Thursday, December 10, 2009
On December 4, University of California San Diego researchers completed a 53-hour procedure methodically slicing and sectioning an entire human brain. The process was recorded and broadcast via live webcast. Viewers blogged, tweeted and debated the ethics of the experiment, communicating with researchers, all in real time.
MAUREEN CAVANAUGH (Host): I'm Maureen Cavanaugh. You're listening to These Days on KPBS. As the world watched, doctors at UCSD's Brain Observatory conducted a most unusual procedure last week. The brain of the man who was the most studied individual in the history of neuroscience was dissected into more than 2,000 paper-thin tissue sections. The 53-hour procedure was broadcast live on the web, and more than 400,000 people tuned in to watch at least one part of the procedure. Here to tell us the story of the amazing individual who donated the brain and how this extraordinary event occurred here in San Diego are my guests. Dr. Jacopo Annese is assistant professor of Radiology at the University of California San Diego. Dr. Annese, welcome to These Days.
DR. JACOPO ANNESE (Assistant Professor of Radiology, University of California San Diego): Hello. Good morning.
CAVANAUGH: And Dr. Suzanne Corkin is professor of Behavioral Neuroscience at MIT’s Department of Brain and Cognitive Sciences. Dr. Corkin, welcome.
DR. SUZANNE CORKIN (Professor, Behavioral Neuroscience, Massachusetts Institute of Technology): Thank you. Good afternoon.
CAVANAUGH: Good afternoon, good morning here. I want to start with Dr. Annese because I tried to encapsulate what happened but perhaps you can tell us a little bit more about what made this procedure such a landmark.
DR. ANNESE: Well, it was a landmark procedure because essentially we were waiting to see inside Mr. Molaison’s brain. The project was conceived to provide a picture, a neurological picture, of the state of Patient H.M.’s brain. It was the only explanation that we could give for validation for like four decades of research. And there were some MRI, magnetic resonance imaging, studies done but, of course, MRI is not – does not provide a very detailed picture. So the truth is in the actual tissues. Now the technologies that we used were very similar to MRI in a sense because it was still tomography, we were still imaging the brain as we were slicing. And – But, again, it was really to give a most clear anatomical picture of who this man was and the way – you know, his condition that was so popular, in fact.
CAVANAUGH: How long did you prepare for this after the death of Patient H.M.?
DR. ANNESE: Well, as soon as Patient H.M. died, Dr. Corkin called me. We had already arranged—and this, much to Dr. Corkin’s credit, everything was very well planned for that moment. And, you know, I had schedules of all the flights that would leave to – from San Diego into Boston. And, in fact, she called me at the afternoon of the second of December last year, and I took a red-eye Jet Blue flight to Boston and I was there in time for the next morning autopsy. Then it was really on my flight back—that was the first sleepless night, one of many—that on the way back I think I conceived the project the way that it’s unfolding now. And, in fact, when I was talking to your colleague Joe Palca last year, I sort of promised that this would be an open science project. I promised that my lab would open its doors to the public because of the enormous interest that the public also had for this fascinating story. And we prepared over this year and as – you know, we don’t really have the luxury of practice brains because all of our donors are part of studies and we also know their biography, so as we studied other cases, we fine tuned our procedures. And when I felt comfortable that we couldn’t really go any further with fine tuning, then that’s when we said we will do it.
CAVANAUGH: And is this the first time an entire brain was dissected?
DR. ANNESE: Disect – So we have…
CAVANAUGH: Sectioned. Sectioned.
DR. ANNESE: Sectioned, yes…
DR. ANNESE: …because the dissection was, for example, what I did to remove the blood vessels…
CAVANAUGH: Right, yes.
DR. ANNESE: …from the – that took about five hours. But – So the sectioning, yes, to, as they say in scientific publications, to the best of our knowledge. One has to be cautious. To the best of our knowledge it is the first time that a whole human brain is sectioned in one stretch, really, and not only sectioned but also imaged while sectioning, and the sections being collected for future study. That’s very important. So not only we were slivering this brain 70 microns at a time, but we were collecting the section and this is really – Those sections are, you know, it’s the pudding, it’s where the truth is. Those will give the histological, the microscopic detail that we need to really make a diagnosis, to really characterize the way this brain was. So, yes, I believe so, and it took forty – 53 hours and – but it was a team effort, and my lab behaved impeccably. I mean, everybody was really – I don’t think it could have gone any better.
CAVANAUGH: Before I speak with Dr. Corkin about the patient himself, I want to just talk to you just a little bit more, Dr. Annese, about the idea of putting this procedure on the web. You told us that you promised to make your lab open but you didn’t promise necessarily to have the whole world inside your lab. Was this a controversial thing to do? To put this procedure on the web?
DR. ANNESE: I – There was some controversy. We had, again, you know, we were open to public opinion and that was – I really wanted to have a direct connection. I did – Well, actually, frankly, it all started – My idea of opening the doors is because it was such a gift, this brain, but also such a responsibility that I really thought we would have to be very candid of what we were doing. And in case anything went wrong, I wanted to show that we were not unprepared or we were not being reckless or we were not being, you know, incompetent. So now we were at the judgment of my peers, my colleagues, and I think what was interesting is that the public – we were able to make a direct connection with the public. You know, sometimes we are, as scientists, are told that when you are speaking about this, imagine you are speaking to an eighth grader, and I don’t – You know, this proved that you can actually show the public and they’re not eighth graders. And, by the way, eighth graders watched and I’m very happy because some eighth graders want to become neuroscientists now. So this is another great, I think, legacy for H.M. If only – In fact, I told one interviewer, I say, if only one person decides to become a scientist or a neuroscientist because of this experiment, I will be happy and H.M. will even have contributed more to the field. And so it was a bit selfish because I wanted to be, you know, sort of not to have this huge responsibility but share it with my colleagues and also I think, yes, what happened it didn’t need PR. We did not have a PR plan. We did not make a fantasmagoric website with flashy images. We simply – You can imagine an artist is painting a painting and he opens the doors of his bodega and people walk by, some stopped, some watched in, some stayed. We had a very loyal following on Tweeter, which helped us through the longest night and this was where – Thursday night. This is not a metaphor. It really was the longest night.
DR. ANNESE: And I think thanks to them, they kept us engaged. We communicated through, again, not much technology there in terms of PR. I communicated via Post-its that I put in front of one small webcam and this sort of retrofilled us so I think apparently we invented analog posting. That’s what they said on Facebook, you know, analog Tweeting.
CAVANAUGH: Dr. Suzanne Corkin, you know, the world knew this gentleman as Patient H.M. but you knew him personally for years. Tell us about Patient H.M.
DR. CORKIN: Okay. Well, he grew up in the Hartford, Connecticut area. When he – And apparently had a normal birth and early life. But when he was a young boy, he was knocked down by a bicycle. He was unconscious for maybe five minutes and he got a cut on his forehead. When he was ten years old, he had his first minor seizure which was just what’s called a petit mal seizure or an absence. And I can tell you, give you a feel for what this was like, he might just be absent for five to 15 seconds and he might sway, bend his head, breathe heavily, and sometimes one hand would start scratching movements and he would scratch his other arm, his clothing, his belt. And then he would wake up, shake his head, and then he might say, I gotta come out of this again. And then he’d be dazed for a couple of seconds and then he would be fine. He would wake up instantly. So that started when he was 10 years old.
CAVANAUGH: And it’s my understanding that these episodes just increased to the point where he couldn’t work, he couldn’t do anything.
DR. CORKIN: Well, there’s more to the story. There’s another chapter here.
DR. CORKIN: When he was 16 years old and he was riding in the car with his parents, he had his first major seizure and your listeners might have seen people having seizures where they’re lying on the ground and they’re shaking and drooling and maybe biting their tongue. It’s a very serious kind of episode. So these started when he was 16. He went to high school and dropped out for a few years because the other boys teased him about his seizures. And then he went back again to East Hartford High School and he graduated when he was 21 years old. Now he was having seizures all this time and he was also receiving high doses of anticonvulsant medication which just weren’t doing the trick. So in – Around 1946, his family doctor referred him to a neurosurgeon at the Hartford Hospital, William Beecher Scoville, and Scoville started following him then, working him up to see if they could localize the seizures to a specific part of his brain but they weren’t able to. So the doses of medication kept increasing to the point where Henry was just pretty incapacitated. He’d had a couple of jobs, one at the Ace Electric Motor Company and one with Royal Typewriter but he had to give up the jobs because of his seizures. So he was basically just sitting home all day long with his parents. So…
CAVANAUGH: And we’re speaking about Henry Molaison, is that how you say his name?
DR. CORKIN: Mollison (phonetically).
DR. CORKIN: Henry Molaison.
CAVANAUGH: Henry Molaison then had this surgery finally…
DR. CORKIN: That’s right.
CAVANAUGH: …to try to stop these seizures that were making it impossible for him to continue his life. But what was the result of the surgery?
DR. CORKIN: He had the surgery in 1953 and as soon as he came out of the anesthesia or as soon as his, you know, confusion cleared after a day or so, it was immediately obvious that he couldn’t establish any new long term memories. He could remember things from before his operation like he could walk and talk and read and write and his vocabulary was normal but he could not establish any new memories or learn any new vocabulary.
CAVANAUGH: Now what kind of amnesia did he have?
DR. CORKIN: It’s called an anterograde amnesia, meaning it begins with an insult to the brain, in this case his operation in 1953, and it’s called global amnesia because his memory is impaired, no matter how you test his memory consciously, no matter what kinds of material you ask him to remember, pictures or words or stories or whatever, and no matter what sensory modality you deliver the information through, so it could be through vision, through hearing, through smell, through touch. So the deficit was indeed global.
CAVANAUGH: We have a clip from an interview with Henry Molaison, and let’s hear that right now. He’s speaking about his condition and how he spends a typical day.
DR. CORKIN: When you’re not at MIT, what do you do during a typical day?
MOLAISON (Patient H.M.): Umm, see, that’s what I don’t – I don’t remember things.
DR. CORKIN: Uh-huh. Do you know what you did yesterday?
MOLAISON: No, I don’t.
DR. CORKIN: How about this morning?
MOLAISON: I don’t even remember that.
DR. CORKIN: Could you tell me what you had for lunch today?
MOLAISON: I don’t know, tell you the truth. I’m not…
DR. CORKIN: What do you think you’ll do tomorrow?
MOLAISON: Whatever’s beneficial.
DR. CORKIN: Good answer. Have we ever met before, you and I?
MOLAISON: Yes. I think we have.
DR. CORKIN: Where?
MOLAISON: Well, in high school.
DR. CORKIN: In high school.
DR. CORKIN: Have we ever met any place besides high school?
MOLAISON: Well, to tell you the truth, I can’t – No, I don’t think so.
DR. CORKIN: Why am I here now?
MOLAISON: Well, you’re just having an interview with me, I see. That’s what I think right now.
DR. CORKIN: How do you feel about answering so many questions and doing all the tests that we give you?
MOLAISON: Well, I don’t mind. What it finds out about me helps you to help others.
DR. CORKIN: That’s right. That’s very true.
MOLAISON: And that – I figure that’s more important in a way.
CAVANAUGH: That was an interview conducted with Henry Molaison by Dr. Suzanne Corkin. And she interviewed Henry in 1992 when he was 66 years old. And, Dr. Corkin, I’m wondering, he knew that his brain was important to science then but tell us why his brain is important to science now.
DR. CORKIN: Well, I think the major reason is that we have over 50 years of behavioral data that we have collected with the cooperation of Henry and this includes measures of different kinds of memory. That’s important because there were certain things like motor skill learning that he could do normally. But it also includes things like measures of IQ, measures of sensory function, vision, hearing, visual perception and so we have – and also motor function, so we have this enormous database and what we can do now is to relate the tasks that he was impaired on to areas in his brain that were damaged and then we can link areas that he – kinds of behavioral performance that was normal to areas in his brain that were preserved. So we can, with the help of the autopsy material, we can make these very precise brain behavior correlations and this is a major component of systems neuroscience.
CAVANAUGH: And I’d like, Dr. Annese, to get your feeling on this as well.
DR. ANNESE: Well, that’s why we did the entire brain, because a normal autopsy or, generally speaking, normal neuropathological exam really examines only very few portions of the brain, a few square centimeters in several locations. Now, we had to, you know, when my lab received the brain, we had to make a job that was commensurate to 50 years of behavioral research, so it was certainly not enough to do an ordinary autopsy. And also because, really, the brain is like a – you can imagine it like an impressionistic painting but made of, in this case, 2400 layers. If you only – if somebody only gave you a little bit of canvas here and there, you would never make up the entire picture. So the techniques that were already under development and that we had generally pretty much mastered at the lab, I think we brought them to really a new level in anticipation of what we had to do eventually on the second of December. And so the goal is now in the second phase, now that we sort of have the first phase successfully completed so we have these sections available, is to stain using – we use antibodies, dyes, this is almost like alchemy in a sense, is to stain these 2400 tissues sections just like fabric, and those will reveal those features that, again – and that’s why this is an open science project. Again, because I cannot – I don’t think throughout my lifetime and throughout my whole career I could study alone H.M.’s brain at this point. So the goal is to just like we made available this procedure, is to make available all the images, all the data that we gradually uncover from this brain, which is like an archeologist who finds an artifact and has – and many different theories about human evolutions are revised because of this artifact. Now, if we make – The goal was we make this brain available, we illustrate it as much as we can using, again, these techniques and now we have digital microscopes that we can use to show almost like a Google map, a Google Earth, from the entire brain to the single cell. The next phase will be making all these images available to researchers worldwide so that everybody, more than just one lab, will contribute to, as I said—I apologize for abusing of metaphors here—but they will contribute to painting the picture of H.M.’s brain like Dr. Corkin explained because it is extremely important for memory research, for system neuroscience, and I think also if you – if I have a couple of seconds, it’s also important, I think, and I hope that it has set new standards in the way that we dissect, as we said in general, a human brain. How we follow up behavioral studies with autopsies and…
CAVANAUGH: And, in fact, I wanted to follow up on that because, in fact, Dr. Corkin, when you were thinking of where Mr. Molaison’s brain was going to be studied, you wanted Dr. Annese to come and meet Henry. And I wonder why that was important to you?
DR. CORKIN: Well, in a way I think it was important to Dr. Annese to see the person whose brain he was going to study so intensively in real life. I mean, this is the most famous brain in the world and we can’t even estimate the amount of knowledge that’s going to come out in the future when we make brain behavior correlations. But I thought that it was important for Dr. Annese to meet the real person while he was alive and, you know, just get a feel for the man and the importance of doing a fabulous job in the neuropathological examination and that’s what he’s done.
CAVANAUGH: And I am anglicizing your name a little bit, Dr. Annese, but…
DR. ANNESE: That’s fine.
CAVANAUGH: …I wonder what you – How that changed the experience for you, actually having met Patient H.M., Henry Molaison before you conducted this procedure.
DR. ANNESE: Well, it was – it added a more philosophical context to the whole study. But, you know, because my role is – has been, since I received the brain, to write a biography of this person based on the evidence that I find in the brain. So it’s a different type of biography than Dr. Corkin is writing. It’s really based on images. And knowing the person – although, you know, we spent about a couple of hours with him during his lunchtime. And it always, for example, during those 53 hours, you know, it is constant – it was a constant reminder of the sound of his voice, of his face, of his mannerism and I think that’s important. It will be carried on throughout this whole study and that’s why I think also these many thousand people were fascinated. I think they also felt the connection with the person. Some people didn’t know he was H.M. and then they went to – Wikipedia had a burst of hits, for example, because people were finding out who this brain was. And again, that’s very important to me, that there is a human aspect of this very rigorous scientific study but there is a story. And, hopefully, this can be replicated in other cases. We have normal donors and I’m working on interviews for their biography. I think it’s very important, the human brain library that we’re establishing at UCSD. It’s about this. H.M. probably will be always the most important manuscript that we’re aiming at preserving in this library but there are other cases that we are already receiving, they’re already – In fact, San Diegans, residents, that have donated their brains that we’re following up. Who will be other books in this library that will, you know, we will illustrate their story as well as we did for H.M. As I said, it’s – as a paradigm shift, it’s a very ambitious project because you’ve seen the amount of work that this entails. But I think the investment is relatively small for the gain. If in 10 years we have a library of several hundred cases, several hundred books, then I think that will be a major contribution to understand how the brain makes what we are.
CAVANAUGH: And I’m just wondering as you described this, this brain library that you are assembling, as I’m understanding you, this is a sort of a form of pure research. We don’t really know what we’re going to be learning but we know we’re going to be learning something.
DR. ANNESE: Well, there are some questions in science that are – still have the halo of mysticism like what makes a person have a talent for music? And then another person – There is a genetic factor. It is – I make this other example when I talk to reporters, for example, to imagine our brain as a musical instrument that we play all our life and we’re given the instrument that we’re given. Some people receive a violin that might not have a resonance or might not have a purity of sound but they can make that into the best music maybe than another person who had the – a really wonderful instrument. The study that we do, the sort of forensic study that we do, analyzes the way people have played this instrument. And from the wear and tear, we can tell, we can find this – the clues that tell us, you know, what kind of music people were playing. Again, this is – It’s almost away from – it’s almost outside of the real rigor of science but, again, we don’t know. MRI is telling us a lot. Thousands of people are being imaged with MRI and we have some correlations already between structure and function and behavior. Now we need to bring it to the next level. We need to go to the cellular level.
CAVANAUGH: Thank you so much. I appreciate both of you speaking with us…
DR. CORKIN: Could I just add something at the end?
DR. CORKIN: I just want to reinforce the thought that anybody who hears H.M.’s story, I think, can connect to it. And one of the – his important contributions is providing a bridge between the science of memory and everyday life. So his contributions to our understanding of the brain organization of memory are almost unfathomable, and also impressive is his equanimity throughout his entire life.
CAVANAUGH: Dr. Suzanne Corkin and Dr. Jacopo Annese thank you both so much for talking to us about this fantastic landmark procedure done at UCSD’s Brain Observatory. Thank you.
DR. ANNESE: Thank you.
DR. CORKIN: Thanks.
CAVANAUGH: Anyone who’d like to comment, please go online, KPBS.org/TheseDays. Coming up, things to do this weekend that have nothing to do with the holidays. Stay with us as These Days continues here on KPBS.