry Tye, and for more on electroconvulsive therapy, check out [www.]ect.org.

Now it's time to play TOTALL.......Y BOGUS. Here are four science stories; only three are true. See if you know which story is TOTALL.......Y BOGUS.

Story number 1: Boy scouts can now earn a merit badge in respecting copyrights.

Story number 2: Two main TV stations will no longer air any news stories about global warming.

Story number 3: Kentucky Fried Chicken is switching to trans-fat-free oil by April.

Story number 4: A new computer game lets high-school students try to solve the Israeli-Palestinian conflict.

We'll be back with the answer, but first Scientific American editor Christine Soares attended an unusual stem cell research symposium last week in New York City. I was in Vermont attending the annual meeting of the Society of Environmental Journalists—more on that next week—and called Christine at her office at Manhattan.

Steve: Hi Christine, how are you?

Christine: I am good Steve. How are you?

Steve: Good. Tell me about the conference you were out at last week.

Christine: It was held at Rockefeller University and it was called a translational stem cell research conference, which means discussion of how to get stem cell research from petri dishes and mice to real human treatments for patients.

Steve: One of the interesting things about the conference is the organizers of the conference.

Christine: Yes, it's called the New York Stem Cell Foundation and it was founded just in the summer of 2005 by two women, Susan Solomon and Mary Elizabeth Bunzel, who are mothers of children with type 1 diabetes. And they set out to find out what they could do to accelerate the development of stem cell research into treatment.

Steve: You mentioned in your blog about this that one of the most encouraging things about this conference was that it was happening at all.

Christine: Well, yes it's a little bit unusual to have senior researchers in a very basic research field presenting their works to doctors to try to explain to them where it stands; why they are pursuing the questions they are pursuing; what they are learning; and what it will take to translate these promising results in the laboratory into treatments that are ready to be tried on people and in particular in the stem cell field. They are a little bit isolated by the lack of normal NIH funding and organization and so what was impressive about this organization and this meeting is that it's an example of the networks that this small foundation is creating between scientists and doctors and students—just faster communication. And they have provided several opportunities for scientists to get together and brainstorm, think of collaboration[s]; they have also built a laboratory where these collaborations can actually take place. They have gone beyond the traditional role of raising and providing funding and letting scientists just figure out what to do with it themselves. They are really creating networks and fostering progress.

Steve: You mentioned in the blog that one of the fears in the whole area of stem cell research is not the one that's often talked about or in addition to the one that's often talked about where you get a brain drain where people leave the U.S. because of their restrictions on the research and go to places like Singapore, where you can do the research; but what are all these folks are really afraid of is that people are just going to leave the field entirely.

Christine: Exactly, especially younger people who look around and see that [the] political and financial difficulties that stem cell researche[r]s [face] aren't there [in other fields] and decide to maybe pursue a politically easier line of work.

Steve: Politically easy, because this is like a career deadend, or you[it] can look that way for some people.

Christine: It can, it can; I mean, there is some funding that's quite a bit of impressive private money flowing into this research, but it's still not enough. I think as we talked about a little bit in a stem cell supplement we published last year, the venture capital world, the financial world is hanging back, you know, because this is a field that has not been able to yet translate its basic promising research into many clinical trials and treatments and they want to wait for that sort of proof. The stem cell field is a little bit isolated unnaturally and NIH plays a role that is beyond writing checks—it's an organizing principal: It fosters consortia just by giving grants for single project to multiple groups, it organizes meetings, its [sets] standards, and all of that is missing in the stem cell field. So, they are little bit out on their own and anything that brings them together in this way is helpful, I think.

Steve: Well, Christine thanks very much.

Christine: My pleasure Steve.

Steve: For more, check out Christine's blog entry at blog.sciam.com called "Found in translation". The entry includes links to the New York Stem Cell Foundation.

Now, it's time to see which story was TOTALL.......Y BOGUS. Let's review the four stories.

Story number 1: Merit badge for copyright respecting.

Story number 2: Two TV stations to ignore any global warming news.

Story number 3: KFC chicken to be trans-fat-free.

Story number 4: Computer game for solving Mideast crisis.

Time's up.

Story number 1 is true. The boy scouts have a "respect copyrights" activity patch—thanks to the Motion Picture Association of America. Make sure you don't make illegal copies of the patch, kids.

Story number 2 is true. Two Maine TV stations under the same general manager will only do global warming stories when "Bar Harbor is underwater." That's according to an article in the New York Times. The GM also likened global warming to the Y2K scare when nothing happened, perhaps because people took care of that problem in advance.

Story number 3 is true. Kentucky Fried Chicken is getting rid of oil with transfats. We will see if wings are still extra crispy with linolenic soybean oil.

All of which means that story number 4, about a computer game allowing kids to solve the Israeli-Palestinian crisis, is TOTALL.......Y BOGUS, not because there is no solution to the crisis, [but] because the new game only allows students to act as virtual journalists moving throughout the region interviewing characters, after which they write articles graded by the computer. Now, that's entertainment. For more, see the October 30th news article on the Scientific American Web site called "Computer Game Takes Journalists' View of Mideast".

Some notes we have been following the picks of baseball mathematician Bruce Bukiet throughout the playoffs. He gave the statistical odds to the Mets over the Cardinals for the NL title and then to the Tigers over the Cards in the World Series, which means his odds-on favorites went only one for seven in the postseason. The math was right, the players got it wrong. You can write to us at podcast@sciam.com. Check out science video news now available on our Web site, www.sciam.com, and sample the daily SciAm podcast, 60-Second Science, at the Web site and at iTunes. For Science Talk, the weekly podcast of Scientific American, I am Steve Mirsky. Thanks for clicking on us.

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