Blood and Guts: A History of Surgery (2008) s01e03 Episode Script
Spare Parts
In 2006, David Savage had a dead person's hand attached to his arm.
The day I woke up from surgery, it was like waking up from a 32-year sleep, it was amazing.
Contains scenes which some viewers may find upsetting.
48-year-old Clint Hallam had the same operation, but two and half years later he was back on the table having it removed.
It had begun to rot.
My partner said you don't realise it, but it's dead.
Transplant surgery had transformed one life, but it had failed to transform another.
I'm almost more handicapped with my new hand than when I just had one and a half hands.
These two men, the success and the failure, are both part of one enduring obsession.
My name's Michael Mosley, and in this programme I'm going to trace the twisted history of the transplant dream and the people who made it happen, often at terrible cost.
In the beginning, transplants were dogged by delay, disaster and death.
That was because surgeons didn't understand they were taking on the most complex efficient killing system we know of, the immune system.
But it's about more than just biology.
I want to track down Clint and David and find out why their stories ended so very differently.
November 29th, 2006 - Louisville Kentucky, USA.
The man on the operating table is David Savage.
More than 30 years ago, he lost his hand in an industrial accident.
But today, in an operation lasting 15 hours, and employing the skills of 34 of the world's leading surgeons, David Savage will have a donor hand attached to his arm.
It is an operation of extraordinary complexity.
First, orthopaedic surgeons join the ends of the tendons in David's arm to the tendons of the donor hand.
Then vascular surgeons begin work on the blood supply.
They sew each of the donor's arteries and veins to the ends of David's own vessels.
Next, the neuro-specialists step in to perform the delicate task of rejoining the donor's nerves to David's stump.
And the final step is to close up the skin.
When he wakes up, David Savage will have a brand-new right hand.
We're on course, everything is going exactly as we would hope that it would, with really minimal problems.
I'm really intrigued by David because to me this is more than just an incredible surgical achievement.
The whole idea of living with a dead man's hand is one I find fascinating, but also disturbing.
A lot of people I've talked to are really freaked by the idea of having something like an arm transplant.
It's also true, frankly, of all the other bits of the body that show, like noses, eyes and face is probably the freakiest of them all.
No other form of surgery impacts on our sense of self in quite the way transplants do.
There is something profoundly strange about swapping body parts, melding your flesh with another's.
And these days there seem to be no limits.
I want to understand where this strange but compelling dream began.
And that takes me to the 1760s and the festering mouths of sweet-toothed aristocrats.
The first serious attempt at human transplants was in the 18th century.
Aristocrats had increasing access to sugar and as a result were developing rotten teeth.
So someone came up with the brilliant idea - why not take healthy teeth from poor people and stick them in the mouths of the rich? The first thing you need is a donor.
What you do is go out in the street and find some poor pauper who is prepared to part with their teeth for a few pennies.
You bring them in and you pull out one of these.
It's a pair of pliers, which you clamp on one of the front teeth.
And you give it a good old shake and you just yank it out.
Now, all of this would have been done without the benefit of any sort of anaesthetic.
If the pauper was lucky he got a bloody rag to chew on.
You take the pauper's tooth and you simply ram it into place.
This whole procedure cost five guineas, which was about the annual wage of a scullery maid.
If you were extremely lucky it would stay in place for about two months, before falling out.
If you were unlucky you would pick up gonorrhoea, syphilis or some other delightful 18th-century disease from the poor soul whose teeth you had pulled out.
So, hardly a rip-roaring success.
They had come up against the would-be transplanter's first big problem.
Before body parts could be swapped, surgeons would have to work out how to reattach them.
A century later, here in Lyon, the sudden brutal murder of a president and the nimble fingers of a Frenchman came together to make transplants more than just a fantastical dream.
This is Lyon University, home to one of the 20th century's greatest and most controversial surgeons.
He won the Nobel prize for medicine, and his pioneering techniques saved the lives and limbs of millions.
But this is not him.
In fact, there are no statues or departments named after him.
And that's because, like transplant surgery itself, the man who started it all had a very dark soul.
His name was Alexis Carrel.
Carrel was an intense, imperious doctor, immaculately dressed, with thick glasses perched on his nose.
But if you took off those glasses and gazed into his small, piercing eyes you'd notice a very unusual trait.
The iris of one of Carrel's eyes was brown, while the other was blue.
And burning behind those mismatched eyes was a dangerous obsession.
Carrel believed the human race could reach perfection.
It was an idea that was to lead him to a great breakthrough, but it would also take him somewhere much darker.
Straight into the arms of the Nazi regime.
Ironically enough, it was politics and murder that led to Carrel's victory over transplant surgery's first great barrier.
It's June, 1894, and the French president, Sadi Carnot, has come here to Lyon.
He's travelling in an open-top cart, like this one, when from amongst the cheering crowd emerges a young man clutching a rolled-up newspaper.
The young man is actually an anarchist, and hidden in the newspaper is a knife.
He rushes up to the President and stabs him in the abdomen.
The president began to bleed to death.
They rushed him to hospital and the best surgeon in Lyon was summoned.
But it was no use.
One of his major blood vessels had been punctured, and in 1894 no-one could repair it.
So all that they could do in that hospital was stand by and watch the French President slowly bleed to death.
This incident made a deep impression on Carrel, who wrote about it in his biography.
His life left him with his blood.
I can still hear it flowing, drop by drop, 50 years later.
Carrel was appalled by the death of the President and the surgeons' failure to save him.
He was convinced that he could find a way to repair broken blood vessels, and against determined medical opposition he set out to prove himself right.
He went looking for Lyon's finest embroideress, who lived at the top of the hill in the silk district.
He needed her to teach him how to do minute delicate stitches.
This is not quite as strange as it might first appear.
Carrel believed if he could master the tiny stitches used in embroidery then he could employ similar techniques to sew delicate blood vessels together.
I've tracked down Lyon's finest embroideress to see for myself the challenge Carrel faced.
I show you one time, and you do it after.
OK.
I admire your confidence.
You have to take the end of the thread in one hand and the needle in the other hand.
OK, very good.
And you turn the thread around the first thread.
OK, yeah.
Very good, very neat.
And a second.
In the other direction.
Have you ever sewn flesh? Skin? Bone? Have you ever tried sewing skin? No, never.
No reason to do so.
Carrel was a perfectionist and a very determined student.
Night after night he slaved away, bent over the intricate needlework.
His stitches had to be so fine that they wouldn't damage the delicate walls of the blood vessels, and so he practiced on paper.
It's said he became so accomplished he could make 500 stitches in a piece of cigarette paper without tearing it.
How many stitches can you put in to something this size, do you think? I don't know.
On one centimetre there is approximately 100 points.
100 stitches? Yes.
Just here.
Even better than Carrel.
As in surgery, as in embroidery, it's very important to be calm and quiet.
I don't know if you say the same.
Which is why I suspect I would have been a terrible surgeon.
Ahhhhh! Do you want to try it? Why not? Yeah.
OK.
No.
No.
No.
Deep breath.
It's not a body.
Not flesh.
Not flesh.
Not dying.
Save me, Dr Mosley! Save me! Right.
OK.
So I go through here, trying to avoid going through my finger.
You have to be very patient.
I can imagine him at home .
.
obsessively sewing this.
That's what's interesting about a lot of these characters in surgery - it's not, in a funny way, that nobody else has tried it before, it's just they do it better than anybody has done it before.
Knots are the thing I'm not terribly good at.
Try and avoid the loop catching.
Inverse.
Inverse it.
What? I'm doing it wrong? I think your patient is dead.
OK, never mind.
OK, never mind.
Once Carrel had become a skilled embroiderer he turned his attention to his real ambition - sewing blood vessels.
And that is significantly more difficult than sewing a flat piece of paper.
Blood vessels are rounded and they tend to collapse inwards.
It's like trying to sew together two very soggy drinking straws.
Carrel solved this problem by inventing a technique that transformed surgery.
It's one of those moments I absolutely love, when a seemingly minute step changes everything.
Dr Richard Gibbs is a vascular surgeon, and some of the techniques he uses are descendents of Carrel's stitch.
He's going to show me why Carrel's work was so revolutionary.
This is a very realistic looking piece of artery.
This is a real artery, it is a pig's aorta, so it's not that dissimilar from human arteries.
What we'll do is chop it in half with these scissors.
Right, OK! Good splash, right?! Blood starts to clot within two or three minutes of being exposed to air, so he must have been very fast.
He also must have had a very meticulous technique.
And one of the important principles is that you try to curve the needle very gently through an arc.
If you drag it you'll tear the artery and it will start to bleed.
It's curious to think that until you could do something as basic as this you couldn't do a transplant.
Exactly, it's still predicated on the need to be able to sew one bit of artery to another bit of artery.
And if that basic step fails then nothing's going to work, no matter how good the technology or the drugs are.
Carrel's first trick was this - he had discovered that if he always passed the needle from inside to out he could sew the insides of the vessels together and this would stop blood from clotting over the join and blocking the vessel.
And his second trick was even better.
By putting three stitches round the edge and pulling on them all at once, he magically created a straight line to sew along.
And that, apparently, is going to make it easier for me when I have my go.
I remember when I started off in medicine, in casualty, on drunks and things like that Do you remember those days? Very well.
I had this awful occasion when I had this drunk guy and he had a big gash in his head, and I did a very careful job of sewing his head, and then, when I reached to pull my hands away I'd sewn my glove to the top of his skull.
Which was a low moment.
I had to call the nurse who came and snipped it away.
It was not the highlight of my sewing career.
OK, so there we are, and now for the acid test.
The blood test.
Are you feeling confident? I'm feeling very confident! Gradually distend that up.
Very good.
You always get a bit of bleeding around the stitch holes, but that would be acceptable.
OK.
Shall we switch over and I'll have a go? Right, we're ready to operate, doctor.
Aye, Dr Finlay.
We're doing this on the kitchen table of a remote Scottish farmhouse.
Aye, Janet! We're ready, Janet, we're ready to go.
Your aneurysm is ruptured! Your aneurysm is ruptured, Janet, and I'm about to operate.
'It does not start well.
' I'm already getting confused.
How do I angle myself? If you pull them like that, rather than holding it like an ape trying to get a coconut open with a hammer.
If you hold it like that it'll be much easier.
Very good.
So I'm going in the other side now? Exactly.
About there? Approximately there.
Little bit bigger bite.
No, no, don't pick it up there, push it from the other side.
And then pick it up.
You don't want those little linear tears in the aorta because as soon as you take the clamps off the blood will flow.
It will spurt.
Push, push, push, push.
That's it.
And now pick it up the other side.
And curve it round.
Follow the curve of the needle.
That's great.
Got it.
Sorry, you need to be A bit deeper? Yeah.
A bit deeper than that.
Is that too deep?No, that's fine.
But now you're losing control.
I am.
Calm down.
Too excitable.
I thought I would be extremely calm about this, but there is something about the challenge Breathe in.
I hope you weren't doing anything this evening.
It fills me with enormous respect for Carrel and, frankly, for surgeons as well.
When I do this sort of stuff.
I have to say, it looked so much easier when you did it.
That's not a true surgical knot.
Really?That's what we call the shoelace knot.
See if I can avoid pricking myself.
Right.
Great.
OK, this is the moment of truth, see if my stitching holds.
Hmm.
Bit of a drip coming out here.
Yeah.
I feel quite tired, I must admit.
It required a lot of focus.
But I'm quite pleased.
I thought it could be terrible.
It was OK.
Thank you, that was fantastic, that was really interesting, really enjoyable.
Carrel had invented vascular surgery.
For the first time surgeons could repair partially severed limbs or damaged arteries.
Emboldened, Carrel's thoughts now turned to a very different surgical challenge - transplants.
Carrel lived in an age of great experimenters.
The Wright brothers launched human beings, briefly, into the skies.
Thomas Edison had sold the world the delights of the phonogram and the light bulb.
And Henry Ford created his Model T motorcar.
So there seemed no good reason why an arrogant young Frenchman should not transplant human organs.
Having perfected his stitches, Carrel was now convinced that organ transplants were within his grasp - all he had to do was practice.
Which he did, on dogs.
Carrel's operating garb was, well, unusual.
He dressed all in black to protect his sensitive eyes from glare.
The effect was truly sinister.
Carrel's experiments were a mixture of the scientific and the grotesque.
He did kidney transplants between dogs but he also took the kidney out of a puppy and put it in a cat.
And he took the front legs off a white dog and attached them to a black dog.
Carrel found that plumbing in the new organs was comparatively easy.
But the problem was, within a short while they stopped working and the animals died.
It was perplexing.
Something inexplicable was causing the animals' death.
He eventually concluded that some mysterious biological force made transplants impossible.
In a letter, he wrote: "The biological side of the question "has to be investigated very much more.
"We must find out how to prevent "the reaction of the organism against a new organ.
" Carrel's experiments were interrupted by the outbreak of the Second World War.
Before then, he had publicly promoted the use of gas chambers to "rid humanity of inferior stock".
Carrel died in November 1944, while under house arrest as a Nazi collaborator.
Carrel's descent from fame to obscurity was sudden and complete.
This unremarkable street is the only place in Lyon that still carries his name, and even this has been changed.
Carrel was a tragedy, a brilliant, flawed, surgical genius.
Carrel had proven it was possible to swap organs.
But in doing so, he had come up against the next great obstacle to doing transplants.
Rejection.
The body's automatic reaction to any foreign invader.
This is a sample of my blood.
It contains some of the most remorseless and versatile killers known to man.
In a sample this big, there wouldbe at least 350 million white blood cells, all of them primed to deal with any foreign threat.
I gave my precious blood to scientists at Imperial College.
From it, they extracted some of the white blood cells responsible for attacking invaders.
These cells are called natural killer cells.
When they detect an invader, they move in, attack and destroy.
My natural killer cells, here coloured red, can be seen vigorously attacking a cancer cell.
Unfortunately, a similar reaction occurs whenyou try to do a transplant.
This microscopic army is part of the immune system.
The hidden force that made Carrel's transplants all fail.
And the battle to overcome it was to define the next phase of the transplant dream.
It was a battle that began as the Second World War ended.
These were hopeful times.
The fighting was over, and out of the carnage had come great surgical innovations.
Advances in plastic surgery, brain surgery and the beginnings of cardiac surgery.
But some body parts remained beyond repair.
Dialysis offered temporary treatment for failing kidneys.
But there was no cure.
The unglamorous kidney was about to reignite the transplant dream.
In Boston USA, surgeons began to wonder if transplants were the answer.
The kidney is easy to remove and because we have two, it would be possible to use a living donor.
But to succeed, they would first have to outwit the immune system.
This footage shows the surgeons transplanting a kidney wrapped in a plastic bag.
The idea was that the bag would prevent the immune cells from attacking the surface of the kidney.
It did not work.
And the patient died.
One of the early pioneers was Dr Joseph Murray.
Today, he's a Bostonian legend.
Back then, he was just plain old Joe Murray, a doctor who believed in transplants.
Well, I believed in it, personally, because it seemed to be reasonable.
These patients were dying, they were young, we had a team of good physicians and surgeons working, and if we weren't going to do it, who would? Joseph Murray got a chance to "do it" when, in 1954, he encountered a most unusual patient.
In October, a 23-year-old man was admitted to this hospital.
He was ranting and raving.
His case notes say he was extremely uncooperative, and he a bit a nurse while she was changing his linen.
The patient was Richard Herrick.
His deranged behaviour was typical of massive, terminal, kidney failure.
Richard was in some ways doubly fortunate.
He had come to the right place at the right time and he also had a very unusual biological quirk, which none of the previous patients had shared.
Richard was one of a set of twins, and his brother, Ronald was willing to donate him a kidney.
Joe Murray believed thatidentical twins did not reject each other's tissue.
We knew that in identical twins you could have successful grafting.
But we never dreamed that we would find an identical twin, one dying of kidney disease and another one willing to give a kidney.
But you know, it is an example of happenstance favouring a prepared mind.
The certainly looked alike, but were they really identical? Joe Murray began a series of tests to find out.
If they weren't, Richard's body would reject Ronald's kidney.
Murray performed 17 tests on the boys.
He compared their eyes.
He examined their skin.
He even took them to the police station to see if their fingerprints matched.
Finally, they took a sample of skin from Ronald's arm and grafted it onto Richard's.
If this failed, then the kidney would also fail.
The skin graft took.
Richard and Ronald were genetically identical.
The transplant could go ahead.
But Richard was worried about accepting his brother's gift.
Even the night before the operation, the potential recipient told the donor, "Get out of here.
Don't come back.
" But the donor said, "I'm here and I'm gonna stay.
" So we went ahead and did it.
Christmas 1954, an incredibly good moment for exchanging gifts.
That morning, surgeons from this hospital removed the healthy kidney from Ronald.
They then wrapped this precious present in a cold wet towel and took it into the next operating theatre.
At 9:53 precisely, Murray began to operate.
Well we went, deliberately, slowly.
We were working under time constraints.
We were well aware of it.
It took about 3 hours before we got the blood vessels attached.
By the time we released the clamps, the kidney began to pour out urine, so copiously that we had to really suck it up and keep it out, for our vision.
The flow of urine was a fabulous sign.
It meant the kidney was working.
This was history.
The next morning was a miracle.
His eyes were sparkling, he was hungry for the first time in months.
Richard Herrick, a man on the brink of death, married his nurse and lived for a further 8 years.
Transplant surgery had finally prolonged a life.
But the operation had only worked because Richard had a twin.
His treatment established a fundamental principle.
Success depends on maximising genetic closeness, of recipient and donor.
Even today, if you need a new kidney, your best chance is a member of your own family.
I don't have an identical twin brother, but I do have two brothers and a sister and I have been running a series of tests to see which would make the best match for me.
Now I would guess that I am closest to my older brother, John, but it could be my sister, Susie.
Or it could be my younger brother, David.
The truth is, I won't know until I have had a look at the DNA.
I persuaded each of my siblings and, for comparison, my wife, to give me a tube of their blood.
This contains their genetic code and should reveal how closely they are matched to me.
Remarkably blue, odd, isn't it? Seeing your life force going out.
I had my blood taken, too.
And dropped the whole lot off at the Anthony Nolan Trust, where they run-tissue matching tests for real transplants.
Here you go, some blood.
Fresh and hot from my veins.
Joyce at the trust ran our blood through this machine, which reads DNA.
She is looking at the genes on chromosome 6, that are markers for the immune system.
The only chance of an exact match is with an identical twin, but a family member should be close.
I've invited my siblings round to my house.
Where we will discover which of us really does have the most in common.
Who do you think you are most like? Who do you think is your closest genetic match?Immediately to mind, David.
OK.
David, who do you think? Probably John.
Right.
And I think, John.
You are the universal donor.
To reveal the results, I've invented a game called Chromosome Snap.
There are 6 different cards, each representing a different immune system gene.
We are looking for matching pairs.
The more matches, the more likely a kidney transplant would succeed.
What we are hoping for is at least three.
Six is really good, that's a perfect match, very, very unlikely.
Nought is very bad you can still do it but the odds are not great.
Really a minimum of three.
There you go.
What I am going to want you to do is turn them over one at a time.
OK, Clare.
Marvellous.
Disappointing.
David Oh, good.
Excellent.
Excellent.
One, two, three.
Very pleased.
After the first card turn, all of my siblings match, but there still 5 more cards to go.
Hurray, wow.
And by the end of the game, there is a clear winner.
My sister Susie and I are matched across all 6 genes.
I wonder what the odds on that are? That's really surprising.
So we should be interested in each other's health? I should make sure that you keep running! You need to look after what I now regard as my internal organs.
If you have a brother or sister, you have a one in 25 chance of making such a match.
But unless you are identical twins, even the closest match will lead to rejection.
Unless the immune system is controlled.
Joseph Murray decided the only way forward was to tackle the immune system head on.
Murray wanted to treat all his patients, not just those who happened to have an identical twin.
To do that, he needed to disable, even destroy the immune system.
Joe Murray decided to go nuclear.
In 1958.
Murray met a 31-year-old woman called Gladys Lowman.
She had been born with only one kidney.
And that kidney had been removed by a blundering surgeon who was trying to remove her appendix.
Unless she had a transplant, she had only weeks to live.
Hiroshima and Nagasaki had demonstrated the frightening power of nuclear radiation.
Ionising radiation attacks all fast-dividing cells, including the cells of the immune system.
Murray knew that high doses of X-rays would produce similar results.
It was clearly dangerous, but he thought it was worth a try.
With Gladys sinking fast, Murray now transplanted a new kidney into her and began irradiating.
He knew he had suppressed the immune system, but doing this was rather like trying to open a front door with a bulldozer.
There was serious risk he would knock the whole house down.
We used total body radiation.
And the patient would lie under the x-ray machine.
And curl up in the foetal position so that all of the lymph nodes, spleen and bone marrow would be irradiated.
Gladys lay under the machine for 3 hours.
She received the equivalent of 600,000 dental X-rays.
With her immune system completely destroyed, Gladys now had to live in a sterile room.
Murray infused her with bone marrow, to replace her annihilated white cells.
But even so, within four weeks, she succumbed to overwhelming infection.
In the years that followed, Murray irradiated 10 patients.
Nine died soon after the treatment.
But Murray still believed it could be done.
It didn't work, but it was a necessary step along the way.
And even in the most discouraging times, there were hints that something might be better.
Maybe I am just a pathological optimist, I've been called that.
After five years of failure, Murray met a young Cambridge doctor with a radically different set of ideas.
From my point of view, I was very interested in trying to prove the critics wrong.
I have always felt that way - if someone says what you are doing is stupid, it is a great pleasure to show that they are wrong.
And when Mr Pathologically Optimistic met Mr Can't Be Wrong, something special was bound to happen.
Roy Calne had been experimenting with another tool for defeating the immune system.
Drugs.
He'd heard about a new drug, called azathioprine that destroyed immune cells in people with cancer.
So, he gave the drug to dogs with transplanted kidneys.
It appeared to work.
And this was enough to encourage Calne and Murray to try the drug in humans.
With the door finally opened, lots of people now joined the party.
In the 1960s, more and more surgeons started to experiment with transplants.
Using azathioprine to control the immune system, they dared to venture into new territory.
They tried transplanting the liver and the lung.
They attempted to put animal organs into people.
And there was an absolute frenzy of media excitement when surgeons began transplanting human hearts.
This is the team that yesterday performed Britain's first human heart transplant operation.
The complete team whose skill, devotion and courage has already made British medical history.
We are going over to the National Heart Hospital now.
Doctor, can you hear me? Yes, I can hear you very well.
This is Raymond Baxter in the television studio.
How is the patient, Mr West? Well, he is doing extremely well at the present moment.
But the optimism was short-lived.
Most transplant patients were still dying.
The problem was the new drug was incredibly difficult to administer.
Too little led to rejection.
But when they tried to increase the dose, azathioprine could completely destroy a patient's immune system.
The new drug was not the magic solution they had hoped for.
There was a feeling that transplantation was not worth it.
I mean, most prestigious medical institutions didn't want to bother with transplantation.
And then, olive oil came to the rescue.
It's one of those wonderfully unlikely but true medical stories.
The tale of how olive oil came to rescue transplant surgery is lovely, beginning, as it does, with a Scandinavian holiday, and a rather unusual souvenir.
This belonged to an employee of the Swiss drugs firm Sandoz.
The enthusiastic employee had returned from a trip to Norway with a suitcase full of soil.
He was hoping to discover a new micro-organism.
In the lab, the researcher carefully analysed the soil, and was rewarded with a new species of fungus, from which they extracted a brand new drug.
They called it Cyclosporine A.
They must have jumped up and down in a quiet, scientific sort of way, because some of the most profitable drugs ever discovered have come from fungi.
Think of penicillin.
Early tests on the fungus showed that it was actually useless at killing bacteria.
But it did suppress the immune system.
And that brought Cyclosporine A to the attention of Roy Calne and his team in Cambridge, who were still searching for better drugs.
Roy contacted Sandoz, and pleaded for a small sample of the magic mushroom.
I've had some dealings with the Swiss drug firm myself, and like Roy, I've persuaded them to send some of the drug over to me, so I can show you what happened next.
Inside here are some Cyclosporine A, and it should be in the pure form that Roy Calne received it.
Yes, it's a white powder, looks harmless enough, but I don't want any of this stuff inside me, so I am going to take some necessary precautions.
This is what they wear in pharmaceutical laboratories when they are handling any dangerous drug.
Although the risk to my health is small, I've been advised to make sure I am gloved up and covered up.
When they got Cyclosporine A back to the lab, Roy and his researchers had a nasty surprise.
The problem was, before humans could ingest it, they had to find a way to dissolve it.
If it wouldn't dissolve, then there was no way it would work.
The drug would be useless.
Right, I am going to put powder in there, that was 0.
4, and I will do the same in another one, here.
Yep, same amount.
Powder in the second one .
.
and put the lid back on.
They tried dissolving it first in water, and I'll demonstrate to you what happens.
I need 40ml.
They tried dissolving it in water, and as you can see, if you shake it up, it just doesn't dissolve.
Floats largely on the surface.
They tried all sorts of other industrial solvents, and none of them worked.
Now it's in there, I can take this stuff off.
Right.
So they had a problem, but they were lucky.
There was a Greek researcher who was working with Roy Calne, and his mother was worried that her boy was going to be affected by the appalling British food, so she sent him a bottle of Greek olive oil.
Now, more in hope than expectation, he took that olive oil, and he added it to the cyclosporine.
And I will show you just what happened.
Vigorous shake As you can see, it is completely dissolved.
The Greek student tried the olive oil formulation on his animals.
He got spectacular results, so spectacular, that I didn't believe him when he first told me.
And I told him to repeat it, which he did, and he got the same results again.
Cyclosporine was THE breakthrough that transplant surgery had been waiting for.
Finally, the immune system could be controlled, and transplant surgeons could start saving lives instead of ending them.
In the 1980s and 90s, kidney and heart transplants became widespread.
The demand for organs soared, and a national donor scheme was launched.
12 million of these new plastic cards are to be distributed.
The new card is being issued because new techniques are increasing the range of organs which can be donated.
This is a multi-donor card, and people have the option of donating their kidneys, their eyes, their heart, their liver, their pancreas, or, indeed, one of those, or all of them, or any other part of their body which they would like to donate.
Transplants became something of an everyday miracle.
Two teams of doctors worked throughout the early hours of this morning to perform the world's first triple organ transplant.
This is BBC One.
When Brook Matthews arrived from Australia in January, she had only a few months to live.
Now, following her four and a half hour operation yesterday at Harefield Hospital, she is making good progress.
It was her only chance of life, and few would blame her parents for taking that chance.
A very special one-year-old had a birthday party today.
She is Kaylee Davidson from Washington in Tyne and Wear, and she's Britain's youngest surviving heart transplant patient.
We can't believe it.
She was really poorly, and she wouldn't do anything, she had no interest in anybody or anything.
And now she's a typical little girl, into everything.
Surgeons, once again, began to dream of new frontiers.
And in 1998, surgeons in France announced that they had pulled off a truly spectacular world first.
On the 24th September, in a blaze of publicity and surgical glory, Clint Hallam became the first person to receive a hand transplant.
The operation pushed the boundaries of what surgeons had believed was possible.
I was certainly impressed, but I also wondered if this was a genuine medical advance, done to improve the life of the patient.
Was it being done simply because it could be done? I first crossed paths with Clint a year after the operation, when I was making a medical series for the BBC.
My first thoughts when I saw my hand was that it was a miracle.
But it was a miracle that was starting to fade.
No, no, no, no.
One of the hard things to accept, for me, is that I am almost more handicapped with my new hand than when I just had one and a half hands.
This is not exactly as the dream was for eight, nine, ten years.
This is not happening like it does in the movies.
Clint was finding it hard to adapt psychologically to the new hand.
A very dear friend who lives in London, I never understood why he used to grab my hand like this, in fact, grab my wrist, simply because he didn't want to touch my hand.
To him, it was quite horrific.
Clint had also started to feel ill, and he suspected that his anti-rejection drugs were intensifying his symptoms.
The two most physical side effects that I notice is first, I have diabetes.
The second side effect is more physical, in that my body has gone from chest to breast, and that's a little bit difficult to deal with.
As Clint cut back on his medication, his hand began to show signs of rejection.
The fingertips had started to get red, and I lost all sensation.
The redness in the fingertips, the fingernails falling off with new nails coming underneath them are all indictors of a serious rejection problem.
By 2001, Clint's immune system had almost completely destroyed his new hand.
Good evening.
Clint Hallam was at the centre of a medical breakthrough two years ago, but now he wants out.
Having had the hand of a dying man attached where his used to be, he's now begging for it to be removed.
I certainly believe that there must come a stage, with the number of rejections that I have experienced with my hand, that yes, my body has or my mind has said enough is enough.
The morning after this interview was recorded, Clint Hallam's dead hand was surgically removed.
I am fascinated by Clint's story, because in him I can see the terrible contradictions of cutting-edge surgery.
There is the fame and glory, at least for the surgeon, of going first.
However, there is the often appalling cost to the patients of being first.
I'm on my way to meet Clint Hallam, who I haven't seen for many years.
I want to find out how he is.
I'm intrigued by the new hand.
Does it move?It does.
It clicks, and goes in circles.
But that's pretty much the range.
That really is its limits.
You can shake hands?Yes.
But it's very limited? It's extremely limited.
It really is cosmetic.
I can do certain things like Hold on.
It will do it.
Very good.
But if you actually tried to put it in your mouth at this point, it would go over your shoulder, would it? I'll give you the hand, you try and put it in your mouth.
I can't do it.
I can get it across my shoulder.
Great at Greek weddings! But otherwise, not perfect.
Ooh, thank you very much.
Clint is clearly not thrilled with his new plastic hand, but what I'm interested in is why he thinks the transplant failed.
Were you never freaked by the idea that this was a hand from a corpse, this was a hand from a dead person? Did that not worry you? No, no.
I was attached to it, but I was detached from everything about it.
Right.
In retrospect, in looking back.
And Were you ashamed of it? I was fucking angry with the doctors, and I'm still angry with the doctors that they didn't match it.
That was a big thing, was it? The matching? You saw it.
I saw it.
OK? It was huge.
It seems Clint's mind rejected his new hand before his body did.
Despite his doctors' warnings, Clint stopped taking his medication, making physical rejection inevitable.
Why did you stop taking the immunosuppressive drugs? Actually, I didn't stop taking all of the drugs all at the same time.
I stopped taking some of the drugs in lesser quantities than I was supposed to.
Why? Because I got sick.
I was surprised, frankly, that you persisted with that hand as long as you did.
It was putrefying.
My partner of the time, and now, said exactly the same thing.
She said "You don't realise it, but it's dead.
" What would your advice be to other people who are thinking about going first? About going first in anything, I would tell them to walk slowly backwards.
Go back down the line, and keep thinking.
Really? Think, and think very carefully.
Do you regret being the first? I regret being the first.
I don't regret having the transplant.
Soon after Clint had the transplanted hand removed, he rang round, asking for another hand transplant.
Unsurprisingly, the surgeons all said no.
The truth is, no matter how good surgical techniques are, they will fail if the patient is not psychologically prepared.
But was it simply that Clint was the wrong patient, or are hands just harder to do? I'm in Kentucky, USA, to meet the surgeon who performed the world's second hand transplant.
Were you upset that you weren't the first? Yeah, I think every human being always wants to be a leader.
But I always told my team, and you can ask them, I emphasised this over and over again, it doesn't matter who does it first, it matters who does it best.
Dr Breidenbach has performed three hand transplants, and the latest is perhaps the most remarkable of all.
In November 2006 he led a team of surgeons in replacing the right hand of 54-year-old David Savage.
David had lost his hand 32 years earlier.
I believe he is the longest time between amputee to transplant.
So we ran into problems which are novel and new, and the analogy I make, it's kind of like closing your house down for 32 years, and then you come back and decide you're going to take a shower.
And you turn on the faucet, and it sputters a little bit.
Sometimes it works, and sometimes it doesn't.
So we had some sputtering last night, as his vessels were trying to get blood into the hand which we were transplanting.
The operation was, in the end, a technical triumph.
But I wonder if David, unlike Clint, is truly comfortable with his new hand.
When I meet him and his wife Karen, I am instantly struck by how different his new hand is to the other one.
Do you mind if I just compare your hands, looking at the two of them? What is quite spooky, I don't know if you find it spooky, there are moments when I actually remember this hand came from somebody else.
Do you think that at all? I think about it all the time.
I think about the family that donated it all the time.
But like I said the first day I woke up from surgery, it's mine.
Yes, it's now yours, isn't it? But they are quite different, in a funny way.
Yeah, they're different.
Have you ever considered the possibility that this could have come from a woman? I thought about it.
It wouldn't have bothered me.
I'm curious, because the only thing that's striking about this is, you have very dark hair.
This hand doesn't.
If you look really closely, you can see it's very fair, isn't it? Yes, it's got, like, blondish hair.
But it's turning dark.
Yeah, and it'll probably grow.
And do the nails grow? Oh, twice as fast as my other hand.
Do you mind if I have a look again? It's curious, because the fingernails on this one are longer and more elegant, and you look like you've bitten them off.
No, they were all clipped at the same time.
Really? How extraordinary.
When you put them next to each other, they are different.
Most people don't get the opportunity to compare like that.
They will see Dave from across the room, and they don't really realise what the difference is.
Absolutely.
And do you think that is important? Yes, because we don't want people to focus on the difference.
We want them to focus on the progress, and the hope of what this transplant can mean to other people.
David and Karen are full of optimism.
And when I watch David's therapy sessions, I can see why.
He already has around 60% of the function of a normal hand, and with more therapy, he may eventually get to 80%.
Last September, my granddaughter, just going to her birthday party, and grabbing hold of her, picking her up.
It was just a fantastic feeling.
Dr Breidenbach believes that David's success is not just down to new drugs or better technique, but to David's personality.
We say this all the time in hand surgery.
It does no good to have only a good surgeon.
If you hook everything up properly, but the patient doesn't use the hand, doesn't do physical therapy, you get a lousy result.
It's extremely important the physical therapy and the cooperation they use, and that's where he's been an excellent patient.
Between 1998, 1999 and now, we now are 30% reduced in theory, from the amount of immunosuppression you need.
We're still a long way that we can put a hand on, or a face on, or transplant a kidney and have the people walk out the office and take one pill a month, and that's it.
Will that ever happen? Yes, everything's gonna eventually happen.
Eventually, we'll be able to grow a spinal cord, and there will be no part of the body that won't be interchangeable.
There is no doubt that transplant surgery has come a long way since Alexis Carrel's daring experiments.
At least half a million transplants are done every year, and the main problem now is organ shortage.
Millions have benefited from transplant's often blood-stained history, and I'm sure that this branch of surgery will continue to push at the possible.
But I'm also sure that the price of progress will be paid by those bold enough to go first.
Next time on The History of Surgery I'm going to reveal the macabre and dark history of plastic surgery.
What surgeons can do, particularly with badly damaged faces, is both awe-inspiring and heart-rending.
It's a 2,500 year journey, from the earliest butchery via quick fixes with deadly substances, to the ultimate in plastic surgery, a human face transplant.
That's me on you.
Good lord!
The day I woke up from surgery, it was like waking up from a 32-year sleep, it was amazing.
Contains scenes which some viewers may find upsetting.
48-year-old Clint Hallam had the same operation, but two and half years later he was back on the table having it removed.
It had begun to rot.
My partner said you don't realise it, but it's dead.
Transplant surgery had transformed one life, but it had failed to transform another.
I'm almost more handicapped with my new hand than when I just had one and a half hands.
These two men, the success and the failure, are both part of one enduring obsession.
My name's Michael Mosley, and in this programme I'm going to trace the twisted history of the transplant dream and the people who made it happen, often at terrible cost.
In the beginning, transplants were dogged by delay, disaster and death.
That was because surgeons didn't understand they were taking on the most complex efficient killing system we know of, the immune system.
But it's about more than just biology.
I want to track down Clint and David and find out why their stories ended so very differently.
November 29th, 2006 - Louisville Kentucky, USA.
The man on the operating table is David Savage.
More than 30 years ago, he lost his hand in an industrial accident.
But today, in an operation lasting 15 hours, and employing the skills of 34 of the world's leading surgeons, David Savage will have a donor hand attached to his arm.
It is an operation of extraordinary complexity.
First, orthopaedic surgeons join the ends of the tendons in David's arm to the tendons of the donor hand.
Then vascular surgeons begin work on the blood supply.
They sew each of the donor's arteries and veins to the ends of David's own vessels.
Next, the neuro-specialists step in to perform the delicate task of rejoining the donor's nerves to David's stump.
And the final step is to close up the skin.
When he wakes up, David Savage will have a brand-new right hand.
We're on course, everything is going exactly as we would hope that it would, with really minimal problems.
I'm really intrigued by David because to me this is more than just an incredible surgical achievement.
The whole idea of living with a dead man's hand is one I find fascinating, but also disturbing.
A lot of people I've talked to are really freaked by the idea of having something like an arm transplant.
It's also true, frankly, of all the other bits of the body that show, like noses, eyes and face is probably the freakiest of them all.
No other form of surgery impacts on our sense of self in quite the way transplants do.
There is something profoundly strange about swapping body parts, melding your flesh with another's.
And these days there seem to be no limits.
I want to understand where this strange but compelling dream began.
And that takes me to the 1760s and the festering mouths of sweet-toothed aristocrats.
The first serious attempt at human transplants was in the 18th century.
Aristocrats had increasing access to sugar and as a result were developing rotten teeth.
So someone came up with the brilliant idea - why not take healthy teeth from poor people and stick them in the mouths of the rich? The first thing you need is a donor.
What you do is go out in the street and find some poor pauper who is prepared to part with their teeth for a few pennies.
You bring them in and you pull out one of these.
It's a pair of pliers, which you clamp on one of the front teeth.
And you give it a good old shake and you just yank it out.
Now, all of this would have been done without the benefit of any sort of anaesthetic.
If the pauper was lucky he got a bloody rag to chew on.
You take the pauper's tooth and you simply ram it into place.
This whole procedure cost five guineas, which was about the annual wage of a scullery maid.
If you were extremely lucky it would stay in place for about two months, before falling out.
If you were unlucky you would pick up gonorrhoea, syphilis or some other delightful 18th-century disease from the poor soul whose teeth you had pulled out.
So, hardly a rip-roaring success.
They had come up against the would-be transplanter's first big problem.
Before body parts could be swapped, surgeons would have to work out how to reattach them.
A century later, here in Lyon, the sudden brutal murder of a president and the nimble fingers of a Frenchman came together to make transplants more than just a fantastical dream.
This is Lyon University, home to one of the 20th century's greatest and most controversial surgeons.
He won the Nobel prize for medicine, and his pioneering techniques saved the lives and limbs of millions.
But this is not him.
In fact, there are no statues or departments named after him.
And that's because, like transplant surgery itself, the man who started it all had a very dark soul.
His name was Alexis Carrel.
Carrel was an intense, imperious doctor, immaculately dressed, with thick glasses perched on his nose.
But if you took off those glasses and gazed into his small, piercing eyes you'd notice a very unusual trait.
The iris of one of Carrel's eyes was brown, while the other was blue.
And burning behind those mismatched eyes was a dangerous obsession.
Carrel believed the human race could reach perfection.
It was an idea that was to lead him to a great breakthrough, but it would also take him somewhere much darker.
Straight into the arms of the Nazi regime.
Ironically enough, it was politics and murder that led to Carrel's victory over transplant surgery's first great barrier.
It's June, 1894, and the French president, Sadi Carnot, has come here to Lyon.
He's travelling in an open-top cart, like this one, when from amongst the cheering crowd emerges a young man clutching a rolled-up newspaper.
The young man is actually an anarchist, and hidden in the newspaper is a knife.
He rushes up to the President and stabs him in the abdomen.
The president began to bleed to death.
They rushed him to hospital and the best surgeon in Lyon was summoned.
But it was no use.
One of his major blood vessels had been punctured, and in 1894 no-one could repair it.
So all that they could do in that hospital was stand by and watch the French President slowly bleed to death.
This incident made a deep impression on Carrel, who wrote about it in his biography.
His life left him with his blood.
I can still hear it flowing, drop by drop, 50 years later.
Carrel was appalled by the death of the President and the surgeons' failure to save him.
He was convinced that he could find a way to repair broken blood vessels, and against determined medical opposition he set out to prove himself right.
He went looking for Lyon's finest embroideress, who lived at the top of the hill in the silk district.
He needed her to teach him how to do minute delicate stitches.
This is not quite as strange as it might first appear.
Carrel believed if he could master the tiny stitches used in embroidery then he could employ similar techniques to sew delicate blood vessels together.
I've tracked down Lyon's finest embroideress to see for myself the challenge Carrel faced.
I show you one time, and you do it after.
OK.
I admire your confidence.
You have to take the end of the thread in one hand and the needle in the other hand.
OK, very good.
And you turn the thread around the first thread.
OK, yeah.
Very good, very neat.
And a second.
In the other direction.
Have you ever sewn flesh? Skin? Bone? Have you ever tried sewing skin? No, never.
No reason to do so.
Carrel was a perfectionist and a very determined student.
Night after night he slaved away, bent over the intricate needlework.
His stitches had to be so fine that they wouldn't damage the delicate walls of the blood vessels, and so he practiced on paper.
It's said he became so accomplished he could make 500 stitches in a piece of cigarette paper without tearing it.
How many stitches can you put in to something this size, do you think? I don't know.
On one centimetre there is approximately 100 points.
100 stitches? Yes.
Just here.
Even better than Carrel.
As in surgery, as in embroidery, it's very important to be calm and quiet.
I don't know if you say the same.
Which is why I suspect I would have been a terrible surgeon.
Ahhhhh! Do you want to try it? Why not? Yeah.
OK.
No.
No.
No.
Deep breath.
It's not a body.
Not flesh.
Not flesh.
Not dying.
Save me, Dr Mosley! Save me! Right.
OK.
So I go through here, trying to avoid going through my finger.
You have to be very patient.
I can imagine him at home .
.
obsessively sewing this.
That's what's interesting about a lot of these characters in surgery - it's not, in a funny way, that nobody else has tried it before, it's just they do it better than anybody has done it before.
Knots are the thing I'm not terribly good at.
Try and avoid the loop catching.
Inverse.
Inverse it.
What? I'm doing it wrong? I think your patient is dead.
OK, never mind.
OK, never mind.
Once Carrel had become a skilled embroiderer he turned his attention to his real ambition - sewing blood vessels.
And that is significantly more difficult than sewing a flat piece of paper.
Blood vessels are rounded and they tend to collapse inwards.
It's like trying to sew together two very soggy drinking straws.
Carrel solved this problem by inventing a technique that transformed surgery.
It's one of those moments I absolutely love, when a seemingly minute step changes everything.
Dr Richard Gibbs is a vascular surgeon, and some of the techniques he uses are descendents of Carrel's stitch.
He's going to show me why Carrel's work was so revolutionary.
This is a very realistic looking piece of artery.
This is a real artery, it is a pig's aorta, so it's not that dissimilar from human arteries.
What we'll do is chop it in half with these scissors.
Right, OK! Good splash, right?! Blood starts to clot within two or three minutes of being exposed to air, so he must have been very fast.
He also must have had a very meticulous technique.
And one of the important principles is that you try to curve the needle very gently through an arc.
If you drag it you'll tear the artery and it will start to bleed.
It's curious to think that until you could do something as basic as this you couldn't do a transplant.
Exactly, it's still predicated on the need to be able to sew one bit of artery to another bit of artery.
And if that basic step fails then nothing's going to work, no matter how good the technology or the drugs are.
Carrel's first trick was this - he had discovered that if he always passed the needle from inside to out he could sew the insides of the vessels together and this would stop blood from clotting over the join and blocking the vessel.
And his second trick was even better.
By putting three stitches round the edge and pulling on them all at once, he magically created a straight line to sew along.
And that, apparently, is going to make it easier for me when I have my go.
I remember when I started off in medicine, in casualty, on drunks and things like that Do you remember those days? Very well.
I had this awful occasion when I had this drunk guy and he had a big gash in his head, and I did a very careful job of sewing his head, and then, when I reached to pull my hands away I'd sewn my glove to the top of his skull.
Which was a low moment.
I had to call the nurse who came and snipped it away.
It was not the highlight of my sewing career.
OK, so there we are, and now for the acid test.
The blood test.
Are you feeling confident? I'm feeling very confident! Gradually distend that up.
Very good.
You always get a bit of bleeding around the stitch holes, but that would be acceptable.
OK.
Shall we switch over and I'll have a go? Right, we're ready to operate, doctor.
Aye, Dr Finlay.
We're doing this on the kitchen table of a remote Scottish farmhouse.
Aye, Janet! We're ready, Janet, we're ready to go.
Your aneurysm is ruptured! Your aneurysm is ruptured, Janet, and I'm about to operate.
'It does not start well.
' I'm already getting confused.
How do I angle myself? If you pull them like that, rather than holding it like an ape trying to get a coconut open with a hammer.
If you hold it like that it'll be much easier.
Very good.
So I'm going in the other side now? Exactly.
About there? Approximately there.
Little bit bigger bite.
No, no, don't pick it up there, push it from the other side.
And then pick it up.
You don't want those little linear tears in the aorta because as soon as you take the clamps off the blood will flow.
It will spurt.
Push, push, push, push.
That's it.
And now pick it up the other side.
And curve it round.
Follow the curve of the needle.
That's great.
Got it.
Sorry, you need to be A bit deeper? Yeah.
A bit deeper than that.
Is that too deep?No, that's fine.
But now you're losing control.
I am.
Calm down.
Too excitable.
I thought I would be extremely calm about this, but there is something about the challenge Breathe in.
I hope you weren't doing anything this evening.
It fills me with enormous respect for Carrel and, frankly, for surgeons as well.
When I do this sort of stuff.
I have to say, it looked so much easier when you did it.
That's not a true surgical knot.
Really?That's what we call the shoelace knot.
See if I can avoid pricking myself.
Right.
Great.
OK, this is the moment of truth, see if my stitching holds.
Hmm.
Bit of a drip coming out here.
Yeah.
I feel quite tired, I must admit.
It required a lot of focus.
But I'm quite pleased.
I thought it could be terrible.
It was OK.
Thank you, that was fantastic, that was really interesting, really enjoyable.
Carrel had invented vascular surgery.
For the first time surgeons could repair partially severed limbs or damaged arteries.
Emboldened, Carrel's thoughts now turned to a very different surgical challenge - transplants.
Carrel lived in an age of great experimenters.
The Wright brothers launched human beings, briefly, into the skies.
Thomas Edison had sold the world the delights of the phonogram and the light bulb.
And Henry Ford created his Model T motorcar.
So there seemed no good reason why an arrogant young Frenchman should not transplant human organs.
Having perfected his stitches, Carrel was now convinced that organ transplants were within his grasp - all he had to do was practice.
Which he did, on dogs.
Carrel's operating garb was, well, unusual.
He dressed all in black to protect his sensitive eyes from glare.
The effect was truly sinister.
Carrel's experiments were a mixture of the scientific and the grotesque.
He did kidney transplants between dogs but he also took the kidney out of a puppy and put it in a cat.
And he took the front legs off a white dog and attached them to a black dog.
Carrel found that plumbing in the new organs was comparatively easy.
But the problem was, within a short while they stopped working and the animals died.
It was perplexing.
Something inexplicable was causing the animals' death.
He eventually concluded that some mysterious biological force made transplants impossible.
In a letter, he wrote: "The biological side of the question "has to be investigated very much more.
"We must find out how to prevent "the reaction of the organism against a new organ.
" Carrel's experiments were interrupted by the outbreak of the Second World War.
Before then, he had publicly promoted the use of gas chambers to "rid humanity of inferior stock".
Carrel died in November 1944, while under house arrest as a Nazi collaborator.
Carrel's descent from fame to obscurity was sudden and complete.
This unremarkable street is the only place in Lyon that still carries his name, and even this has been changed.
Carrel was a tragedy, a brilliant, flawed, surgical genius.
Carrel had proven it was possible to swap organs.
But in doing so, he had come up against the next great obstacle to doing transplants.
Rejection.
The body's automatic reaction to any foreign invader.
This is a sample of my blood.
It contains some of the most remorseless and versatile killers known to man.
In a sample this big, there wouldbe at least 350 million white blood cells, all of them primed to deal with any foreign threat.
I gave my precious blood to scientists at Imperial College.
From it, they extracted some of the white blood cells responsible for attacking invaders.
These cells are called natural killer cells.
When they detect an invader, they move in, attack and destroy.
My natural killer cells, here coloured red, can be seen vigorously attacking a cancer cell.
Unfortunately, a similar reaction occurs whenyou try to do a transplant.
This microscopic army is part of the immune system.
The hidden force that made Carrel's transplants all fail.
And the battle to overcome it was to define the next phase of the transplant dream.
It was a battle that began as the Second World War ended.
These were hopeful times.
The fighting was over, and out of the carnage had come great surgical innovations.
Advances in plastic surgery, brain surgery and the beginnings of cardiac surgery.
But some body parts remained beyond repair.
Dialysis offered temporary treatment for failing kidneys.
But there was no cure.
The unglamorous kidney was about to reignite the transplant dream.
In Boston USA, surgeons began to wonder if transplants were the answer.
The kidney is easy to remove and because we have two, it would be possible to use a living donor.
But to succeed, they would first have to outwit the immune system.
This footage shows the surgeons transplanting a kidney wrapped in a plastic bag.
The idea was that the bag would prevent the immune cells from attacking the surface of the kidney.
It did not work.
And the patient died.
One of the early pioneers was Dr Joseph Murray.
Today, he's a Bostonian legend.
Back then, he was just plain old Joe Murray, a doctor who believed in transplants.
Well, I believed in it, personally, because it seemed to be reasonable.
These patients were dying, they were young, we had a team of good physicians and surgeons working, and if we weren't going to do it, who would? Joseph Murray got a chance to "do it" when, in 1954, he encountered a most unusual patient.
In October, a 23-year-old man was admitted to this hospital.
He was ranting and raving.
His case notes say he was extremely uncooperative, and he a bit a nurse while she was changing his linen.
The patient was Richard Herrick.
His deranged behaviour was typical of massive, terminal, kidney failure.
Richard was in some ways doubly fortunate.
He had come to the right place at the right time and he also had a very unusual biological quirk, which none of the previous patients had shared.
Richard was one of a set of twins, and his brother, Ronald was willing to donate him a kidney.
Joe Murray believed thatidentical twins did not reject each other's tissue.
We knew that in identical twins you could have successful grafting.
But we never dreamed that we would find an identical twin, one dying of kidney disease and another one willing to give a kidney.
But you know, it is an example of happenstance favouring a prepared mind.
The certainly looked alike, but were they really identical? Joe Murray began a series of tests to find out.
If they weren't, Richard's body would reject Ronald's kidney.
Murray performed 17 tests on the boys.
He compared their eyes.
He examined their skin.
He even took them to the police station to see if their fingerprints matched.
Finally, they took a sample of skin from Ronald's arm and grafted it onto Richard's.
If this failed, then the kidney would also fail.
The skin graft took.
Richard and Ronald were genetically identical.
The transplant could go ahead.
But Richard was worried about accepting his brother's gift.
Even the night before the operation, the potential recipient told the donor, "Get out of here.
Don't come back.
" But the donor said, "I'm here and I'm gonna stay.
" So we went ahead and did it.
Christmas 1954, an incredibly good moment for exchanging gifts.
That morning, surgeons from this hospital removed the healthy kidney from Ronald.
They then wrapped this precious present in a cold wet towel and took it into the next operating theatre.
At 9:53 precisely, Murray began to operate.
Well we went, deliberately, slowly.
We were working under time constraints.
We were well aware of it.
It took about 3 hours before we got the blood vessels attached.
By the time we released the clamps, the kidney began to pour out urine, so copiously that we had to really suck it up and keep it out, for our vision.
The flow of urine was a fabulous sign.
It meant the kidney was working.
This was history.
The next morning was a miracle.
His eyes were sparkling, he was hungry for the first time in months.
Richard Herrick, a man on the brink of death, married his nurse and lived for a further 8 years.
Transplant surgery had finally prolonged a life.
But the operation had only worked because Richard had a twin.
His treatment established a fundamental principle.
Success depends on maximising genetic closeness, of recipient and donor.
Even today, if you need a new kidney, your best chance is a member of your own family.
I don't have an identical twin brother, but I do have two brothers and a sister and I have been running a series of tests to see which would make the best match for me.
Now I would guess that I am closest to my older brother, John, but it could be my sister, Susie.
Or it could be my younger brother, David.
The truth is, I won't know until I have had a look at the DNA.
I persuaded each of my siblings and, for comparison, my wife, to give me a tube of their blood.
This contains their genetic code and should reveal how closely they are matched to me.
Remarkably blue, odd, isn't it? Seeing your life force going out.
I had my blood taken, too.
And dropped the whole lot off at the Anthony Nolan Trust, where they run-tissue matching tests for real transplants.
Here you go, some blood.
Fresh and hot from my veins.
Joyce at the trust ran our blood through this machine, which reads DNA.
She is looking at the genes on chromosome 6, that are markers for the immune system.
The only chance of an exact match is with an identical twin, but a family member should be close.
I've invited my siblings round to my house.
Where we will discover which of us really does have the most in common.
Who do you think you are most like? Who do you think is your closest genetic match?Immediately to mind, David.
OK.
David, who do you think? Probably John.
Right.
And I think, John.
You are the universal donor.
To reveal the results, I've invented a game called Chromosome Snap.
There are 6 different cards, each representing a different immune system gene.
We are looking for matching pairs.
The more matches, the more likely a kidney transplant would succeed.
What we are hoping for is at least three.
Six is really good, that's a perfect match, very, very unlikely.
Nought is very bad you can still do it but the odds are not great.
Really a minimum of three.
There you go.
What I am going to want you to do is turn them over one at a time.
OK, Clare.
Marvellous.
Disappointing.
David Oh, good.
Excellent.
Excellent.
One, two, three.
Very pleased.
After the first card turn, all of my siblings match, but there still 5 more cards to go.
Hurray, wow.
And by the end of the game, there is a clear winner.
My sister Susie and I are matched across all 6 genes.
I wonder what the odds on that are? That's really surprising.
So we should be interested in each other's health? I should make sure that you keep running! You need to look after what I now regard as my internal organs.
If you have a brother or sister, you have a one in 25 chance of making such a match.
But unless you are identical twins, even the closest match will lead to rejection.
Unless the immune system is controlled.
Joseph Murray decided the only way forward was to tackle the immune system head on.
Murray wanted to treat all his patients, not just those who happened to have an identical twin.
To do that, he needed to disable, even destroy the immune system.
Joe Murray decided to go nuclear.
In 1958.
Murray met a 31-year-old woman called Gladys Lowman.
She had been born with only one kidney.
And that kidney had been removed by a blundering surgeon who was trying to remove her appendix.
Unless she had a transplant, she had only weeks to live.
Hiroshima and Nagasaki had demonstrated the frightening power of nuclear radiation.
Ionising radiation attacks all fast-dividing cells, including the cells of the immune system.
Murray knew that high doses of X-rays would produce similar results.
It was clearly dangerous, but he thought it was worth a try.
With Gladys sinking fast, Murray now transplanted a new kidney into her and began irradiating.
He knew he had suppressed the immune system, but doing this was rather like trying to open a front door with a bulldozer.
There was serious risk he would knock the whole house down.
We used total body radiation.
And the patient would lie under the x-ray machine.
And curl up in the foetal position so that all of the lymph nodes, spleen and bone marrow would be irradiated.
Gladys lay under the machine for 3 hours.
She received the equivalent of 600,000 dental X-rays.
With her immune system completely destroyed, Gladys now had to live in a sterile room.
Murray infused her with bone marrow, to replace her annihilated white cells.
But even so, within four weeks, she succumbed to overwhelming infection.
In the years that followed, Murray irradiated 10 patients.
Nine died soon after the treatment.
But Murray still believed it could be done.
It didn't work, but it was a necessary step along the way.
And even in the most discouraging times, there were hints that something might be better.
Maybe I am just a pathological optimist, I've been called that.
After five years of failure, Murray met a young Cambridge doctor with a radically different set of ideas.
From my point of view, I was very interested in trying to prove the critics wrong.
I have always felt that way - if someone says what you are doing is stupid, it is a great pleasure to show that they are wrong.
And when Mr Pathologically Optimistic met Mr Can't Be Wrong, something special was bound to happen.
Roy Calne had been experimenting with another tool for defeating the immune system.
Drugs.
He'd heard about a new drug, called azathioprine that destroyed immune cells in people with cancer.
So, he gave the drug to dogs with transplanted kidneys.
It appeared to work.
And this was enough to encourage Calne and Murray to try the drug in humans.
With the door finally opened, lots of people now joined the party.
In the 1960s, more and more surgeons started to experiment with transplants.
Using azathioprine to control the immune system, they dared to venture into new territory.
They tried transplanting the liver and the lung.
They attempted to put animal organs into people.
And there was an absolute frenzy of media excitement when surgeons began transplanting human hearts.
This is the team that yesterday performed Britain's first human heart transplant operation.
The complete team whose skill, devotion and courage has already made British medical history.
We are going over to the National Heart Hospital now.
Doctor, can you hear me? Yes, I can hear you very well.
This is Raymond Baxter in the television studio.
How is the patient, Mr West? Well, he is doing extremely well at the present moment.
But the optimism was short-lived.
Most transplant patients were still dying.
The problem was the new drug was incredibly difficult to administer.
Too little led to rejection.
But when they tried to increase the dose, azathioprine could completely destroy a patient's immune system.
The new drug was not the magic solution they had hoped for.
There was a feeling that transplantation was not worth it.
I mean, most prestigious medical institutions didn't want to bother with transplantation.
And then, olive oil came to the rescue.
It's one of those wonderfully unlikely but true medical stories.
The tale of how olive oil came to rescue transplant surgery is lovely, beginning, as it does, with a Scandinavian holiday, and a rather unusual souvenir.
This belonged to an employee of the Swiss drugs firm Sandoz.
The enthusiastic employee had returned from a trip to Norway with a suitcase full of soil.
He was hoping to discover a new micro-organism.
In the lab, the researcher carefully analysed the soil, and was rewarded with a new species of fungus, from which they extracted a brand new drug.
They called it Cyclosporine A.
They must have jumped up and down in a quiet, scientific sort of way, because some of the most profitable drugs ever discovered have come from fungi.
Think of penicillin.
Early tests on the fungus showed that it was actually useless at killing bacteria.
But it did suppress the immune system.
And that brought Cyclosporine A to the attention of Roy Calne and his team in Cambridge, who were still searching for better drugs.
Roy contacted Sandoz, and pleaded for a small sample of the magic mushroom.
I've had some dealings with the Swiss drug firm myself, and like Roy, I've persuaded them to send some of the drug over to me, so I can show you what happened next.
Inside here are some Cyclosporine A, and it should be in the pure form that Roy Calne received it.
Yes, it's a white powder, looks harmless enough, but I don't want any of this stuff inside me, so I am going to take some necessary precautions.
This is what they wear in pharmaceutical laboratories when they are handling any dangerous drug.
Although the risk to my health is small, I've been advised to make sure I am gloved up and covered up.
When they got Cyclosporine A back to the lab, Roy and his researchers had a nasty surprise.
The problem was, before humans could ingest it, they had to find a way to dissolve it.
If it wouldn't dissolve, then there was no way it would work.
The drug would be useless.
Right, I am going to put powder in there, that was 0.
4, and I will do the same in another one, here.
Yep, same amount.
Powder in the second one .
.
and put the lid back on.
They tried dissolving it first in water, and I'll demonstrate to you what happens.
I need 40ml.
They tried dissolving it in water, and as you can see, if you shake it up, it just doesn't dissolve.
Floats largely on the surface.
They tried all sorts of other industrial solvents, and none of them worked.
Now it's in there, I can take this stuff off.
Right.
So they had a problem, but they were lucky.
There was a Greek researcher who was working with Roy Calne, and his mother was worried that her boy was going to be affected by the appalling British food, so she sent him a bottle of Greek olive oil.
Now, more in hope than expectation, he took that olive oil, and he added it to the cyclosporine.
And I will show you just what happened.
Vigorous shake As you can see, it is completely dissolved.
The Greek student tried the olive oil formulation on his animals.
He got spectacular results, so spectacular, that I didn't believe him when he first told me.
And I told him to repeat it, which he did, and he got the same results again.
Cyclosporine was THE breakthrough that transplant surgery had been waiting for.
Finally, the immune system could be controlled, and transplant surgeons could start saving lives instead of ending them.
In the 1980s and 90s, kidney and heart transplants became widespread.
The demand for organs soared, and a national donor scheme was launched.
12 million of these new plastic cards are to be distributed.
The new card is being issued because new techniques are increasing the range of organs which can be donated.
This is a multi-donor card, and people have the option of donating their kidneys, their eyes, their heart, their liver, their pancreas, or, indeed, one of those, or all of them, or any other part of their body which they would like to donate.
Transplants became something of an everyday miracle.
Two teams of doctors worked throughout the early hours of this morning to perform the world's first triple organ transplant.
This is BBC One.
When Brook Matthews arrived from Australia in January, she had only a few months to live.
Now, following her four and a half hour operation yesterday at Harefield Hospital, she is making good progress.
It was her only chance of life, and few would blame her parents for taking that chance.
A very special one-year-old had a birthday party today.
She is Kaylee Davidson from Washington in Tyne and Wear, and she's Britain's youngest surviving heart transplant patient.
We can't believe it.
She was really poorly, and she wouldn't do anything, she had no interest in anybody or anything.
And now she's a typical little girl, into everything.
Surgeons, once again, began to dream of new frontiers.
And in 1998, surgeons in France announced that they had pulled off a truly spectacular world first.
On the 24th September, in a blaze of publicity and surgical glory, Clint Hallam became the first person to receive a hand transplant.
The operation pushed the boundaries of what surgeons had believed was possible.
I was certainly impressed, but I also wondered if this was a genuine medical advance, done to improve the life of the patient.
Was it being done simply because it could be done? I first crossed paths with Clint a year after the operation, when I was making a medical series for the BBC.
My first thoughts when I saw my hand was that it was a miracle.
But it was a miracle that was starting to fade.
No, no, no, no.
One of the hard things to accept, for me, is that I am almost more handicapped with my new hand than when I just had one and a half hands.
This is not exactly as the dream was for eight, nine, ten years.
This is not happening like it does in the movies.
Clint was finding it hard to adapt psychologically to the new hand.
A very dear friend who lives in London, I never understood why he used to grab my hand like this, in fact, grab my wrist, simply because he didn't want to touch my hand.
To him, it was quite horrific.
Clint had also started to feel ill, and he suspected that his anti-rejection drugs were intensifying his symptoms.
The two most physical side effects that I notice is first, I have diabetes.
The second side effect is more physical, in that my body has gone from chest to breast, and that's a little bit difficult to deal with.
As Clint cut back on his medication, his hand began to show signs of rejection.
The fingertips had started to get red, and I lost all sensation.
The redness in the fingertips, the fingernails falling off with new nails coming underneath them are all indictors of a serious rejection problem.
By 2001, Clint's immune system had almost completely destroyed his new hand.
Good evening.
Clint Hallam was at the centre of a medical breakthrough two years ago, but now he wants out.
Having had the hand of a dying man attached where his used to be, he's now begging for it to be removed.
I certainly believe that there must come a stage, with the number of rejections that I have experienced with my hand, that yes, my body has or my mind has said enough is enough.
The morning after this interview was recorded, Clint Hallam's dead hand was surgically removed.
I am fascinated by Clint's story, because in him I can see the terrible contradictions of cutting-edge surgery.
There is the fame and glory, at least for the surgeon, of going first.
However, there is the often appalling cost to the patients of being first.
I'm on my way to meet Clint Hallam, who I haven't seen for many years.
I want to find out how he is.
I'm intrigued by the new hand.
Does it move?It does.
It clicks, and goes in circles.
But that's pretty much the range.
That really is its limits.
You can shake hands?Yes.
But it's very limited? It's extremely limited.
It really is cosmetic.
I can do certain things like Hold on.
It will do it.
Very good.
But if you actually tried to put it in your mouth at this point, it would go over your shoulder, would it? I'll give you the hand, you try and put it in your mouth.
I can't do it.
I can get it across my shoulder.
Great at Greek weddings! But otherwise, not perfect.
Ooh, thank you very much.
Clint is clearly not thrilled with his new plastic hand, but what I'm interested in is why he thinks the transplant failed.
Were you never freaked by the idea that this was a hand from a corpse, this was a hand from a dead person? Did that not worry you? No, no.
I was attached to it, but I was detached from everything about it.
Right.
In retrospect, in looking back.
And Were you ashamed of it? I was fucking angry with the doctors, and I'm still angry with the doctors that they didn't match it.
That was a big thing, was it? The matching? You saw it.
I saw it.
OK? It was huge.
It seems Clint's mind rejected his new hand before his body did.
Despite his doctors' warnings, Clint stopped taking his medication, making physical rejection inevitable.
Why did you stop taking the immunosuppressive drugs? Actually, I didn't stop taking all of the drugs all at the same time.
I stopped taking some of the drugs in lesser quantities than I was supposed to.
Why? Because I got sick.
I was surprised, frankly, that you persisted with that hand as long as you did.
It was putrefying.
My partner of the time, and now, said exactly the same thing.
She said "You don't realise it, but it's dead.
" What would your advice be to other people who are thinking about going first? About going first in anything, I would tell them to walk slowly backwards.
Go back down the line, and keep thinking.
Really? Think, and think very carefully.
Do you regret being the first? I regret being the first.
I don't regret having the transplant.
Soon after Clint had the transplanted hand removed, he rang round, asking for another hand transplant.
Unsurprisingly, the surgeons all said no.
The truth is, no matter how good surgical techniques are, they will fail if the patient is not psychologically prepared.
But was it simply that Clint was the wrong patient, or are hands just harder to do? I'm in Kentucky, USA, to meet the surgeon who performed the world's second hand transplant.
Were you upset that you weren't the first? Yeah, I think every human being always wants to be a leader.
But I always told my team, and you can ask them, I emphasised this over and over again, it doesn't matter who does it first, it matters who does it best.
Dr Breidenbach has performed three hand transplants, and the latest is perhaps the most remarkable of all.
In November 2006 he led a team of surgeons in replacing the right hand of 54-year-old David Savage.
David had lost his hand 32 years earlier.
I believe he is the longest time between amputee to transplant.
So we ran into problems which are novel and new, and the analogy I make, it's kind of like closing your house down for 32 years, and then you come back and decide you're going to take a shower.
And you turn on the faucet, and it sputters a little bit.
Sometimes it works, and sometimes it doesn't.
So we had some sputtering last night, as his vessels were trying to get blood into the hand which we were transplanting.
The operation was, in the end, a technical triumph.
But I wonder if David, unlike Clint, is truly comfortable with his new hand.
When I meet him and his wife Karen, I am instantly struck by how different his new hand is to the other one.
Do you mind if I just compare your hands, looking at the two of them? What is quite spooky, I don't know if you find it spooky, there are moments when I actually remember this hand came from somebody else.
Do you think that at all? I think about it all the time.
I think about the family that donated it all the time.
But like I said the first day I woke up from surgery, it's mine.
Yes, it's now yours, isn't it? But they are quite different, in a funny way.
Yeah, they're different.
Have you ever considered the possibility that this could have come from a woman? I thought about it.
It wouldn't have bothered me.
I'm curious, because the only thing that's striking about this is, you have very dark hair.
This hand doesn't.
If you look really closely, you can see it's very fair, isn't it? Yes, it's got, like, blondish hair.
But it's turning dark.
Yeah, and it'll probably grow.
And do the nails grow? Oh, twice as fast as my other hand.
Do you mind if I have a look again? It's curious, because the fingernails on this one are longer and more elegant, and you look like you've bitten them off.
No, they were all clipped at the same time.
Really? How extraordinary.
When you put them next to each other, they are different.
Most people don't get the opportunity to compare like that.
They will see Dave from across the room, and they don't really realise what the difference is.
Absolutely.
And do you think that is important? Yes, because we don't want people to focus on the difference.
We want them to focus on the progress, and the hope of what this transplant can mean to other people.
David and Karen are full of optimism.
And when I watch David's therapy sessions, I can see why.
He already has around 60% of the function of a normal hand, and with more therapy, he may eventually get to 80%.
Last September, my granddaughter, just going to her birthday party, and grabbing hold of her, picking her up.
It was just a fantastic feeling.
Dr Breidenbach believes that David's success is not just down to new drugs or better technique, but to David's personality.
We say this all the time in hand surgery.
It does no good to have only a good surgeon.
If you hook everything up properly, but the patient doesn't use the hand, doesn't do physical therapy, you get a lousy result.
It's extremely important the physical therapy and the cooperation they use, and that's where he's been an excellent patient.
Between 1998, 1999 and now, we now are 30% reduced in theory, from the amount of immunosuppression you need.
We're still a long way that we can put a hand on, or a face on, or transplant a kidney and have the people walk out the office and take one pill a month, and that's it.
Will that ever happen? Yes, everything's gonna eventually happen.
Eventually, we'll be able to grow a spinal cord, and there will be no part of the body that won't be interchangeable.
There is no doubt that transplant surgery has come a long way since Alexis Carrel's daring experiments.
At least half a million transplants are done every year, and the main problem now is organ shortage.
Millions have benefited from transplant's often blood-stained history, and I'm sure that this branch of surgery will continue to push at the possible.
But I'm also sure that the price of progress will be paid by those bold enough to go first.
Next time on The History of Surgery I'm going to reveal the macabre and dark history of plastic surgery.
What surgeons can do, particularly with badly damaged faces, is both awe-inspiring and heart-rending.
It's a 2,500 year journey, from the earliest butchery via quick fixes with deadly substances, to the ultimate in plastic surgery, a human face transplant.
That's me on you.
Good lord!