In one or two cases we got there in time. I illustrate them in rather better
drawn charts. In fact Erasmus was able to do a whole lot of them but we hadn't
had time to do those things. I put most of the charts and records and some of
the slides into the Welcome Historical Museum for archival purposes.
If the damage was small they recovered after about 2 or 3 weeks. But we saw some of those in a disaster we investigated in the tube entrance in Bethnel Green, When bomb warning sirens started, everybody rushed down to the tube shelters all over London and here in Bethnel Green a large number of people rushed down and somebody fell and the whole lot of the entrance steps were absolutely crammed those people and some died of suffocation, and we came down and looked round the local hospitals. Most of them were all right but some showed signs of pressure necrosis. I think 2 or 3 showed uremia and I think one recovered, and so on. It depends on the extent of the injury and the amount of acidosis and so on.
Bombing of London Crush Syndrome
So I had charge of beds and so on and it seemed to me that my whole life was changed when we got the bombing. That began on September 16, 1940. On that day two people were admitted who had been buried underneath debris and had been brought into hospital. They were all right. Blood pressure OK, everything and of course the centres had lots of other things to do and they were just put into bed. Then about a few hours later they collapsed and became very white, blood pressure right down and we had to resuscitate them with plasma and everything else. But it wasn't until about 5 or 6 days afterwards that they died of uremia. These were the two cases, followed by two more which started onto what we ultimately called "crush syndrome".
Devon Beale was in charge of the routine biochemistry lab and he did all my biochemistry on these patients which was quite considerable. I've lost track of him since. He was Canadian. But we did a lot of blood and urine tests on these patients who came in and in fact the Professor of Surgery really objected to these 300 tests we did on a single person every week and of course he reckoned the systolic and the diastolic pressure were two things and so on.
And he told the audience at a lecture I was giving that I was misusing my powers doing all this on injured people - biochemistry and blood pressures and everything else and he said this in front of an audience of army medical officers and so on in the lecture theatre where I was talking and he said, "I won't ask you to see another patient of mine again or come into my ward." But it's interesting. He was a fine surgeon. He'd been invited down from Newcastle but he was a loner. He had no idea of team work at all and of course that was the beginning of team work really - in the London hospitals.
I lived next to Regent Street for seven of my eighteen years and then I went to school where the chemistry master interested me in small animals called rotifers - a hundredth of an inch long, which you can see down a microscope. They're transparent so you can see all their guts and this was a great introduction. When my father came to see the headmaster about what I should be, the headmaster said, "Well, he's interested in ants and rotifers and he should go into medicine. So I went to Middlesex.
I worked for about 3 or 4 years after qualification in the biochemistry, pathology and hematology labs and saw patients occasionally at my own volition but mainly I was working on them metabolism of cartilage and one day Walter Barr from the MGH in Boston came over and asked me why I was fiddling around with cartilage from rabbits. He said if I went with him for a year or so to Boston, he could give me great big cows' cartilages and calves and so on. So, I went off that. And that was really the beginning of my interest in rheumatology because he was one of the best regarded rheumatological specialists in the United States and I was eager to get to the United States - the system here was pretty poor.
The war was looming so we came back early. I had had the opportunity to go all over the United States and see all the big departments and I enjoyed that very much. But when I got back the choice was between Guy's and Thomas's, Middlesex and so on but there had been started a wonderful new beginning - the British Postgraduate School of Medicine in an old poor ward hospital in Hammersmith and Francis Fraser from Bart's had been appointed Chief of Medicine and Charles Gray-Turner, the surgeon. And new little cubby holes in what they called fabric buildings were all over the sight and so I started there in rheumatology.
Bywaters and Cameron-Color Art in Early Papers
JSC: I was interested to see your paper with Diebel, the second of the two most famous paper I guess, in that you had some photomicrographs in black and white but you had some very nice color illustrations and one can't help noticing that they are signed "E. Bywaters" and are in fact watercolors.
EB: Yes I've always done watercolors and I think that drawings often show more than photographs really. You can show things up much better, So I've always done that.
JSC: I also noticed, although they weren't signed in the original Bywaters and Beale paper, the diagrams which are incredibly complex. I also noticed that they were hand-drawn which I don't think many journals would put up with today. Did you draw those as well?
EB: Oh they were terrible! But I got better at it and by the end of the war we were doing quite decent charts and diagrams and not as complicated as they were to start with. I shudder when I think of those early pictures!
JSC: Learning by experience. I guess the other thing - was color photography possible during the war?
EB: Not generally but we got onto the box and they took a number of color photographs about 6 inches by 4 of the organs - the crushed muscles, the kidneys. And I got a lot of those kidneys sliced in half, photographed and in fact we've still got some in bottles stored somewhere around Hammersmith but they've got lost like most things.
JSC: You've got some very nice drawings also of the whole kidneys which we will include in this presentation.
Yes, we heard, about 1943 or 1944, that in a small village in Holland called Campen there was a general practitioner who, despite the German occupation, had managed to knock together with sausage skin, slats and a bit of a motor engine I think, a machine which was later called an artificial kidney. That was Kolff and he was a marvellous chap. He did it all on his own and he dialyzed by about '44 - when that monograph I showed you finished - he dialyzed a number of patients and a number of them recovered. They were mainly accidents they weren't war injuries or bomb injuries but people who died ultimately of pulmonary edema but had been in accidents or car injury.
We then went out to see Kolff in Campen - a modest little house - and he showed us these things and we finally got him to come back after the war with one of these machines to Hammersmith and from then of course he has gone from strength to strength. They were very bulky things. We installed one in Hammersmith. It had a great big bath full of saline. A cranking machine for the sausage skin to get around. Very often you had to intubate the arteries of course - the veins - and very often the floor of this disused ward as it was, was covered with bath water and gloves and we had a terrible time. But we did manage to dialyze 11 or 12 patients. We weren't very good at that though. Kolff's patients were mostly glomerulonephritis patients and we made the mistake - also of dealing with established renal damage - only two of our patients I think survived - two out of 12 of our dialyzed patients. But we also got a barbiturate poisoning dialyzed.
Hiding from Bombs Under the Autopsy Table
They were coming down all over and you only had a little bit of notice with the doodlebugs. They stopped their whirring and then later exploded so you had time to take shelter which we did! And as you remarked, at one time under an autopsy table or any other convenient shelter. That produced a great crop. We then had quite a lot of patients around London. Fortunately, Hammersmith wasn't really hit at all during the war. I lived there part of the time. A pig was killed in a field near by and a bomb went off on the railway line - the tube line near us - which threw me out of bed and broke a window but nothing else. So we were able to get on with these things very peaceably. I remember the first night we all went to the shelters under the main hospital corridor but after that nobody worried.
Older Reports of Similar Conditions
Things like unconsciousness, Saturday night paralysis and nowadays barbiturates produce a very similar syndrome. There's kidney failure. They have these pressure marks in the skin and necrotic muscle and this was first actually mentioned a very long time ago during the Peninsular Wars when in Portugal the troops huddled around the campfires because of the cold and were close to them and the campfires emitted carbon monoxide and they reeled off into a coma and developed necrotic muscles I suppose but later kidney disease.
JSC: But they got paralysis and this is recorded nearly two hundred years
EB: Yes, something like that.
Post Mortem Studies - Myoglobin Precipitation
The ordinary pathology autopsies were really terrible in those days. You know, they never went below the pelvis and they never looked at the back and they missed all the muscles so we ultimately had to do our own autopsies but at that time, Diebel's department did them and regular things. I became very interested in the histopathology of the condition which largely revolved around the kidney and the muscle.
Well it was a very interesting challenge because right at the beginning nobody knew what this was or why the kidneys were affected and it was only later that people began to notice as these unfortunate victims lay in their beds that their limbs became very swollen and there was a great deal of serum and plasma in the muscle which on incision turned out to be necrotic and this was due to pressure, we know now, of more than two hours under debris and when the pressure was released of course, blood flow came into it and washed out the potassium and the creatine and the phosphorus and the myoglobin which we only found out later.
The resemblance to the transfusion kidney was very close and so we began looking at the muscle pigment. One time I left a solution of this human muscle pigment in the fridge and it crystallized out. I was one of the first people to crystallize myoglobin and then we did have the use of a small pocket spectroscope (we didn't get a reversion one until much later) and we began to realize that you could detect myoglobin as against hemoglobin even from met-hemoglobin compounds by reducing it and then bubbling carbon monoxide into it. The bands were quite different. That was very useful. You could even do it in the pocket microscope.
In alkaline it is quite soluble. In fact much more soluble than hemoglobin and we were puzzled sometimes why we didn't find myoglobin in the serum because you can with mismatched transfusions the serum comes out in the urine but with myoglobinuria it is much more soluble. It "whistles" through the kidneys. It's got a very low renal threshold compared with hemoglobin. And so unless you've got a specimen right at the release of the compression or tourniquet if you are working with rabbits or other animals, you never saw it in the blood. We only had one patient who showed myoglobin in the serum. We got him very early. It was a machinery accident in Newcastle and it was plainly visible within a very short time .
By that time, September 1939, when I joined, war had broken out but it was a phony war for some time. But the people at Hammersmith, Fraser being appointed Supremo of the emergency medical services and his place was taken by his Reader, Jack McMichael and so I continued there really forever after until I retired. Jack was a wonderful person. He had a very good team and they were all interested in shock, mainly physiologically. The effects of bleeding, transfusion and things like that.
He was primarily a cardiologist but Peter Shaffer was there, Otto Ekholm and a number of others - Sheila Haworth now Lady McMichael and Sheila Sherlock. A lot of people were in there at the beginning and they were working on bleeding. They offered their bodies for bleeding and retransfusion and so on!
The Term "Crush Syndrome"
We had a lot of cases. And of course other people in London and
other bombed cities had lots of cases too. There was a big struggle right
at the beginning with the MRC and the Medical Research Society meetings as to what this should be called. Should it be called "compression injury"?
We finally settled for a term we called "ischemic muscle necrosis" although most people refer to it as "crush syndrome" because that the word we first used.
We had I think 55 cases of people crushed in machinery or road accidents and we finally established with 55 patients or so, and it used to be called "traumatic anuria". The surgeons had always talked about traumatic anuria and we finally found that in fact most of the cases had areas of muscle necrosis which hadn't been realized before and the mechanism was the same as in the crush syndrome. Sometimes we only saw pieces. I remember particularly one woman patient who was very obese and was having a cholecystectomy and the surgeon was also very obese. So there was difficulty getting down there and two strong medical students or housemen were pulling on retractors down the middle of the tummy and when we did the post mortem - she died four days later of anuria - we found that there was a bit of the rectus abdominus which was completely necrotic and she died four days later. So there are surgical problems too.
We had one crush syndrome patient at Hammersmith and as a classical case, came to post mortem. The kidneys showed classical changes with normal glomeruli and pigment in the second convoluted tubules which were hollow casts and then sometimes bursting into the interstitial tissue or into the veins, tubular venous aneurysms. But I was an amateur pathologist and so I took the precaution of looking at a number of other cases of the kidneys. And one of them, which was the next case, PM1831 (and PM1830) showed exactly the same changes. I was very mystified by this and they looked up the clinical history and it was a case of acute nephritis. I had a big battle with one of the pathologists there because he said I'd mixed up the sections or something like that. I finally took it to Professor Diebel who agreed with me that they hadn't been mixed up. We finally wrote the case up. There was some interest because it was a case of a rather rare disease called "acute myoglobinuric myolysis" in a young man. We got this by going back on his history and found that he'd had several of these attacks in his past and had gone weak and pale and so on. On one or two occasions he'd passed red urine.
Animal Experiments Characterizing Crush Syndrome
A lull came in the Nazi bombardment - late '41 I think it was. And we had time to do some animal experiments where we showed in rabbits that tourniquet compression produced all the symptoms of shock after release but no myoglobinuria. It was very simple - the rabbits' muscles we were compressing didn't have myoglobin. But when you injected myoglobin into the animal and with acidosis, even without compression, you could get a pretty good picture of a crush syndrome kidney.
It had been hinted at by one of the people after the first world war. There were I think 126 cases in Germany recorded by Frankenthal in 1916 and they went into the Germany textbooks and then there was an earthquake at Massina described by von Kalmers and later by Minami and I think Minami mentioned the possibility but nothing of the crush syndrome was seen in any of the post war surgical textbooks.