Christopher Wren’s Medical Discoveries: the ‘Architect of Human Anatomy’

Thank you for inviting me to give this talk on Christopher Hen's medical discoveries, uh, entitled with a subtitle, architect of Human Anatomy. And that word, architect underlines, of course, his role in the visual portrayal of the results of the dissection and the experiments that his colleagues, uh, were doing, uh, with his collaboration. But also, uh, it was, as you'll see, much more than that, that he was an active participant in those experiments, uh, and dis uh, dissections and discoveries. So this was very much beyond just dry anatomy of, of the bones or tissues. It was very much function, physiology, uh, functional architecture you could say. So, bio lecture, out outline. I'm going to focus on five main areas, uh, of re's contributions. First in anatomy. Uh, then in his role in introducing intravascular access. Uh, third, his role in advances in lung function and the near discovery of oxygen, which in turn led to cardiopulmonary resuscitation, cpr, and then what I call some, some other things. So group of, of other things that don't fall into any of the above four categories. Um, so quite a range. Um, and, uh, you know, these are incredible topics. If, if Ren had had done just that in the biomedical sciences, that would be enough to have a a 300 celebration on. But as you know, uh, uh, and has been introduced, um, there were these other topics that he, uh, made enormous contributions to, astronomy, physics, particularly optics, mathematics, architecture, of course. And if that wasn't enough, he was a member of Parliament for, uh, several couple of decades. And if he founded the Raw Society in his spare time, um, so it was the most remarkable, um, individual and his work in the medical sciences, which is the focus of today's talk. Um, we must rem remind ourselves that he was not a qualified physician. So it really makes it all the more remarkable, uh, when we, uh, will touch upon what he actually did. But in some other ways, this lecture really isn't about Ren, uh, you know, it's not a ha geography. It's not just Ren ren Ren. The, the key thing to emphasize, and, and, and I think it's a very important thing, is that this was the world's first, arguably, the world's first research collaboration, the world's first research group that got together and systematically applied their skills and efforts to solving the problems, uh, that we will talk about soon. And they themselves are very famous, uh, names Robert Boyle, uh, Boyles Law in Physics, uh, hook of Hook's law in physics. And in fact, his portrait, uh, is at the back of the hall there, uh, at this college, Richard Lower John May, the Great Thomas Willis and many others. And of course, in the background was William Harvey, who, as you see from the dates, overlapped somewhat with them and indeed did meet and discuss things with them. But because of his age, wasn't an active participant, uh, of this very active research group. So, in a sense of disentangling, who did what they're going to be, uh, in the history of some blurred margins, they were all at it together. Um, and this sense of collaboration particularly applies to Ren. So to tease out some of his character, his biographers emphasized by how gracious he was in sharing his ideas. Uh, and that's why perhaps his name may not be attributed to many of the medical discoveries, and it's more along the architectural lines, but you'll see it, it probably well should have been. So as Biograph is right, Wen's notes were few. He gladly allowed others to borrow his ideas without attribution. Re's contributions were significant. In his own right, he saw the need for cooperative attack on problems. So bringing different skills together to solve, uh, these problems of the time, and especially through his ideas, discovery, or pieces of apparatus cheerfully appropriated by contemporaries like hook and boil. So the biographers are saying that some of the things we attribute to them actually were probably his. Um, there's also a, a, a character of humility, uh, in Ren. And here I defer to my architectural experts. Uh, so apologies if I've got the architectural details, uh, you know, slightly incorrect, but roughly, the Windsor Guild Hall story goes like this, that at the peak of his powers as a, an internationally famous architect, Ren was commissioned by the councilors of Windsor to, uh, build design this guild Hall, uh, which is still there. And he designed it, uh, but with pillars only on the outside. And the councilors objected saying, well, the ceiling's going to fall down. We, we insist on pillars inside as well, to keep the thing up. And this went to and fro with Ren submitting different versions of the, of, of the diagrams because, uh, you know, he knew that they were wrong anyway. And his humility is such that he exceeded, he, he did what they wanted, and he built the pillars, you know, internationally famous architect, as it were, respecting the wishes of, you know, random counselors with no architectural experience. Anyway, a couple of hundred years later, the roof, the ceiling needed some work. And the workman discovered that there was a gap between the top of the pillars and the ceiling <laugh>. And, uh, they were useless pillars. They, they were non-sporting pillars, um, a tiny gap. But it was there, and it was Rens humility that he simply said yes, at the end of the day, but also, he had the last laugh. Of course, he was right. These things were not needed at all. But there they are to this day. So to turn to the first theme away from architecture, back to home territory in medical sciences, uh, the circle of Willis and Brain Anatomy. Now, Ren was part of this active research group, and he was actively dissecting. So this is, uh, a print from the day, uh, with, uh, Willis leading the dissections. And there, uh, next to him is Ren, um, and Willis's interest. Willis was driven by an interest between the soul and the body, and particularly to understand species differences. And he believed in this vague theory that this, there were three types of soul, what he called the vital, the rational, and immortal. And he was using the process of dissection to try and understand that better, particularly dissection of the brain. And in these researchers, the group named, I won't go through the list, but named, uh, all these parts of the brain, uh, as new things. Now, the, the list in itself forms almost the entire brain. I mean, that is an awful lot of structures that they, uh, discovered or rediscovered, uh, and named, you know, key structures that, uh, neuroscientists, neurosurgeons today will well recognize. I'm indebted to my colleague at St. John's, uh, a successor of Willis's as professor of anatomy who, uh, marked, uh, the birth of Thomas Willis, uh, with an article. And, uh, professor Ultan Moar noted that Willison Ren through those identification of structures that corrected much of the previous anatomy, uh, of the previous few hundred years, but even they did get some things wrong. For example, there are 12 cranial nerves, but they mistakenly lumped two of them together to form one the seventh and the eighth. And, um, even more remarkably, the ninth, 10th, and 11th, they seemed somehow to mis differentiating. So they did get things wrong, but these were huge advances, and Ren was doing the drawings, so Willis was doing the dissection. But all the drawings you see, uh, in Cerebro and ato, which is the key book that Willis published, uh, are, are Rens, uh, alone. And in that drawings, it's worth considering how the brain's been portrayed through the ages. So, of course, uh, in ancient times, it was just, you know, circles, circles within circles. Um, although there, you can see, uh, in the Egyptian, uh, print, you know, the, the sense of nerves, uh, just at the, just at the bottom of that circle, and of course, da Vinci and Vaus in the 16th century made huge advantages through dissection. But in a sense, their, um, portrayals were, as they saw it, this was the brain as they dissected it, it's rather messy. It's very accurate in terms of what you see, but it's not particularly useful. And what becomes useful is re's very clear, crisp portrayal of the structures that he saw. Arguably, this is not what you actually see when you dissect the brain. It's what you think you see. In fact, today we're, we're almost using re's picture to map onto what we see. Um, and it was with function in mind that, uh, we think he did this, that he knew that this was going to be a map for future experimentation, perhaps for future dissection and future surgery. And this was the roadmap that pointed the way, a reference point. So it's very much more of a reference brain than is Da Vinci's or a SALs. Now, in all this, Ren was helped by several things, obviously, um, artistic developments, you know, developments in the arts, um, for example, perspective, a much greater appreciation of that. And Ren in fact, invented a device, a machine called the pers spectograph, wherein he could, uh, sort of trace out, uh, uh, things using the machine, uh, from what he saw, and that would help him draw the perspectives, artist tool him improved, uh, and of course, print printing and improved so that books like Cerebra and NATO could actually be published in high quality. As I've said, Ren was really interested in presenting the pictures as a result of, uh, as the result of experimental dissection, rather than simply, uh, as, as art pieces of art as what we saw. This was really important. The third element, uh, that helped was, uh, his invention of injection of vessels, intravascular injection, which I will talk about in, uh, the next slides. But he was able, using that invention to inject dye into the vessels, to provide contrast, which enabled Willis better to dissect and, uh, to have a clearer result of the anatomy of the brain. Now today, this is still used and has been used for many years in a process called cerebral angiography, where radiologists do inject to die, usually now radiopaque die, rather than the visible dye to outline the, uh, form and structure of the vessels of the brain. They also had some good luck. This was the fourth element. Well, it was lucky for them, but not so lucky for poor Samuel Mashburn, the waam student, who was unfortunately struck by lightning and killed while punting, uh, uh, in the university parks. Now, this was, um, uh, sort of good luck for dissection because here the two most, almost all the dissection, uh, were on damaged, traumatized corpses, that whether they were, um, accidents, uh, or hanging, uh, or other mishaps, uh, it was very rare to find, uh, a can that was, uh, physically untouched. And we now know today that electrocution, uh, really doesn't damage, uh, structurally any of the internal organs. So they're completely, perfectly preserved. This is just electrical, um, uh, electrical death as it were. Um, and, uh, the mishap to the individual, uh, enabled them to have a very clear, um, uh, brain structure to work on, to produce their results. So the key result, uh, that, uh, apart from lots of other structures in the brain, the particular key result, which Willis's name is attached to, is what's called the circle of Willis. This is a group of arteries at the base of the brain, and you see it there, but, uh, I've delineated it in red, uh, freeze, uh, of appearance there. And, uh, that's with the neural tissue stripped away. And the brain is supplied by four vessels, two carotid arteries, and two vertebra arteries. And the circle of Willis is a system by which they are interconnected. What was so what as it were, whether, so what of it is that this is of, uh, uh, great functional significance? Uh, if there was no circle and one of the arteries was blocked, uh, then, uh, that entire part of the brain supplied by the artery, are you roughly a quarter I'll simplify the proportions, uh, would be damaged with effectively a stroke. What the circle allows is contra lateral flow, collateral flow. So even if one of the vessels is blocked, the blood could use the blood flow, can use the circle to bypass it automatically. And that's the functional advantage. In evolutionary terms, it's an advantageous to have this evolutionary, um, trait, uh, and, uh, inherited. Now, the disease, the blockage can be caused by this process of atherosclerosis, the narrowing, the firing up of the arteries. And if it happens in the carotid artery, carotid artery, atheros, grasis, this can be treated surgically. But to operate on the vessel, the surgeon needs first to apply the clamp and to clamp the vessel so it doesn't continue to bleed during the surgery. But then we reach a paradox because the surgeon is clamping an obstructing flow and thereby stopping flow in the very vessel that they want to reduce, restore blood flow to you. And that could itself cause a stroke. So the dilemma is how under general anesthesia would, you know, that the circle of Willis is patent in functioning well, when the surgeon applies the clamp, and the patient's not going to wake up having had a stroke. So that's the dilemma that one doesn't actually know it's very difficult unless you do the whole operation of the patient awake. So awake carotid ectomy is, uh, a recommended, advantageous way forward to successfully operate on this carotid artery. And there's the carotid artery with the surgeon just about to place a clamp on the right hand side, and the patient is awake. And this is done by various means of injecting local anesthesia into the neck. But that needs to be precise for a successful, uh, local anesthetic is of course, the surgeons operating on a vital artery. And one of my connections. And at the end of the talk, I'm going to try and tease out some connections I have, albeit 10 years, although I'm very proud of them with Ren, uh, and Willis and this group because, um, I was, uh, privileged enough to do some research to describe, uh, a more effective way of achieving this form of local anesthesia. And I did so with the help of Professor John Morris, uh, who is another successor of Thomas Willis's, professor of Anatomy in Oxford. And he and I did some classical dissection studies on the neck. Uh, and without going into details, we made some discoveries around what's called the deep ccal fascia, which enabled the placement of the local anesthetic much more effectively to achieve more successful surgery. But they're still in further dilemma. The patient's comfortable and awake, the surgeon's operating and starts to put a clamp, but then the patient starts to show symptoms. And so the surgeon releases a clamp and realizes they can't clamp what to do. Now, does the operation have to be abandoned? Not quite. It is possible to do a smaller operation and insert a shunt into the vessel that bypasses the area to be clamped. So we know the circle of Willis isn't patent, but we can then apply shunt to bypass locally, as it were, the obstruction. Uh, and that allows the area to be clamped and operated on. One shunt was invented by the roll dial that, uh, many of you in know of or heard of, read his books. And Dar invented it for, um, treatment of hydrous, which is swelling of the brain, the cerebral spinal fluid. And he did so because unfortunately, his son at the age of four had a traumatic, uh, car accident and developed hydrous and the shunts of those days to shunt away the cerebral spinal fluid kept blocking. So Daral invented a new type of shunt, so it wasn't for this particular operation, but the principle was the same. Willis in Dayum described the formation of cerebral spinal fluid, again, assisted by re's drawings through comparative anatomy, they realized how cerebral spinal fluid was there across many of the species, and approximately, quite accurately how it was formed and its circulation. So there are these interesting connections, um, in that, uh, sphere. So we'll leave that aside and we'll move on to the second theme, which is intravascular access, which I've already said. Uh, Ren uh, invented, uh, to help Willis delineate the vessels. And Ren was, um, the first person as far as we know, to cannulate a, a vein and to describe the equipment to do so. And there is a picture of probably roughly what he used. It may not be his exact one, but the feeling is that, that this is what it looked like. Now, it's not that easy necessary, it's not that straightforward. Now, these days we regard it as a routine thing to do, but a cannula has to be sharp to obviously pierce the skin and enter the vessel. And to be sharp, it has to be narrow and thin. But if it's too narrow and thin, well, that's no good. You won't be able to inject anything. So it has to be both sharp, but also wide. So there's that balance, and it has to be long enough to hold. If it's really short, you can't do anything with it. But if it's too long against, there'll be that resistance to flow. So again, it just has to be just right. And then finally, you need a means of injection. And the syringe was invented much later, but at that time, they used a bladder attached to, uh, the end of the cannula. And as I've said, Ren used this to delineate the vessels, uh, of Circle of Willis. But there was more, Harvey had set the scene with his discovery of the circulation of blood. And I will go onto the background to that. So the question arose, well, what's the purpose of blood? What's the function of this circulation? Or can it be given a function? Can we use it in some way? And re's friend Boyle was, you know, thinking and linking this to whether new drugs could be administered by this root into the blood. So here, the two drugs were only ever ingested, but now that the blood's there circulating, and Ren has discovered a way of getting things into the blood, can we do something more? I'll digress a little to talk about Harvey's, uh, discovery of circulation, cuz it's quite central to the thinking that went on. The older theory was that blood sort of ebbed and flowed. It went to and from the heart in a sort of pendulum like motion. But that theory relied on the blood mixing within the heart. And Harvey overturned that thinking in several ways. First, through anatomical, um, dissections, he demonstrated as had others. And he brought historical works to substantiate what he discovered, uh, that there is a septum in the heart that is not poorest. So the septum of the heart divides the two sides of the heart and blood cannot mix. And secondly, valves in the veins don't permit backflow. So blood can only flow one way because of the valves in the veins. And varios veins are when they fail, and it goes the other way. But he added to that with experimental work. And this is an experiment that's done in schools and in early medical school, which is easy to do. It's literally one you can do at home if you want, uh, which is you tie ligature at the upper arm and the the veins will become engorged, and you then use a finger to, uh, squeeze blood outta the veins. And then you will see that they only fill in one direction and not the other direction. And of course, above the ligature, they don't fill at all. So very simple, elegant experiment, but put together with everything else, it proves as it worthy, uh, circulation of the blood and overturns the ebb and flow theory. So there's the blood circulating and there's boil, poised to, uh, um, you know, do something with this idea. So what did Ren and Boyle do? They gave the first anesthetic to a dog. And I'm indebted to my colleague, just retired Professor Keith Dorrington, professor of physiology and anesthesia in Oxford, who's written the beautiful article in great detail of this particular, uh, ren uh, uh, discovery. Now, boy overturned to a, turned on its head a saying of Peric Celsis. The German physician of Peric Celsis had said, what differentiate a poisoned from a drug is the dose. So drugs and poisons are the same thing, and a poison is simply a drug in overdose. And Boyle said, well, hang on, I'm going to take that dictum and turn it on his head. If that's the case, then if I take a poison, something regardless of poison and give it in sufficiently controlled and smaller dose, I have a beneficial drug. And he summarized that philosophy in an essay of turning poisons into medicines. So that was his, his thesis. This was his driver. So, and it's, it's unclear why they, they did it this way, but that's what they did. The poisons they chose were opium and alcohol. And using re's discovery of intravenous injection, intravascular injection, they injected a dog with opium and alcohol, and the dog became anesthetized and re's words. These re's words are fascinating. The tincture, this mixture getting into the massive blood, was quickly by the circular motion of that carried to the brain before the opium began to disclose its narcotic quality. And presently after the dog appeared, ed. So the words are really important that the circular motion was here, really important for the success of this. They were putting something in that circulated to the tissues, and they knew that this mixture was acting on the brain, that this is where consciousness resided and where you could induce anesthesia, no other part of the body. And the word narcosis is used interchangeably today with anesthesia. You know, we could anize patients, anesthetized patients. Unfortunately, they didn't take the next step, which is to realize they could operate on the dog without sensation and actually do something with this anesthesia that they had so elegantly described. They just regarded this as almost as an interesting thing. And the fact the dog survived proved boils theory of being able to turn a poison into a beneficial medicine boil was actually interested more in, um, treating, uh, sickness, uh, and diarrhea rather than, uh, inventing anesthesia. Now, the first true anesthetics were actually inhaled anesthetics that were introduced much later in the mid, uh, 18 hundreds. Uh, and, uh, you know, there's the famous picture of how they're given, uh, originally. Um, and, uh, one of the dangers of inhalational anesthesia. So intravenous anesthesia was forgotten. An inhalational anesthesia a couple of hundred years later came in. Now one danger is what we call stage two of anesthesia. So just below the picture, you see a very rough sketch based on, uh, a man called gadel who is anesthetist at the turn of the last century, who described very carefully what happened, uh, as someone went to sleep with an ether anesthetic. And stage one is when the patient starts falling asleep. But stage two is this paradoxical excitement. So the patient becomes agitated, moves the arms and legs can bite, the tongue can vomit. It's a very dangerous phase. And if the anesthetist is brave enough to keep holding the mask on and go through that stage two, you then enter the peace and calm and tranquility of stage three. And then you can do this at the operation. So the idea is to go through stage two, and then you are in safe territory, intravenous anesthetics being rapid in action, avoid or zipped through stage two, without there being anything to see. Okay? And that way arguably much more beneficial. And they were reintroduced in the 1930s with thito. But the rapid action on the brain also involves rapid action on other organs. And we see much more depression of the heart and blood pressure. And this is the unfortunate Pearl Harbor story, slightly apocryphal, but useful nonetheless. The Japanese in 1940 of course attacked Pearl Harbor and there were many casualties. In fact, the casualties weren't that severe. Uh, they were relatively moderate, uh, injuries. Unfortunately. What they found was that a large number of the soldiers died, uh, during surgery, disproportionate to the extent of their injuries. And late in the day it was worked out. The reason was that thone, which had recently been introduced and was the rage of the day, was being given far too liberally and far too rapidly without prior resuscitation of the blood pressure. So this effect in zipping through stage two also zipped through the heart and the blood pressure in a most unfortunate way, remarkably, as intravenous anesthetics were refined, we find that Rens anesthetic mix was used until the 1970s, somewhat rediscovered. So some very distinguished anesthetist were describing its use, opiate alcohol mixture, exactly the same, uh, for cardiac bypass. Now, the reason is in cardiac bypass, a bit like the shunt, the heart and the lungs are bypassed, okay then. And therefore, if the lungs are bypassed, they can't absorb the inhaled anesthetic. So you can't keep a patient asleep with an inhaled anesthetic during bypass. It has to be an intravenous anesthetic. But drugs like thone accumulate too much. So the patient will take days or weeks to wake up. But opiate alcohol is just the right mix to achieve that balance and allow appropriate wakeup time and it doesn't accumulate. So that's a picture of how you bypass the heart and the lungs, and a modern day bypass machine picture on the right. So this is still under the banner of, uh, intravenous cannulation and where it led us, because the next stage it led us to his blood transfusion. Now this is where Ren took a step back and left lower his colleague, uh, to exploit it and lower developed, uh, the cannula. And you see there the, the development of the cannula with lower and particularly the flanges to tie it down. Cuz of course, for a blood transfusion, which is what lower was going to be interested in, it needed to be in place for a prolonged period. And that's really interesting cuz you compare the picture above with what we use today. You see the similarities start to develop, you know, it's that long ago, hundreds of years ago. It's fascinating. And lower was the first to do an animal to animal transfusion. He was beaten to animal to man by Dennis in Paris. But I don't think he should have felt too sad about that, because very soon afterwards, unsurprisingly, Dennis also had the first patient death and was arrested and got into a lot of trouble. And unfortunately though, it was like these inventions where something becomes all the rage, everyone starts to do it for whatever reason, you know, headaches, minor ailments, uh, and then the side effects start to appear. And these were very dramatic side effects. And of course, they weren't going to be solved until the discovery of, uh, um, blood groups, uh, in the 20th century. But anyway, it was recorded and the ability to do it, uh, was in posterity. So moving away from intravenous access to the third theme, which is lung function, this was a fascinating comment at the time. Uh, Dr. Ren made use of this experiment, which was one of, uh, his colleagues' experiments, uh, which will come to Mayos to explain the motion of the muscles by explosion. So Ren was interested in the question of how muscles worked, and he felt that there was literally an explosion in the muscles that caused the contraction. And he was actually right because the explosion in the sense of modern biochemical parlance is this equation, which is glucose combining with oxygen exploding as it were to yield carbon dioxide and water. And of course, atp, which is the molecule of energy, but it's a combustion process, what we call cellular respiration. And what Ren was referring to as an explosion was this combination, this volatile combination of some form of energy with some form of what we call oxygen. So this is the modern view of what Ren was describing, which is extremely interesting. In other words, Ren recognized in this and other observations that there was some link between the air that we breathe and a muscle explosion going on in the tissues. He further imagined that if you could somehow control the air that we breathe, you know, limit the volume, uh, you could have an instrument of respiration and by straining the breath from ous vapors to try whether the same breath so purified will serve again. Can you rere the air if it's confined in a bag or a sack? Now we know we can't because we need to remove something that is ous from it. So remarkably, what Ren was describing here was a rebreathing apparatus. So long as that rebreathing could suck away what we know to be carbon dioxide. And this is exactly what we do today in an anesthetic breathing circuit. We use commonly throughout the world, something called the circle system, where we rebreathe the air in exactly the way that Ren described. The carbon dioxide is scrubbed by soda lime again, in exactly the way that Ren described. And this saves on gas flows, it saves on oxygen, and it saves on anesthetic vapors. So it's cost effective. But of course, in today's, uh, interests, uh, it's also got a very good carbon footprint. So you only need about a couple of hundred mills of fresh air going in for an overall minute, volume of five liters a minute. So extremely efficient. So there I've drawn a diagram where on the left, the fresh air comes in at this very low rate, it picks up the anesthetic and goes into the circle system. The patient breathes and rereads that in a circular manner with the CO2 being absorbed by the CO2 absorber that you see there. And this can go on indefinitely, and there's the modern day picture of it. So it's fascinating that Ren imagined this to be possible and desirable. And this was all linked to his friend John Mayo's work on the, what we now know to be the near discovery of oxygen. So he used an adaptation of, you know, Rens imagined breathing device to design a sort of volumetric analysis of what happens with the air. Now, the prevailing theory of the time, rather like Harvey's e flow theory in respiration terms, was this theory of flod stone. Now, it's really difficult to explain Flod stone. It's like a reverse oxygen. That's the closest I can come. It's actually something given off by burning objects is flos stone and deflated air is therefore purified. There. It's, i it's impossible to describe it. Well, but I hope you get the gist of it. As you come to see John Mayo's experiment, what he did was basically use an inverted flask over a a, a tray of water. And inside the flask, he placed a small animal, or at times a piece of burning wood or coal that he was able to ignite with a magnifying glass. And what he found was that with time, the level of water in the tray rose up inside the flask. Okay? The inescapable conclusion was that something was taken from the atmosphere, and we now know this to be oxygen. Now, he was lucky in those experiments because the water had impurities that were able to absorb the carbon dioxide to give this result. If you do it with distilled water or plastic, you don't get the same result. But, um, it was much more dramatic because of, uh, the, um, equipment that he used. So this was re's rebreathing system used as volumetric analysis to prove that something was taken away from the air. Again, achingly, they didn't take that step and say, this is now oxygen. We have now overturned the fluk theory. They tried to interpret it in a complex way within the paradigm of fluk, which is unfortunate, and left it to La wasier in France, uh, over a hundred years later to actually discover oxygen. Uh, by chemical experiments he observed that burning metals gained weight, they were oxidized, and they gained weight rather than lost weight. So they did not give off legon. But combining this with early experiments, then the weight of evidence was towards oxygen. The fourth theme, cardiopulmonary resuscitation. Now before, um, uh, the 17th century, uh, there were various ways it was recognized that you could resuscitate the apparently dead, particularly recent drowning victims. This was a popular method, uh, which was to flog them. Uh, so you pull the victim out and you start flogging them with branches and birches. Um, this was suitably called the Russian method, which was to pack the victim in ice and hope for the best. And the opposite of that was to, um, essentially set fire to the, to the pit. Uh, and, uh, you know, and neither worked terribly well. And then of course, there was the trotting horse method where you put the body over a horse and trotted round and round. And again, hope that there was no rhyme or reason to any of these at all. Uh, because as we now know, in order to have successful resuscitation, you need to know what the heart does, and you need to know what the lungs do. And that's how you can have, uh, cardiac compression and, uh, pulmonary ventilation, which is the mainstay of cardiopulmonary resuscitation. But in fact, um, our friends and Rens friends knew all that because they had knowledge of the circulation and the knowledge of the heart as a pump from Harvey. And they were working on that lower, had used cardiac massage in his experiments, uh, in an animal to pump blood out of an artery to collect it. And he also noted that as he did so and ventilated the animal's lungs, the blood remained red. There was this inkling of something persisting here. Ren had developed this fantastic method of intravenous injection of drugs. And mayo had nearly discovered oxygen, you know, knew that there was something good about the air. So putting all that together, they were ready to apply this, and they had their opportunity with the unfortunate but later fortunate story of Anne Green. Anne Green was a maid who had a stillbirth, but hid it. And, uh, when the, uh, body of the child, the fetus was found, she was tried and very rapidly convicted of murder and hanged On the 14th of December, in 16th 15, Carfax in Oxford, in the center of Oxford, the friends Willis Petty, who was Reader Anatomy, as was their right under the university statute, claimed the corpse and dragged Anne Green's body to Beam Hall, where they lived, where Willis lived. And they did their experiments. And this is where the friends got together, and she stayed there for some weeks. So, uh, it's inevitable Ren would've been involved. It's difficult at this, uh, distance from history to know who did what, but they applied their discoveries to resuscitate her. What they did is unclear, probably all of the above, but they were successful. She survived the hanging, and this was truly a miraculous, uh, uh, result. So much so that her conviction was quashed. And Anne lived for 15 years longer and bought three children. And this is all documented as the world's first resuscitation, applying all those early, uh, methods. So the fifth group, this, uh, uh, you know, hodgepodge of other contributions, which in themselves are extremely significant, uh, microscopy. So Hook wrote the beautiful, uh, book Micrographia using, uh, the new newly found, uh, technique of microscopy. But Ren got their first and Rens drawings, which aren't actually in micrograph. The Rens are in the royal collection, are very, very similar. And, uh, hook was inspired by them, uh, to, to draw these small animals. Operative surgery. For some reason, that is still unfathomable. Uh, Renn wrote a monograph on how to perform a splenectomy, the taking out the spleen in a dog. Now, I dunno why he did it, but, uh, he did. Uh, and it's a very difficult operation. It's a major operation to do, it's done for a number of reasons these days, including some cancers or trauma. But, um, in his description, he was emphasizing the care with surgical ligatures to prevent blood loss as being something good to have good outcomes, careful suturing of skin, attention to detail, including postoperative care. So look after the dog afterwards. So, very holistic. It's not just the surgery and anatomy, but he was looking at surgical outcomes. So it's a fascinating, uh, uh, but isolated insight into his interest in surgery. He, um, drew, uh, biopsy specimens for Willis and his medical friends. Uh, this is from the welcome collection. At the first site, it looks like perhaps, uh, you know, beautifully dyed cloth from an exotic far eastern country. What it actually is, the, is the intestine died, uh, for the pathology, and it shows hemorrhagic lesions, possibly due to colitis or tuberculosis, but it's a beautiful picture of itself. Again, re's drawings, his rendition of, uh, yeah, pathology, which is otherwise crude, uh, and inelegant one could say. But this is, uh, you know, pure elegance. Hospital design, not just experimental science, but the design of places to care for the sick. The Royal Hospital in Chelsea, uh, wings of Greenwich Hospital, a hospital in Ireland. And, uh, the now, um, it, it's no longer exist, but the then College of Physicians in, in Warwick Lane with the floor diagrams and, uh, pictures. I'm going to finish with some personal points of contact, uh, that I've had. I've mentioned, uh, you know, this link with my interest in awake carotid surgery and the circle of Willis, and how important that is, Mayo's oxygen consumption. And this volumetric gas analysis was developed much later at the turn of the last century by a man called CG Douglas, who was tutor at St. John's College, Oxford, who invented the Douglas bag that generations of medical students have used. And what it is, it's a bag filled with oxygen, and you either rebreathe from it or you breathe, uh, one way with a one way valve, breathe out into another bag. But the principle is the same as maus. You are looking at the volume of oxygen that you are consuming and breathing and using that to estimate your metabolism, which is where that explosion of the muscles goes on. Douglass was the first of the modern day respiratory physiology fellows at St. John's College. Oxford succeeded by Bob Torrance. And the link there is that I've succeeded Torrance. So still using the volumetric analysis that may, uh, described all those hundreds of years ago in the same city. Another St. John's connection, I mean that to Professor Katherine Bland, who's Gresham professor of astronomy, um, who, uh, discovered this. I don't know how she did it. And, and neither of us knows how it happened or why, but Christopher Re's father was a student at St. John's College, Oxford. And somehow he etched or got his name etched in a glass panel in a window of our old library. There's the, there's the window, there's the panel, and if I blow it up, you just about see his signature. I don't even know how you get that done on glass. So that's probably the subject of somebody else's lecture. And finally, the link is that many of these experiments that I've described were done in this building, beam Hall. And Beam Hall is interesting, uh, because it was built in 1187 and it's been in continuous occupation and use by students and professors. It's the oldest building, university building in the world as a result of that. And the resuscitation of Anne Green happened here. This in discovery of the circle of Willis happened here. May's experiments, everything was, was here. And it's had two important residents, obviously Thomas Willis, where he lived at this period, uh, and me, uh, because I was housed there as an undergraduate, it's now part of Corpus Christi College. And I just thought it was the most incredible thing to be living in the rooms where these things actually happened and have been documented as happening. So I finished, but I normally it's the question, it's the, you know, it's the audience that asks the questions, but I do have burning questions. I have two. One is, what would Ren and the Oxford Group make of what we know now, especially in relation to anesthesia, which is my subject, or oxygen, which is what I research in. And I think their response would be rather mixed. I think they'd be kicking themselves because, because they were there. They, they got it, they got both of it, you know? Right. But then they would concede that. Yeah, we knew it all along, you know, we knew it was gonna happen. We knew we were right. So I think it was me. The second question I have is, of all these things that went Ren was doing from architectures in front of me to medical science, which did he enjoy the most? What gave him the most satisfaction? You know, everything from splenectomy to designing St. Paul's. You know what, and I, I, I'm afraid, I don't know. So I'll leave it there. Thank you very much. Thank you for listening. Um, I'm gonna take a question that's come in from outside. So it, in regards to the circle of Willis, do we know that the possibility of alternative roots of perfusion around the circle of Willis, presumably was evolutionary adaptive? And which vertebra share it? Oh, that's of, gosh, that's comparative. And then testing my comparative anatomy here. Um, evolution. Well, evolution one's easier because, um, there's a saying that, uh, nothing makes sense except in the context of evolution. So if we see something, uh, we assume, uh, and we're probably right that it has evolved, uh, and it persists. Uh, so it's likely to be a, a good thing. Comparative anatomy, I'm afraid you've got me there. I think almost all the mammals, but beyond that, uh, I, I'm, I'm really pushed <laugh>. Maybe there's someone Please, uh, there's a question at the front here. Thank you. Forgive me if I've missed something obvious, but when you described the fraught, um, position that they were in when they tried to operate on the cardiac artery, on the, uh, cardiac artery with, um, general anesthesia, but they could do it under local anesthesia, um, how did they know that the circle of Willis was functional in one method and not the other? Yeah, I'll, I'll go more into that. I probably summarized, uh, too much. So, um, when you clamp, uh, the artery, and if the circle isn't patent, if it's, uh, blocked itself in some way, uh, the patient will show some adverse response. Uh, so if they're squeezing, therefore they, they might not be able to with one hand, or if they're speaking, they might lose, uh, the power of speech or some words, or they might even, uh, change their conscious level. So that's how we know in the awake patient that the circle is, is not working. But all of that's impossible in the anesthetized patient. You just have to hope. Okay. So Near the beginning of your talk, you spoke about the great, uh, anatomical features in the brain, which this group, um, observed and gave names to. Um, now I've heard it said that the, in, in a living person, the brain has a consistency, rather like porridge. And when medical students dissect the brain, they do so in a brain which has been fixed and hardened with formalin or something like that. Um, were, um, rens group able to fix the brain in some way? That's a really good question. Um, and I'll answer it, advisedly in general, not they were operating on fresh cas. They, they literally claimed the bodies, uh, as they, uh, died. Uh, uh, you know, if they were hanged, uh, as in the case of Van Green, uh, and, uh, uh, started dissecting straight away, uh, uh, I'm not aware that they actively preserve them for, uh, um, you know, later, uh, dissection in the way that we do now. But your points well made and, and you're right, there is a difference between the fresh er and the, uh, preserved, uh, category. And that's why, you know, that lightning strike student was, was so important for the particular discovery. It's not, not so much porridge as a good panco <laugh>, Um, the, um, Uh, sort of striking, especially in a hall like this, surrounded by these portraits of people from that era. And as we both grown up in a world of hyper specialization, whether there's a place or whether a polymath can emerge from our current education system, or whether we constrain the creativity of great minds, I think that's a very good question. And it's not in, it's a student level, I fear. It's at researcher level, the whole exercise of the research, excellent framework and so on, it doesn't give credit to polymaths at all. You have to dig deeper and deeper and just do one, you know, fewer and fewer things to gain the, the relevant credit. So I, I, I think we've, we've not structured our system, uh, from start to finish, you could say, to encourage that, uh, approach. And I think that's why institutions like this is so important actually, to bring people together and say, look, this is an opportunity, an outlet to discuss these wider things of interest. You could argue that the, the guilds that have grown up in cities like London and Amsterdam were actually constraining that the building boundaries between people rather than breaking them down. Yeah, yeah, yeah. On the resuscitation of Anne Green, I dunno how available the observations are. What's your theory on the pathology that she suffered that was sufficient enough for her to be verified as dead? I dunno how that was done in that, in that era, but, but, you know, able to be resuscitated. That's a great question. Um, and, and, you know, without too much gruesome detail, um, you know, if you're correctly hanged, uh, then, uh, the hangman's fracture is something that severs the spinal cord and, and is a non-res resuscitate thing. So at best we can, uh, speculate that she was partially asphyxiated. Uh, and so what she needed, uh, and she was probably cold, which helped her, and what she needed was the, was the oxygen, the purified air, so some form of ventilation and, you know, perhaps the degree of cardiac compression just to bring her around. So I think she was lucky that it wasn't, uh, you know, it was a botched, a botched job. Uh, and she was lucky that she found this group of people who, who knew sort of roughly what to do. So I think that's my best guess on, on that. Angry, I think the, the root cause analysis group would probably say it was bad, not tying or a short stool. Yes,<laugh>, That would be the answers. Thank you. Well, thank you very much everybody. Professor Pene, absolutely brilliant lecture. Thank you very much. I hope you.