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JOE PALCA, host:

And now, the next chapter in a very unusual life of the man known as HM. Henry Gustav Molaison died earlier this month at the age of 82. But the scientific world knew him and, in fact, the world in general knew him only as HM because, when he was a kid, he was hit by a car, and as a result, he suffered from severe seizures, and at the age of 27, he underwent experimental brain surgery to try and control these seizures. Now, the surgery was a success, but it left him with this very unusual problem. He could not form new long-term memories, and he became a research subject.

And it's typical in research subjects that you don't identify them by them to protect their identity. So, the world knew him as HM. But it turns out that HM's misfortune was a boon to brain researchers, who spent years studying him. The result was a far better understanding of how our brains makes new memories, and researchers were able to tease out the differences between short-term and long-term memory creation. Now, as I said, HM lost the ability to form new long-term memories, but he could still form short-term memories, very short, though. Here he is being interviewed by neuroscientist Suzanne Corkin.

(Soundbite of interview)

Dr. SUZANNE CORKIN (Behavioral Neuroscience, Massachusetts Institute of Technology): Do you know what you did yesterday?

Mr. HENRY MOLAISON (Famous Memory-Impaired Patient): No, I don't.

Dr. CORKIN: How about this morning?

Mr. MOLAISON: I don't even remember that.

Dr. CORKIN: Could you tell me what you had for lunch today?

Mr. MOLAISON: I don't know, to tell you the truth.

PALCA: But the thing is that you could get him to say, you know, pick up a coin, put it down and say, what did you just do? And he said, well, I just picked up a coin. But there was a period for about 30 seconds or maybe a little longer that he could retain something in his memory and then it was gone. Amazing.

Well, there's another chapter about to start in his life. HM and his guardians agreed - after his life, I should say - HM and his guardians agreed that on his death the brain would - his brain would be donated to scientists for future study. The process of preserving his brain has already begun, and joining me now to talk more about that is my guest, Jacopo Annese. He's the director of the Brain Observatory at the University of California-San Diego. Thank you for being with me today, Dr. Annese.

Dr. JACOPO ANNESE (Director, The Brain Observatory, University of California, San Diego): Hello, good afternoon.

PALCA: Good afternoon. Now, this is really interesting. You've known that this brain was coming your way for some time now, haven't you?

Dr. ANNESE: For quite a few years. Dr. Corkin followed - well, followed my career for a few years, and then followed the progress of my laboratory, especially since I settled at UCSD.

PALCA: And where is the brain now?

Dr. ANNESE: The brain now is still at Massachusetts General Hospital. It was removed the morning after Mr. Molaison's death. And it's presently being fixed in formalin. It was too delicate to be moved while it was still fresh.

PALCA: I see. And what are you going to do with - after it's fixed by the formalin, you'll move it to California. What are you going to do with it there?

Dr. ANNESE: So, yes, as you said, you know that we had quite some time to plan. It was quite an exceptional project setup in advance, and to this we need to give credit to Dr. Corkin for thinking pretty much about everything, every possible detail about this project. And things are organized as such that when the brain is ready to be move here, the first step is a second round of MRI scans. The great thing about MRI is that it gives you an image of the brain - of the whole brain before it is, quote, "destroyed," by the histological techniques. So, we...

PALCA: And histological - I'm just going to interrupt. So, histological techniques are this business of making slices of the brain so you can actually study the tissue.

Dr. ANNESE: Exactly. So, MRI has this wonderful feature of being able to give you a volume representing an entire brain. The problem with MRI is resolution. So, still, the only way to be able to image structures or processes that are at the cellular level in a brain, we need to cut it into slices that are thin enough to be looked at under a microscope, pretty much. So, actually when I was flying to MGH the night that HM died, to be there for the autopsy, my colleagues were already running a scan of HM as if he were alive, get a final picture of the brain.

PALCA: MGH, we don't have to keep anonymous. We can tell people that stand...

Dr. ANNESE: Yes, it's the acronym for the General.

PALCA: Exactly. So, why is it important to get this kind of precise - are you trying - I mean, obviously people have been able to study Mr. Molaison and his behavioral deficit and his learning deficit, his memory deficit. But what could you learn from seeing the fine sections of his brain?

Dr. ANNESE: We - exactly because he was studied so extensively. So, we wanted to make sure that we understand what structures were removed, and by that infer what structures are important for the different aspects of memory, that the study of HM help to tease out. And this, of course, you know, if done at microscopic resolution, would give the information that we need to know exactly which - as these cognitive abilities have been teased out to see if there is a neural substrate for each of these different capabilities.

PALCA: So, in other words, you may be able to identify particular - I mean, we know that there was some damage during this surgical procedure that Mr. Molaison had, but - and we know in sort of a gross sense of where in the brain it is. But this is going to get you down to the level of almost - well, not exactly individual connections, but certainly very small sections of the brain.

Dr. ANNESE: Well, certainly individuals cells so...

PALCA: Really?

Dr. ANNESE: We'll be able to count the number of cells in the area that is around the lesion. But you know, when you take a - when you take out a piece, a structure, out of a brain, not only you create a deficit in a particular area, but you also affect the circuits that include that area. So, that's why we also wanted to have different approach. We wanted to slice the entire brain into giant histological sections so that we can navigate the brain in different areas and see what happened also to structures that we know are normally functionally connected to the medial temporal lobe, which is the area that suffered the lesion during the surgery.

PALCA: How big are these slices that you're making?

Dr. ANNESE: The slices will be five-by-seven inches. It's a size of the - one of the picture frame, which is enough to accommodate the entire slice.

PALCA: We're talking with - I'm sorry, we're talking with Dr. Jacopo Annese about the work that's going to be done on the brain of HM, a famous amnesiac patient who died last week, and his brain is going to be, well, not dissected but inspected, we'll say...

Dr. ANNESE: Inspected.

PALCA: Inspected to be - to see exactly what the nature of his deficit was and hope to understand how that affected his memory. I'm Joe Palca, and this is Talk of the Nation from NPR News. One of the things about this project that I think is so fascinating is you're planning to do this, you know, almost under the public eye. Anybody who wants to see this process can go to your Web site and watch it unfold.

Dr. ANNESE: Yes. We actually create also a dedicated Web site for HM. I wanted to make sure that initially as we set protocol up to start the work, we will give the opportunity to experts and other investigators to make suggestions and to eventually also add to the protocol. And also, people that have in-person studied HM have very important suggestions on which way to go. Because, you know, unfortunately, one cannot do everything on one particular specimen. There are compromises that need to be made, priorities that need to be set, which, you know, determine which kind of stains one uses, depending on what we want see in that brain.

So, I thought that producing the first step, a blog or a forum of experts to discuss the coming project, and then also, as you mentioned, have actually a completely open environment to the public so that every procedure that we are beginning and, you know, we are running can actually be looked at. I think it would be a good occasion for the public, given that there is this enormous interest in this case generally, really an interest in the brain in generally, I think it will be a very close, hands-on, you know - how do you say it? - approach to the study. It won't be done in closed doors and then the results will come out. So, literally we plan to have webcasts of every procedure.

PALCA: It'll be very interesting, and I hope what we can do is have you back when some of the results begin to come out of this study. But I'm afraid we're out of time, so we'll do that the next time. Thanks so much for joining us.

Dr. ANNESE: Thank you very much.

PALCA: Dr. Jacopo Annese is the director of the Brain Observatory at the University of California, San Diego.

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