Interview: Robert White, MD PhD
Over his forty-year career, Dr. Robert White founded a brain research laboratory, published hundreds of articles, participated in work that was nominated for the Nobel Prize, visited Russia in the midst of the Cold War and handled Lenin’s brain, advised multiple Popes on scientific ethics, became a target of animal rights activists, and raised ten children. Oh yeah, and he also transplanted a monkey’s head to another monkey’s body.
In 1961, the Harvard Med-educated MD/PhD student White was barely finished with his doctorate work at the Mayo Clinic when he was offered a joint position in Cleveland at Case Western Reserve University and the Cleveland Metropolitan Hospital. Over the next decade, in addition to teaching and working as a practicing neurosurgeon, he established the Brain Research Lab at CWRU/CMH and generated a publication record that any full-time junior scientist would be jealous of; in addition to articles in Surgery, the Journal of Neurosurgery, and Experimental Neurology, he first-authored papers in either Science or Nature every year from 1963 through 1966.
Within the field of neurosurgery, White's most-cited work is on the effects of hypothermia on neural tissues. This work centered on two questions: How long can the chilled brain survive without circulation? And what are the protective effects of cooling the brain and spinal cord during surgery or following injury? Despite his extensive publication record on these questions and a variety of other subjects in neurosurgery and neurophysiology, he is undoubtedly best known in the popular press for a single poorly-cited 1971 publication: Cephalic Exchange Transplantation in the Monkey. In this Surgery article, White and four co-authors describe how they removed the living head from one monkey and attached it to another monkey’s decapitated body.
While this surgery is often described as being unprecedented (among other things), it was actually a natural (or perhaps unnatural) extension of a decade of work at the BRL on extracorporeal perfusion: techniques to keep the brain alive using a donor animal or artificial pump to circulate the blood. As early as 1963, White had isolated the brain from one monkey and attached it to the circulatory system of another animal. In a 1965 Science article, he described having performed a “brain transplant”, in which the isolated brain of one dog was implanted in the neck of another so that the two animals shared a circulatory system. In all of these procedures, the isolated or transplanted brain retained “normal” patterns of EEG activity for hours to a day or more.
In the early 1960s, Dr. White’s work at the BRL attracted attention and invitations from scientists of the former Soviet Union, and his scientific expertise and devout Catholicism eventually led him to an appointment into the exclusive Pontifical Academy of Sciences. Meanwhile, the head-swapping and brain isolation that went on at the BRL was heavily criticized by animal rights organizations – and occasionally by his own colleagues – as “barbaric” and “unnecessary”. After he described his research in a 1985 Reader’s Digest article, he was assailed by a wave of protests, his family was targeted with prank phone calls, and a hospital lab that was mistakenly thought to be his was trashed.
I asked Dr. White about his work at the Brain Research Lab in the 1960s and early 70s, his thoughts about the future of human head transplantation, and his beliefs about the relationship between the soul and the brain. I also asked him about his experiences in the Soviet Union, and his views on the use of animals in research. What follows is an edited transcript of that conversation.
Jake Reimer: So tell me about your doctorate work at the Mayo Clinic. I’ve read The Physiological Consequences of Total Hemispherectomy in the Monkey, where you describe removing half of the brain to see what sorts of deficits monkeys would have …
Robert White: Yeah, but the point of that work was – even today, hemispherectomies are being performed on humans for epilepsy, and to some degree in those days they were being done for tumors. So there were some human equivalents. We wanted to see if we could do a true hemispherectomy – most of the operations in humans used the thalamus as the plane for the removal, and they often missed a good bit of the temporal lobe, for example. So what we wanted to ask was what would happen if you truly removed half the brain down to the midbrain.
JR: But once you left the Mayo Clinic you moved on to other research. How did you get involved with surgeries that you developed in Cleveland?
RW: Well, you want to remember now – a thesis was a thesis, but at the Mayo I studied with an incredible Scotch veterinarian who had a PhD in physiology, and in addition to the hemispherectomy experiments, we did a number of things that involved cooling the dog’s brain and cooling the monkey’s brain.
JR: Who was that?
RW: Dr. David Donald – he’s dead now.
We worked a great deal using extracorporeal systems where we were attempting to cool just the brain; first the brain of a dog, and then the brain of a monkey. And in order to accomplish that, and more importantly, to develop a preparation in which the entire circulation to the brain could be stopped in an intact animal, we had to do a lot of dissection, a lot of surgery, and so in the process of cooling the monkey brain and cooling the dog brain (the dog brain was done first), we worked out the necessary vasculature. It taught me a great deal of vascular anatomy, not only of the brain, but of the neck of both the dog and the monkey; and it was my impression after all that work, all that dissection, that I could isolate the brain. Up until that time, no-one had ever been able to isolate the brain – they could isolate liver and the kidneys, and the heart, and so forth, but no-one had ever been able to isolate the brain.
JR: And then you continued this work at the Brain Research Lab?
RW: Well, when I got to Cleveland, I had nothing. I was granted space, and I was granted a few thousand dollars from the medical school itself. All these things were worked out and there was some equipment left over in the laboratory, so we were able to literally start working right away, and there are a number of laboratory advances that we made that occurred in the early months that were indirectly related to organ isolation, organ transplantation and cooling of the brain.
JR: So that seems like for somebody just fresh out of an MD/PhD program, that seems like a pretty prestigious position to be put in, as director of the Brain Research Lab.
RW: Well no, because before I came there was no BRL!
JR: So what sorts of problems did you work on during your time at the BRL?
RW: Well, so the main interest of my research at the BRL – and all of those people that came to work with me, some of them left and developed their own laboratories – the major thrust was actually cooling [the nervous system]. Now, the isolation of the brain, the transplantation of the brain, and eventually the transplantation of the head or body…all those preparations took place along the way, but they were not the major thrust of the lab. The major thrust of the lab was to uncover the metabolic, physiological and rheological changes that took place when the monkey’s brain was cooled – sometimes all the way down to 5 degrees centigrade – and then warmed back. And then we wanted to determine how long a period of time [the brain could remain in suspended animation], using an educated model, a monkey that was actually trained. We used in those days what was called the Wisconsin training device, a special cage, and these animals were trained for 6 months to a year. We used to call them the Monkey Case Medical Students. We felt that some of them were smarter … Anyway, what we would do is we would cool these brains in situ, we would not remove them, because we used the anatomy and the extracorporeal information we’d gained from Mayo. We dissected all that area and we knew where to put the cannulas to cool just the brain and where to recover the venous side of the circulation, and then we – now these were educated monkeys – and then we had worked out through anatomical dissection and rheological studies where to close off the blood vessels in the neck temporarily in the monkey so that we could examine long periods of ischemia, or long periods of circulatory arrest to the brain only in monkeys.
JR: So what was the clinical aim of these experimental surgeries?
RW: Well, the clinical aim was really two things. First of all, as an overall technology to treat brain injuries, and spinal cord injuries. You want to remember that a parallel track of our interest in hypothermia was to examine the phenomenon of spinal cord injury. And what we did there, we used a group of beagle dogs and then we used monkeys in which a scientific injury – which was calibrated – was delivered to the spinal cord first in the dog group and then in the monkey group. It’s all calibrated so we knew how much weight had to be dropped on the spinal cord for the animal to maintain paraplegia for good, and these cords were examined histologically to see what happened to them. And then we took the same injury model in the dogs and in monkeys and then cooled – not the animal – we just cooled the area with a laminectomy. So we circulated iced saline in the spinal cord, because after all your spinal cord is surrounded by fluid, right?
JR: Sure, yeah.
RW: Yeah, so that’s where the idea came to me – why not use the water jacket that’s already there, why not lower the temperature – and these animals got up and ran around afterwards.
So hypothermia was the main track, or main thrust of the laboratory; not only to be able to develop models of injury and so forth, but the other thing was we also wanted to see how long a highly-trained animals brain could go without circulation, when it was not injured. And that has been spun off in neurosurgery and been used a lot in cardiac surgery where the whole body is cooled to cool the brain, or in specific cases, just the brain is cooled so they can operate on the body with a cool brain, or in our case, we operate – neurosurgeons do – on the brain that’s been cooled.
JR: So that is in use today?
RW: Yeah, uh-huh.
JR: So what about the spinal cord cooling technique, has that been applied clinically?
RW: Well, the spinal cord cooling: that was really great, was terrific, but yeah, why aren’t they doing it now? Well the problem was simply this: First of all, you had to examine these people and find out if they were total, and then you had to get permissions from families to operate on them, you had to admit that this was an experimental procedure, and then you had a laminectomy, which is fairly extensive, you know not too short a procedure. And the trouble was with the animals, we could get tremendous recovery if we could start cooling within 4 hours, but when you’re dealing with human patients, if you could get in there by eight hours, you were damn lucky. So we never got the results – we got some improvements, but we never got the results that we saw in the animals.
But to this day, this whole track should be followed through with somebody else, because you could put catheters now above and below the injury, and you could circulate the ice-cold fluid in and out, without ever opening up the spine.
JR: Yeah, that sounds like a good idea – is anyone doing that?
RW: I don’t know, they might be doing it in Japan, you never can trust them there. [laughs]
JR: Well, so if I fall off a ladder, I should try to get myself in an ice bath as soon as possible?
RW: Well, the only problem with that is that what you need is – well, you don’t need very much. The machines that were designed to circulate ice-cold saline into the wound, the bottom of which represented your injured spinal cord, were not very complicated, you could actually make it up – you just take plastic hose and a heat exchanger and circulate it in there. No, the other major problem of course, was that the treatment and handling of spinal cord injuries is a setup as far as malpractice was concerned. It became an issue right here in Cleveland, and somewhat nationally. You see, if someone came into a hospital and was total, and it was the judgment of the doctors that he or she wasn’t going to move again…well, if they didn’t do anything they could be sued because they should have cooled the cord. But now the other side is if someone came in and was total and you cooled the cord and they didn’t get any better, then somebody would say hell, if you’d left them alone they’d have gotten better. So it became really contentious and a lot of fine people asked us you know, just don’t do it any more. I mean we couldn’t do everything! Were cooling the brain, cooling the spinal cord, and trying to make a living at the same time.