WEBVTT 00:00:01.750 --> 00:00:08.600 In a glass jar, in a museum in London, there once sat a stone. 00:00:09.700 --> 00:00:12.605 It was larger than a hen's egg. 00:00:12.699 --> 00:00:17.384 It had grown, slowly, inside the bladder of a boy. 00:00:17.478 --> 00:00:22.914 And that boy had been buried in the desert of Upper Egypt, 00:00:23.007 --> 00:00:28.630 before the first pharaoh, more than five thousand years ago. 00:00:31.280 --> 00:00:35.923 The man who found it, at the start of the twentieth century, 00:00:36.001 --> 00:00:40.876 had come to the cemetery of El Amrah to look at ancient brains. 00:00:40.954 --> 00:00:41.650 He wrote: 00:00:43.150 --> 00:00:46.777 [Elliot Smith] In the first Egyptian grave that I looked into, 00:00:46.854 --> 00:00:49.787 I saw the skeleton of an Egyptian boy, 00:00:49.864 --> 00:00:53.800 in whose pelvis there was a large vesical calculus. 00:00:56.450 --> 00:01:01.587 It was long held to be the oldest bladder stone ever found. 00:01:01.674 --> 00:01:04.112 It is not in that jar today. 00:01:04.199 --> 00:01:07.420 I shall tell you why, before we part. 00:01:11.070 --> 00:01:14.701 This is the history of two obsessions. 00:01:14.797 --> 00:01:16.995 The first is the stone: 00:01:17.090 --> 00:01:20.531 how to get it out, and at what cost. 00:01:20.626 --> 00:01:22.920 The second is the glass: 00:01:23.015 --> 00:01:27.984 the long, stubborn wish to see inside a living body, 00:01:28.080 --> 00:01:31.520 and to know what is happening there. 00:01:32.620 --> 00:01:39.757 For most of that history, physicians were certain of things that were not so. 00:01:39.849 --> 00:01:41.888 Keep one lesson close: 00:01:41.981 --> 00:01:45.596 a thing repeated is not a thing proven. 00:01:45.688 --> 00:01:50.601 A few were brave enough to doubt, and to go and look. 00:01:50.693 --> 00:01:52.176 Listen for them. 00:01:52.269 --> 00:01:57.645 Some of what we repeat today will not survive the looking; 00:01:57.737 --> 00:02:01.630 finding out which is the work still ahead. 00:02:19.380 --> 00:02:25.072 Egypt has left us some of the oldest written medicine in the world: 00:02:25.157 --> 00:02:29.745 long rolls of papyrus, copied and recopied by scribes. 00:02:29.830 --> 00:02:35.607 Among their prescriptions are remedies for urine that will not come, 00:02:35.692 --> 00:02:38.750 and for urine that comes with blood. 00:02:41.400 --> 00:02:46.009 Blood in the urine has long been common along the Nile. 00:02:46.093 --> 00:02:50.367 In 1851, in Cairo, Theodor Bilharz found the cause: 00:02:50.451 --> 00:02:55.228 a blood fluke that lives in the veins around the bladder. 00:02:55.312 --> 00:03:01.932 Then, in 1910, the pathologist Marc Armand Ruffer took the dried kidneys of two 00:03:02.016 --> 00:03:04.782 mummies of the Twentieth Dynasty, 00:03:04.866 --> 00:03:10.397 soaked them in a solution until they were soft enough to cut thin, 00:03:10.481 --> 00:03:13.330 and put them under his microscope. 00:03:14.430 --> 00:03:17.569 He found the fluke's eggs, calcified. 00:03:17.654 --> 00:03:22.406 The parasite had been there three thousand years before. 00:03:22.491 --> 00:03:28.600 Whether it explains the bloody urine of the papyri we cannot be certain, 00:03:28.685 --> 00:03:31.400 but it is the likeliest culprit. 00:03:36.050 --> 00:03:40.840 On the wall of a tomb at Saqqara, carved about 2300 B.C., 00:03:40.924 --> 00:03:47.394 a kneeling man works with a small blade upon a youth whose arms are held from 00:03:47.478 --> 00:03:48.067 behind. 00:03:48.151 --> 00:03:52.940 It is usually read as the oldest picture of circumcision. 00:03:53.025 --> 00:04:00.083 At least one Egyptologist has asked whether it shows an emergency operation instead. 00:04:00.167 --> 00:04:02.100 The stone does not say. 00:04:04.750 --> 00:04:10.810 You will often read that the Egyptians drew off urine through hollow reeds. 00:04:10.891 --> 00:04:12.265 Perhaps they did. 00:04:12.346 --> 00:04:15.901 But no papyrus we have clearly describes it, 00:04:15.982 --> 00:04:20.184 and no such instrument has been securely identified. 00:04:20.264 --> 00:04:22.608 Let that be our first lesson. 00:04:22.689 --> 00:04:25.840 A thing repeated is not a thing proven. 00:04:34.090 --> 00:04:40.378 In India, a great Sanskrit book of surgery bears the name of Sushruta. 00:04:40.467 --> 00:04:43.701 It was compiled over many centuries; 00:04:43.791 --> 00:04:50.797 its core may be two thousand years old, and tradition places it earlier still. 00:04:50.887 --> 00:04:57.085 Among a great many operations, it describes, with remarkable candour, 00:04:57.174 --> 00:04:59.420 how to cut for the stone. 00:05:02.070 --> 00:05:06.961 The book sorts stones by what was thought to make them: 00:05:07.050 --> 00:05:12.298 three kinds by the humours of the body, and one from semen. 00:05:12.387 --> 00:05:16.655 A stone of phlegm, it says, is white and glossy, 00:05:16.744 --> 00:05:20.302 and may grow to the size of a hen's egg. 00:05:20.391 --> 00:05:22.258 Medicines come first. 00:05:22.347 --> 00:05:27.061 Only when they fail does the book consider the knife. 00:05:27.150 --> 00:05:29.640 And then it gives a warning. 00:05:31.140 --> 00:05:39.493 [Sushruta] The death of the patient is almost certain without a surgical operation, 00:05:39.609 --> 00:05:45.990 and the result to be derived from it is also uncertain. 00:05:47.090 --> 00:05:55.323 [Sushruta] A skilled surgeon should perform such operations only with the permission of the 00:05:55.425 --> 00:05:55.940 king. 00:05:58.590 --> 00:06:05.242 Consent, you see, was to be sought from the crown, because the operation might kill. 00:06:05.321 --> 00:06:07.459 The method itself is exact. 00:06:07.539 --> 00:06:12.528 Two fingers of the surgeon's left hand, passed into the rectum, 00:06:12.607 --> 00:06:14.428 push the stone forward. 00:06:14.508 --> 00:06:18.071 A fist presses on the belly to hold it there. 00:06:18.150 --> 00:06:22.347 The cut is made beside the midline seam, on the left, 00:06:22.427 --> 00:06:25.040 at the distance of a barley-corn. 00:06:26.140 --> 00:06:29.291 And the text records a disagreement. 00:06:29.378 --> 00:06:34.367 Several authorities, it says, prefer to cut on the right. 00:06:34.454 --> 00:06:38.830 Even then, surgeons argued over which side to cut. 00:06:39.930 --> 00:06:43.083 Through the cut, the stone was drawn out. 00:06:43.160 --> 00:06:49.465 In a grown man, a wound carried down to the bladder at that point must have passed 00:06:49.542 --> 00:06:54.156 through the prostate, though the text never names the gland. 00:06:54.233 --> 00:06:58.308 Then the patient was set in a cauldron of warm water, 00:06:58.385 --> 00:07:01.692 given a treacle drink to clear the passage, 00:07:01.769 --> 00:07:06.229 and the wound was dressed with honey and clarified butter. 00:07:06.306 --> 00:07:09.228 How many lived, the text does not say. 00:07:09.305 --> 00:07:14.380 It promises only that without the knife, death was almost certain. 00:07:17.030 --> 00:07:23.401 For a narrowed outlet of the urine, Sushruta advises tubes of iron, wood, 00:07:23.489 --> 00:07:30.122 or shellac, open at both ends, smeared with clarified butter, passed gently, 00:07:30.209 --> 00:07:34.137 and changed for thicker ones every third day. 00:07:34.224 --> 00:07:39.723 Elsewhere the text describes the condition as a tight foreskin; 00:07:39.810 --> 00:07:44.348 its translator called it a stricture of the urethra; 00:07:44.436 --> 00:07:46.792 scholars read it both ways. 00:07:46.879 --> 00:07:53.600 Either way, it is the principle of the graduated dilator, still in use today. 00:08:01.850 --> 00:08:06.296 The physicians who wrote under the name of Hippocrates, 00:08:06.377 --> 00:08:11.550 four or five centuries before Christ, watched the urine closely, 00:08:11.631 --> 00:08:14.460 and some of what they saw was true. 00:08:15.960 --> 00:08:20.890 [Hippocratic] When bubbles settle on the surface of the urine, 00:08:20.993 --> 00:08:29.210 they indicate disease of the kidneys, and that the complaint will be protracted. 00:08:30.710 --> 00:08:32.359 Froth on the urine. 00:08:32.445 --> 00:08:37.565 We would now say protein, leaking through a damaged kidney. 00:08:37.652 --> 00:08:43.813 They noticed it two thousand years before anyone knew what protein was. 00:08:43.900 --> 00:08:50.321 They noticed too that women suffer the stone less often than men, because, 00:08:50.408 --> 00:08:54.920 they explained, a woman's urethra is short and wide. 00:08:57.570 --> 00:09:00.139 And then there is the Oath. 00:09:00.234 --> 00:09:04.230 Every young doctor knows it, in some form. 00:09:04.326 --> 00:09:07.180 Few notice its strangest line. 00:09:08.680 --> 00:09:13.943 [Hippocratic] I will not cut persons labouring under the stone, 00:09:14.050 --> 00:09:21.890 but will leave this to be done by men who are practitioners of this work. 00:09:23.390 --> 00:09:27.807 Why should a physician swear never to cut for the stone? 00:09:27.886 --> 00:09:30.805 Some say it was a division of labour: 00:09:30.884 --> 00:09:33.960 leave the operation to the specialists. 00:09:34.039 --> 00:09:36.011 Some say it was prudence: 00:09:36.090 --> 00:09:40.586 the operation killed so often that it ruined reputations. 00:09:40.665 --> 00:09:44.372 A translation of 1923 reads it more sweepingly: 00:09:44.451 --> 00:09:49.815 I will not use the knife, not even, verily, on sufferers from stone. 00:09:49.894 --> 00:09:55.810 And one scholar argued that the Oath came from the followers of Pythagoras, 00:09:55.889 --> 00:09:58.650 and renounced the knife altogether. 00:09:58.728 --> 00:10:02.041 The Greek will bear more than one reading. 00:10:02.120 --> 00:10:04.960 The argument has never been settled. 00:10:06.060 --> 00:10:12.048 Whatever it meant, for much of the next two thousand years, in Europe at least, 00:10:12.124 --> 00:10:16.596 cutting for the stone was left largely to a separate trade: 00:10:16.672 --> 00:10:18.870 the travelling stone-cutters. 00:10:21.520 --> 00:10:26.345 In Alexandria, perhaps two centuries before Christ, 00:10:26.439 --> 00:10:32.021 a surgeon named Ammonius met a stone too large to draw out. 00:10:32.115 --> 00:10:37.886 He held it with a hook at the wound and split it with a blow. 00:10:37.981 --> 00:10:42.238 They called him Lithotomos, the stone-cutter. 00:10:42.332 --> 00:10:43.940 Keep him in mind. 00:10:44.035 --> 00:10:51.130 His idea, to break the stone rather than enlarge the wound, will come back. 00:10:53.780 --> 00:10:59.924 The Roman writer Celsus, probably in the time of the Emperor Tiberius, 00:11:00.012 --> 00:11:02.733 set the operation down in full. 00:11:02.821 --> 00:11:09.228 Cut only in spring, he says, and only in a boy between nine and fourteen. 00:11:09.316 --> 00:11:14.933 A strong assistant on a high stool holds the child on his knees. 00:11:15.021 --> 00:11:21.779 The surgeon, his nails pared, finds the stone with two fingers in the rectum, 00:11:21.867 --> 00:11:26.870 presses it down, and makes a crescent-shaped cut over it. 00:11:27.970 --> 00:11:30.553 One knife, one hook, and speed. 00:11:30.637 --> 00:11:37.053 This "lesser apparatus" remained the standard operation in Europe for fifteen 00:11:37.137 --> 00:11:38.303 hundred years. 00:11:38.387 --> 00:11:41.637 Celsus also describes bronze catheters: 00:11:41.720 --> 00:11:46.553 three lengths for men and two for women, "a little curved, 00:11:46.637 --> 00:11:53.220 but more so for men." Bronze catheters have been dug from the ashes of Pompeii. 00:11:55.870 --> 00:11:58.646 Now an experiment, and a quarrel. 00:11:58.730 --> 00:12:01.002 Where does urine come from? 00:12:01.086 --> 00:12:07.479 Asclepiades, a celebrated physician of Rome some two centuries before Galen, 00:12:07.563 --> 00:12:13.116 had taught that what we drink passes into the bladder as a vapour, 00:12:13.200 --> 00:12:14.882 and condenses there. 00:12:14.966 --> 00:12:19.341 The kidneys, in his view, had nothing to do with it. 00:12:19.425 --> 00:12:21.360 He still had followers. 00:12:22.460 --> 00:12:25.849 Galen of Pergamon thought this absurd. 00:12:25.938 --> 00:12:30.398 Vapours rise, he said, and the bladder lies below. 00:12:30.487 --> 00:12:36.820 Any butcher can see the tubes that run from the kidneys to the bladder. 00:12:36.909 --> 00:12:39.674 But Galen did not merely argue. 00:12:39.763 --> 00:12:41.190 He demonstrated. 00:12:42.690 --> 00:12:46.731 [Galen] One has to divide the peritoneum in front of the ureters, 00:12:46.802 --> 00:12:52.049 then secure these with ligatures, and next, having bandaged up the animal, 00:12:52.120 --> 00:12:52.900 let him go. 00:12:54.400 --> 00:12:57.298 The animal stops passing water. 00:12:57.392 --> 00:13:00.570 Later, Galen loosens the bandages. 00:13:02.070 --> 00:13:06.257 [Galen] One loosens the external bandages, and shows the bladder empty, 00:13:06.324 --> 00:13:11.840 and the ureters quite full and distended, in fact almost on the point of rupturing. 00:13:12.940 --> 00:13:14.979 [Galen] On removing the ligature from them, 00:13:15.037 --> 00:13:18.590 one then plainly sees the bladder becoming filled with urine. 00:13:21.240 --> 00:13:22.622 He went further. 00:13:22.708 --> 00:13:26.854 He tied the penis and squeezed the full bladder: 00:13:26.940 --> 00:13:30.308 nothing ran back up toward the kidneys. 00:13:30.395 --> 00:13:31.863 There is a valve. 00:13:31.949 --> 00:13:35.663 He tied one ureter and left the other free: 00:13:35.750 --> 00:13:38.945 only the free one filled the bladder. 00:13:39.031 --> 00:13:44.559 That is a control, in an experiment some eighteen centuries old. 00:13:44.645 --> 00:13:50.086 Then he cut the swollen ureter, and the urine spurted, he says, 00:13:50.173 --> 00:13:52.850 like blood from an opened vein. 00:13:54.350 --> 00:13:59.663 [Galen] Like slaves, then, caught in the act of stealing, these two are quite bewildered; 00:13:59.729 --> 00:14:04.320 and while the one says nothing, the other indulges in shameless lying. 00:14:08.970 --> 00:14:15.945 That was his verdict on Asclepiades, and on the great anatomist Erasistratus, 00:14:16.035 --> 00:14:17.394 both long dead. 00:14:17.485 --> 00:14:21.832 Galen was right that the kidneys make the urine. 00:14:21.923 --> 00:14:22.648 But how? 00:14:22.738 --> 00:14:27.630 Not, he insisted, by straining the blood like a sieve. 00:14:27.720 --> 00:14:33.064 The kidney drew the watery part of the blood toward itself, 00:14:33.155 --> 00:14:35.510 as a lodestone draws iron. 00:14:35.601 --> 00:14:42.666 So great was Galen's authority that this answer stood for some fifteen hundred 00:14:42.757 --> 00:14:43.300 years. 00:14:51.550 --> 00:14:56.841 For centuries, the emblem of the physician was not a knife, 00:14:56.930 --> 00:14:59.262 and not yet a stethoscope. 00:14:59.351 --> 00:15:00.427 It was this: 00:15:00.517 --> 00:15:05.897 a round glass flask, shaped like a bladder, called a matula. 00:15:05.987 --> 00:15:10.560 The doctor held it to the light and read the water. 00:15:11.660 --> 00:15:18.927 In the seventh century, a Byzantine writer named Theophilus devoted a whole book to 00:15:19.015 --> 00:15:24.706 urine, and defined it, beautifully, as the filtrate of the blood. 00:15:24.794 --> 00:15:26.633 Remember that phrase. 00:15:26.720 --> 00:15:33.550 Medicine will take thirteen hundred years to find out how nearly right it was. 00:15:36.200 --> 00:15:44.062 From Kairouan to Salerno to Paris, scholars built a whole science on the flask. 00:15:44.161 --> 00:15:51.028 Charts set out the colours of urine in a wheel, about twenty of them, 00:15:51.128 --> 00:15:58.790 from crystal clear, through straw and gold and wine red, to green, and livid, 00:15:58.890 --> 00:15:59.885 and black. 00:15:59.984 --> 00:16:02.970 Black, as a rule, meant death. 00:16:05.620 --> 00:16:08.566 And the flask was a map of the body. 00:16:08.648 --> 00:16:12.903 The ring at the top of the liquid spoke of the head. 00:16:12.984 --> 00:16:15.439 The upper layer, of the chest. 00:16:15.521 --> 00:16:18.549 The middle, of the stomach and liver. 00:16:18.630 --> 00:16:24.522 The sediment, of the kidneys, the bladder, and the organs of generation. 00:16:24.604 --> 00:16:28.613 Often the physician never saw the patient at all. 00:16:28.695 --> 00:16:32.950 The water arrived in a basket, carried by a servant. 00:16:35.600 --> 00:16:41.915 Meanwhile, in Córdoba, around the year one thousand, the surgeon al-Zahrawi, 00:16:41.998 --> 00:16:48.644 known in Europe as Albucasis, drew some two hundred surgical instruments for his 00:16:48.728 --> 00:16:50.389 great encyclopaedia. 00:16:50.472 --> 00:16:51.386 Among them: 00:16:51.469 --> 00:16:58.116 a fine drill, turned gently against a stone stuck in the urethra until it broke; 00:16:58.199 --> 00:17:00.110 a long silver catheter; 00:17:00.193 --> 00:17:06.508 and a syringe for washing out the bladder, with three tiny holes at its tip. 00:17:06.591 --> 00:17:12.490 Translated into Latin, his book taught European surgeons for centuries. 00:17:15.140 --> 00:17:17.789 Not everyone trusted the flask. 00:17:17.875 --> 00:17:24.114 In the tenth century Isaac Israeli, author of a celebrated Book of Urine, 00:17:24.200 --> 00:17:30.268 warned against fools who prophesied from it without seeing the patient. 00:17:30.353 --> 00:17:33.430 By Shakespeare's day, it was a joke. 00:17:34.930 --> 00:17:39.620 [Falstaff] Sirrah, you giant, what says the doctor to my water? 00:17:41.120 --> 00:17:43.862 [Page] He said, sir, the water itself was a good healthy water; 00:17:43.911 --> 00:17:47.730 but, for the party that owed it, he might have more diseases than he knew for. 00:17:50.380 --> 00:17:54.554 In 1637 an English physician, Thomas Brian, 00:17:54.651 --> 00:17:58.728 published a book called The Pisse-Prophet. 00:17:58.825 --> 00:17:59.990 His verdict: 00:18:01.490 --> 00:18:07.020 [Brian] There is no certaine knowledge of any Disease to be gathered from the Urine alone. 00:18:08.520 --> 00:18:12.770 And elsewhere, borrowing a Latin tag: 00:18:14.270 --> 00:18:18.280 [Brian] The Urine is an Harlot, or a Lyer. 00:18:19.780 --> 00:18:21.885 It was also a confession. 00:18:21.969 --> 00:18:27.021 Brian admitted that he had played the pisse-prophet himself, 00:18:27.106 --> 00:18:32.242 quizzing the messenger and then pretending to read the glass, 00:18:32.326 --> 00:18:38.641 and that one lady had praised him as the cunningest doctor in all the town, 00:18:38.725 --> 00:18:44.030 because he had told her, by her water, that she was with child. 00:18:45.130 --> 00:18:50.301 Uroscopy ruled learned medicine for about a thousand years, 00:18:50.389 --> 00:18:55.384 and patients went on demanding it for two centuries more. 00:18:55.472 --> 00:18:59.679 And yet the flask was not wrong to be looked at. 00:18:59.766 --> 00:19:02.396 It had been looked at wrongly. 00:19:02.483 --> 00:19:08.180 What came next was to taste it, to boil it, and to take it apart. 00:19:16.430 --> 00:19:22.100 Uroscopists had always sniffed the urine, and some had tasted it. 00:19:22.187 --> 00:19:27.333 In the 1670s the English physician Thomas Willis tasted it, 00:19:27.421 --> 00:19:30.648 and wrote down exactly what he found. 00:19:30.735 --> 00:19:36.841 Of a nobleman who passed nearly a gallon and a half of water in a day, 00:19:36.928 --> 00:19:38.760 he wrote that it was: 00:19:40.260 --> 00:19:44.350 [Willis] Wonderfully sweet, as though Honey were mixt in it. 00:19:45.850 --> 00:19:53.294 A century later in Liverpool, Matthew Dobson evaporated such urine to a white cake 00:19:53.385 --> 00:19:57.106 that, he wrote, smelled like brown sugar. 00:19:57.197 --> 00:20:00.919 Then he tasted the patient's blood serum. 00:20:01.010 --> 00:20:05.912 It was sweetish too, though not so sweet as the urine. 00:20:06.003 --> 00:20:11.540 The sugar was in the blood before it ever reached the kidney. 00:20:12.640 --> 00:20:19.784 Diabetes, from the Greek for a siphon, had long meant only a great flow of water. 00:20:19.872 --> 00:20:23.488 Willis's taste picked out the sweet kind, 00:20:23.576 --> 00:20:30.632 and later in that century the Scottish physician William Cullen gave it a second 00:20:30.720 --> 00:20:31.161 name: 00:20:31.249 --> 00:20:38.040 diabetes mellitus, honeyed, to set it apart from a rarer kind whose urine was 00:20:38.128 --> 00:20:39.010 tasteless. 00:20:41.660 --> 00:20:44.949 Others had seen urine curdle with heat. 00:20:45.033 --> 00:20:48.154 In 1827, at Guy's Hospital in London, 00:20:48.238 --> 00:20:53.972 Richard Bright warmed a spoonful of a patient's urine over a candle, 00:20:54.057 --> 00:20:57.261 and watched it cloud before it boiled. 00:20:57.346 --> 00:21:01.984 Then he followed his patients to the post-mortem table: 00:21:02.068 --> 00:21:08.646 patients with dropsy, the old name for a body swollen with water, in the legs, 00:21:08.730 --> 00:21:10.670 the belly and the face. 00:21:12.170 --> 00:21:17.406 [Bright] I have never yet examined the body of a patient dying with dropsy, 00:21:17.486 --> 00:21:24.071 attended with coagulable urine, in whom some obvious derangement was not discovered 00:21:24.150 --> 00:21:25.340 in the kidneys. 00:21:26.840 --> 00:21:33.227 For a century afterwards, kidney disease with dropsy and protein in the urine was 00:21:33.306 --> 00:21:35.751 simply called Bright's disease. 00:21:35.830 --> 00:21:39.930 The Hippocratic bubbles had found their explanation. 00:21:42.580 --> 00:21:45.952 The stone, too, was put to the test. 00:21:46.046 --> 00:21:51.291 Physicians had long thought it earthy, a kind of gravel. 00:21:51.384 --> 00:21:58.128 In 1776 the Swedish chemist Scheele found in a bladder stone a new acid, 00:21:58.222 --> 00:22:00.844 which we now call uric acid. 00:22:00.938 --> 00:22:08.056 In 1810 William Wollaston described another stone, yellowish and glistening; 00:22:08.150 --> 00:22:12.927 the first had come from a child of five in Norwich. 00:22:13.021 --> 00:22:18.172 He named its substance cystic oxide, after the bladder. 00:22:18.266 --> 00:22:20.045 We call it cystine: 00:22:20.139 --> 00:22:27.070 one of the very first amino acids ever found, and it was found in a stone. 00:22:29.720 --> 00:22:36.050 In 1828, in Berlin, the young chemist Friedrich Wöhler made urea, 00:22:36.147 --> 00:22:44.035 the chief solid of urine, in a flask, from simple salts, with no kidney involved. 00:22:44.132 --> 00:22:50.170 He wrote to his old teacher in Stockholm, the great Berzelius: 00:22:51.670 --> 00:22:55.025 [Wohler] I cannot, so to speak, hold my chemical water, 00:22:55.098 --> 00:22:59.692 and must tell you that I can make urea without needing kidneys, 00:22:59.765 --> 00:23:03.120 or indeed any animal at all, be it man or dog. 00:23:04.620 --> 00:23:11.828 The textbooks will tell you that this one experiment killed the old belief in a 00:23:11.919 --> 00:23:13.014 vital force. 00:23:13.106 --> 00:23:14.109 It did not. 00:23:14.200 --> 00:23:17.211 That belief lingered for decades. 00:23:17.303 --> 00:23:19.310 But a door had opened. 00:23:21.960 --> 00:23:25.470 Which brings us back to Galen's question. 00:23:25.555 --> 00:23:28.209 How does the kidney make urine? 00:23:28.295 --> 00:23:32.489 In 1842 a young London anatomist, William Bowman, 00:23:32.575 --> 00:23:39.167 looked again at the tiny tufts of blood vessels that Malpighi had seen in the 00:23:39.252 --> 00:23:44.902 kidney, and showed that each sits in a cup that opens into a tube. 00:23:44.988 --> 00:23:48.070 The tuft, he thought, let out water; 00:23:48.155 --> 00:23:54.490 the living cells of the tube did the real work, secreting everything else. 00:23:55.590 --> 00:24:01.562 The very next year, Carl Ludwig in Germany proposed something colder. 00:24:01.649 --> 00:24:06.756 The tuft was a filter, driven by the pressure of the blood, 00:24:06.842 --> 00:24:11.343 and the tubes simply concentrated what came through. 00:24:11.430 --> 00:24:13.594 Filtration, or secretion. 00:24:13.681 --> 00:24:15.931 Physics, or living labour. 00:24:16.018 --> 00:24:20.692 Dyes injected into animals seemed to favour secretion; 00:24:20.778 --> 00:24:24.500 arguments from physics favoured filtration. 00:24:24.587 --> 00:24:27.443 The quarrel ran for eighty years. 00:24:27.530 --> 00:24:34.627 In 1917 Arthur Cushny argued for filtration and reabsorption, in a book he titled, 00:24:34.714 --> 00:24:38.349 of all things, The Secretion of the Urine. 00:24:38.436 --> 00:24:45.620 He called his account, rather boldly, "the modern view." But no one could prove it, 00:24:45.707 --> 00:24:51.160 because no one had ever sampled what came out of a single tuft. 00:24:53.810 --> 00:24:59.815 Then, in Philadelphia, Joseph Wearn and Alfred Newton Richards tried. 00:24:59.902 --> 00:25:05.993 They anaesthetised a frog, laid open its kidney under a blazing light, 00:25:06.080 --> 00:25:11.824 and guided a fine glass pipette into the cup around a single tuft. 00:25:11.911 --> 00:25:15.740 They drew out a droplet of the fluid inside. 00:25:16.840 --> 00:25:21.007 The droplet contained sugar, and it contained salt. 00:25:21.089 --> 00:25:26.809 The frog's bladder urine, taken at the same moment, contained neither. 00:25:26.891 --> 00:25:29.506 And the droplet held no protein. 00:25:29.588 --> 00:25:35.961 Here, it seemed, was the blood's fluid, filtered, with its proteins held back. 00:25:36.043 --> 00:25:42.090 Somewhere along the tubes, the sugar and salt were being taken back again. 00:25:43.190 --> 00:25:46.338 When they first reported it, in 1921, 00:25:46.423 --> 00:25:50.933 someone objected at once that a frog is not a mammal. 00:25:51.018 --> 00:25:54.761 Richards's reply, I am told, won an ovation. 00:25:54.846 --> 00:26:01.398 Their own colleague wrote that the result suggested, though it did not prove, 00:26:01.483 --> 00:26:02.419 filtration. 00:26:02.504 --> 00:26:05.482 The mammals came later, and agreed. 00:26:05.567 --> 00:26:12.714 Theophilus had called urine the filtrate of the blood thirteen hundred years before. 00:26:12.799 --> 00:26:16.628 Here it was, very nearly, in a glass pipette. 00:26:16.713 --> 00:26:20.882 And Bowman, I should add, was not entirely wrong: 00:26:20.967 --> 00:26:23.179 the tubes secrete as well. 00:26:23.264 --> 00:26:28.880 The best quarrels in science often end with both sides half right. 00:26:39.130 --> 00:26:43.627 Now back to the stone, and to those who cut for it. 00:26:43.715 --> 00:26:47.507 You must understand how common it once was. 00:26:47.595 --> 00:26:54.208 In parts of Europe, bladder stone was above all a disease of poor children, 00:26:54.296 --> 00:26:58.793 probably from a diet of little but bread and gruel. 00:26:58.882 --> 00:27:06.200 The hospital at Norwich operated on some fifteen hundred patients for stone between 00:27:06.288 --> 00:27:13.254 1772 and 1909, and kept every stone, labelled, with the patient's name and age. 00:27:13.342 --> 00:27:15.811 The collection ends in 1909. 00:27:15.900 --> 00:27:17.399 Nobody closed it. 00:27:17.487 --> 00:27:24.100 The disease had simply disappeared, and we are still not entirely sure why. 00:27:26.750 --> 00:27:32.175 A good method for the stone could feed a family for generations, 00:27:32.260 --> 00:27:35.396 and it was guarded as a trade secret. 00:27:35.481 --> 00:27:41.753 In France, the Colot family were stone-cutters for some eight generations. 00:27:41.838 --> 00:27:48.111 In Italy, around 1520, a surgeon called de Romanis devised a new approach, 00:27:48.196 --> 00:27:51.332 described by his pupil Mariano Santo: 00:27:51.417 --> 00:27:58.537 a grooved metal staff, passed down the urethra into the bladder, to guide the knife. 00:27:58.622 --> 00:28:04.640 It used so many instruments that it was called the "greater apparatus." 00:28:07.290 --> 00:28:11.542 In the middle of the sixteenth century, Pierre Franco, 00:28:11.621 --> 00:28:15.007 a barber-surgeon who worked in Switzerland, 00:28:15.086 --> 00:28:20.362 could not get a large stone out of a two-year-old child from below. 00:28:20.441 --> 00:28:23.591 The parents begged him to try something. 00:28:23.669 --> 00:28:27.686 So he did what the Hippocratic rule said was fatal: 00:28:27.764 --> 00:28:30.520 he cut into the bladder from above. 00:28:30.599 --> 00:28:31.859 The child lived. 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 00:28:38.238 --> 00:28:38.631 like. 00:28:38.710 --> 00:28:44.380 The "high operation" lay almost forgotten for a hundred and sixty years. 00:28:47.030 --> 00:28:50.573 In 1697 a strange figure arrived in Paris: 00:28:50.658 --> 00:28:57.154 Jacques Beaulieu, a stone-cutter dressed in a monk's habit of his own design, 00:28:57.238 --> 00:29:00.022 who called himself Frère Jacques. 00:29:00.107 --> 00:29:05.591 He cut at the side of the perineum, into the neck of the bladder. 00:29:05.675 --> 00:29:08.965 Paris let him operate in its hospitals. 00:29:09.050 --> 00:29:13.099 Of about sixty patients, about twenty-five died. 00:29:13.184 --> 00:29:16.643 The figures vary, but they were dreadful. 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 00:29:23.645 --> 00:29:24.320 another. 00:29:25.420 --> 00:29:27.508 You may be hearing a tune. 00:29:27.589 --> 00:29:33.854 It is often said that the nursery round "Frère Jacques" was written about him. 00:29:33.934 --> 00:29:35.782 Historians have looked. 00:29:35.862 --> 00:29:37.870 They found no connection. 00:29:37.951 --> 00:29:43.493 The melody first appears decades after his death, under another name. 00:29:43.573 --> 00:29:47.670 A thing repeated, as I said, is not a thing proven. 00:29:48.770 --> 00:29:50.446 But Jacques learned. 00:29:50.530 --> 00:29:57.484 He studied anatomy, adopted a grooved staff, and his later results were far better. 00:29:57.568 --> 00:30:02.176 In Amsterdam, a surgeon named Rau, who had watched him, 00:30:02.260 --> 00:30:09.047 perfected the side approach, and is said to have hidden his method from onlookers 00:30:09.131 --> 00:30:11.980 by keeping his thumb in the wound. 00:30:14.630 --> 00:30:21.826 In London, William Cheselden of St Thomas's Hospital made the side operation his 00:30:21.916 --> 00:30:22.276 own. 00:30:22.366 --> 00:30:23.175 Remember: 00:30:23.265 --> 00:30:25.514 there was no anaesthetic. 00:30:25.604 --> 00:30:27.043 Speed was mercy. 00:30:27.133 --> 00:30:33.520 One eyewitness reported an operation of his lasting fifty-four seconds. 00:30:36.170 --> 00:30:40.227 But what marks Cheselden out is not his speed. 00:30:40.315 --> 00:30:41.285 He counted. 00:30:41.373 --> 00:30:44.901 He published his results at St Thomas's: 00:30:44.989 --> 00:30:51.780 two hundred and thirteen patients, twenty deaths, and he set them out by age. 00:30:51.868 --> 00:30:57.247 Of a hundred and five children aged ten or under, three died. 00:30:57.336 --> 00:31:04.567 In Paris, by his reckoning, the old method was losing nearly two patients in five. 00:31:04.655 --> 00:31:11.799 His tables are among the earliest records of surgical results ever broken down by 00:31:11.887 --> 00:31:12.240 age. 00:31:12.328 --> 00:31:14.180 He also left us this: 00:31:15.680 --> 00:31:22.150 [Cheselden] No one ever endured more anxiety and sickness before an operation, 00:31:22.248 --> 00:31:28.130 yet from the time I began to operate, all uneasiness ceased; 00:31:28.228 --> 00:31:33.129 and if I have had better success than some others, 00:31:33.227 --> 00:31:36.854 I do not impute it to more knowledge, 00:31:36.952 --> 00:31:43.814 but to the happiness of a mind that was never ruffled or disconcerted, 00:31:43.912 --> 00:31:49.010 and a hand that never trembled during any operation. 00:31:53.160 --> 00:31:56.700 The patients have left us their voices too. 00:31:56.782 --> 00:32:03.203 Samuel Pepys, the diarist, was cut for the stone on the twenty-sixth of March, 00:32:03.286 --> 00:32:06.414 1658, at his cousin's house in London. 00:32:06.496 --> 00:32:10.530 He survived, and kept the anniversary as a feast. 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. 00:32:17.056 --> 00:32:18.773 Turner's in Salisbury Court. 00:32:18.834 --> 00:32:21.960 And did resolve while I live to keep it a festival. 00:32:23.460 --> 00:32:26.061 He had a case made for the stone. 00:32:26.140 --> 00:32:32.289 It cost him twenty-four shillings, which, he noted, was a great deal of money, 00:32:32.368 --> 00:32:35.285 but it was well done and pleased him. 00:32:35.364 --> 00:32:41.670 When he died, many years later, seven more stones were found in his left kidney. 00:32:44.320 --> 00:32:52.385 Across the Atlantic, in 1752, Benjamin Franklin's brother John was suffering from 00:32:52.484 --> 00:32:53.480 the stone. 00:32:53.580 --> 00:32:55.770 Franklin wrote to him: 00:32:57.270 --> 00:33:01.847 [Franklin] Reflecting yesterday on your Desire to have a flexible Catheter, 00:33:01.918 --> 00:33:06.280 a Thought struck into my Mind how one might possibly be made. 00:33:07.780 --> 00:33:13.291 He went straight to a silversmith, and sat by until it was finished, 00:33:13.372 --> 00:33:15.966 so that it might catch the post. 00:33:16.047 --> 00:33:20.342 It was a tube of silver wire wound in a tight spiral, 00:33:20.423 --> 00:33:24.394 supple enough to follow the turns of the passage. 00:33:24.475 --> 00:33:29.500 Franklin is often said to have invented the flexible catheter. 00:33:29.581 --> 00:33:30.473 He did not; 00:33:30.554 --> 00:33:35.579 an Italian had made one much like it some thirty years before. 00:33:35.660 --> 00:33:39.550 But I like to picture him in that shop, waiting. 00:33:47.800 --> 00:33:52.500 Remember Ammonius, who split the stone in the wound? 00:33:52.591 --> 00:33:57.652 In January 1824, in Paris, Jean Civiale went one better. 00:33:57.743 --> 00:34:04.341 He passed a straight steel instrument up the urethra of a living patient, 00:34:04.431 --> 00:34:11.843 opened three claws inside the bladder, seized the stone, and drilled it to pieces. 00:34:11.933 --> 00:34:13.199 No cut at all. 00:34:13.289 --> 00:34:18.170 Rivals crowded round him, among them Baron Heurteloup, 00:34:18.261 --> 00:34:25.130 whose instrument gripped the stone and was then struck with a little hammer. 00:34:27.780 --> 00:34:30.919 Then Civiale did something remarkable. 00:34:31.001 --> 00:34:37.774 He gathered the results of thousands of cutting operations reported across Europe, 00:34:37.856 --> 00:34:40.747 set them against his own crushings, 00:34:40.830 --> 00:34:45.124 and laid the numbers before the Academy of Sciences. 00:34:45.207 --> 00:34:49.337 After cutting, about one patient in five had died. 00:34:49.419 --> 00:34:52.310 After crushing, about one in forty. 00:34:53.410 --> 00:34:57.789 In 1835 the Academy appointed four men to judge: 00:34:57.881 --> 00:35:01.804 a chemist, a military surgeon, a physician, 00:35:01.895 --> 00:35:06.365 and the great mathematician Siméon-Denis Poisson. 00:35:06.457 --> 00:35:10.288 Large numbers, they agreed, were valuable. 00:35:10.380 --> 00:35:17.405 But these numbers had been gathered from many surgeons, chosen who knows how, 00:35:17.496 --> 00:35:19.777 and judged who knows how. 00:35:19.868 --> 00:35:23.700 They could not prove what Civiale claimed. 00:35:24.800 --> 00:35:31.018 And the physician among them, Double, objected to counting patients at all. 00:35:31.101 --> 00:35:33.837 To use statistics, he complained, 00:35:33.920 --> 00:35:38.065 one must first forget that a man is an individual, 00:35:38.148 --> 00:35:42.127 and treat him as a mere fraction of the species. 00:35:42.210 --> 00:35:48.096 Certainty of that kind, he said, belongs to astronomy, not to medicine. 00:35:48.179 --> 00:35:49.671 Poisson disagreed. 00:35:49.754 --> 00:35:54.314 It is a quarrel between the average and the individual, 00:35:54.397 --> 00:35:57.050 and I assure you it is not over. 00:35:59.700 --> 00:36:01.929 Crushing had its own dogma. 00:36:02.012 --> 00:36:07.379 The bladder, Civiale taught, could not bear instruments for long. 00:36:07.461 --> 00:36:10.434 A sitting should last a few minutes; 00:36:10.516 --> 00:36:14.232 the fragments were left to pass on their own, 00:36:14.314 --> 00:36:18.938 and a large stone might need dozens of painful sessions. 00:36:19.020 --> 00:36:21.002 Even emperors submitted. 00:36:21.085 --> 00:36:27.772 In January 1873 the exiled Napoleon the Third was twice operated upon in England, 00:36:27.855 --> 00:36:29.259 under chloroform. 00:36:29.341 --> 00:36:31.983 He died, of his failing kidneys, 00:36:32.066 --> 00:36:37.350 an hour and a quarter before the third sitting was due to begin. 00:36:40.000 --> 00:36:45.885 The man who broke that rule was a Boston surgeon, Henry Jacob Bigelow. 00:36:45.969 --> 00:36:52.527 In 1846 he had published the first report of operations performed under ether. 00:36:52.611 --> 00:36:59.253 Thirty-two years later he reasoned that a bladder under anaesthesia need not be 00:36:59.337 --> 00:37:00.010 hurried. 00:37:01.510 --> 00:37:06.675 [Bigelow] My own conviction is that it is better to protract the operation indefinitely in 00:37:06.740 --> 00:37:12.099 point of time, if thus the whole stone can be removed without serious injury to the 00:37:12.163 --> 00:37:12.680 bladder. 00:37:14.180 --> 00:37:18.018 He crushed the whole stone at one sitting, 00:37:18.109 --> 00:37:24.139 and washed every fragment out with a rubber bulb and a glass trap. 00:37:24.231 --> 00:37:29.713 His longest operation lasted three hours and three quarters. 00:37:29.804 --> 00:37:34.190 A rule half a century old fell in a single book. 00:37:36.840 --> 00:37:43.577 Anaesthesia, and soon Lister's antisepsis, opened the body to the surgeon. 00:37:43.669 --> 00:37:50.861 In Heidelberg in 1869 Gustav Simon faced a woman of forty-six, Margaretha Kleb, 00:37:50.952 --> 00:37:55.869 whose ureter had been injured in an earlier operation, 00:37:55.960 --> 00:37:59.693 so that urine leaked from her constantly. 00:37:59.784 --> 00:38:03.335 He had failed three times to repair it. 00:38:03.426 --> 00:38:06.977 The only cure was to remove the kidney. 00:38:07.068 --> 00:38:09.890 But can a person live with one? 00:38:10.990 --> 00:38:15.550 Simon first removed a kidney from each of thirty dogs, 00:38:15.635 --> 00:38:20.786 and saw the remaining kidney grow larger to take up the work. 00:38:20.870 --> 00:38:23.911 Then, on the second of August, 1869, 00:38:23.995 --> 00:38:28.471 he removed Margaretha Kleb's kidney in forty minutes. 00:38:28.555 --> 00:38:31.342 She was out of bed in four weeks. 00:38:31.427 --> 00:38:33.200 One kidney is enough. 00:38:41.450 --> 00:38:46.552 For most of history the inside of the living body stayed dark. 00:38:46.634 --> 00:38:51.160 Physicians guessed at it from symptoms, from the flask, 00:38:51.242 --> 00:38:55.521 and from the click of a metal sound against a stone. 00:38:55.603 --> 00:39:01.692 In the first years of the nineteenth century, a young doctor in Frankfurt, 00:39:01.774 --> 00:39:05.148 Philipp Bozzini, asked a simple question. 00:39:05.230 --> 00:39:06.300 Why not look? 00:39:07.400 --> 00:39:12.625 His "light conductor" was a vase about the height of a wine bottle. 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 00:39:19.097 --> 00:39:20.033 burned down. 00:39:20.111 --> 00:39:23.932 A concave mirror sent the light down one channel; 00:39:24.010 --> 00:39:30.170 the doctor's eye looked back up another, so that the glare would not blind him. 00:39:31.670 --> 00:39:36.077 [Bozzini] The usefulness of the light conductor is so general that it must have, 00:39:36.140 --> 00:39:41.240 directly or indirectly, the most significant influence on every part of medicine. 00:39:43.890 --> 00:39:47.295 Too poor to travel, he sent it to Vienna. 00:39:47.378 --> 00:39:52.112 At the army's medical academy they tried it on a cadaver, 00:39:52.195 --> 00:39:55.434 declared that it met every expectation, 00:39:55.517 --> 00:39:59.337 and built an improved model within two months. 00:39:59.420 --> 00:40:04.984 At the University faculty, their rivals, the verdict was different. 00:40:05.068 --> 00:40:09.220 As it was later recovered from the Viennese files: 00:40:10.720 --> 00:40:15.450 [Vienna faculty] It will always remain a mere toy. 00:40:16.950 --> 00:40:20.293 A biographer, writing long afterwards, 00:40:20.381 --> 00:40:25.396 says they mocked it as a magic lantern in the human body. 00:40:25.484 --> 00:40:28.740 It was not the light that killed him. 00:40:28.828 --> 00:40:35.515 In 1809 typhus swept Frankfurt, and Bozzini served as an epidemic physician. 00:40:35.602 --> 00:40:38.418 There was no cure, only nursing; 00:40:38.506 --> 00:40:43.169 forty-two of his patients are recorded as recovering. 00:40:43.257 --> 00:40:47.040 Then he caught the fever himself, and died. 00:40:47.128 --> 00:40:48.800 He was thirty-five. 00:40:51.450 --> 00:40:57.896 In Paris in 1826, Pierre Ségalas showed the Academy a lighted speculum for the 00:40:57.978 --> 00:40:58.639 urethra; 00:40:58.722 --> 00:41:04.589 and, as he later told the story, the physicist Fresnel, on his way out, 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 00:41:11.613 --> 00:41:12.192 mirror. 00:41:12.275 --> 00:41:15.911 In 1853 Antonin Desormeaux did exactly that. 00:41:15.993 --> 00:41:20.456 He burned alcohol and turpentine in a tall brass lamp, 00:41:20.538 --> 00:41:27.397 coined the word "endoscope," and looked into the urethra and bladder of the living. 00:41:27.480 --> 00:41:30.620 His colleagues were not all convinced. 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: 00:41:39.249 --> 00:41:42.427 We can see well with your instrument; 00:41:42.513 --> 00:41:45.090 but what is the use of seeing? 00:41:46.590 --> 00:41:52.489 Desormeaux considered the new electric light, and rejected it. 00:41:52.584 --> 00:41:54.963 Too cumbersome, he wrote; 00:41:55.058 --> 00:41:59.720 it would need an assistant, and double the price. 00:42:02.370 --> 00:42:08.316 The decisive step came from a young doctor in Dresden, Maximilian Nitze. 00:42:08.399 --> 00:42:13.188 The story goes that, cleaning a dusty microscope eyepiece, 00:42:13.271 --> 00:42:19.465 he saw through it a tiny upside-down image of the church across the street, 00:42:19.547 --> 00:42:25.824 and understood that a telescope could carry a picture out of a hollow organ. 00:42:25.906 --> 00:42:29.457 He put the light inside the bladder itself: 00:42:29.540 --> 00:42:36.064 a platinum wire, made white-hot by a current, cooled by a stream of iced water, 00:42:36.146 --> 00:42:39.780 at the tip of a slender tube full of lenses. 00:42:40.880 --> 00:42:45.164 Built with the Viennese instrument-maker Josef Leiter, 00:42:45.243 --> 00:42:50.716 it was shown on a living patient in Vienna on the ninth of May, 1879. 00:42:50.796 --> 00:42:54.683 The two soon quarrelled bitterly over the credit; 00:42:54.762 --> 00:42:59.759 history, diplomatically, gives the instrument both their names. 00:42:59.839 --> 00:43:02.695 Six months after that demonstration, 00:43:02.774 --> 00:43:06.978 Thomas Edison filed his patent for the electric lamp. 00:43:07.057 --> 00:43:13.166 By 1887 tiny bulbs glowed at the tips of cystoscopes in Vienna and in Berlin, 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 00:43:19.750 --> 00:43:22.050 section under the microscope. 00:43:24.700 --> 00:43:27.262 Now the urologist could steer. 00:43:27.348 --> 00:43:34.181 In Paris, around 1897, Joaquín Albarrán fitted a tiny hinged lever at the tip of 00:43:34.266 --> 00:43:40.160 the cystoscope, to lift a fine catheter into the opening of a ureter, 00:43:40.245 --> 00:43:44.345 and so draw the urine of each kidney separately. 00:43:44.430 --> 00:43:51.263 And in 1912, at Johns Hopkins, Hugh Hampton Young slid a child's cystoscope up a 00:43:51.349 --> 00:43:55.278 ureter enormously widened by a blockage below. 00:43:55.363 --> 00:43:59.805 It is usually counted as the first look up a ureter, 00:43:59.890 --> 00:44:03.990 though he did not report it for seventeen years. 00:44:06.640 --> 00:44:09.862 Then came a different kind of light. 00:44:09.951 --> 00:44:16.484 In November 1895 Wilhelm Röntgen discovered rays that pass through flesh. 00:44:16.574 --> 00:44:23.733 Within months John Macintyre in Glasgow had photographed a stone inside a living 00:44:23.823 --> 00:44:24.449 kidney. 00:44:24.539 --> 00:44:31.430 The great kidney surgeon Henry Morris welcomed the rays, but added a warning. 00:44:31.520 --> 00:44:35.994 If they could show only whether a stone was there, 00:44:36.084 --> 00:44:40.290 and not the other diseases that mimic it, then: 00:44:41.790 --> 00:44:46.916 [Morris] It will, I fear, be the means of putting back renal surgery, 00:44:47.001 --> 00:44:53.665 by deterring many patients from submitting to surgical explorations who can be 00:44:53.750 --> 00:44:57.680 cured by no other treatment than an operation. 00:44:59.180 --> 00:45:03.769 Morris had made his name by opening the kidney itself: 00:45:03.854 --> 00:45:08.528 in 1880 he cut a stone from a kidney otherwise healthy, 00:45:08.613 --> 00:45:11.332 the first operation of its kind. 00:45:11.417 --> 00:45:17.876 To such a surgeon, the knife and the finger were still the surest diagnosis, 00:45:17.961 --> 00:45:21.190 and a clear plate a dangerous comfort. 00:45:23.840 --> 00:45:30.461 In 1906, surgeons learned to fill the kidney with a silver solution through a 00:45:30.547 --> 00:45:34.245 ureteric catheter and photograph its shape. 00:45:34.331 --> 00:45:37.685 But that meant a cystoscopy every time. 00:45:37.771 --> 00:45:44.908 The answer came in 1929, in Hamburg and Berlin, from a young American, Moses Swick. 00:45:44.994 --> 00:45:51.615 Testing compounds of iodine that chemists had made for quite another purpose, 00:45:51.701 --> 00:45:55.915 he found one that the kidneys passed out quickly. 00:45:56.001 --> 00:45:59.612 Injected into a vein, it drew the kidneys, 00:45:59.698 --> 00:46:04.170 the ureters and the bladder in white upon the plate. 00:46:05.270 --> 00:46:10.880 The professor in whose clinic he worked presented the discovery to the world. 00:46:13.530 --> 00:46:19.619 And with the light of the cystoscope and the X-ray came a flourishing of modern 00:46:19.696 --> 00:46:20.313 urology: 00:46:20.390 --> 00:46:26.633 a field that already looks far more like the one we know today than like anything 00:46:26.710 --> 00:46:28.020 that came before. 00:46:30.120 --> 00:46:34.588 Young Swick's part, though, was overlooked for decades; 00:46:34.670 --> 00:46:37.919 he received a medal for it only in 1966. 00:46:38.000 --> 00:46:44.256 And that the professor who presented his work was himself, a few years later, 00:46:44.337 --> 00:46:49.537 driven from his posts in Germany because of his Jewish ancestry. 00:46:49.618 --> 00:46:54.330 History rarely arranges its heroes and villains so neatly. 00:46:57.980 --> 00:47:04.685 In 1954 the British physicist Harold Hopkins, with a young research student, 00:47:04.774 --> 00:47:12.097 Narinder Kapany, showed that an ordered bundle of glass fibres could carry an image 00:47:12.185 --> 00:47:13.332 round a bend. 00:47:13.420 --> 00:47:17.302 And then he turned the telescope inside out. 00:47:17.390 --> 00:47:23.919 The old cystoscope was a tube of air with a few thin lenses held in rings. 00:47:24.008 --> 00:47:28.243 Hopkins filled the tube with long rods of glass, 00:47:28.331 --> 00:47:32.301 and let thin gaps of air serve as the lenses. 00:47:32.389 --> 00:47:37.771 More light could pass, more cleanly, through a narrower tube: 00:47:37.860 --> 00:47:41.830 as much as eighty times more, by one account. 00:47:42.930 --> 00:47:46.107 British makers declined to build it. 00:47:46.195 --> 00:47:50.165 A German firm in Tuttlingen, Karl Storz, did. 00:47:50.254 --> 00:47:53.254 From 1967 the rod-lens cystoscope, 00:47:53.342 --> 00:47:58.107 lit through glass fibres from a lamp outside the body, 00:47:58.195 --> 00:48:01.107 became the eye of modern urology. 00:48:01.195 --> 00:48:07.460 After eighty years inside the bladder, the light had gone back outside, 00:48:07.548 --> 00:48:10.460 where Bozzini had put his candle. 00:48:21.210 --> 00:48:24.685 Below the bladder, wrapped around the urethra, 00:48:24.761 --> 00:48:30.804 lies a gland whose name comes from a Greek word meaning "one who stands before." 00:48:30.880 --> 00:48:33.751 The Greeks are often given the credit, 00:48:33.826 --> 00:48:38.963 but the anatomists of Alexandria seem to have used a different word, 00:48:39.039 --> 00:48:41.608 and the name was fixed much later. 00:48:41.683 --> 00:48:45.914 The gland was first plainly described in Venice in 1536, 00:48:45.989 --> 00:48:48.860 and drawn by Vesalius two years later. 00:48:51.510 --> 00:48:55.677 Anatomists have always compared it to food: 00:48:55.774 --> 00:49:02.654 a pair of kernels, a walnut, a small grape, and, when enlarged, a pear. 00:49:02.751 --> 00:49:08.371 Later surgeons spoke of chestnuts, oranges, even coconuts. 00:49:08.468 --> 00:49:16.026 For in older men the prostate grows, and as it grows it can close the passage. 00:49:16.123 --> 00:49:21.840 For centuries, the remedy was the catheter, often for life. 00:49:24.490 --> 00:49:27.640 In 1893 the Philadelphia surgeon J. 00:49:27.730 --> 00:49:34.840 William White reasoned that if removing the ovaries could shrink growths of the 00:49:34.930 --> 00:49:39.610 womb, removing the testes might shrink the prostate. 00:49:39.700 --> 00:49:41.950 In castrated dogs it did. 00:49:42.040 --> 00:49:49.330 Surgeons took up the idea, and by 1895 White could report on a hundred and eleven 00:49:49.420 --> 00:49:50.680 castrated men. 00:49:50.770 --> 00:49:53.380 In most, the prostate shrank. 00:49:53.470 --> 00:49:58.690 Nearly one in five died, many of them already gravely ill. 00:49:58.780 --> 00:50:01.570 The fashion was soon abandoned. 00:50:01.660 --> 00:50:03.370 Remember it anyway. 00:50:03.460 --> 00:50:09.580 White was right about the biology, and that will matter in a moment. 00:50:12.230 --> 00:50:16.195 The surgeons turned to removing the gland itself. 00:50:16.276 --> 00:50:22.993 In Leeds in 1887, Arthur McGill was operating for a bladder stone when he noticed a 00:50:23.074 --> 00:50:27.283 lump at the neck of the bladder and twisted it free. 00:50:27.364 --> 00:50:30.439 It came away, it is said, in his hand. 00:50:30.520 --> 00:50:35.376 Two years later he showed a meeting of doctors his patients, 00:50:35.456 --> 00:50:38.613 each holding his own prostate in a jar. 00:50:38.694 --> 00:50:45.087 Eugene Fuller of New York described shelling out the enlarged gland through the 00:50:45.168 --> 00:50:47.029 opened bladder in 1895. 00:50:47.110 --> 00:50:51.966 Peter Freyer of London performed the same operation in 1900, 00:50:52.047 --> 00:50:57.307 called it total removal of the prostate, published it as his own, 00:50:57.388 --> 00:51:00.625 performed it more than a thousand times, 00:51:00.706 --> 00:51:05.400 and caused a great deal of anger in New York and in Leeds. 00:51:08.050 --> 00:51:13.291 Surgeons had already tried to reach the gland through the urethra: 00:51:13.371 --> 00:51:18.056 blind, with an electrically heated blade, in Pavia in 1874, 00:51:18.136 --> 00:51:20.995 and with Hugh Young's punch in 1909. 00:51:21.074 --> 00:51:24.489 The method that lasted needed three things. 00:51:24.568 --> 00:51:31.080 In 1926 Maximilian Stern of New York made a wire loop that cut with high-frequency 00:51:31.160 --> 00:51:31.795 current. 00:51:31.874 --> 00:51:36.798 Theodore Davis, an electrical engineer before he was a doctor, 00:51:36.877 --> 00:51:43.389 helped build a generator that could cut with one current and seal bleeding vessels 00:51:43.469 --> 00:51:46.884 with another, at the press of a foot pedal. 00:51:46.963 --> 00:51:50.616 And in 1931 Joseph McCarthy put loop, current, 00:51:50.695 --> 00:51:54.507 and a good lens together in an insulated sheath. 00:51:54.587 --> 00:51:56.254 Three keys, one lock. 00:51:56.334 --> 00:52:02.846 The transurethral resection of the prostate remained the standard operation for an 00:52:02.925 --> 00:52:06.340 enlarged gland for the rest of the century. 00:52:08.990 --> 00:52:13.139 In Chicago, Charles Huggins was collecting drops. 00:52:13.224 --> 00:52:17.628 He had found a way to isolate the prostate of a dog, 00:52:17.712 --> 00:52:23.979 so that its secretion could be gathered alone and measured, day after day, 00:52:24.063 --> 00:52:24.995 for months. 00:52:25.080 --> 00:52:30.669 Remove the testes, and the secretion stopped and the gland shrank. 00:52:30.753 --> 00:52:34.056 Give the male hormone, and it returned. 00:52:34.141 --> 00:52:38.036 Give the female hormone, and it stopped again. 00:52:38.121 --> 00:52:41.000 White's biology, measured at last. 00:52:42.100 --> 00:52:44.327 Then a stroke of fortune. 00:52:44.416 --> 00:52:48.782 Some of the old dogs had tumours of the prostate. 00:52:48.871 --> 00:52:55.999 The dog, Huggins said later, is the only laboratory animal in which such tumours 00:52:56.088 --> 00:52:56.622 occur. 00:52:56.711 --> 00:52:59.206 So he asked a bold question. 00:52:59.295 --> 00:53:05.710 If the gland depends on male hormone, might its cancer depend on it too? 00:53:08.360 --> 00:53:13.112 He needed a number to measure it by, and in New York, 00:53:13.202 --> 00:53:17.596 Alexander and Ethel Gutman had just supplied one: 00:53:17.685 --> 00:53:25.038 an enzyme, acid phosphatase, that rose in the blood when prostate cancer spread to 00:53:25.128 --> 00:53:26.024 the bones. 00:53:26.114 --> 00:53:31.853 In 1941 Huggins and Clarence Hodges castrated men with advanced, 00:53:31.942 --> 00:53:36.246 painful prostate cancer, or gave them oestrogen. 00:53:36.336 --> 00:53:37.771 The enzyme fell. 00:53:37.860 --> 00:53:39.205 The pain eased. 00:53:39.295 --> 00:53:43.330 When male hormone was given instead, it rose. 00:53:44.430 --> 00:53:51.062 A spreading cancer, it turned out, need not be master of its own growth. 00:53:51.154 --> 00:53:55.759 Of the first twenty-one men treated by castration, 00:53:55.851 --> 00:53:59.996 four were alive more than twelve years later. 00:54:00.088 --> 00:54:03.680 Huggins shared the Nobel Prize in 1966. 00:54:04.780 --> 00:54:08.184 From that work also grew a further fear: 00:54:08.269 --> 00:54:13.629 that giving testosterone to any man might feed a hidden cancer. 00:54:13.714 --> 00:54:18.820 For some sixty years doctors were reluctant to prescribe it. 00:54:18.905 --> 00:54:25.712 Some now argue that the evidence for that particular fear came down, in the end, 00:54:25.797 --> 00:54:31.158 to a single untreated man given testosterone for eighteen days. 00:54:31.243 --> 00:54:33.030 The argument goes on. 00:54:35.680 --> 00:54:42.776 Removing the whole prostate for cancer was, in those years, a brutal operation. 00:54:42.865 --> 00:54:47.985 It bled terribly, and almost every man was left impotent. 00:54:48.075 --> 00:54:54.811 Surgeons believed that the nerves of erection ran through the gland itself, 00:54:54.901 --> 00:54:57.146 so nothing could be done. 00:54:57.236 --> 00:55:03.883 Then, in 1977, a patient of Patrick Walsh at Johns Hopkins mentioned that, 00:55:03.973 --> 00:55:08.104 after the operation, his potency had returned. 00:55:08.194 --> 00:55:10.170 Walsh began to wonder. 00:55:11.270 --> 00:55:18.906 In February 1981, in Leiden, he sat with a retired Dutch urologist, Pieter Donker, 00:55:19.000 --> 00:55:24.680 who was tracing the nerves of the bladder under a microscope, 00:55:24.773 --> 00:55:32.131 in the body of a stillborn infant, where such fine nerves are easier to follow. 00:55:32.224 --> 00:55:36.880 Walsh asked him where the nerves to the penis ran. 00:55:38.380 --> 00:55:39.590 [Donker] I've never looked. 00:55:41.090 --> 00:55:47.465 Three hours later they had found them, running not through the prostate, 00:55:47.553 --> 00:55:50.121 but alongside it, outside it. 00:55:50.209 --> 00:55:53.308 On the twenty-sixth of April, 1982, 00:55:53.396 --> 00:55:58.620 Walsh performed the first operation designed to spare them. 00:55:59.720 --> 00:56:04.548 Back at Johns Hopkins, Walsh's resident, Herbert Lepor, 00:56:04.636 --> 00:56:08.849 traced the same nerves through the adult pelvis, 00:56:08.937 --> 00:56:15.697 and in 1985 they published a precise map of their course beside the prostate. 00:56:15.784 --> 00:56:18.330 Surgeons still operate by it. 00:56:20.980 --> 00:56:22.926 Then came a blood test. 00:56:23.010 --> 00:56:29.524 Prostate-specific antigen, a protein made by the gland, was proposed in 1987, 00:56:29.609 --> 00:56:33.331 in a landmark paper, as a marker for cancer. 00:56:33.416 --> 00:56:35.615 Read that paper carefully. 00:56:35.700 --> 00:56:40.268 It found the protein rose with the size of the cancer, 00:56:40.353 --> 00:56:43.821 and vanished after the gland was removed. 00:56:43.906 --> 00:56:50.082 But it also found the protein raised in most men with simple enlargement, 00:56:50.166 --> 00:56:56.257 and concluded, in its authors' words, that "neither marker is specific": 00:56:56.342 --> 00:57:00.910 neither the new antigen, nor the old acid phosphatase. 00:57:02.010 --> 00:57:04.010 Screening spread anyway. 00:57:04.093 --> 00:57:08.093 In 2009, two great trials reported side by side. 00:57:08.176 --> 00:57:12.176 A European one found that screening saved lives. 00:57:12.259 --> 00:57:15.426 An American one found that it did not, 00:57:15.509 --> 00:57:22.258 though so many of its unscreened men had been tested anyway that it was comparing 00:57:22.342 --> 00:57:24.841 screening with less screening. 00:57:24.925 --> 00:57:31.091 American advisers recommended against the test in 2012, and then, in 2018, 00:57:31.174 --> 00:57:34.174 for men of fifty-five to sixty-nine, 00:57:34.257 --> 00:57:38.257 for a conversation between a man and his doctor. 00:57:38.340 --> 00:57:41.340 That conversation is still going on. 00:57:49.590 --> 00:57:51.692 Some revolutions are small. 00:57:51.770 --> 00:57:55.662 Around 1930 an American urologist, Frederic Foley, 00:57:55.740 --> 00:58:00.955 designed a soft rubber catheter with a little balloon near its tip, 00:58:01.033 --> 00:58:07.105 inflated inside the bladder, at first to stop bleeding after prostate surgery, 00:58:07.182 --> 00:58:10.374 and to keep the catheter where it is put. 00:58:10.452 --> 00:58:16.212 It may be the most used urological device on earth, and it bears his name. 00:58:16.290 --> 00:58:20.182 The patent, after a dispute, went to someone else: 00:58:20.260 --> 00:58:23.451 Paul Raiche, of the Davol Rubber Company. 00:58:23.529 --> 00:58:27.577 Foley won it on appeal, Raiche won it back in court, 00:58:27.655 --> 00:58:31.080 and the name on the catheter stayed Foley's. 00:58:33.730 --> 00:58:37.585 On the twenty-third of December, 1954, in Boston, 00:58:37.664 --> 00:58:41.126 Richard Herrick was dying of kidney failure. 00:58:41.205 --> 00:58:45.060 His identical twin, Ronald, offered him a kidney. 00:58:45.139 --> 00:58:51.669 The surgeons first proved the twins identical by grafting a patch of skin from each 00:58:51.748 --> 00:58:52.928 onto the other. 00:58:53.007 --> 00:58:58.043 The urologist Hartwell Harrison removed Ronald's healthy kidney, 00:58:58.121 --> 00:59:01.190 and Joseph Murray placed it in Richard. 00:59:01.269 --> 00:59:05.360 It worked at once, and it went on working for years: 00:59:05.439 --> 00:59:11.104 the first transplant of an organ to succeed for years rather than weeks. 00:59:11.183 --> 00:59:17.084 It also meant putting a healthy man under the knife for his brother's sake, 00:59:17.162 --> 00:59:22.591 and before they agreed, the surgeons consulted physicians and clergy. 00:59:22.670 --> 00:59:25.660 Murray later received the Nobel Prize. 00:59:28.310 --> 00:59:29.469 And the stone? 00:59:29.551 --> 00:59:32.365 It met its strangest enemy of all. 00:59:32.448 --> 00:59:39.151 Engineers at the German aircraft firm Dornier were studying how raindrops pit the 00:59:39.233 --> 00:59:43.454 skin of an aircraft flying near the speed of sound: 00:59:43.536 --> 00:59:47.260 each drop drives a shock wave into the metal. 00:59:47.343 --> 00:59:54.046 An engineer who touched a target as a shock wave struck it felt something like an 00:59:54.129 --> 00:59:57.604 electric shock, yet his skin was unharmed. 00:59:57.687 --> 01:00:01.080 The wave had passed straight through him. 01:00:03.730 --> 01:00:06.691 Now, here is the beautiful part. 01:00:06.783 --> 01:00:08.264 Take an ellipse. 01:00:08.356 --> 01:00:14.556 A wave that starts at one focus, and reflects from the curved wall, 01:00:14.649 --> 01:00:17.147 gathers again at the other. 01:00:17.239 --> 01:00:21.218 Put an underwater spark at the first focus. 01:00:21.311 --> 01:00:25.475 Put the patient's kidney stone at the second. 01:00:25.567 --> 01:00:32.692 Doctors and engineers in Munich tested the idea on human stones placed in the 01:00:32.784 --> 01:00:34.265 kidneys of dogs. 01:00:34.357 --> 01:00:40.557 On the seventh of February, 1980, they treated their first patient, 01:00:40.649 --> 01:00:46.479 lying in a bath of water, with crossed X-ray beams to take aim. 01:00:46.571 --> 01:00:48.607 The stone broke apart. 01:00:48.700 --> 01:00:50.180 No knife at all. 01:00:55.330 --> 01:01:01.487 In the same years, surgeons were learning to reach stones through a small puncture 01:01:01.562 --> 01:01:05.917 in the back, or with fine telescopes passed up the ureter, 01:01:05.992 --> 01:01:09.746 and soon to break them with pulses of laser light. 01:01:09.821 --> 01:01:12.900 Ammonius would have understood perfectly. 01:01:15.550 --> 01:01:18.843 The abdomen, too, was opened less and less. 01:01:18.920 --> 01:01:23.975 In 1990, in St Louis, Ralph Clayman removed the whole kidney of an 01:01:24.051 --> 01:01:27.957 eighty-five-year-old woman through small punctures, 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 01:01:34.314 --> 01:01:36.765 opening about a centimetre wide. 01:01:36.841 --> 01:01:42.739 The first such removals of the prostate took more than nine hours on average, 01:01:42.815 --> 01:01:48.866 and their own surgeons concluded the method had no advantage over open surgery. 01:01:48.942 --> 01:01:50.474 Then came the robot. 01:01:50.550 --> 01:01:56.907 In the year 2000, in Frankfurt, surgeons removed a prostate using a robotic system: 01:01:56.984 --> 01:02:02.039 the surgeon at a console, the instruments held by mechanical arms. 01:02:02.115 --> 01:02:06.327 Soon afterwards, at the Henry Ford Hospital in Detroit, 01:02:06.404 --> 01:02:12.148 the city of the assembly line, Mani Menon built a program around the robot, 01:02:12.225 --> 01:02:16.743 and his team refined the operation over thousands of cases. 01:02:16.820 --> 01:02:19.960 Their method carried it around the world. 01:02:21.060 --> 01:02:26.319 Robotic surgery spread faster than good evidence could follow it, 01:02:26.400 --> 01:02:31.578 and few surgical instruments have since been studied so closely. 01:02:31.659 --> 01:02:36.351 Head-to-head trials have not shown that it cures more men, 01:02:36.432 --> 01:02:40.882 or restores more function, than a skilled open surgeon. 01:02:40.963 --> 01:02:47.678 But it bleeds far less, and it lets surgeons attempt operations few had envisioned. 01:02:47.759 --> 01:02:52.856 In many countries a bloody open operation became a robotic one. 01:02:52.937 --> 01:02:58.034 In 2018 a single-port robot, working through one small opening, 01:02:58.115 --> 01:03:01.837 was cleared for urological surgery in America. 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. 01:03:19.140 --> 01:03:22.584 Let me end where we began, with the flask. 01:03:22.666 --> 01:03:28.817 For most of the twentieth century, students were taught that healthy urine, 01:03:28.899 --> 01:03:31.441 inside the bladder, is sterile. 01:03:31.523 --> 01:03:33.656 It was never quite proven. 01:03:33.738 --> 01:03:37.100 In the 1950s Edward Kass set a threshold, 01:03:37.182 --> 01:03:41.036 a hundred thousand bacteria in each millilitre, 01:03:41.118 --> 01:03:44.563 to tell infection from mere contamination. 01:03:44.645 --> 01:03:48.417 Ordinary cultures, in ordinary air, for a day, 01:03:48.499 --> 01:03:51.780 grew nothing from most healthy bladders, 01:03:51.862 --> 01:03:55.470 and nothing was taken to mean nothing there. 01:03:56.570 --> 01:04:01.663 In 2012 and 2014, investigators near Chicago looked again. 01:04:01.751 --> 01:04:07.810 They took urine straight from the bladder, by catheter and by needle; 01:04:07.898 --> 01:04:11.147 they searched it for bacterial genes; 01:04:11.235 --> 01:04:18.085 and they cultured a hundred times more of it, in many atmospheres, for longer. 01:04:18.172 --> 01:04:22.212 Bacteria grew from four samples in every five, 01:04:22.300 --> 01:04:26.778 taken from women with and without bladder symptoms, 01:04:26.866 --> 01:04:33.979 and nearly all of those had been reported, by the routine method, as "no growth". 01:04:34.067 --> 01:04:37.228 The bladder has its own inhabitants. 01:04:37.316 --> 01:04:41.180 We are only beginning to learn what they do. 01:04:43.830 --> 01:04:45.987 And the stone in the jar? 01:04:46.073 --> 01:04:52.976 It sat in the museum of the Royal College of Surgeons in London for forty years. 01:04:53.062 --> 01:04:57.549 In May 1941, in the Blitz, bombs struck the College, 01:04:57.635 --> 01:05:02.036 and more than half of its specimens were destroyed. 01:05:02.122 --> 01:05:06.091 The stone once called the oldest in the world, 01:05:06.177 --> 01:05:11.699 which had lain more than five thousand years in the desert, was, 01:05:11.785 --> 01:05:17.480 in the words of a later surgeon, crushed and completely dispersed. 01:05:23.130 --> 01:05:26.436 We still do not fully know why stones form. 01:05:26.513 --> 01:05:31.972 At least half of those who pass one will form another within ten years. 01:05:32.049 --> 01:05:37.200 We do not fully know why the prostate begins to grow in middle age, 01:05:37.277 --> 01:05:41.660 or which of its cancers will matter and which will sleep. 01:05:42.760 --> 01:05:46.700 Every age in this story believed it saw clearly: 01:05:46.782 --> 01:05:50.147 the uroscopist with his wheel of colours, 01:05:50.229 --> 01:05:54.005 the surgeon who would not cut above the pubis, 01:05:54.087 --> 01:05:57.370 the faculty that called the light a toy. 01:05:57.452 --> 01:06:02.706 Somewhere, in what we are sure of today, there is another flask, 01:06:02.788 --> 01:06:05.250 waiting to be looked at again. 01:06:07.850 --> 01:06:10.620 So look again.