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In a glass jar, in a museum in London, there once sat a stone.

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It was larger than a hen's egg.

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It had grown, slowly, inside the bladder of a boy.

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And that boy had been buried in the desert of Upper Egypt,

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before the first pharaoh, more than five thousand years ago.

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The man who found it, at the start of the twentieth century,

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had come to the cemetery of El Amrah to look at ancient brains.

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He wrote:

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[Elliot Smith] In the first Egyptian grave that I looked into,

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I saw the skeleton of an Egyptian boy,

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in whose pelvis there was a large vesical calculus.

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It was long held to be the oldest bladder stone ever found.

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It is not in that jar today.

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I shall tell you why, before we part.

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This is the history of two obsessions.

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The first is the stone:

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how to get it out, and at what cost.

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The second is the glass:

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the long, stubborn wish to see inside a living body,

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and to know what is happening there.

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For most of that history, physicians were certain of things that were not so.

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Keep one lesson close:

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a thing repeated is not a thing proven.

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A few were brave enough to doubt, and to go and look.

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Listen for them.

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Some of what we repeat today will not survive the looking;

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finding out which is the work still ahead.

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Egypt has left us some of the oldest written medicine in the world:

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long rolls of papyrus, copied and recopied by scribes.

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Among their prescriptions are remedies for urine that will not come,

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and for urine that comes with blood.

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Blood in the urine has long been common along the Nile.

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In 1851, in Cairo, Theodor Bilharz found the cause:

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a blood fluke that lives in the veins around the bladder.

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Then, in 1910, the pathologist Marc Armand Ruffer took the dried kidneys of two

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mummies of the Twentieth Dynasty,

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soaked them in a solution until they were soft enough to cut thin,

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and put them under his microscope.

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He found the fluke's eggs, calcified.

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The parasite had been there three thousand years before.

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Whether it explains the bloody urine of the papyri we cannot be certain,

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but it is the likeliest culprit.

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On the wall of a tomb at Saqqara, carved about 2300 B.C.,

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a kneeling man works with a small blade upon a youth whose arms are held from

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behind.

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It is usually read as the oldest picture of circumcision.

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At least one Egyptologist has asked whether it shows an emergency operation instead.

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The stone does not say.

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You will often read that the Egyptians drew off urine through hollow reeds.

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Perhaps they did.

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But no papyrus we have clearly describes it,

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and no such instrument has been securely identified.

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Let that be our first lesson.

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A thing repeated is not a thing proven.

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In India, a great Sanskrit book of surgery bears the name of Sushruta.

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It was compiled over many centuries;

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its core may be two thousand years old, and tradition places it earlier still.

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Among a great many operations, it describes, with remarkable candour,

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how to cut for the stone.

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The book sorts stones by what was thought to make them:

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three kinds by the humours of the body, and one from semen.

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A stone of phlegm, it says, is white and glossy,

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and may grow to the size of a hen's egg.

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Medicines come first.

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Only when they fail does the book consider the knife.

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And then it gives a warning.

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[Sushruta] The death of the patient is almost certain without a surgical operation,

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and the result to be derived from it is also uncertain.

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[Sushruta] A skilled surgeon should perform such operations only with the permission of the

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king.

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Consent, you see, was to be sought from the crown, because the operation might kill.

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The method itself is exact.

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Two fingers of the surgeon's left hand, passed into the rectum,

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push the stone forward.

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A fist presses on the belly to hold it there.

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The cut is made beside the midline seam, on the left,

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at the distance of a barley-corn.

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And the text records a disagreement.

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Several authorities, it says, prefer to cut on the right.

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Even then, surgeons argued over which side to cut.

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Through the cut, the stone was drawn out.

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In a grown man, a wound carried down to the bladder at that point must have passed

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through the prostate, though the text never names the gland.

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Then the patient was set in a cauldron of warm water,

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given a treacle drink to clear the passage,

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and the wound was dressed with honey and clarified butter.

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How many lived, the text does not say.

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It promises only that without the knife, death was almost certain.

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For a narrowed outlet of the urine, Sushruta advises tubes of iron, wood,

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or shellac, open at both ends, smeared with clarified butter, passed gently,

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and changed for thicker ones every third day.

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Elsewhere the text describes the condition as a tight foreskin;

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its translator called it a stricture of the urethra;

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scholars read it both ways.

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Either way, it is the principle of the graduated dilator, still in use today.

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The physicians who wrote under the name of Hippocrates,

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four or five centuries before Christ, watched the urine closely,

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and some of what they saw was true.

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[Hippocratic] When bubbles settle on the surface of the urine,

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they indicate disease of the kidneys, and that the complaint will be protracted.

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Froth on the urine.

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We would now say protein, leaking through a damaged kidney.

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They noticed it two thousand years before anyone knew what protein was.

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They noticed too that women suffer the stone less often than men, because,

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they explained, a woman's urethra is short and wide.

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And then there is the Oath.

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Every young doctor knows it, in some form.

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Few notice its strangest line.

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[Hippocratic] I will not cut persons labouring under the stone,

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but will leave this to be done by men who are practitioners of this work.

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Why should a physician swear never to cut for the stone?

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Some say it was a division of labour:

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leave the operation to the specialists.

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Some say it was prudence:

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the operation killed so often that it ruined reputations.

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A translation of 1923 reads it more sweepingly:

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I will not use the knife, not even, verily, on sufferers from stone.

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And one scholar argued that the Oath came from the followers of Pythagoras,

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and renounced the knife altogether.

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The Greek will bear more than one reading.

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The argument has never been settled.

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Whatever it meant, for much of the next two thousand years, in Europe at least,

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cutting for the stone was left largely to a separate trade:

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the travelling stone-cutters.

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In Alexandria, perhaps two centuries before Christ,

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a surgeon named Ammonius met a stone too large to draw out.

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He held it with a hook at the wound and split it with a blow.

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They called him Lithotomos, the stone-cutter.

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Keep him in mind.

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His idea, to break the stone rather than enlarge the wound, will come back.

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The Roman writer Celsus, probably in the time of the Emperor Tiberius,

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set the operation down in full.

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Cut only in spring, he says, and only in a boy between nine and fourteen.

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A strong assistant on a high stool holds the child on his knees.

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The surgeon, his nails pared, finds the stone with two fingers in the rectum,

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presses it down, and makes a crescent-shaped cut over it.

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One knife, one hook, and speed.

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This "lesser apparatus" remained the standard operation in Europe for fifteen

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hundred years.

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Celsus also describes bronze catheters:

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three lengths for men and two for women, "a little curved,

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but more so for men." Bronze catheters have been dug from the ashes of Pompeii.

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Now an experiment, and a quarrel.

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Where does urine come from?

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Asclepiades, a celebrated physician of Rome some two centuries before Galen,

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had taught that what we drink passes into the bladder as a vapour,

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and condenses there.

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The kidneys, in his view, had nothing to do with it.

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He still had followers.

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Galen of Pergamon thought this absurd.

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Vapours rise, he said, and the bladder lies below.

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Any butcher can see the tubes that run from the kidneys to the bladder.

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But Galen did not merely argue.

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He demonstrated.

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[Galen] One has to divide the peritoneum in front of the ureters,

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then secure these with ligatures, and next, having bandaged up the animal,

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let him go.

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The animal stops passing water.

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Later, Galen loosens the bandages.

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[Galen] One loosens the external bandages, and shows the bladder empty,

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and the ureters quite full and distended, in fact almost on the point of rupturing.

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[Galen] On removing the ligature from them,

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one then plainly sees the bladder becoming filled with urine.

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He went further.

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He tied the penis and squeezed the full bladder:

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nothing ran back up toward the kidneys.

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There is a valve.

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He tied one ureter and left the other free:

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only the free one filled the bladder.

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That is a control, in an experiment some eighteen centuries old.

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Then he cut the swollen ureter, and the urine spurted, he says,

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like blood from an opened vein.

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[Galen] Like slaves, then, caught in the act of stealing, these two are quite bewildered;

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and while the one says nothing, the other indulges in shameless lying.

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That was his verdict on Asclepiades, and on the great anatomist Erasistratus,

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both long dead.

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Galen was right that the kidneys make the urine.

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But how?

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Not, he insisted, by straining the blood like a sieve.

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The kidney drew the watery part of the blood toward itself,

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as a lodestone draws iron.

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So great was Galen's authority that this answer stood for some fifteen hundred

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years.

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For centuries, the emblem of the physician was not a knife,

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and not yet a stethoscope.

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It was this:

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a round glass flask, shaped like a bladder, called a matula.

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The doctor held it to the light and read the water.

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In the seventh century, a Byzantine writer named Theophilus devoted a whole book to

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urine, and defined it, beautifully, as the filtrate of the blood.

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Remember that phrase.

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Medicine will take thirteen hundred years to find out how nearly right it was.

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From Kairouan to Salerno to Paris, scholars built a whole science on the flask.

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Charts set out the colours of urine in a wheel, about twenty of them,

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from crystal clear, through straw and gold and wine red, to green, and livid,

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and black.

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Black, as a rule, meant death.

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And the flask was a map of the body.

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The ring at the top of the liquid spoke of the head.

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The upper layer, of the chest.

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The middle, of the stomach and liver.

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The sediment, of the kidneys, the bladder, and the organs of generation.

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Often the physician never saw the patient at all.

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The water arrived in a basket, carried by a servant.

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Meanwhile, in Córdoba, around the year one thousand, the surgeon al-Zahrawi,

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known in Europe as Albucasis, drew some two hundred surgical instruments for his

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great encyclopaedia.

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Among them:

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a fine drill, turned gently against a stone stuck in the urethra until it broke;

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a long silver catheter;

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and a syringe for washing out the bladder, with three tiny holes at its tip.

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Translated into Latin, his book taught European surgeons for centuries.

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Not everyone trusted the flask.

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In the tenth century Isaac Israeli, author of a celebrated Book of Urine,

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warned against fools who prophesied from it without seeing the patient.

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By Shakespeare's day, it was a joke.

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[Falstaff] Sirrah, you giant, what says the doctor to my water?

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[Page] He said, sir, the water itself was a good healthy water;

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but, for the party that owed it, he might have more diseases than he knew for.

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In 1637 an English physician, Thomas Brian,

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published a book called The Pisse-Prophet.

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His verdict:

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[Brian] There is no certaine knowledge of any Disease to be gathered from the Urine alone.

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And elsewhere, borrowing a Latin tag:

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[Brian] The Urine is an Harlot, or a Lyer.

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It was also a confession.

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Brian admitted that he had played the pisse-prophet himself,

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quizzing the messenger and then pretending to read the glass,

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and that one lady had praised him as the cunningest doctor in all the town,

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because he had told her, by her water, that she was with child.

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Uroscopy ruled learned medicine for about a thousand years,

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and patients went on demanding it for two centuries more.

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And yet the flask was not wrong to be looked at.

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It had been looked at wrongly.

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What came next was to taste it, to boil it, and to take it apart.

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Uroscopists had always sniffed the urine, and some had tasted it.

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In the 1670s the English physician Thomas Willis tasted it,

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and wrote down exactly what he found.

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Of a nobleman who passed nearly a gallon and a half of water in a day,

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he wrote that it was:

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00:19:40,260 --> 00:19:44,350
[Willis] Wonderfully sweet, as though Honey were mixt in it.

242
00:19:45,850 --> 00:19:53,294
A century later in Liverpool, Matthew Dobson evaporated such urine to a white cake

243
00:19:53,385 --> 00:19:57,106
that, he wrote, smelled like brown sugar.

244
00:19:57,197 --> 00:20:00,919
Then he tasted the patient's blood serum.

245
00:20:01,010 --> 00:20:05,912
It was sweetish too, though not so sweet as the urine.

246
00:20:06,003 --> 00:20:11,540
The sugar was in the blood before it ever reached the kidney.

247
00:20:12,640 --> 00:20:19,784
Diabetes, from the Greek for a siphon, had long meant only a great flow of water.

248
00:20:19,872 --> 00:20:23,488
Willis's taste picked out the sweet kind,

249
00:20:23,576 --> 00:20:30,632
and later in that century the Scottish physician William Cullen gave it a second

250
00:20:30,720 --> 00:20:31,161
name:

251
00:20:31,249 --> 00:20:38,040
diabetes mellitus, honeyed, to set it apart from a rarer kind whose urine was

252
00:20:38,128 --> 00:20:39,010
tasteless.

253
00:20:41,660 --> 00:20:44,949
Others had seen urine curdle with heat.

254
00:20:45,033 --> 00:20:48,154
In 1827, at Guy's Hospital in London,

255
00:20:48,238 --> 00:20:53,972
Richard Bright warmed a spoonful of a patient's urine over a candle,

256
00:20:54,057 --> 00:20:57,261
and watched it cloud before it boiled.

257
00:20:57,346 --> 00:21:01,984
Then he followed his patients to the post-mortem table:

258
00:21:02,068 --> 00:21:08,646
patients with dropsy, the old name for a body swollen with water, in the legs,

259
00:21:08,730 --> 00:21:10,670
the belly and the face.

260
00:21:12,170 --> 00:21:17,406
[Bright] I have never yet examined the body of a patient dying with dropsy,

261
00:21:17,486 --> 00:21:24,071
attended with coagulable urine, in whom some obvious derangement was not discovered

262
00:21:24,150 --> 00:21:25,340
in the kidneys.

263
00:21:26,840 --> 00:21:33,227
For a century afterwards, kidney disease with dropsy and protein in the urine was

264
00:21:33,306 --> 00:21:35,751
simply called Bright's disease.

265
00:21:35,830 --> 00:21:39,930
The Hippocratic bubbles had found their explanation.

266
00:21:42,580 --> 00:21:45,952
The stone, too, was put to the test.

267
00:21:46,046 --> 00:21:51,291
Physicians had long thought it earthy, a kind of gravel.

268
00:21:51,384 --> 00:21:58,128
In 1776 the Swedish chemist Scheele found in a bladder stone a new acid,

269
00:21:58,222 --> 00:22:00,844
which we now call uric acid.

270
00:22:00,938 --> 00:22:08,056
In 1810 William Wollaston described another stone, yellowish and glistening;

271
00:22:08,150 --> 00:22:12,927
the first had come from a child of five in Norwich.

272
00:22:13,021 --> 00:22:18,172
He named its substance cystic oxide, after the bladder.

273
00:22:18,266 --> 00:22:20,045
We call it cystine:

274
00:22:20,139 --> 00:22:27,070
one of the very first amino acids ever found, and it was found in a stone.

275
00:22:29,720 --> 00:22:36,050
In 1828, in Berlin, the young chemist Friedrich Wöhler made urea,

276
00:22:36,147 --> 00:22:44,035
the chief solid of urine, in a flask, from simple salts, with no kidney involved.

277
00:22:44,132 --> 00:22:50,170
He wrote to his old teacher in Stockholm, the great Berzelius:

278
00:22:51,670 --> 00:22:55,025
[Wohler] I cannot, so to speak, hold my chemical water,

279
00:22:55,098 --> 00:22:59,692
and must tell you that I can make urea without needing kidneys,

280
00:22:59,765 --> 00:23:03,120
or indeed any animal at all, be it man or dog.

281
00:23:04,620 --> 00:23:11,828
The textbooks will tell you that this one experiment killed the old belief in a

282
00:23:11,919 --> 00:23:13,014
vital force.

283
00:23:13,106 --> 00:23:14,109
It did not.

284
00:23:14,200 --> 00:23:17,211
That belief lingered for decades.

285
00:23:17,303 --> 00:23:19,310
But a door had opened.

286
00:23:21,960 --> 00:23:25,470
Which brings us back to Galen's question.

287
00:23:25,555 --> 00:23:28,209
How does the kidney make urine?

288
00:23:28,295 --> 00:23:32,489
In 1842 a young London anatomist, William Bowman,

289
00:23:32,575 --> 00:23:39,167
looked again at the tiny tufts of blood vessels that Malpighi had seen in the

290
00:23:39,252 --> 00:23:44,902
kidney, and showed that each sits in a cup that opens into a tube.

291
00:23:44,988 --> 00:23:48,070
The tuft, he thought, let out water;

292
00:23:48,155 --> 00:23:54,490
the living cells of the tube did the real work, secreting everything else.

293
00:23:55,590 --> 00:24:01,562
The very next year, Carl Ludwig in Germany proposed something colder.

294
00:24:01,649 --> 00:24:06,756
The tuft was a filter, driven by the pressure of the blood,

295
00:24:06,842 --> 00:24:11,343
and the tubes simply concentrated what came through.

296
00:24:11,430 --> 00:24:13,594
Filtration, or secretion.

297
00:24:13,681 --> 00:24:15,931
Physics, or living labour.

298
00:24:16,018 --> 00:24:20,692
Dyes injected into animals seemed to favour secretion;

299
00:24:20,778 --> 00:24:24,500
arguments from physics favoured filtration.

300
00:24:24,587 --> 00:24:27,443
The quarrel ran for eighty years.

301
00:24:27,530 --> 00:24:34,627
In 1917 Arthur Cushny argued for filtration and reabsorption, in a book he titled,

302
00:24:34,714 --> 00:24:38,349
of all things, The Secretion of the Urine.

303
00:24:38,436 --> 00:24:45,620
He called his account, rather boldly, "the modern view." But no one could prove it,

304
00:24:45,707 --> 00:24:51,160
because no one had ever sampled what came out of a single tuft.

305
00:24:53,810 --> 00:24:59,815
Then, in Philadelphia, Joseph Wearn and Alfred Newton Richards tried.

306
00:24:59,902 --> 00:25:05,993
They anaesthetised a frog, laid open its kidney under a blazing light,

307
00:25:06,080 --> 00:25:11,824
and guided a fine glass pipette into the cup around a single tuft.

308
00:25:11,911 --> 00:25:15,740
They drew out a droplet of the fluid inside.

309
00:25:16,840 --> 00:25:21,007
The droplet contained sugar, and it contained salt.

310
00:25:21,089 --> 00:25:26,809
The frog's bladder urine, taken at the same moment, contained neither.

311
00:25:26,891 --> 00:25:29,506
And the droplet held no protein.

312
00:25:29,588 --> 00:25:35,961
Here, it seemed, was the blood's fluid, filtered, with its proteins held back.

313
00:25:36,043 --> 00:25:42,090
Somewhere along the tubes, the sugar and salt were being taken back again.

314
00:25:43,190 --> 00:25:46,338
When they first reported it, in 1921,

315
00:25:46,423 --> 00:25:50,933
someone objected at once that a frog is not a mammal.

316
00:25:51,018 --> 00:25:54,761
Richards's reply, I am told, won an ovation.

317
00:25:54,846 --> 00:26:01,398
Their own colleague wrote that the result suggested, though it did not prove,

318
00:26:01,483 --> 00:26:02,419
filtration.

319
00:26:02,504 --> 00:26:05,482
The mammals came later, and agreed.

320
00:26:05,567 --> 00:26:12,714
Theophilus had called urine the filtrate of the blood thirteen hundred years before.

321
00:26:12,799 --> 00:26:16,628
Here it was, very nearly, in a glass pipette.

322
00:26:16,713 --> 00:26:20,882
And Bowman, I should add, was not entirely wrong:

323
00:26:20,967 --> 00:26:23,179
the tubes secrete as well.

324
00:26:23,264 --> 00:26:28,880
The best quarrels in science often end with both sides half right.

325
00:26:39,130 --> 00:26:43,627
Now back to the stone, and to those who cut for it.

326
00:26:43,715 --> 00:26:47,507
You must understand how common it once was.

327
00:26:47,595 --> 00:26:54,208
In parts of Europe, bladder stone was above all a disease of poor children,

328
00:26:54,296 --> 00:26:58,793
probably from a diet of little but bread and gruel.

329
00:26:58,882 --> 00:27:06,200
The hospital at Norwich operated on some fifteen hundred patients for stone between

330
00:27:06,288 --> 00:27:13,254
1772 and 1909, and kept every stone, labelled, with the patient's name and age.

331
00:27:13,342 --> 00:27:15,811
The collection ends in 1909.

332
00:27:15,900 --> 00:27:17,399
Nobody closed it.

333
00:27:17,487 --> 00:27:24,100
The disease had simply disappeared, and we are still not entirely sure why.

334
00:27:26,750 --> 00:27:32,175
A good method for the stone could feed a family for generations,

335
00:27:32,260 --> 00:27:35,396
and it was guarded as a trade secret.

336
00:27:35,481 --> 00:27:41,753
In France, the Colot family were stone-cutters for some eight generations.

337
00:27:41,838 --> 00:27:48,111
In Italy, around 1520, a surgeon called de Romanis devised a new approach,

338
00:27:48,196 --> 00:27:51,332
described by his pupil Mariano Santo:

339
00:27:51,417 --> 00:27:58,537
a grooved metal staff, passed down the urethra into the bladder, to guide the knife.

340
00:27:58,622 --> 00:28:04,640
It used so many instruments that it was called the "greater apparatus."

341
00:28:07,290 --> 00:28:11,542
In the middle of the sixteenth century, Pierre Franco,

342
00:28:11,621 --> 00:28:15,007
a barber-surgeon who worked in Switzerland,

343
00:28:15,086 --> 00:28:20,362
could not get a large stone out of a two-year-old child from below.

344
00:28:20,441 --> 00:28:23,591
The parents begged him to try something.

345
00:28:23,669 --> 00:28:27,686
So he did what the Hippocratic rule said was fatal:

346
00:28:27,764 --> 00:28:30,520
he cut into the bladder from above.

347
00:28:30,599 --> 00:28:31,859
The child lived.

348
00:28:31,938 --> 00:28:38,159
Franco put it down to luck, and wrote that he would not advise anyone to do the

349
00:28:38,238 --> 00:28:38,631
like.

350
00:28:38,710 --> 00:28:44,380
The "high operation" lay almost forgotten for a hundred and sixty years.

351
00:28:47,030 --> 00:28:50,573
In 1697 a strange figure arrived in Paris:

352
00:28:50,658 --> 00:28:57,154
Jacques Beaulieu, a stone-cutter dressed in a monk's habit of his own design,

353
00:28:57,238 --> 00:29:00,022
who called himself Frère Jacques.

354
00:29:00,107 --> 00:29:05,591
He cut at the side of the perineum, into the neck of the bladder.

355
00:29:05,675 --> 00:29:08,965
Paris let him operate in its hospitals.

356
00:29:09,050 --> 00:29:13,099
Of about sixty patients, about twenty-five died.

357
00:29:13,184 --> 00:29:16,643
The figures vary, but they were dreadful.

358
00:29:16,727 --> 00:29:23,561
Witnesses said there was no part of the region that he had not cut at one time or

359
00:29:23,645 --> 00:29:24,320
another.

360
00:29:25,420 --> 00:29:27,508
You may be hearing a tune.

361
00:29:27,589 --> 00:29:33,854
It is often said that the nursery round "Frère Jacques" was written about him.

362
00:29:33,934 --> 00:29:35,782
Historians have looked.

363
00:29:35,862 --> 00:29:37,870
They found no connection.

364
00:29:37,951 --> 00:29:43,493
The melody first appears decades after his death, under another name.

365
00:29:43,573 --> 00:29:47,670
A thing repeated, as I said, is not a thing proven.

366
00:29:48,770 --> 00:29:50,446
But Jacques learned.

367
00:29:50,530 --> 00:29:57,484
He studied anatomy, adopted a grooved staff, and his later results were far better.

368
00:29:57,568 --> 00:30:02,176
In Amsterdam, a surgeon named Rau, who had watched him,

369
00:30:02,260 --> 00:30:09,047
perfected the side approach, and is said to have hidden his method from onlookers

370
00:30:09,131 --> 00:30:11,980
by keeping his thumb in the wound.

371
00:30:14,630 --> 00:30:21,826
In London, William Cheselden of St Thomas's Hospital made the side operation his

372
00:30:21,916 --> 00:30:22,276
own.

373
00:30:22,366 --> 00:30:23,175
Remember:

374
00:30:23,265 --> 00:30:25,514
there was no anaesthetic.

375
00:30:25,604 --> 00:30:27,043
Speed was mercy.

376
00:30:27,133 --> 00:30:33,520
One eyewitness reported an operation of his lasting fifty-four seconds.

377
00:30:36,170 --> 00:30:40,227
But what marks Cheselden out is not his speed.

378
00:30:40,315 --> 00:30:41,285
He counted.

379
00:30:41,373 --> 00:30:44,901
He published his results at St Thomas's:

380
00:30:44,989 --> 00:30:51,780
two hundred and thirteen patients, twenty deaths, and he set them out by age.

381
00:30:51,868 --> 00:30:57,247
Of a hundred and five children aged ten or under, three died.

382
00:30:57,336 --> 00:31:04,567
In Paris, by his reckoning, the old method was losing nearly two patients in five.

383
00:31:04,655 --> 00:31:11,799
His tables are among the earliest records of surgical results ever broken down by

384
00:31:11,887 --> 00:31:12,240
age.

385
00:31:12,328 --> 00:31:14,180
He also left us this:

386
00:31:15,680 --> 00:31:22,150
[Cheselden] No one ever endured more anxiety and sickness before an operation,

387
00:31:22,248 --> 00:31:28,130
yet from the time I began to operate, all uneasiness ceased;

388
00:31:28,228 --> 00:31:33,129
and if I have had better success than some others,

389
00:31:33,227 --> 00:31:36,854
I do not impute it to more knowledge,

390
00:31:36,952 --> 00:31:43,814
but to the happiness of a mind that was never ruffled or disconcerted,

391
00:31:43,912 --> 00:31:49,010
and a hand that never trembled during any operation.

392
00:31:53,160 --> 00:31:56,700
The patients have left us their voices too.

393
00:31:56,782 --> 00:32:03,203
Samuel Pepys, the diarist, was cut for the stone on the twenty-sixth of March,

394
00:32:03,286 --> 00:32:06,414
1658, at his cousin's house in London.

395
00:32:06,496 --> 00:32:10,530
He survived, and kept the anniversary as a feast.

396
00:32:12,030 --> 00:32:16,995
[Pepys] This day it is two years since it pleased God that I was cut of the stone at Mrs.

397
00:32:17,056 --> 00:32:18,773
Turner's in Salisbury Court.

398
00:32:18,834 --> 00:32:21,960
And did resolve while I live to keep it a festival.

399
00:32:23,460 --> 00:32:26,061
He had a case made for the stone.

400
00:32:26,140 --> 00:32:32,289
It cost him twenty-four shillings, which, he noted, was a great deal of money,

401
00:32:32,368 --> 00:32:35,285
but it was well done and pleased him.

402
00:32:35,364 --> 00:32:41,670
When he died, many years later, seven more stones were found in his left kidney.

403
00:32:44,320 --> 00:32:52,385
Across the Atlantic, in 1752, Benjamin Franklin's brother John was suffering from

404
00:32:52,484 --> 00:32:53,480
the stone.

405
00:32:53,580 --> 00:32:55,770
Franklin wrote to him:

406
00:32:57,270 --> 00:33:01,847
[Franklin] Reflecting yesterday on your Desire to have a flexible Catheter,

407
00:33:01,918 --> 00:33:06,280
a Thought struck into my Mind how one might possibly be made.

408
00:33:07,780 --> 00:33:13,291
He went straight to a silversmith, and sat by until it was finished,

409
00:33:13,372 --> 00:33:15,966
so that it might catch the post.

410
00:33:16,047 --> 00:33:20,342
It was a tube of silver wire wound in a tight spiral,

411
00:33:20,423 --> 00:33:24,394
supple enough to follow the turns of the passage.

412
00:33:24,475 --> 00:33:29,500
Franklin is often said to have invented the flexible catheter.

413
00:33:29,581 --> 00:33:30,473
He did not;

414
00:33:30,554 --> 00:33:35,579
an Italian had made one much like it some thirty years before.

415
00:33:35,660 --> 00:33:39,550
But I like to picture him in that shop, waiting.

416
00:33:47,800 --> 00:33:52,500
Remember Ammonius, who split the stone in the wound?

417
00:33:52,591 --> 00:33:57,652
In January 1824, in Paris, Jean Civiale went one better.

418
00:33:57,743 --> 00:34:04,341
He passed a straight steel instrument up the urethra of a living patient,

419
00:34:04,431 --> 00:34:11,843
opened three claws inside the bladder, seized the stone, and drilled it to pieces.

420
00:34:11,933 --> 00:34:13,199
No cut at all.

421
00:34:13,289 --> 00:34:18,170
Rivals crowded round him, among them Baron Heurteloup,

422
00:34:18,261 --> 00:34:25,130
whose instrument gripped the stone and was then struck with a little hammer.

423
00:34:27,780 --> 00:34:30,919
Then Civiale did something remarkable.

424
00:34:31,001 --> 00:34:37,774
He gathered the results of thousands of cutting operations reported across Europe,

425
00:34:37,856 --> 00:34:40,747
set them against his own crushings,

426
00:34:40,830 --> 00:34:45,124
and laid the numbers before the Academy of Sciences.

427
00:34:45,207 --> 00:34:49,337
After cutting, about one patient in five had died.

428
00:34:49,419 --> 00:34:52,310
After crushing, about one in forty.

429
00:34:53,410 --> 00:34:57,789
In 1835 the Academy appointed four men to judge:

430
00:34:57,881 --> 00:35:01,804
a chemist, a military surgeon, a physician,

431
00:35:01,895 --> 00:35:06,365
and the great mathematician Siméon-Denis Poisson.

432
00:35:06,457 --> 00:35:10,288
Large numbers, they agreed, were valuable.

433
00:35:10,380 --> 00:35:17,405
But these numbers had been gathered from many surgeons, chosen who knows how,

434
00:35:17,496 --> 00:35:19,777
and judged who knows how.

435
00:35:19,868 --> 00:35:23,700
They could not prove what Civiale claimed.

436
00:35:24,800 --> 00:35:31,018
And the physician among them, Double, objected to counting patients at all.

437
00:35:31,101 --> 00:35:33,837
To use statistics, he complained,

438
00:35:33,920 --> 00:35:38,065
one must first forget that a man is an individual,

439
00:35:38,148 --> 00:35:42,127
and treat him as a mere fraction of the species.

440
00:35:42,210 --> 00:35:48,096
Certainty of that kind, he said, belongs to astronomy, not to medicine.

441
00:35:48,179 --> 00:35:49,671
Poisson disagreed.

442
00:35:49,754 --> 00:35:54,314
It is a quarrel between the average and the individual,

443
00:35:54,397 --> 00:35:57,050
and I assure you it is not over.

444
00:35:59,700 --> 00:36:01,929
Crushing had its own dogma.

445
00:36:02,012 --> 00:36:07,379
The bladder, Civiale taught, could not bear instruments for long.

446
00:36:07,461 --> 00:36:10,434
A sitting should last a few minutes;

447
00:36:10,516 --> 00:36:14,232
the fragments were left to pass on their own,

448
00:36:14,314 --> 00:36:18,938
and a large stone might need dozens of painful sessions.

449
00:36:19,020 --> 00:36:21,002
Even emperors submitted.

450
00:36:21,085 --> 00:36:27,772
In January 1873 the exiled Napoleon the Third was twice operated upon in England,

451
00:36:27,855 --> 00:36:29,259
under chloroform.

452
00:36:29,341 --> 00:36:31,983
He died, of his failing kidneys,

453
00:36:32,066 --> 00:36:37,350
an hour and a quarter before the third sitting was due to begin.

454
00:36:40,000 --> 00:36:45,885
The man who broke that rule was a Boston surgeon, Henry Jacob Bigelow.

455
00:36:45,969 --> 00:36:52,527
In 1846 he had published the first report of operations performed under ether.

456
00:36:52,611 --> 00:36:59,253
Thirty-two years later he reasoned that a bladder under anaesthesia need not be

457
00:36:59,337 --> 00:37:00,010
hurried.

458
00:37:01,510 --> 00:37:06,675
[Bigelow] My own conviction is that it is better to protract the operation indefinitely in

459
00:37:06,740 --> 00:37:12,099
point of time, if thus the whole stone can be removed without serious injury to the

460
00:37:12,163 --> 00:37:12,680
bladder.

461
00:37:14,180 --> 00:37:18,018
He crushed the whole stone at one sitting,

462
00:37:18,109 --> 00:37:24,139
and washed every fragment out with a rubber bulb and a glass trap.

463
00:37:24,231 --> 00:37:29,713
His longest operation lasted three hours and three quarters.

464
00:37:29,804 --> 00:37:34,190
A rule half a century old fell in a single book.

465
00:37:36,840 --> 00:37:43,577
Anaesthesia, and soon Lister's antisepsis, opened the body to the surgeon.

466
00:37:43,669 --> 00:37:50,861
In Heidelberg in 1869 Gustav Simon faced a woman of forty-six, Margaretha Kleb,

467
00:37:50,952 --> 00:37:55,869
whose ureter had been injured in an earlier operation,

468
00:37:55,960 --> 00:37:59,693
so that urine leaked from her constantly.

469
00:37:59,784 --> 00:38:03,335
He had failed three times to repair it.

470
00:38:03,426 --> 00:38:06,977
The only cure was to remove the kidney.

471
00:38:07,068 --> 00:38:09,890
But can a person live with one?

472
00:38:10,990 --> 00:38:15,550
Simon first removed a kidney from each of thirty dogs,

473
00:38:15,635 --> 00:38:20,786
and saw the remaining kidney grow larger to take up the work.

474
00:38:20,870 --> 00:38:23,911
Then, on the second of August, 1869,

475
00:38:23,995 --> 00:38:28,471
he removed Margaretha Kleb's kidney in forty minutes.

476
00:38:28,555 --> 00:38:31,342
She was out of bed in four weeks.

477
00:38:31,427 --> 00:38:33,200
One kidney is enough.

478
00:38:41,450 --> 00:38:46,552
For most of history the inside of the living body stayed dark.

479
00:38:46,634 --> 00:38:51,160
Physicians guessed at it from symptoms, from the flask,

480
00:38:51,242 --> 00:38:55,521
and from the click of a metal sound against a stone.

481
00:38:55,603 --> 00:39:01,692
In the first years of the nineteenth century, a young doctor in Frankfurt,

482
00:39:01,774 --> 00:39:05,148
Philipp Bozzini, asked a simple question.

483
00:39:05,230 --> 00:39:06,300
Why not look?

484
00:39:07,400 --> 00:39:12,625
His "light conductor" was a vase about the height of a wine bottle.

485
00:39:12,703 --> 00:39:19,019
Inside it burned a wax candle, held by springs so the flame stayed in place as it

486
00:39:19,097 --> 00:39:20,033
burned down.

487
00:39:20,111 --> 00:39:23,932
A concave mirror sent the light down one channel;

488
00:39:24,010 --> 00:39:30,170
the doctor's eye looked back up another, so that the glare would not blind him.

489
00:39:31,670 --> 00:39:36,077
[Bozzini] The usefulness of the light conductor is so general that it must have,

490
00:39:36,140 --> 00:39:41,240
directly or indirectly, the most significant influence on every part of medicine.

491
00:39:43,890 --> 00:39:47,295
Too poor to travel, he sent it to Vienna.

492
00:39:47,378 --> 00:39:52,112
At the army's medical academy they tried it on a cadaver,

493
00:39:52,195 --> 00:39:55,434
declared that it met every expectation,

494
00:39:55,517 --> 00:39:59,337
and built an improved model within two months.

495
00:39:59,420 --> 00:40:04,984
At the University faculty, their rivals, the verdict was different.

496
00:40:05,068 --> 00:40:09,220
As it was later recovered from the Viennese files:

497
00:40:10,720 --> 00:40:15,450
[Vienna faculty] It will always remain a mere toy.

498
00:40:16,950 --> 00:40:20,293
A biographer, writing long afterwards,

499
00:40:20,381 --> 00:40:25,396
says they mocked it as a magic lantern in the human body.

500
00:40:25,484 --> 00:40:28,740
It was not the light that killed him.

501
00:40:28,828 --> 00:40:35,515
In 1809 typhus swept Frankfurt, and Bozzini served as an epidemic physician.

502
00:40:35,602 --> 00:40:38,418
There was no cure, only nursing;

503
00:40:38,506 --> 00:40:43,169
forty-two of his patients are recorded as recovering.

504
00:40:43,257 --> 00:40:47,040
Then he caught the fever himself, and died.

505
00:40:47,128 --> 00:40:48,800
He was thirty-five.

506
00:40:51,450 --> 00:40:57,896
In Paris in 1826, Pierre Ségalas showed the Academy a lighted speculum for the

507
00:40:57,978 --> 00:40:58,639
urethra;

508
00:40:58,722 --> 00:41:04,589
and, as he later told the story, the physicist Fresnel, on his way out,

509
00:41:04,672 --> 00:41:11,531
advised him to put the light at the side and reflect it down the tube with a tilted

510
00:41:11,613 --> 00:41:12,192
mirror.

511
00:41:12,275 --> 00:41:15,911
In 1853 Antonin Desormeaux did exactly that.

512
00:41:15,993 --> 00:41:20,456
He burned alcohol and turpentine in a tall brass lamp,

513
00:41:20,538 --> 00:41:27,397
coined the word "endoscope," and looked into the urethra and bladder of the living.

514
00:41:27,480 --> 00:41:30,620
His colleagues were not all convinced.

515
00:41:32,120 --> 00:41:39,163
[Desormeaux] When, in its infancy, it was shown to some of my colleagues, one of whom remarked:

516
00:41:39,249 --> 00:41:42,427
We can see well with your instrument;

517
00:41:42,513 --> 00:41:45,090
but what is the use of seeing?

518
00:41:46,590 --> 00:41:52,489
Desormeaux considered the new electric light, and rejected it.

519
00:41:52,584 --> 00:41:54,963
Too cumbersome, he wrote;

520
00:41:55,058 --> 00:41:59,720
it would need an assistant, and double the price.

521
00:42:02,370 --> 00:42:08,316
The decisive step came from a young doctor in Dresden, Maximilian Nitze.

522
00:42:08,399 --> 00:42:13,188
The story goes that, cleaning a dusty microscope eyepiece,

523
00:42:13,271 --> 00:42:19,465
he saw through it a tiny upside-down image of the church across the street,

524
00:42:19,547 --> 00:42:25,824
and understood that a telescope could carry a picture out of a hollow organ.

525
00:42:25,906 --> 00:42:29,457
He put the light inside the bladder itself:

526
00:42:29,540 --> 00:42:36,064
a platinum wire, made white-hot by a current, cooled by a stream of iced water,

527
00:42:36,146 --> 00:42:39,780
at the tip of a slender tube full of lenses.

528
00:42:40,880 --> 00:42:45,164
Built with the Viennese instrument-maker Josef Leiter,

529
00:42:45,243 --> 00:42:50,716
it was shown on a living patient in Vienna on the ninth of May, 1879.

530
00:42:50,796 --> 00:42:54,683
The two soon quarrelled bitterly over the credit;

531
00:42:54,762 --> 00:42:59,759
history, diplomatically, gives the instrument both their names.

532
00:42:59,839 --> 00:43:02,695
Six months after that demonstration,

533
00:43:02,774 --> 00:43:06,978
Thomas Edison filed his patent for the electric lamp.

534
00:43:07,057 --> 00:43:13,166
By 1887 tiny bulbs glowed at the tips of cystoscopes in Vienna and in Berlin,

535
00:43:13,245 --> 00:43:19,670
and one American wrote that a tumour of the bladder could be seen as plainly as a

536
00:43:19,750 --> 00:43:22,050
section under the microscope.

537
00:43:24,700 --> 00:43:27,262
Now the urologist could steer.

538
00:43:27,348 --> 00:43:34,181
In Paris, around 1897, Joaquín Albarrán fitted a tiny hinged lever at the tip of

539
00:43:34,266 --> 00:43:40,160
the cystoscope, to lift a fine catheter into the opening of a ureter,

540
00:43:40,245 --> 00:43:44,345
and so draw the urine of each kidney separately.

541
00:43:44,430 --> 00:43:51,263
And in 1912, at Johns Hopkins, Hugh Hampton Young slid a child's cystoscope up a

542
00:43:51,349 --> 00:43:55,278
ureter enormously widened by a blockage below.

543
00:43:55,363 --> 00:43:59,805
It is usually counted as the first look up a ureter,

544
00:43:59,890 --> 00:44:03,990
though he did not report it for seventeen years.

545
00:44:06,640 --> 00:44:09,862
Then came a different kind of light.

546
00:44:09,951 --> 00:44:16,484
In November 1895 Wilhelm Röntgen discovered rays that pass through flesh.

547
00:44:16,574 --> 00:44:23,733
Within months John Macintyre in Glasgow had photographed a stone inside a living

548
00:44:23,823 --> 00:44:24,449
kidney.

549
00:44:24,539 --> 00:44:31,430
The great kidney surgeon Henry Morris welcomed the rays, but added a warning.

550
00:44:31,520 --> 00:44:35,994
If they could show only whether a stone was there,

551
00:44:36,084 --> 00:44:40,290
and not the other diseases that mimic it, then:

552
00:44:41,790 --> 00:44:46,916
[Morris] It will, I fear, be the means of putting back renal surgery,

553
00:44:47,001 --> 00:44:53,665
by deterring many patients from submitting to surgical explorations who can be

554
00:44:53,750 --> 00:44:57,680
cured by no other treatment than an operation.

555
00:44:59,180 --> 00:45:03,769
Morris had made his name by opening the kidney itself:

556
00:45:03,854 --> 00:45:08,528
in 1880 he cut a stone from a kidney otherwise healthy,

557
00:45:08,613 --> 00:45:11,332
the first operation of its kind.

558
00:45:11,417 --> 00:45:17,876
To such a surgeon, the knife and the finger were still the surest diagnosis,

559
00:45:17,961 --> 00:45:21,190
and a clear plate a dangerous comfort.

560
00:45:23,840 --> 00:45:30,461
In 1906, surgeons learned to fill the kidney with a silver solution through a

561
00:45:30,547 --> 00:45:34,245
ureteric catheter and photograph its shape.

562
00:45:34,331 --> 00:45:37,685
But that meant a cystoscopy every time.

563
00:45:37,771 --> 00:45:44,908
The answer came in 1929, in Hamburg and Berlin, from a young American, Moses Swick.

564
00:45:44,994 --> 00:45:51,615
Testing compounds of iodine that chemists had made for quite another purpose,

565
00:45:51,701 --> 00:45:55,915
he found one that the kidneys passed out quickly.

566
00:45:56,001 --> 00:45:59,612
Injected into a vein, it drew the kidneys,

567
00:45:59,698 --> 00:46:04,170
the ureters and the bladder in white upon the plate.

568
00:46:05,270 --> 00:46:10,880
The professor in whose clinic he worked presented the discovery to the world.

569
00:46:13,530 --> 00:46:19,619
And with the light of the cystoscope and the X-ray came a flourishing of modern

570
00:46:19,696 --> 00:46:20,313
urology:

571
00:46:20,390 --> 00:46:26,633
a field that already looks far more like the one we know today than like anything

572
00:46:26,710 --> 00:46:28,020
that came before.

573
00:46:30,120 --> 00:46:34,588
Young Swick's part, though, was overlooked for decades;

574
00:46:34,670 --> 00:46:37,919
he received a medal for it only in 1966.

575
00:46:38,000 --> 00:46:44,256
And that the professor who presented his work was himself, a few years later,

576
00:46:44,337 --> 00:46:49,537
driven from his posts in Germany because of his Jewish ancestry.

577
00:46:49,618 --> 00:46:54,330
History rarely arranges its heroes and villains so neatly.

578
00:46:57,980 --> 00:47:04,685
In 1954 the British physicist Harold Hopkins, with a young research student,

579
00:47:04,774 --> 00:47:12,097
Narinder Kapany, showed that an ordered bundle of glass fibres could carry an image

580
00:47:12,185 --> 00:47:13,332
round a bend.

581
00:47:13,420 --> 00:47:17,302
And then he turned the telescope inside out.

582
00:47:17,390 --> 00:47:23,919
The old cystoscope was a tube of air with a few thin lenses held in rings.

583
00:47:24,008 --> 00:47:28,243
Hopkins filled the tube with long rods of glass,

584
00:47:28,331 --> 00:47:32,301
and let thin gaps of air serve as the lenses.

585
00:47:32,389 --> 00:47:37,771
More light could pass, more cleanly, through a narrower tube:

586
00:47:37,860 --> 00:47:41,830
as much as eighty times more, by one account.

587
00:47:42,930 --> 00:47:46,107
British makers declined to build it.

588
00:47:46,195 --> 00:47:50,165
A German firm in Tuttlingen, Karl Storz, did.

589
00:47:50,254 --> 00:47:53,254
From 1967 the rod-lens cystoscope,

590
00:47:53,342 --> 00:47:58,107
lit through glass fibres from a lamp outside the body,

591
00:47:58,195 --> 00:48:01,107
became the eye of modern urology.

592
00:48:01,195 --> 00:48:07,460
After eighty years inside the bladder, the light had gone back outside,

593
00:48:07,548 --> 00:48:10,460
where Bozzini had put his candle.

594
00:48:21,210 --> 00:48:24,685
Below the bladder, wrapped around the urethra,

595
00:48:24,761 --> 00:48:30,804
lies a gland whose name comes from a Greek word meaning "one who stands before."

596
00:48:30,880 --> 00:48:33,751
The Greeks are often given the credit,

597
00:48:33,826 --> 00:48:38,963
but the anatomists of Alexandria seem to have used a different word,

598
00:48:39,039 --> 00:48:41,608
and the name was fixed much later.

599
00:48:41,683 --> 00:48:45,914
The gland was first plainly described in Venice in 1536,

600
00:48:45,989 --> 00:48:48,860
and drawn by Vesalius two years later.

601
00:48:51,510 --> 00:48:55,677
Anatomists have always compared it to food:

602
00:48:55,774 --> 00:49:02,654
a pair of kernels, a walnut, a small grape, and, when enlarged, a pear.

603
00:49:02,751 --> 00:49:08,371
Later surgeons spoke of chestnuts, oranges, even coconuts.

604
00:49:08,468 --> 00:49:16,026
For in older men the prostate grows, and as it grows it can close the passage.

605
00:49:16,123 --> 00:49:21,840
For centuries, the remedy was the catheter, often for life.

606
00:49:24,490 --> 00:49:27,640
In 1893 the Philadelphia surgeon J.

607
00:49:27,730 --> 00:49:34,840
William White reasoned that if removing the ovaries could shrink growths of the

608
00:49:34,930 --> 00:49:39,610
womb, removing the testes might shrink the prostate.

609
00:49:39,700 --> 00:49:41,950
In castrated dogs it did.

610
00:49:42,040 --> 00:49:49,330
Surgeons took up the idea, and by 1895 White could report on a hundred and eleven

611
00:49:49,420 --> 00:49:50,680
castrated men.

612
00:49:50,770 --> 00:49:53,380
In most, the prostate shrank.

613
00:49:53,470 --> 00:49:58,690
Nearly one in five died, many of them already gravely ill.

614
00:49:58,780 --> 00:50:01,570
The fashion was soon abandoned.

615
00:50:01,660 --> 00:50:03,370
Remember it anyway.

616
00:50:03,460 --> 00:50:09,580
White was right about the biology, and that will matter in a moment.

617
00:50:12,230 --> 00:50:16,195
The surgeons turned to removing the gland itself.

618
00:50:16,276 --> 00:50:22,993
In Leeds in 1887, Arthur McGill was operating for a bladder stone when he noticed a

619
00:50:23,074 --> 00:50:27,283
lump at the neck of the bladder and twisted it free.

620
00:50:27,364 --> 00:50:30,439
It came away, it is said, in his hand.

621
00:50:30,520 --> 00:50:35,376
Two years later he showed a meeting of doctors his patients,

622
00:50:35,456 --> 00:50:38,613
each holding his own prostate in a jar.

623
00:50:38,694 --> 00:50:45,087
Eugene Fuller of New York described shelling out the enlarged gland through the

624
00:50:45,168 --> 00:50:47,029
opened bladder in 1895.

625
00:50:47,110 --> 00:50:51,966
Peter Freyer of London performed the same operation in 1900,

626
00:50:52,047 --> 00:50:57,307
called it total removal of the prostate, published it as his own,

627
00:50:57,388 --> 00:51:00,625
performed it more than a thousand times,

628
00:51:00,706 --> 00:51:05,400
and caused a great deal of anger in New York and in Leeds.

629
00:51:08,050 --> 00:51:13,291
Surgeons had already tried to reach the gland through the urethra:

630
00:51:13,371 --> 00:51:18,056
blind, with an electrically heated blade, in Pavia in 1874,

631
00:51:18,136 --> 00:51:20,995
and with Hugh Young's punch in 1909.

632
00:51:21,074 --> 00:51:24,489
The method that lasted needed three things.

633
00:51:24,568 --> 00:51:31,080
In 1926 Maximilian Stern of New York made a wire loop that cut with high-frequency

634
00:51:31,160 --> 00:51:31,795
current.

635
00:51:31,874 --> 00:51:36,798
Theodore Davis, an electrical engineer before he was a doctor,

636
00:51:36,877 --> 00:51:43,389
helped build a generator that could cut with one current and seal bleeding vessels

637
00:51:43,469 --> 00:51:46,884
with another, at the press of a foot pedal.

638
00:51:46,963 --> 00:51:50,616
And in 1931 Joseph McCarthy put loop, current,

639
00:51:50,695 --> 00:51:54,507
and a good lens together in an insulated sheath.

640
00:51:54,587 --> 00:51:56,254
Three keys, one lock.

641
00:51:56,334 --> 00:52:02,846
The transurethral resection of the prostate remained the standard operation for an

642
00:52:02,925 --> 00:52:06,340
enlarged gland for the rest of the century.

643
00:52:08,990 --> 00:52:13,139
In Chicago, Charles Huggins was collecting drops.

644
00:52:13,224 --> 00:52:17,628
He had found a way to isolate the prostate of a dog,

645
00:52:17,712 --> 00:52:23,979
so that its secretion could be gathered alone and measured, day after day,

646
00:52:24,063 --> 00:52:24,995
for months.

647
00:52:25,080 --> 00:52:30,669
Remove the testes, and the secretion stopped and the gland shrank.

648
00:52:30,753 --> 00:52:34,056
Give the male hormone, and it returned.

649
00:52:34,141 --> 00:52:38,036
Give the female hormone, and it stopped again.

650
00:52:38,121 --> 00:52:41,000
White's biology, measured at last.

651
00:52:42,100 --> 00:52:44,327
Then a stroke of fortune.

652
00:52:44,416 --> 00:52:48,782
Some of the old dogs had tumours of the prostate.

653
00:52:48,871 --> 00:52:55,999
The dog, Huggins said later, is the only laboratory animal in which such tumours

654
00:52:56,088 --> 00:52:56,622
occur.

655
00:52:56,711 --> 00:52:59,206
So he asked a bold question.

656
00:52:59,295 --> 00:53:05,710
If the gland depends on male hormone, might its cancer depend on it too?

657
00:53:08,360 --> 00:53:13,112
He needed a number to measure it by, and in New York,

658
00:53:13,202 --> 00:53:17,596
Alexander and Ethel Gutman had just supplied one:

659
00:53:17,685 --> 00:53:25,038
an enzyme, acid phosphatase, that rose in the blood when prostate cancer spread to

660
00:53:25,128 --> 00:53:26,024
the bones.

661
00:53:26,114 --> 00:53:31,853
In 1941 Huggins and Clarence Hodges castrated men with advanced,

662
00:53:31,942 --> 00:53:36,246
painful prostate cancer, or gave them oestrogen.

663
00:53:36,336 --> 00:53:37,771
The enzyme fell.

664
00:53:37,860 --> 00:53:39,205
The pain eased.

665
00:53:39,295 --> 00:53:43,330
When male hormone was given instead, it rose.

666
00:53:44,430 --> 00:53:51,062
A spreading cancer, it turned out, need not be master of its own growth.

667
00:53:51,154 --> 00:53:55,759
Of the first twenty-one men treated by castration,

668
00:53:55,851 --> 00:53:59,996
four were alive more than twelve years later.

669
00:54:00,088 --> 00:54:03,680
Huggins shared the Nobel Prize in 1966.

670
00:54:04,780 --> 00:54:08,184
From that work also grew a further fear:

671
00:54:08,269 --> 00:54:13,629
that giving testosterone to any man might feed a hidden cancer.

672
00:54:13,714 --> 00:54:18,820
For some sixty years doctors were reluctant to prescribe it.

673
00:54:18,905 --> 00:54:25,712
Some now argue that the evidence for that particular fear came down, in the end,

674
00:54:25,797 --> 00:54:31,158
to a single untreated man given testosterone for eighteen days.

675
00:54:31,243 --> 00:54:33,030
The argument goes on.

676
00:54:35,680 --> 00:54:42,776
Removing the whole prostate for cancer was, in those years, a brutal operation.

677
00:54:42,865 --> 00:54:47,985
It bled terribly, and almost every man was left impotent.

678
00:54:48,075 --> 00:54:54,811
Surgeons believed that the nerves of erection ran through the gland itself,

679
00:54:54,901 --> 00:54:57,146
so nothing could be done.

680
00:54:57,236 --> 00:55:03,883
Then, in 1977, a patient of Patrick Walsh at Johns Hopkins mentioned that,

681
00:55:03,973 --> 00:55:08,104
after the operation, his potency had returned.

682
00:55:08,194 --> 00:55:10,170
Walsh began to wonder.

683
00:55:11,270 --> 00:55:18,906
In February 1981, in Leiden, he sat with a retired Dutch urologist, Pieter Donker,

684
00:55:19,000 --> 00:55:24,680
who was tracing the nerves of the bladder under a microscope,

685
00:55:24,773 --> 00:55:32,131
in the body of a stillborn infant, where such fine nerves are easier to follow.

686
00:55:32,224 --> 00:55:36,880
Walsh asked him where the nerves to the penis ran.

687
00:55:38,380 --> 00:55:39,590
[Donker] I've never looked.

688
00:55:41,090 --> 00:55:47,465
Three hours later they had found them, running not through the prostate,

689
00:55:47,553 --> 00:55:50,121
but alongside it, outside it.

690
00:55:50,209 --> 00:55:53,308
On the twenty-sixth of April, 1982,

691
00:55:53,396 --> 00:55:58,620
Walsh performed the first operation designed to spare them.

692
00:55:59,720 --> 00:56:04,548
Back at Johns Hopkins, Walsh's resident, Herbert Lepor,

693
00:56:04,636 --> 00:56:08,849
traced the same nerves through the adult pelvis,

694
00:56:08,937 --> 00:56:15,697
and in 1985 they published a precise map of their course beside the prostate.

695
00:56:15,784 --> 00:56:18,330
Surgeons still operate by it.

696
00:56:20,980 --> 00:56:22,926
Then came a blood test.

697
00:56:23,010 --> 00:56:29,524
Prostate-specific antigen, a protein made by the gland, was proposed in 1987,

698
00:56:29,609 --> 00:56:33,331
in a landmark paper, as a marker for cancer.

699
00:56:33,416 --> 00:56:35,615
Read that paper carefully.

700
00:56:35,700 --> 00:56:40,268
It found the protein rose with the size of the cancer,

701
00:56:40,353 --> 00:56:43,821
and vanished after the gland was removed.

702
00:56:43,906 --> 00:56:50,082
But it also found the protein raised in most men with simple enlargement,

703
00:56:50,166 --> 00:56:56,257
and concluded, in its authors' words, that "neither marker is specific":

704
00:56:56,342 --> 00:57:00,910
neither the new antigen, nor the old acid phosphatase.

705
00:57:02,010 --> 00:57:04,010
Screening spread anyway.

706
00:57:04,093 --> 00:57:08,093
In 2009, two great trials reported side by side.

707
00:57:08,176 --> 00:57:12,176
A European one found that screening saved lives.

708
00:57:12,259 --> 00:57:15,426
An American one found that it did not,

709
00:57:15,509 --> 00:57:22,258
though so many of its unscreened men had been tested anyway that it was comparing

710
00:57:22,342 --> 00:57:24,841
screening with less screening.

711
00:57:24,925 --> 00:57:31,091
American advisers recommended against the test in 2012, and then, in 2018,

712
00:57:31,174 --> 00:57:34,174
for men of fifty-five to sixty-nine,

713
00:57:34,257 --> 00:57:38,257
for a conversation between a man and his doctor.

714
00:57:38,340 --> 00:57:41,340
That conversation is still going on.

715
00:57:49,590 --> 00:57:51,692
Some revolutions are small.

716
00:57:51,770 --> 00:57:55,662
Around 1930 an American urologist, Frederic Foley,

717
00:57:55,740 --> 00:58:00,955
designed a soft rubber catheter with a little balloon near its tip,

718
00:58:01,033 --> 00:58:07,105
inflated inside the bladder, at first to stop bleeding after prostate surgery,

719
00:58:07,182 --> 00:58:10,374
and to keep the catheter where it is put.

720
00:58:10,452 --> 00:58:16,212
It may be the most used urological device on earth, and it bears his name.

721
00:58:16,290 --> 00:58:20,182
The patent, after a dispute, went to someone else:

722
00:58:20,260 --> 00:58:23,451
Paul Raiche, of the Davol Rubber Company.

723
00:58:23,529 --> 00:58:27,577
Foley won it on appeal, Raiche won it back in court,

724
00:58:27,655 --> 00:58:31,080
and the name on the catheter stayed Foley's.

725
00:58:33,730 --> 00:58:37,585
On the twenty-third of December, 1954, in Boston,

726
00:58:37,664 --> 00:58:41,126
Richard Herrick was dying of kidney failure.

727
00:58:41,205 --> 00:58:45,060
His identical twin, Ronald, offered him a kidney.

728
00:58:45,139 --> 00:58:51,669
The surgeons first proved the twins identical by grafting a patch of skin from each

729
00:58:51,748 --> 00:58:52,928
onto the other.

730
00:58:53,007 --> 00:58:58,043
The urologist Hartwell Harrison removed Ronald's healthy kidney,

731
00:58:58,121 --> 00:59:01,190
and Joseph Murray placed it in Richard.

732
00:59:01,269 --> 00:59:05,360
It worked at once, and it went on working for years:

733
00:59:05,439 --> 00:59:11,104
the first transplant of an organ to succeed for years rather than weeks.

734
00:59:11,183 --> 00:59:17,084
It also meant putting a healthy man under the knife for his brother's sake,

735
00:59:17,162 --> 00:59:22,591
and before they agreed, the surgeons consulted physicians and clergy.

736
00:59:22,670 --> 00:59:25,660
Murray later received the Nobel Prize.

737
00:59:28,310 --> 00:59:29,469
And the stone?

738
00:59:29,551 --> 00:59:32,365
It met its strangest enemy of all.

739
00:59:32,448 --> 00:59:39,151
Engineers at the German aircraft firm Dornier were studying how raindrops pit the

740
00:59:39,233 --> 00:59:43,454
skin of an aircraft flying near the speed of sound:

741
00:59:43,536 --> 00:59:47,260
each drop drives a shock wave into the metal.

742
00:59:47,343 --> 00:59:54,046
An engineer who touched a target as a shock wave struck it felt something like an

743
00:59:54,129 --> 00:59:57,604
electric shock, yet his skin was unharmed.

744
00:59:57,687 --> 01:00:01,080
The wave had passed straight through him.

745
01:00:03,730 --> 01:00:06,691
Now, here is the beautiful part.

746
01:00:06,783 --> 01:00:08,264
Take an ellipse.

747
01:00:08,356 --> 01:00:14,556
A wave that starts at one focus, and reflects from the curved wall,

748
01:00:14,649 --> 01:00:17,147
gathers again at the other.

749
01:00:17,239 --> 01:00:21,218
Put an underwater spark at the first focus.

750
01:00:21,311 --> 01:00:25,475
Put the patient's kidney stone at the second.

751
01:00:25,567 --> 01:00:32,692
Doctors and engineers in Munich tested the idea on human stones placed in the

752
01:00:32,784 --> 01:00:34,265
kidneys of dogs.

753
01:00:34,357 --> 01:00:40,557
On the seventh of February, 1980, they treated their first patient,

754
01:00:40,649 --> 01:00:46,479
lying in a bath of water, with crossed X-ray beams to take aim.

755
01:00:46,571 --> 01:00:48,607
The stone broke apart.

756
01:00:48,700 --> 01:00:50,180
No knife at all.

757
01:00:55,330 --> 01:01:01,487
In the same years, surgeons were learning to reach stones through a small puncture

758
01:01:01,562 --> 01:01:05,917
in the back, or with fine telescopes passed up the ureter,

759
01:01:05,992 --> 01:01:09,746
and soon to break them with pulses of laser light.

760
01:01:09,821 --> 01:01:12,900
Ammonius would have understood perfectly.

761
01:01:15,550 --> 01:01:18,843
The abdomen, too, was opened less and less.

762
01:01:18,920 --> 01:01:23,975
In 1990, in St Louis, Ralph Clayman removed the whole kidney of an

763
01:01:24,051 --> 01:01:27,957
eighty-five-year-old woman through small punctures,

764
01:01:28,034 --> 01:01:34,237
bagging it and breaking it up inside her so that it could be drawn out through an

765
01:01:34,314 --> 01:01:36,765
opening about a centimetre wide.

766
01:01:36,841 --> 01:01:42,739
The first such removals of the prostate took more than nine hours on average,

767
01:01:42,815 --> 01:01:48,866
and their own surgeons concluded the method had no advantage over open surgery.

768
01:01:48,942 --> 01:01:50,474
Then came the robot.

769
01:01:50,550 --> 01:01:56,907
In the year 2000, in Frankfurt, surgeons removed a prostate using a robotic system:

770
01:01:56,984 --> 01:02:02,039
the surgeon at a console, the instruments held by mechanical arms.

771
01:02:02,115 --> 01:02:06,327
Soon afterwards, at the Henry Ford Hospital in Detroit,

772
01:02:06,404 --> 01:02:12,148
the city of the assembly line, Mani Menon built a program around the robot,

773
01:02:12,225 --> 01:02:16,743
and his team refined the operation over thousands of cases.

774
01:02:16,820 --> 01:02:19,960
Their method carried it around the world.

775
01:02:21,060 --> 01:02:26,319
Robotic surgery spread faster than good evidence could follow it,

776
01:02:26,400 --> 01:02:31,578
and few surgical instruments have since been studied so closely.

777
01:02:31,659 --> 01:02:36,351
Head-to-head trials have not shown that it cures more men,

778
01:02:36,432 --> 01:02:40,882
or restores more function, than a skilled open surgeon.

779
01:02:40,963 --> 01:02:47,678
But it bleeds far less, and it lets surgeons attempt operations few had envisioned.

780
01:02:47,759 --> 01:02:52,856
In many countries a bloody open operation became a robotic one.

781
01:02:52,937 --> 01:02:58,034
In 2018 a single-port robot, working through one small opening,

782
01:02:58,115 --> 01:03:01,837
was cleared for urological surgery in America.

783
01:03:01,918 --> 01:03:08,390
The wound that once ran the length of the belly can now be the width of a thumb.

784
01:03:19,140 --> 01:03:22,584
Let me end where we began, with the flask.

785
01:03:22,666 --> 01:03:28,817
For most of the twentieth century, students were taught that healthy urine,

786
01:03:28,899 --> 01:03:31,441
inside the bladder, is sterile.

787
01:03:31,523 --> 01:03:33,656
It was never quite proven.

788
01:03:33,738 --> 01:03:37,100
In the 1950s Edward Kass set a threshold,

789
01:03:37,182 --> 01:03:41,036
a hundred thousand bacteria in each millilitre,

790
01:03:41,118 --> 01:03:44,563
to tell infection from mere contamination.

791
01:03:44,645 --> 01:03:48,417
Ordinary cultures, in ordinary air, for a day,

792
01:03:48,499 --> 01:03:51,780
grew nothing from most healthy bladders,

793
01:03:51,862 --> 01:03:55,470
and nothing was taken to mean nothing there.

794
01:03:56,570 --> 01:04:01,663
In 2012 and 2014, investigators near Chicago looked again.

795
01:04:01,751 --> 01:04:07,810
They took urine straight from the bladder, by catheter and by needle;

796
01:04:07,898 --> 01:04:11,147
they searched it for bacterial genes;

797
01:04:11,235 --> 01:04:18,085
and they cultured a hundred times more of it, in many atmospheres, for longer.

798
01:04:18,172 --> 01:04:22,212
Bacteria grew from four samples in every five,

799
01:04:22,300 --> 01:04:26,778
taken from women with and without bladder symptoms,

800
01:04:26,866 --> 01:04:33,979
and nearly all of those had been reported, by the routine method, as "no growth".

801
01:04:34,067 --> 01:04:37,228
The bladder has its own inhabitants.

802
01:04:37,316 --> 01:04:41,180
We are only beginning to learn what they do.

803
01:04:43,830 --> 01:04:45,987
And the stone in the jar?

804
01:04:46,073 --> 01:04:52,976
It sat in the museum of the Royal College of Surgeons in London for forty years.

805
01:04:53,062 --> 01:04:57,549
In May 1941, in the Blitz, bombs struck the College,

806
01:04:57,635 --> 01:05:02,036
and more than half of its specimens were destroyed.

807
01:05:02,122 --> 01:05:06,091
The stone once called the oldest in the world,

808
01:05:06,177 --> 01:05:11,699
which had lain more than five thousand years in the desert, was,

809
01:05:11,785 --> 01:05:17,480
in the words of a later surgeon, crushed and completely dispersed.

810
01:05:23,130 --> 01:05:26,436
We still do not fully know why stones form.

811
01:05:26,513 --> 01:05:31,972
At least half of those who pass one will form another within ten years.

812
01:05:32,049 --> 01:05:37,200
We do not fully know why the prostate begins to grow in middle age,

813
01:05:37,277 --> 01:05:41,660
or which of its cancers will matter and which will sleep.

814
01:05:42,760 --> 01:05:46,700
Every age in this story believed it saw clearly:

815
01:05:46,782 --> 01:05:50,147
the uroscopist with his wheel of colours,

816
01:05:50,229 --> 01:05:54,005
the surgeon who would not cut above the pubis,

817
01:05:54,087 --> 01:05:57,370
the faculty that called the light a toy.

818
01:05:57,452 --> 01:06:02,706
Somewhere, in what we are sure of today, there is another flask,

819
01:06:02,788 --> 01:06:05,250
waiting to be looked at again.

820
01:06:07,850 --> 01:06:10,620
So look again.