JAD ABUMRAD: Hello, I'm Jad Abumrad.

ROBERT KRULWICH: And I'm Robert Krulwich.

JAD: This is Radiolab. This hour we're gonna be talking about diagnoses.

ROBERT: Diagnosis, the easy kind, we're not gonna talk about it, no. Easy would be you come into my office and I'm a doctor. You have a broken arm, I take a picture, I say, "Hey, you've got a broken arm. The picture says so."

JAD: Yeah, because you can see the break right there.

ROBERT: But, let's suppose you came into my office and you were sad.

JAD: Mmm.

ROBERT: You tell me that your sex drive is down.

JAD: Hey!

ROBERT: I'm the doctor, so it's just between you and me.

JAD: All right.

ROBERT: Well right away, my learning tells me that you may be a candidate for depression. But how do I know that you're depressed?

JAD: What do you mean, "How do I know?" We talk about it. You just said.

ROBERT: Well, you can't measure sadness or depression. You can't go to a test tube and count anything.

JAD: Right.

ROBERT: It's not hard science.

JAD: Yeah, because ...

ROBERT: Until now! What if I put you in, you know, one of those FMRI machines that we've talked about so often?

JAD: Yeah.

ROBERT: I snap a picture of your brain in action, and I look at it. And from your picture I say, "You are depressed."

JAD: You're gonna tell me I'm depressed just from looking at a picture of my brain?

ROBERT: Yes.

JAD: What? No way.

ERIC KANDEL: Look, it's now here.

ROBERT: Photographic diagnosis of mental illness.

ERIC KANDEL: This is happening. There is no question.

ROBERT: And that, by the way, is Eric Kandel, a professor at Columbia University who just happens to have won [coughs] the Nobel Prize for Medicine.

ERIC KANDEL: Let me give you a little historical background.

ROBERT: Did you get a Nobel? I don't think you did.

JAD: [laughs] I still don't believe you. And what, just because he's got a Nobel Prize, I'm gonna suddenly turn around and ...

ROBERT: No, no, no. You're not. So let's do this step by step, okay?

ANNOUNCER: Step one.

ROBERT: Imagine you're slipping into an FMRI machine, okay?

JAD: All right.

ROBERT: Now I want you to just look at my face.

JAD: Why?

ROBERT: Is that so difficult?

JAD: No, I just want to know where this is going. Anyway, I'm looking at your face.

ROBERT: So now that you're looking at my face ...

ERIC KANDEL: Different regions of the brain, they become active.

ROBERT: There are cells in your brain that are saying, "I know him."

ERIC KANDEL: The cells are more active. They need energy. Just like when you run, you have to breathe fast.

ROBERT: And to get the energy ...

ERIC KANDEL: Your heart pumps more blood.

ROBERT: The body sends a rush of fresh blood to that particular group of cells. And because the blood has iron in it, the magnet in the brain scanner can see the iron, and therefore see the blood flow and take pictures of it—many, many pictures in real time.

ERIC KANDEL: I'll show you a very nice example of this.

ROBERT: Eric's now heading off across his ample office with an extraordinary view of the Hudson Valley.

ROBERT: And he brought over a picture of a human brain with different colors in different areas. And he told me, when you look at a face ...

ERIC KANDEL: When you imagine the face, this area lights up.

ROBERT: You're pointing to an area of the brain?

ERIC KANDEL: An area of the brain.

ROBERT: Up above your—on your forehead kind of.

ERIC KANDEL: That's right. That's right. If you look at a house, some other area lights up, but this area does not light up. You look at another face, this area lights up again.

JAD: Every time you see a face, the same area?

ROBERT: Yep.

JAD: Hmm. But you haven't told me anything about emotions yet.

ROBERT: That's true. So let's move onto step ...

ANNOUNCER: Two.

ROBERT: Because we use faces to tell what someone else is thinking or someone else is feeling, looking at faces also triggers ...

ERIC KANDEL: ... an area deep in the brain that is concerned with emotion.

ROBERT: Called the amygdala.

ERIC KANDEL: [clears throat]

ROBERT: Now very recently ...

ERIC KANDEL: A number of people have looked at the amygdala while looking at faces, and it's extremely interesting.

ANNOUNCER: Step three.

CYNTHIA FU: Okay.

ROBERT: I'm gonna take you now to London.

CYNTHIA FU: Hello?

ROBERT: Hi.

CYNTHIA FU: Yeah, hi.

ROBERT: Yeah, that's good. That's good.

JAD: Hey, who's this?

ROBERT: Oh, right. Sorry.

ROBERT: Who are you?

CYNTHIA FU: I'm Cynthia Fu. I'm a psychiatrist at The Institute of Psychiatry, King's College, London.

ROBERT: And are you, like, in your 30s or your 40s or your 50s?

CYNTHIA FU: [laughs] Is this is part of the interview?

ROBERT: [laughs] Because I ...

JAD: Rude!

ROBERT: No, I wanted to establish that she came into psychiatry ...

CYNTHIA FU: I'm trying to think. When did I graduate medical school?

ROBERT: ... at a very critical time.

CYNTHIA FU: I finished my training in '97, my training in psychiatry in '97.

ROBERT: That's 1997, when the FMRI machines were first becoming available. And so Cynthia was able to do a rather amazing study.

JAD: What?

CYNTHIA FU: In this study ...

ROBERT: ... she got together a group of people who were clinically depressed.

CYNTHIA FU: Depressed people.

ROBERT: And then another group of people who were normal.

CYNTHIA FU: Healthy people.

ROBERT: And she put them in the brain scan machine and showed them ...

CYNTHIA FU: ... facial expressions.

ROBERT: ... faces.

CYNTHIA FU: Ranging from more neutral expressions to more sad expressions.

ROBERT: So they saw a sad face and then a neutral face and then a sad face?

CYNTHIA FU: That's right.

ROBERT: And what the person in the machine was supposed to do is ...

CYNTHIA FU: ... to look at these faces, and decide whether it was a man or a woman's face.

JAD: Huh? What does that have to do with anything?

ROBERT: Because—because while they were doing that ...

CYNTHIA FU: While they're making this decision, the emotion of the face is being processed automatically.

ROBERT: The amygdala sees the emotion on the faces at that moment, and the machine ...

CYNTHIA FU: ... is like "Tick, tick, tick, tick, tick." [laughs] And there were hundreds of pictures.

ROBERT: Tenth of a second to tenth of a second to tenth of a second.

CYNTHIA FU: That's right.

ROBERT: Did you see a difference between the people who were depressed and the people who were normal?

CYNTHIA FU: Yes.

ROBERT: Was it a significant difference or a just barely difference?

CYNTHIA FU: As a group, it was a significant difference.

ROBERT: And now she takes the big step.

ANNOUNCER: Step four.

ROBERT: From the pattern she sees in bunches of people, she feeds all those patterns into a computer ...

CYNTHIA FU: ... called machine learning. Told the program, "This is a pattern of brain activity in depressed people, and this is a pattern of brain activity in healthy people." And then ...

ROBERT: ... she shows the computer a brain scan of a new person.

JAD: So this is someone the computer's never met before?

CYNTHIA FU: Exactly.

ROBERT: And she did this a bunch of times.

CYNTHIA FU: Right. A whole bunch of people.

ROBERT: And each time, the computer tries to guess. Is this new person ...

CYNTHIA FU: ... depressed or not?

JAD: Oh!

ROBERT: And what happened?

CYNTHIA FU: More than 85 percent of the time, 86 percent of the time, the algorithm correctly diagnosed whether that person was depressed or healthy.

ROBERT: With just a brain scan, a computer and a patient, no doctor needed, Cynthia's computer got the diagnosis right 86 percent of the time. A computer.

CYNTHIA FU: So we saw the results. It was like, "Wow, this is amazing!"

JAD: Wait a second. Has she repeated this?

ROBERT: Well, this is actually the very first time that this has been done with depression, and so it's just a pilot study. And like you say, someone else will have to do it again and then again and again. But according to Cynthia ...

CYNTHIA FU: The potential is fantastic.

ERIC KANDEL: Psychiatry is going to be absolutely revolutionized by this.

CYNTHIA FU: I think this method can be applied to any psychiatric disorder.

JAD: Any?

ROBERT: Autism.

ERIC KANDEL: Schizophrenia.

ROBERT: Obsessive-compulsive disorder.

JAD: No way! Come on!

ERIC KANDEL: Why not? Every one of these illnesses ultimately must have an anatomical basis. Every one of these illnesses.

ROBERT: So this means that it will soon or one day be possible for a patient to come in, and you take a picture of him in real time—or of her, and you will have a diagnostic tool. That's what you're saying.

ERIC KANDEL: Absolutely. Absolutely.

JAD: You mean to tell me that they're gonna put people in machines and just go boop!

ROBERT: No, no. Wait, wait. This is not a casual thing. You go to the doctor, you tell the doctor that you're feeling a certain way. The doctor will talk to you, and then he would come to you and say, "Well, my learning and the test tells me that you're ill." So that's all that's happening here is now the mental doctor will say ...

JAD: Okay. Yeah, sure, sure, sure. But there's nothing—there's nothing in this that feels invasive to you?

ROBERT: Well, obviously ...

JAD: It's tunneling into the deep depths of your personhood.

ROBERT: No you're not. No, this is—if you believe that mental illness is a mental illness, it is a structural condition which can be fixed. So it's not the deep inner you, it's the broken you.

JAD: So it's like the broken arm thing you started off with.

ROBERT: Yes.

JAD: So you would put the two side-by-side?

ROBERT: I think I would. And then of course you get to the next ...

JAD: No. Come on, Robert. I mean, human beings are way too messy for that. They're too messy for it to be that easy. No. No way.

ROBERT: So you think this is out of science's reach? Really? It's just too ...

JAD: There's a part of me that does think it is out of science.

ROBERT: I think it's because you think—you think that they're looking deep inside you. That's what you don't like.

JAD: I do. I mean, don't get me wrong. I find brain scans fascinating when it comes to questions like, "Where is the soul? What is consciousness?" That kind of stuff. But don't kind of get in my head and tell me what's right and what's wrong.

ROBERT: What if you're feeling sad and sick? Don't you want to get better?

JAD: Yes, but I enjoy the comfortable ambiguity that would come from a situation like sitting in a therapist's office and saying, "Well, how am I feeling? I'm feeling this way or that way." And in the messiness of trying to describe how you're feeling, there's a vast landscape of things that can happen, choices you can make, therapies you can pursue.

ROBERT: But let me just do it this way. Let's say you are sick and you know that you're sick—machine or no, okay?

JAD: Uh-huh.

ROBERT: If you are feeling badly, wouldn't it be nice if a machine could help you find the right kind of help?

JAD: What do you mean?

ROBERT: Well, Eric took me through a little thought experiment.

ERIC KANDEL: A mind experiment. You've developed a psychotherapy and I've developed a psychotherapy. We each claim it's the best in the world. Now we have an objective way of seeing. This machine allows you to, independently of any evaluation, see the outcome of treatment.

JAD: Oh, so you can audit the doctor.

ROBERT: Audit the doctor, and give you evidence that it's working or no.

JAD: Okay, I think I'm a little bit on board.

ROBERT: Yay! [laughs]

JAD: I can give you 10 percent buy-in now.

ROBERT: Okay.

JAD: So how far off is this stuff? Is it gonna come soon?

ROBERT: This is very early in the game, obviously, but I did ask him, like, how far into the future are we talking about here?

ROBERT: Soon? Or after—long after you're dead?

ERIC KANDEL: I'm gonna be around a long time.

ROBERT: [laughs] But the question stands: will you make it to see that people will actually have ...

ERIC KANDEL: You know, one can't in medicine, in all honesty, give a timeline for many of these things. Imaging methodology right now is quite sophisticated, but it's still primitive compared to where it needs to be. You're picking this up in statu nascendi. You become excited as the thing is beginning to emerge. We see it for the first time on the horizon.

ROBERT: So you're saying we got to this story too early. That's what you're suggesting.

ERIC KANDEL: Just right. It's not gonna be interesting 20 years from now, it'll be obvious.

JAD: Or in 20 years, it'll be obvious that we were wrong.

ROBERT: [laughs]

JAD: Okay? That's a real possibility, because what we don't know is a lot. Is vast.

ROBERT: Yeah.

JAD: And I want to tell you a story now about just how wrong people can be.

ROBERT: Okay.

JAD: It begins with a mystery.

ROBERT SAPOLSKY: Sudden Infant Death Syndrome. A perfectly healthy child goes to sleep and dies during the night.

JAD: It's about the worst thing that can happen to a parent. And each year it does happen about 7,000 times. And still no one knows why. Oh, and by the way, that was Robert Sapolsky. He's a ...

ROBERT SAPOLSKY: Professor of neuroscience at Stanford University.

JAD: And Sapolsky tells this story of the moment SIDS was diagnosed for the first time—or at least classified—in a terrible mistake that was made.

ROBERT SAPOLSKY: Around 1900 or so, people were beginning to recognize this is a disease entity, and nobody knew what was up. So people decided let's go dissect SIDS kids.

JAD: Meaning when a baby would die, they would perform an autopsy.

ROBERT SAPOLSKY: Exactly.

JAD: You know, check the baby's insides.

ROBERT SAPOLSKY: And see if there's anything different in them from normal kids.

JAD: That seems logical.

ROBERT SAPOLSKY: Absolutely.

JAD: They'd measure the size of the baby's lungs.

ROBERT SAPOLSKY: Yup.

JAD: That looked normal. And then they'd measure the size of the heart.

ROBERT SAPOLSKY: Yup.

JAD: Nothing strange there. Stomach.

ROBERT SAPOLSKY: Yup.

JAD: Kidney.

ROBERT SAPOLSKY: Yup.

JAD: Liver.

ROBERT SAPOLSKY: Yup.

JAD: Those are all fine. Then they would look in the throat.

ROBERT SAPOLSKY: They'd look in there and they'd say, "Oh, my God, these SIDS kids, they have enormous thymus glands!"

JAD: The thymus!

ROBERT: The thymus!

JAD: What is the thymus, you may wonder?

ROBERT: [laughs] Yeah, what is a thymus?

JAD: Well, it is a little tiny pink gland that is right here behind your collarbone at the base of your throat. And its job is to help you fight disease.

ROBERT SAPOLSKY: It makes one type of cell critical to your immune system.

JAD: Especially in times of stress.

ROBERT: Hmm.

JAD: In any case, normally this little organ is about the size of a tiny tube of toothpaste, like the travel kind.

ROBERT: Uh-huh.

JAD: But in these SIDS kids, it was ...

ROBERT SAPOLSKY: Huge. Humongous. Enormous.

JAD: ... twice the size.

ROBERT SAPOLSKY: Exactly.

JAD: And since the thymus is dangerously close to the windpipe, doctors came up with a hypothesis.

ROBERT SAPOLSKY: A perfectly reasonable hypothesis.

JAD: Which was that maybe, if you're one of these babies with an enlarged thymus and you're asleep and somehow you roll over wrong ...

ROBERT: Uh-huh.

JAD: Well, that gland might ...

ROBERT SAPOLSKY: ... press down on your trachea and suffocate you during the night.

ROBERT: Oh!

JAD: So ding ding ding! Medical mystery solved.

ROBERT: Really?

JAD: No.

ROBERT SAPOLSKY: They even came up with a name for it. It was called Status thymico-lymphaticus. It was in all the pediatric textbooks by the 1920s. And you would look in there and there'd be pictures, there would be pictures of the dissected thymuses. Normal size, and here on the right?

JAD: Enlarged.

ROBERT SAPOLSKY: Abnormally large Status thymico-lymphaticus.

JAD: And in no time at all, doctors came up with a treatment.

ROBERT SAPOLSKY: A perfectly logical therapy.

JAD: Which is that if we're gonna help these babies, we've gotta shrink their thymus glands. And to do that, the best solution obviously is to ...

ROBERT SAPOLSKY: Irradiate their throats. Irradiate their throats to shrink their thymus gland.

JAD: Zap the child's throat with trillions of radioactive particles.

ROBERT: Literally?

ROBERT SAPOLSKY: You betcha.

JAD: And this was considered, like, something every good, loving parent should do?

ROBERT SAPOLSKY: Absolutely. If you worry about your child being at risk for SIDS, go and get their throats irradiated to shrink the thymus glands.

JAD: And—and did it work?

ROBERT SAPOLSKY: Yes, it shrank the thymus glands.

JAD: But he says it did have another effect.

ROBERT SAPOLSKY: Decades later, you've killed 20 to 30,000 people with thyroid cancer.

ROBERT: 20-30,000 deaths. That's a—that's a real number.

ROBERT SAPOLSKY: Yeah. That's a—that's a fairly big one.

JAD: So here's my question.

ROBERT: Uh-huh.

JAD: How could these doctors have gotten it so, so, so, so, so wrong? Do you know what I mean?

ROBERT: I do. Well, don't you know what you mean? You just answered your own question a minute ago.

JAD: No, I didn't. I'm about to answer it right now.

ROBERT: They're—they're playing with radiation. You just said that. But what they—what they didn't know that radiation would hurt you. They had no—it was a brand new technology.

JAD: Yeah, but that's not what I was gonna—ah!

ROBERT SAPOLSKY: This was, you know, a couple of decades into radiation having been discovered.

[NEWS CLIP: Isotopes are performing near miracles of diagnosis and discovery.]

ROBERT SAPOLSKY: People were just tossing around radiation all over the place.

[NEWS CLIP: Iodine-131.]

[NEWS CLIP: Radioactive sodium.]

[NEWS CLIP: Radon.]

[NEWS CLIP: Gamma rays.]

[NEWS CLIP: Neutrons.]

ROBERT SAPOLSKY: And this was a period with Madame Curie, like, dipping her arm into vats of uranium.

[NEWS CLIP: Radioactivity is harmless.]

ROBERT SAPOLSKY: And dying soon afterward from cancer. People would go into shoe stores, and they would have their feet x-rayed.

[NEWS CLIP: Yes, x-ray is a wonderful invention.]

ROBERT: I had that!

ROBERT SAPOLSKY: You had that?

ROBERT: I did! Yeah. Take off your shoes, and then you could look at your bones.

ROBERT SAPOLSKY: That's exactly what they'd do.

JAD: Why would you do that?

ROBERT: That's what—that was the thing you could do at the shoe store. It was very cool.

ROBERT SAPOLSKY: Yeah, it's showing how cutting edge of a shoe store they are.

ROBERT: [laughs] Yeah.

ROBERT: So that's your explanation.

JAD: No! That may look like the explanation. I mean, sure, radiation played a role, but if you'd have let me say what I was gonna say, I would have told you the real explanation ...

ROBERT: Yes?

JAD: ... Preceded the radiation by, like, a couple hundred years.

ROBERT: Whoa! I have no idea what you're talking about.

JAD: [laughs] I'm gonna tell you. Back in the 1700s, okay?

ROBERT: Oh, that far back? Okay.

JAD: That far back. Before radiation, before your grandpa.

ROBERT: Before—before the Civil War or the Eiffel Tower or Napoleon!

JAD: I'm talking when the Redcoats ...

ROBERT: Were still wearing red.

JAD: Yeah.

ROBERT SAPOLSKY: Yeah. This was shortly after the Revolutionary War.

JAD: Right about this time, says Sapolsky, the first med schools started to pop up in America, and a supply and demand issue came into effect, because with these med schools came med students.

ROBERT SAPOLSKY: Medical students.

JAD: Who needed to learn about anatomy. And of course, in order to do that ...

ROBERT SAPOLSKY: ... they needed bodies.

JAD: You know, to dissect.

ROBERT SAPOLSKY: This produced this whole occupation. You could be a resurrectionist.

ROBERT: A resurrectionist?

ROBERT SAPOLSKY: Yup. And they would go out and dig up bodies at night, and sell them to the anatomists, to the medical schools.

[ACTOR, anatomist: "I'll need two more by Thursday."]

JAD: Now here's the key point: since demand was so high, the resurrectionists had to go where the bodies were easiest to get, which meant, you know, avoiding the fancy graveyards.

ROBERT SAPOLSKY: If you were wealthy you could have yourself buried in what was called a "patent coffin," which was a triple-layer coffin, which was meant to be resurrectionist proof.

JAD: But if you were not wealthy, no fancy coffin for you. You'd probably just be buried in a sack in some paupers' field just a few inches under the soil. Very accessible for these resurrectionists.

ROBERT SAPOLSKY: Not surprisingly, that's where they went.

ROBERT: Are we still on the same topic? Are you explaining why children die?

JAD: Yes, yes, yes. Bear with me.

ROBERT: All right.

JAD: What I'm trying to make is that the graverobbers targeted the poor so much so that sometimes when, you know, people would catch these resurrectionists in the act and see, like, "Oh my God, that's my dad you're digging up!" There'd be riots!

ROBERT SAPOLSKY: Troops were called out and rioters were shot.

JAD: Are we talking, like, hundreds of people, torch-bearing?

ROBERT SAPOLSKY: Yeah, it was townies versus the people who were trying to dissect their dead relatives.

ROBERT: Okay, okay, okay. This is a lot of history and I'm very "fascinated" in quotes, but what does this have to do with kids dying of ...?

JAD: All right. Let me bring it home.

ROBERT: Not that it hasn't been interesting, but bring it home.

JAD: Okay. As a result of all of this hubbub over graverobbing, country after country throughout Europe decided well, let's standardize how science gets its cadavers. Forget all this graverobbing. So they passed laws.

ROBERT SAPOLSKY: Which formalized anyone who died in a poor house, their body would be turned over to the anatomists.

JAD: This was like the cadaver version of direct deposit, okay? So graverobbing was gone, but now all the bodies used by medicine—not just some, but nearly all—now came from the poor.

ROBERT SAPOLSKY: Estimates were by the end of that century, 99 percent of the bodies used for anatomy lessons had been derived from poor houses.

JAD: And that seemed okay. Until ...

ROBERT SAPOLSKY: 1936, a guy named Hans Selye showed ...

JAD: ... that being poor actually warps your body. And now, Robert, now we come back to the case of the mysteriously enlarged thymus. Because if you're poor ...

ROBERT: Mm-hmm.

JAD: ... you're worried about your job. You're worried about feeding your family, you're worried about the bills. In other words, you are stressed out.

ROBERT SAPOLSKY: And during chronic stress, your immune system goes down the tubes.

JAD: And since the thymus is part of the immune system ...

ROBERT SAPOLSKY: If you are chronically stressed, the thymus gland shrinks.

JAD: Oh!

ROBERT: Oh!

JAD: For 150 years, doctors had been dissecting cadavers, pointing at organs which they thought were normal, but which were, in fact, shrunken from a life of poverty and stress and saying, "That's normal." So that when these SIDS babies show up with these gigantic thymuses, "Oh, my God!" In fact, that was the first time they'd ever seen a normal one.

ROBERT SAPOLSKY: People had no idea what was normal and what was abnormal. And they got it backwards.

JAD: Killing about 30,000 people in the process. Now the scary thing, says Sapolsky, is that these doctors were not dumb.

ROBERT SAPOLSKY: No. These were the best, most careful researchers at the time. And these were the only logical conclusions that could have been made. And nonetheless, it produced an utter disaster. There's, you know, not the slightest reason to think we're not doing the same thing right now.

JAD: Robert Sapolsky is a professor of neuroscience at Stanford University. He's the author of many great books, including Monkeyluv and The Trouble With Testosterone. For more information on him or anything that you heard in this hour, visit our website Radiolab.org. And you can send us an email while you're there.

ROBERT: Radiolab(@)wnyc.org is actually ...

JAD: That is the address.

ROBERT: Remember that.

JAD: Yep. I'm Jad Abumrad.

ROBERT: I'm Robert Krulwich.

JAD: Thanks for listening.

[ANSWERING MACHINE: Message 10. New. From an external number.]

[ROBERT SAPOLSKY: Okay. Radiolab is produced by Ellen Horne and Jad Abumrad. Our staff includes Lulu Miller, Jonathan Mitchell, Soren Wheeler, Amanda Aronczyk and Jessica Benko.]

[LISTENER: With help from Ann Boiko-Weyrauch, Ike Sriskandarajah, Hsi-Chang Lin, Heather Radke and Sally Herships. Special thanks to Karen Hablick, Justin Paul, Dr. Allen Olstrike and Taylor Dupree of 12K.com.]

[LISTENER: Radiolab is produced by WNYC, and distributed by National Public Radio.]

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