Samuel Natelson lecture to the Ohio Valley Section of the American Association for Clinical Chemistry
- 1992
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Transcript
00:00:01 25 years ago, actually a little bit less, I arrived at Michael Reeves Hospital after a brilliant post-doctoral fellowship, learning physical biochemistry and realizing that I was not cut out to be a physical biochemist.
00:00:19 So I took a job at Michael Reeves Hospital doing biochemical research with a nephrologist by the name of Victor Pollack.
00:00:26 At that time, Dr. Natelson was two floors up. He said to me, Pesce, what do you do? I said, why do you do research? He said, the grants are going to run out one day. You're going to have to earn an honest living.
00:00:39 So I said, what do I do?
00:00:43 25 years later, you're still waiting.
00:00:45 I'm still waiting for an honest living. But he said, become a clinical chemist. He said he would teach me clinical chemistry if I spent an hour a day with him.
00:00:52 So I did that for six years, and lo and behold, I became a clinical chemist.
00:00:56 I forgot to say that I sprinkled the holy water on him, too.
00:01:00 That's right, he does. He sprinkles water on people and makes them clinical chemists. This is all part of the ritual.
00:01:06 Which, to some extent, I sprinkled water on Brian Collins when he first came into the laboratory. I haven't sprinkled any water on chemists.
00:01:13 So anyhow, that makes him a clinical chemist.
00:01:17 Dr. Nadelson was trained as an organic chemist.
00:01:21 Graduated in the middle of the Depression.
00:01:23 When he got his Ph.D., they said, Nadelson, congratulations, you're unemployed.
00:01:27 At which point, he taught high school.
00:01:32 He positioned himself with a research company in the 1930s.
00:01:40 He started his own business, but he's about as poor a businessman as I am.
00:01:44 He's never done well in business ventures.
00:01:47 Then he went off to, but he did make enough in the Second World War to retire after he taught in Rockford, Illinois.
00:01:52 And then, this is basically the story where he is going to start to tell you about what he did in Rockford, Illinois.
00:01:59 Which was the beginnings of pediatric clinical chemistry in the United States.
00:02:02 Thank you, Dr. Nadelson.
00:02:04 Thank you.
00:02:05 I want to thank Dr. Pesci.
00:02:09 Because I have forgotten about this material, and I realized it was time to recall it.
00:02:15 And you'll see when I'm finished why I say that.
00:02:19 I was, you got one part right.
00:02:23 In 1931, I got my unemployment certificate.
00:02:27 It said Ph.D., New York University.
00:02:29 But that's what it was.
00:02:30 It was an unemployment certificate.
00:02:32 It meant that I ceased to be a teaching fellow, which I had been employed since 1928.
00:02:38 And that I had to go look for a job.
00:02:40 So I went to the New York testing labs.
00:02:42 They had no room.
00:02:44 And I became a consultant chemist in the industry.
00:02:47 They gave me space, because they had no business.
00:02:50 And they said, go find a business.
00:02:53 Well, one of my clients was a person who wanted a plastic with high electrical resistance.
00:02:59 So I made styrene resins for him.
00:03:02 And I have a letter home which says, there is no future for styrene resins.
00:03:08 Because of the pressure of cold flows.
00:03:11 On the other hand, I published a death war in the industrial engineering chemistry.
00:03:17 And in 1950, I received an award for the ACS as the most significant paper in the first 50 years.
00:03:24 So you can see I was a pretty well-known organic chemist.
00:03:28 And along came a man by the name of Benjamin Cramer.
00:03:31 Benjamin Cramer was an interesting person, because he had a master's degree from the University of Indiana in chemistry.
00:03:40 And he was appointed the first clinical chemist.
00:03:43 They didn't call him clinical chemist.
00:03:45 At Johns Hopkins University to run the laboratory.
00:03:49 And what was the laboratory doing mostly?
00:03:51 Looking for methods for doing calcium regeneration.
00:03:54 Because your floors were loaded with kids with the English disease.
00:03:59 The English disease, the English conchite, was rickets.
00:04:05 And I lost two of my brothers in looking up their death certificates.
00:04:10 The age of two, apparently, died of rickets.
00:04:15 It says English disease on the death certificate.
00:04:20 When Benjamin Cramer came into my laboratory, he had a problem.
00:04:24 He developed a technique of giving strontium to these rickety children.
00:04:30 That decalcified them.
00:04:32 Then he straightened out their bones, and then he gave them calcium.
00:04:36 The only trouble was, he couldn't get the calcium into them.
00:04:39 He had to give it intramuscularly or intermediately using calcium glucate.
00:04:45 Calcium carbonate wouldn't dissolve.
00:04:47 It wouldn't go into them.
00:04:48 Calcium phosphate wouldn't go into them.
00:04:50 And the calcium, and several others.
00:04:53 In the meantime, I worked out a method for doing strontium and calcium in the same serum.
00:05:01 He was the famous Cramer-Tisdall method for calcium.
00:05:05 Tisdall was also a chemist.
00:05:07 Which later on became the Clark-Collip method.
00:05:10 The modification that Clark-Collip was,
00:05:13 Cramer used one cc of serum.
00:05:15 Clark-Collip used two cc of serum.
00:05:17 That was the modification.
00:05:20 But the interesting thing was, Cramer showed me a letter which said,
00:05:26 this author proposes to analyze one cc of serum for calcium.
00:05:34 There's no way in which you can possibly do that.
00:05:37 And their set of papers should be rejected.
00:05:39 So he framed that and hunkered it up on his wall.
00:05:41 And, of course, that's why he came to me.
00:05:44 Because he had heard that I had got my Ph.D. with a student at Pratt Hills
00:05:49 who had taught me microchemistry.
00:05:51 And I had published several papers on microchemical organic analysis.
00:05:55 And that's how he came to recommend it to me.
00:06:00 And finally he offered me space at the Jewish Hospital in Brooklyn, New York.
00:06:04 Gave me 5,000 square feet.
00:06:06 Which I did my consulting work without pay from him.
00:06:09 And I was consultant to the Department of Pediatrics.
00:06:12 And my first job was to find a way to get calcium into these kids.
00:06:17 And I had a client for whom I had made a tenosine triphosphate.
00:06:24 He sold it under the name of MYBDEN, M-Y-B-D-E-N.
00:06:28 He sold it as a proprietary for pecking people up.
00:06:32 And it's an interesting report because when I was at Rockford,
00:06:36 I had a man on IV fluids for 54 days.
00:06:39 And he wouldn't wake up.
00:06:41 And I started shooting him with MYBDEN.
00:06:44 Because I measured his red cell ATP level.
00:06:47 It was very low.
00:06:48 I raised his ATP level and he aroused.
00:06:51 It was a very interesting drug.
00:06:53 But anyway, in making ATP, you've got to involve,
00:06:56 you've got a nuisance in the earth that you've got to precipitate.
00:06:59 Which turned out to be calcium fructose triphosphate.
00:07:03 If you put yeast on, let's say, glucose or some glucose source,
00:07:09 it will phosphorylate the glucose, convert it to the glucose triphosphate,
00:07:16 then split it in the middle.
00:07:19 Now, you can make it split in the middle completely.
00:07:23 I mean, stop that splitting in the middle by adding a little bit of iodoacetic acid.
00:07:28 It's an ammeter for aldolase.
00:07:30 And then you add a little calcium and you get a huge precipitate.
00:07:33 And you have it by the gallon or by the pound.
00:07:37 So I took the calcium fructose triphosphate.
00:07:39 I reasoned this way.
00:07:41 That since calcium could be absorbed in milk,
00:07:45 it was absorbed as a phosphate attached to a polypeptide.
00:07:49 And to find that calcium phosphate polypeptide out of milk was a tough job.
00:07:54 I figured I'd try calcium fructose triphosphate.
00:07:56 And I did.
00:07:58 This is essentially the subject of the first slide.
00:08:03 Let's see.
00:08:12 You have a slide that says this.
00:08:16 Outcome of Nagelson's Pediatric Studies.
00:08:19 And I put this because my pediatric studies ended in 1958 when I left Boston.
00:08:26 And I was blackballed by all the physicians.
00:08:29 Prematures and full-time infants are now monitored by signs of dehydration
00:08:34 and blood-composed, especially hematopoietic electrolytes,
00:08:38 the age of one kid, on a routine basis.
00:08:42 As a result of World War II,
00:08:43 a marked reduction in mortality rates as a result.
00:08:46 As a result of this, there are 1.8 million people alive today
00:08:50 who would not have been alive if this had not developed.
00:08:54 In any pediatric department in the world,
00:08:56 it will look like the pediatric department that I have set up in Boston.
00:09:00 Milk formulas are now designed to simulate the composition of breast milk.
00:09:04 I'll prove that.
00:09:06 What had happened was the pediatricians were practicing medicine
00:09:10 just the way they did in medieval days.
00:09:12 They never measured anything.
00:09:14 They got the impression that something would work,
00:09:17 that they bled President Washington.
00:09:20 And when he didn't respond, they bled him some more.
00:09:23 All they had to do was take a hematocrit.
00:09:25 They found out that he was probably anemic.
00:09:28 But anyway, they killed him.
00:09:31 Milk formulas are now designed to simulate the composition of breast milk.
00:09:35 And starch hydrolysis is a competing place.
00:09:38 I'll demonstrate that I wrote that.
00:09:41 I had a pH meter.
00:09:44 And I measured the pH of these children on high-protein milks.
00:09:48 They were in acidosis.
00:09:49 I measured their urea levels.
00:09:51 Their urea is at 30 and 40,
00:09:53 while on breast milk they had urea of 6 and 7 and 8.
00:09:56 There was no question that the high-protein milk was causing an acidosis
00:10:00 and putting a load from getting rid of the nitrogen on the infant.
00:10:04 When that happened, I made an enemy.
00:10:07 The man who was the protagonist of high-protein milks
00:10:10 was Charles Levine, who was at Hopkins.
00:10:13 At Hopkins, he was the chief consultant to Similac
00:10:18 and a number of other companies.
00:10:20 And I said that what he was making was garbage.
00:10:23 And that, of course, didn't make him very friendly with me.
00:10:26 And, of course, he was the editor of the journal Pediatrics,
00:10:29 and I never got a paper published there again.
00:10:32 As a matter of fact, my assistant tried to publish a paper there
00:10:35 saying that, confirming some of the work I had done,
00:10:38 that premature newborns have high hematocrits.
00:10:41 And he got a letter, which I read, which said,
00:10:44 Nathanson's work is unreliable, and I'll publish this if you don't refer to Nathanson.
00:10:50 Dr. Menard said, Michael, he says to me,
00:10:53 Nathanson, everybody knows that you somehow or other
00:10:57 have to do with the survival of prematures.
00:11:00 But when I look in the literature for a reference, I can't find any.
00:11:03 I can't find any either. No one would publish my paper.
00:11:07 Calcium administration is now carried out exclusively
00:11:10 with chelated calcium carbonate, especially with hexose phosphates.
00:11:14 I didn't know how important that was,
00:11:17 because when they took this calcium fructose diphosphate
00:11:21 and fed it to these McKinney kids, all of them didn't have records.
00:11:25 A number of them had been given vitamin D.
00:11:28 We didn't have vitamin D, but we did have cod liver oil concentrates,
00:11:31 and I made a lot of it.
00:11:34 Some of them would not respond to cod liver oil.
00:11:37 Once you gave them calcium fructose diphosphate, it would absorb.
00:11:42 So calcium fructose diphosphate somehow or other, and it's never been clarified,
00:11:46 is involved in the absorption of calcium from the gut.
00:11:50 I still believe that.
00:11:53 Because Dr. Kramer came to me and said,
00:11:58 Nathanson, you missed getting your name in headlines by just a little.
00:12:02 I said, what do you mean by a little?
00:12:05 He said, if vitamin D didn't become available in milk,
00:12:08 everybody would be using calcium fructose diphosphate to cure rickets.
00:12:12 Let me have the next slide, please.
00:12:15 I'm talking to myself.
00:12:18 It's okay.
00:12:21 Now, what this demonstrates two things.
00:12:24 What the clinical chemist is doing at that time,
00:12:27 he's working with the physician, getting the problem,
00:12:30 and then going to the laboratory and solving it,
00:12:33 and going back and working with the physician again.
00:12:36 Here, this is published in General Clinical Investigations,
00:12:39 just before I became an outlaw.
00:12:42 Change in serum levels after administration of six grams of calcium fructose diphosphate.
00:12:46 These are all volunteers.
00:12:49 Now, the easiest animal to do research with is the human.
00:12:52 He's intelligent, somewhat odd anyway,
00:12:55 and he will follow directions,
00:12:58 get plenty of blood from him,
00:13:01 and you can get him to do all kinds of things.
00:13:04 But if he tried today, you'll be sued for everything you've got.
00:13:07 Some lawyer will find out, and they'll sue you.
00:13:10 So this will be impossible today.
00:13:13 Now, I would like to call something to your attention.
00:13:16 When they get calcium for vitamin D,
00:13:19 the organic phosphate was 0.6, 0.4, 0.4, 0.6, 1.2, 1.1.
00:13:22 Then it goes up to 3.4.
00:13:26 Now, 3.4 is about between 5 and 6 times 0.6.
00:13:29 Tremendous rise.
00:13:32 And with the fructose diphosphate, it goes in.
00:13:35 And in so doing, it pulls in the calcium.
00:13:38 Now, let's see the calcium growth.
00:13:41 Where is the calcium growth?
00:13:47 Oh, here it is, right over here.
00:13:50 Now, you notice 10.1 and 10.3, 10.4.
00:13:54 Well, you see, there's no significant difference.
00:13:57 But look at every single case.
00:14:00 The calcium is going up.
00:14:03 Now, it's very difficult to change the calcium when your calcium level is normal.
00:14:06 If you raise the calcium,
00:14:09 calcitonin will knock it into the bones.
00:14:12 If you lower the calcium, paracetamol will pull some out.
00:14:15 So here we're fighting that mechanism, and we're getting this.
00:14:18 Now, how significant is this?
00:14:21 I was interviewing the technicians in 1932 and 1933.
00:14:24 I think this was probably in 48 at that time.
00:14:27 First of all, every technician had to have a bachelor's degree in chemistry
00:14:30 with a major in analytical chemistry.
00:14:33 Secondly, the methods were done gravimetrically or by hand.
00:14:36 For example, when you do a carbon-hydrogen today,
00:14:39 you've got to report 86.23% carbon.
00:14:42 If you report 83.73%,
00:14:45 you've got to report 86.23% carbon.
00:14:48 If you report 83.73%,
00:14:51 it will not be acceptable.
00:14:54 But in a clinical lab, if you report 80 and 90,
00:14:57 whether it's a sugar of 80 or 90 doesn't make any difference.
00:15:00 That's why the modern machinery
00:15:03 has degraded repeatedly
00:15:06 the accuracy and the reproducibility.
00:15:09 They're reproducible, but not accurate.
00:15:12 But in those days,
00:15:15 what this calcium method was this.
00:15:18 Kramer had titrated calcium oxalate with bromaginate.
00:15:21 He changed the method
00:15:24 to ash the oxalate
00:15:27 and then titrate it with acid
00:15:30 because acidometric titration was more accurate.
00:15:33 I can tell you this.
00:15:36 These technicians would do every one of these in replicate.
00:15:39 This would be 10.3, 10.25, and 10.3.
00:15:42 You don't need a statistician.
00:15:45 When every result is exactly in the same direction,
00:15:48 it is significant.
00:15:51 This one here
00:15:54 also shows the same thing.
00:15:57 These are more of the same patient.
00:16:00 This one went to 8.1,
00:16:03 this one went to 8.5.
00:16:06 But of course, in those days,
00:16:09 I have the next slide, please.
00:16:12 Now, in back of this,
00:16:15 this is the summary of all the data.
00:16:18 This is the calcium.
00:16:21 This is the phosphorus.
00:16:24 It shows the same thing.
00:16:27 That's also under control.
00:16:30 And the organic phosphate,
00:16:33 that's citrate,
00:16:36 it doesn't give the fastened,
00:16:39 but the percent rise over fastened.
00:16:42 You'll see here,
00:16:45 it's a very big number,
00:16:48 only here, it's the last one.
00:16:51 Percent rise over fastened organic phosphate
00:16:54 is 173%.
00:16:57 There was no question about its rise.
00:17:00 And when you watch these children,
00:17:03 they didn't want to go home
00:17:06 because their calcium level was measured.
00:17:09 If you have a calcium of 5,
00:17:12 and you give calcium of 5,
00:17:15 it becomes a 10 right away.
00:17:18 If you have a 10,
00:17:21 it's very hard to get it off the 10 to 10.1.
00:17:24 So, I didn't see very much of this work,
00:17:27 and I forgot about it,
00:17:30 being probably one of the most important papers
00:17:33 in calcium absorption.
00:17:36 And all of the preparations
00:17:39 that have oral calcium
00:17:42 are hexose phosphates today.
00:17:45 May I have the next slide, please?
00:17:48 What this is, you have to have a control.
00:17:51 So, I needed something that was identical
00:17:54 to what we were doing.
00:17:57 The Ice Bishop Company made this material
00:18:00 in two forms. They made a hydrate,
00:18:03 and they also made an anhydrous.
00:18:06 The anhydrous was stable. The hydrate was not.
00:18:09 So, I got from them a 9-month-old hydrate
00:18:12 which was completely hydrolyzed.
00:18:15 It had no calcium phosphate.
00:18:18 The water was calcium phosphate and phosphate.
00:18:21 And it didn't work.
00:18:25 And you see, there was practically no...
00:18:28 In other words, 0.6 to 0.8.
00:18:31 In other words, instead of a 173% rise,
00:18:34 you had maybe a fracture,
00:18:37 a very small percentage, not significant.
00:18:40 So, that was the control showing that the phosphate
00:18:43 was being absorbed as a whole.
00:18:46 And you have to have a chelate in order to absorb calcium.
00:18:49 And that's why it amuses me.
00:18:53 It appears in the stool. None of that is absorbed.
00:18:56 You take bone care. We try ground bones.
00:18:59 They sell that at $10 a bottle now in health stores.
00:19:02 You take a pill of ground bones,
00:19:05 it's supposed to help.
00:19:08 That's why you don't want
00:19:11 hypocalcemia in the agent.
00:19:14 It helps. I don't believe it.
00:19:17 It doesn't absorb.
00:19:20 Next slide, please.
00:19:23 Now, at that point,
00:19:26 when I worked with the Milks,
00:19:29 Dr. Kramer gave me a project.
00:19:32 He would come in and sit down.
00:19:35 We would sit down with his staff and we would decide on a project.
00:19:38 And that was what the clinical chemist was doing.
00:19:41 This was my main job.
00:19:44 My job, the technicians that do analysis.
00:19:48 Now,
00:19:51 Dr. Kramer said that
00:19:54 a number of formulas have been proposed using lactose
00:19:57 in breast molasses and milk sugar.
00:20:00 They all fail.
00:20:03 He says, you get foul-smelling stools. Tell me what's in the stool.
00:20:06 Well, I said, all the lactose is in the stool.
00:20:09 It's not being absorbed. I said, well, at least 90% of it is.
00:20:12 And the urine is loaded with lactose, too.
00:20:16 I looked for lactose. I couldn't find any significant amount.
00:20:19 I said, lactose can't be utilized.
00:20:22 So we ran a study in which we measured
00:20:25 carbohydrate levels, glucose.
00:20:30 And this was raw breast milk.
00:20:33 You have a rise from
00:20:36 70
00:20:39 all the way up to 180.
00:20:42 And it was being absorbed and utilized.
00:20:45 This is
00:20:48 27 cases or something like that.
00:20:51 I can't read it.
00:20:54 But anyway, if you focus it in, I'll be able to read the number.
00:20:57 Forty?
00:21:00 Forty cases.
00:21:03 About 40 cases.
00:21:06 This is lactose.
00:21:09 The difference is that this has been heated.
00:21:12 Let me show the next slide and show you that it wasn't
00:21:15 the mother's milk.
00:21:18 This is raw cow's milk.
00:21:21 In those days, women would have it.
00:21:24 Remember the certified milk?
00:21:27 It's extinct.
00:21:30 And this was the lactose
00:21:33 in the world.
00:21:36 This is pasteurized milk.
00:21:39 What you do is
00:21:42 heat it until the phosphatase test is negative.
00:21:45 Therefore, an enzyme is being destroyed
00:21:48 which causes, which hydrolyzes lactose.
00:21:51 May I have the next slide?
00:21:57 Now, this is
00:22:00 milk with lactose.
00:22:03 I was using cartose, which is a competitor of mine,
00:22:06 which is a starch hydrolyzer.
00:22:09 And it's on this basis that the Lee-Johnson company made a fortune.
00:22:12 Lactose was out.
00:22:15 And from then on, every formula had to have Getsky maltose or
00:22:18 cartose.
00:22:21 I didn't get anything out of it.
00:22:24 Not only that, but I got severe criticism from Lee-Johnson.
00:22:27 I said to them, why do you criticize me?
00:22:30 Because all the doctors whom we talk to are up in arms
00:22:33 because you, Nadelson, are publishing papers in medicine.
00:22:36 And you see, they didn't realize
00:22:39 that that's standard practice in Europe.
00:22:42 In France, that's no publishing papers in medicine, you might say.
00:22:45 And Wieland,
00:22:48 I was in his house in Germany,
00:22:51 he got the Nobel Prize, he was a clinical chemist,
00:22:54 for what he did on diabetes. May I have the next slide?
00:22:57 Wieland, who was Van Slyke,
00:23:00 was publishing papers in medicine.
00:23:03 And Somogyi was publishing papers on diabetes.
00:23:06 That was the clinical chemist in those days.
00:23:09 Now, this is a very interesting thing
00:23:12 because I, therefore, proceeded to
00:23:15 analyze this high-pro milk
00:23:18 to see what the problem was.
00:23:21 Because I wanted to make an artificial formula, too.
00:23:24 The first thing I knew was that in casein,
00:23:27 the lactalbumin ratio was 4 to 6,
00:23:30 while in breast milk, it was 82 to 18.
00:23:33 In other words,
00:23:36 in cow's milk,
00:23:39 there was four times as much casein as albumin,
00:23:42 while in human milk, there was less casein.
00:23:45 And if you sit down and figure out
00:23:48 the percentage of body weight is bone,
00:23:51 it checks out to be that the more bone you have,
00:23:54 the more casein. This was a study which led me
00:23:57 to the calcium fructose diphosphate idea
00:24:00 because I figured that the calcium was being absorbed
00:24:03 in the casein. May I have the next slide, please?
00:24:06 Now, when I went to Rockford,
00:24:09 and I'm getting ahead of my time a little,
00:24:12 I went to the Dean Milk Company
00:24:15 when I was there and talked them into spending
00:24:18 $40,000 to build two formulas.
00:24:21 One, which is 60% albumin,
00:24:24 they call it non-casein protein,
00:24:27 and the rest 40% casein.
00:24:30 And the other one was 11% albumin
00:24:33 and 89% casein.
00:24:36 Those were the two different formulas.
00:24:39 And it was breast milk.
00:24:42 Now, you'll notice that these formulas
00:24:45 were 90% protein.
00:24:48 I made it 2%.
00:24:51 Breast milk was only 1.42%
00:24:54 in the first seven days. How did I get these numbers?
00:24:57 I went around to the mothers and collected their milk
00:25:00 and analyzed it. Now, you don't see that data
00:25:03 very often. The pediatricians would not do it.
00:25:06 It took a chemist to do it. Let's have the next slide.
00:25:10 Now,
00:25:13 when I fed these to the babies,
00:25:16 this is their protein level,
00:25:19 I realized that breast milk was the ideal
00:25:22 and the casein formula was producing more protein
00:25:25 and the albumin, and this is more or less evidence,
00:25:28 that the albumin is the source of plasma protein
00:25:31 and not casein. Let's have the next slide.
00:25:34 Casein is a calcium carrier.
00:25:37 Now, all the work that was being done by Charles Levine,
00:25:40 for example, I criticized him. That's why he
00:25:43 didn't like me, was the fact that
00:25:46 they took the birth weight and they measured
00:25:49 the rate of gain up to the, oh, maybe tenth day.
00:25:52 Now, this is the worst place in the world
00:25:55 to do a research study. In this study that
00:25:58 cemented the idea that high-protein milk
00:26:01 was good for children, there were six cases.
00:26:04 Three girls, three boys.
00:26:07 I averaged the weight of the three girls that was heavier than the weight of the three boys.
00:26:10 The statistics was nonsense.
00:26:13 When I published the paper with Benjamin Cramer's name on it,
00:26:16 of course, I had to use Benjamin Cramer
00:26:19 to protect me.
00:26:22 Charles Levine was furious. He was just furious.
00:26:25 Can I have the next slide, please?
00:26:28 Now, this is a demonstration
00:26:31 that a high casein formula results in high urea.
00:26:34 This is urea. In the case of
00:26:37 high-protein milks, this is two percent work.
00:26:40 The urea would be way up there.
00:26:43 Can I have the next slide, please?
00:26:46 This shows how stupid it is to measure
00:26:49 weight gain in the first few days.
00:26:52 This is breast milk where the mother is not putting out any milk.
00:26:55 Until she starts putting out the full flow in about seven days,
00:26:58 the formula intake was practically nil,
00:27:01 mostly getting glucose and water in.
00:27:04 This is when you give them an artificial formula.
00:27:07 Can I have the next slide, please?
00:27:10 Now, in order to do this work,
00:27:13 I had to have methodology.
00:27:16 A lot of this methodology was developed in Brooklyn
00:27:19 before I came to Roth.
00:27:22 This tube here is open on this end.
00:27:25 You notice it has no rubber attached to it.
00:27:28 All you do is... Incidentally, that's the wrong place.
00:27:31 You puncture it back here.
00:27:34 All you do is let the blood run in by itself.
00:27:37 Let me have the next slide.
00:27:43 Then I would use the sealing wax to seal the end.
00:27:46 Here are those already sealed as well.
00:27:49 Then centrifuge. Next slide.
00:27:52 Then I would measure the hematocrit,
00:27:55 which you got for nothing without wasting any material.
00:27:58 Go to the next slide.
00:28:01 Then I would cut the tube.
00:28:04 You see there's air coming in from this side.
00:28:07 Just let it flow into these solid pipettes
00:28:10 and various types of pipettes and do all my tests.
00:28:13 Can I have the next slide, please?
00:28:16 I could also sample the red cells
00:28:19 for purposes like doing ATP in the red cell
00:28:22 and things like that.
00:28:25 Can I have the next slide?
00:28:28 Then I developed this micro-gasometer.
00:28:31 One of the doctors, his name was Rourke,
00:28:34 he said to me, Nielsen, you can have all these methods,
00:28:37 but you're not going to develop a micro-method for CO2.
00:28:40 So I did.
00:28:43 This is the micro-gasometer.
00:28:47 They know for the methodology, which is nonsense.
00:28:50 None of this methodology is in use today.
00:28:53 Anybody who spends his lifetime developing methodology
00:28:56 is not looking ahead to the future.
00:28:59 If you use the methodology, if you develop methodology,
00:29:02 develop it for a purpose.
00:29:05 Here I'm putting the serum from this open tube into here
00:29:08 so I can sample it into the micro-gasometer.
00:29:11 Next slide.
00:29:14 This plunger moves back and forth.
00:29:17 If you look at it very carefully, you'll see that all I did
00:29:20 was take the old Van Slyke apparatus where he had leveling bulbs,
00:29:23 replace it with a plunger, and make everything smaller,
00:29:26 and that was the micro-gasometer.
00:29:29 So you can compare Van Slyke with the system more than me.
00:29:32 The next slide.
00:29:35 I had to develop methods for 10 microliters or less.
00:29:38 That's routine today.
00:29:42 Remember, in those days, that was considered insane.
00:29:45 Some of the people criticized my work.
00:29:48 With due respect to Nielsen, one fellow wrote,
00:29:51 I just don't believe these results with microliters.
00:29:54 They're absolutely unreliable.
00:29:57 Anyway, I had this long cuvette made for the Coleman,
00:30:00 in respect to the Dominant.
00:30:03 This was for the Coleman, and this was for the Klepp,
00:30:06 using a long cuvette.
00:30:09 Using the principle of getting more carbon.
00:30:12 Next slide.
00:30:15 Here I'm sampling with a micro-gasometer.
00:30:18 Next slide.
00:30:21 Also, I had a friend in the Bronx
00:30:24 at the Farrand Optical Company
00:30:27 who was an expert in light,
00:30:30 and he was the one who developed the interference filter.
00:30:33 An interference filter is two pieces of glass
00:30:36 with a little glue in between,
00:30:39 and you push them together,
00:30:42 and the distance between the two determines what color goes through.
00:30:45 The color goes through, back and forth,
00:30:48 and if it's of the order of a second wavelength,
00:30:51 that wavelength will be taken out, or will be reinforced.
00:30:54 So you have what is known as an interference filter.
00:30:57 This is the absorption spectrum,
00:31:00 in effect, of the urea color.
00:31:03 This is the interference filter,
00:31:06 cutting out this percentage of the urea.
00:31:09 And here is the ordinary Klepp filter, which is just colored glass.
00:31:12 And you can see that you're increasing specificity.
00:31:15 Let's call this white area,
00:31:18 which you're actually reading, let's say at 90%,
00:31:21 and here you've got about 50%.
00:31:24 So you've increased your sensitivity
00:31:27 by a factor of at least two, by using an interference filter,
00:31:30 and there's no extra effort in the methodology.
00:31:33 Of course, that's routine today.
00:31:36 Now, these micro-cuvettes were not available in those days.
00:31:39 I had a fellow, a glassblower by the name of Kopp,
00:31:42 and he made them for me.
00:31:45 And at that time, this was quite a sensation,
00:31:48 to line up the spectrum together.
00:31:51 But I'm sure anybody who worked in those days struggled to line up these cuvettes.
00:31:54 And you can see I have one with the same light path.
00:31:57 The reading would be the same for all three.
00:32:00 But this would be between a half cc, and this would be only a half cc.
00:32:03 That's five times the sensitivity.
00:32:06 May I have the next slide, please?
00:32:09 And here's the setup with all the solutions,
00:32:12 including the solution that went into the flame photometer and so on.
00:32:15 That's the setup for one kit for one day.
00:32:18 May I have the next slide?
00:32:21 Now, one of the things I discovered,
00:32:25 Benjamin Cramer kept telling me,
00:32:28 alkalosis is a condition produced by resonance.
00:32:31 He said, if you give a bicarbonate,
00:32:34 you're sure to end in alkalosis,
00:32:37 because you can't control it.
00:32:40 I learned how to control it.
00:32:43 I learned how to control it by building a pH meter
00:32:46 and plotting and then calculating both.
00:32:49 For example, here,
00:32:52 we've given 20% of the bicarbonate that a kid needs,
00:32:55 and there's no change with a pH of 6.9,
00:32:58 no change in pH significantly.
00:33:01 40%, and the pH is still 7.05.
00:33:04 60%, and the pH is 6.
00:33:07 At this point, the doctor will call down and say,
00:33:10 you people don't know how to do pHs,
00:33:13 because that's what they would tell me.
00:33:16 I've given a huge amount of material,
00:33:19 and the pH has gone from 6.9 to 7.05.
00:33:22 But now, when you get to 80%,
00:33:25 you've got a pH of 7.25,
00:33:28 which is still acidosis,
00:33:31 but now if you give the rest of it,
00:33:34 the 20%, it shoots right up.
00:33:37 All you have to do is give 10% more,
00:33:40 and you're up to a pH of 7.6.
00:33:43 Now you see why alkalosis is very easy to do with bicarbonate.
00:33:46 I knew that lactate didn't work.
00:33:49 How do I know that lactate didn't work?
00:33:52 Because I had a piece of filter paper,
00:33:55 and I dipped it in the sodium lactate,
00:33:58 and it turned red, the litmus paper.
00:34:01 So I called the company and said,
00:34:04 how come your sodium lactate is acid?
00:34:07 Oh, we put an extra lactic acid as a preservative.
00:34:10 And then I found that all lactate has that.
00:34:13 And they were using lactate.
00:34:16 Now if a youngster cannot handle his own lactate,
00:34:19 how could he burn up the lactate that was in the sodium lactate?
00:34:22 It was a waste of time, and I'll demonstrate that soon.
00:34:25 And why was lactate given?
00:34:28 Sodium lactate was given in acidosis
00:34:31 on a theory that the lactate would be metabolized or excreted,
00:34:34 and the sodium would be utilized.
00:34:37 And there's a famous solution. What's the name of it?
00:34:41 Lactate ringers.
00:34:44 No, there's a man's name attached to it.
00:34:47 Ringers.
00:34:50 And he was the one who introduced lactate to correct alcoholism.
00:34:53 You see, it didn't have to do anything.
00:34:56 Everything they did was not to do anything.
00:34:59 For example, you say leave the child alone for 48 hours.
00:35:02 Well, you don't have a problem. You don't have anything to do.
00:35:05 Use ringers lactate to correct the alcoholism.
00:35:09 Then you don't have to worry about too much.
00:35:12 This is a ray bug we read.
00:35:15 I doubt whether a lot of you are young or people have seen this.
00:35:18 You just turn this and mercury comes out and pushes the stuff out.
00:35:21 And this is where we did chloride.
00:35:24 We used to titrate the chloride.
00:35:27 Now, you can do a chloride within a half a percent this way.
00:35:30 You can do it better with amperometric titration,
00:35:33 but when you start going to colorimetric methods and you autoanalyze it,
00:35:36 you're at plus or minus 10%.
00:35:39 Now, this was a chart of a youngster.
00:35:45 And remember, this is why adrenal immaturity does not mean
00:35:48 that I know that the adrenal is at fault.
00:35:51 The child loses salt.
00:35:54 But I'm not focusing on salt.
00:35:57 I'm focusing on the hematocrit.
00:36:00 You notice the hematocrit is high.
00:36:04 There was only one hematocrit reported in the literature when I started this work,
00:36:08 and that was a very low one of a child that was about six months old.
00:36:11 No one knew that prematures and newborns had very high hematocrits.
00:36:17 Around 60 is normal for a newborn baby.
00:36:20 There's an X-line.
00:36:23 No way to imagine that.
00:36:25 Now, the first thing I did was I said,
00:36:27 I'm going to do exactly what they say.
00:36:29 Here's a child that weighed 800 grams, 754 grams.
00:36:34 That meant that 99 out of 100 would die.
00:36:37 That's what it meant.
00:36:38 It was a death sentence.
00:36:40 So the doctor, Crawford, said,
00:36:42 Nelson, you can have this kid.
00:36:44 It's garbage.
00:36:45 It's not going to survive.
00:36:47 So I said, okay.
00:36:48 So I put her on a scale,
00:36:50 and periodically I took the reading and put part of the weight.
00:36:55 And I found that in 24 hours,
00:36:57 and I was supposed to leave her alone for 72 hours,
00:37:00 according to the directions in Clement Smith's book.
00:37:04 And it had lost, give or take six or ten days of death.
00:37:09 It died at the end of 24 hours,
00:37:11 and it lost 20% of its body weight.
00:37:15 May I have the next slide, please?
00:37:21 I said, therefore, we've got the secret of how to manage a premature.
00:37:26 Let's keep them hydrated.
00:37:28 And how do you keep them hydrated?
00:37:30 The way you do it with adults.
00:37:32 Well, let's see what we did here.
00:37:34 This is Louis Cacciatore.
00:37:35 Louis Cacciatore is a butcher in Rockford, Illinois.
00:37:39 He's still alive.
00:37:40 He's about 40 years old now.
00:37:43 When I'm going to Chicago in the fall, I'll accept why,
00:37:46 because he always invites me to his steak dinner.
00:37:51 First of all, I have to get the fluids in.
00:37:53 I'm a chemist.
00:37:54 I know nothing about how to handle a premature.
00:37:56 So I figured the best way to do it is to do what they do in Cincinnati.
00:38:02 You may not know it, but there's a reference to two doctors here in Cincinnati
00:38:06 who work with the polyethylene tube.
00:38:08 Do you know who they are?
00:38:11 Go put the lights on.
00:38:14 I want to ask if anybody knows these doctors.
00:38:16 They're still alive.
00:38:17 They're still alive.
00:38:18 I'd like to talk to them.
00:38:30 Could you find a picture of someone, a baby with a polyethylene tube?
00:38:36 I don't know if there's an end.
00:38:37 I don't think there's an end.
00:38:40 Down below, it'll give you the name of two Cincinnati doctors.
00:38:45 This side and this side.
00:38:49 If anybody finds the page, let me know.
00:38:54 Okay, here they are.
00:38:56 Here's a polyethylene tube and some of the babies.
00:38:59 And now let's look at the previous page.
00:39:07 Credit should be given to Dr. Daniel V. Jones and Eve Wagner
00:39:11 of the Cincinnati General Hospital
00:39:13 for stimulating the use of indwelling polyethylene tubes.
00:39:17 Does anybody know these two doctors here?
00:39:19 Ever heard of them?
00:39:20 That was 40 years ago.
00:39:22 Assuming they were 30 then, they'd be about 70 now,
00:39:24 and they probably were more than 30 then.
00:39:27 But anyway, I didn't invent the polyethylene tube,
00:39:30 but I used it on prematures, which no one had ever done.
00:39:33 Put the light on.
00:39:37 So I put a polyethylene tube in,
00:39:39 and at 8 hours arbitrarily, I said,
00:39:41 I'm not going to wait 24 hours.
00:39:43 I'm going to start giving this youngster food at 8 hours.
00:39:46 So let's see.
00:39:47 This is the paradigm of the whole treatment.
00:39:51 I gave 10 mL of saline, 23 mL of linseed oil,
00:39:54 and 5% glucose in water through a polyethylene tube.
00:39:58 Now look at this.
00:39:59 The stomach capacity of that infant was 4 cc.
00:40:03 You know what 4 cc is.
00:40:05 The empty time was 3 cc.
00:40:09 So that, how much could you get in?
00:40:11 3 cc per hour times 24 hours is about 70-some-odd cc.
00:40:16 He needed about 150.
00:40:18 So I set up a clysis.
00:40:22 What's a clysis?
00:40:24 What does it say, clysis?
00:40:25 Right there.
00:40:26 Right there.
00:40:27 Where your pointer is.
00:40:28 Clysis.
00:40:29 About 15 days.
00:40:30 There's a clysis up here too.
00:40:32 A clysis, right.
00:40:33 A clysis.
00:40:34 10 mL of saline plus 23 mL of linseed oil.
00:40:37 And to my amazement, the clysis went in.
00:40:39 This was absorbed like in a dry sponge.
00:40:42 And at this 15 days and so on.
00:40:47 Meanwhile, I wasn't doing any chemistries on him
00:40:49 because I was busy trying to take care of this father.
00:40:53 By this time, when he got into trouble,
00:40:56 I was sitting in my office and his father came in
00:40:59 and wanted to take the body.
00:41:01 Of course, they had called him
00:41:02 and told him the baby wasn't breathing.
00:41:05 But I had an anesthesiologist who pumped him,
00:41:09 and I said, no, we don't give up.
00:41:11 And I got a sample of blood, and here's what I found.
00:41:15 115 chloride and 137 sodium.
00:41:18 What does that mean?
00:41:19 It's an acidosis.
00:41:21 So it gave him a little bicarbonate.
00:41:24 The urea was 33, and he was drying out.
00:41:28 So he increased everything.
00:41:30 And now I started pumping breast milk.
00:41:33 The reason I got breast milk
00:41:35 is because his mother started to pour breast milk
00:41:37 that was available, and I couldn't get it.
00:41:40 I had to borrow it from some other people.
00:41:42 Anyway, we started using breast milk,
00:41:45 and what we did was put salt in the breast milk.
00:41:48 I'm going to try to hold it.
00:41:50 It was 120 sodium, 85 chloride.
00:41:54 We kept giving him salt in his breast milk.
00:41:57 It kept dropping off.
00:41:59 And we came to the conclusion
00:42:01 that there was a salt-losing phenomenon in these kids,
00:42:04 that they didn't have a mature adrenal system.
00:42:09 In other words, what I was saying is
00:42:11 they don't produce aldosterone.
00:42:14 This went on until I'll show you.
00:42:18 I made a very interesting discovery at this point here.
00:42:22 We gave five milliliters of blood.
00:42:24 The reason we gave five milliliters of blood
00:42:26 was we saw this dropping hematically.
00:42:28 And I didn't know whether 41 was good or bad for premature.
00:42:32 But I didn't see any premature.
00:42:34 So I said, let's give him five milliliters.
00:42:36 As soon as we gave him five milliliters of blood,
00:42:38 and then we saw a sharp rise in chloride.
00:42:42 Now, let's see.
00:42:44 Let me have the next slide, please.
00:42:48 Finally, we kept on giving blood,
00:42:50 because he seemed to look better.
00:42:52 And there was a sharp rise.
00:42:54 Notice the chloride here and the chloride up here.
00:42:59 Now, we didn't give him any more salt.
00:43:01 We concluded there was a hormone in blood
00:43:03 which was holding the salt.
00:43:06 And that's when we started giving him
00:43:08 desoxychorticosterone five hours.
00:43:11 In other words, five hours.
00:43:15 In other words, by the time he was 61 days,
00:43:18 we moved the polyethylene to him.
00:43:20 He had a good circuit reflex.
00:43:22 And we gave him, orally, in other words,
00:43:24 we took the breast milk, added a gram of salt,
00:43:28 mixed it up, and then fed it to him.
00:43:30 He was getting about 150 to 200 cc of breast milk a day.
00:43:35 And desoxychorticosterone.
00:43:37 Finally, desoxychorticosterone was discontinued.
00:43:40 And we sent him home.
00:43:42 We sent him home.
00:43:43 Ten months later, he was perfectly normal.
00:43:46 And then we realized we had made a discovery,
00:43:49 because we found this to be true in every low-weight premature.
00:43:53 Now, the secret to maintaining a low-weight premature
00:43:55 was to give him two things, salt and hormone support.
00:43:58 And the best way to give him hormone support
00:44:00 was to give him a little blood.
00:44:02 But if you didn't, it was not very effective.
00:44:05 But we didn't know how the steroid at that time.
00:44:07 Today, I imagine there are some.
00:44:09 I was hoping Tsang would be here
00:44:11 to find out if they give him allopurinol.
00:44:13 May I have the next slide, please?
00:44:16 This is what he looked at at birth.
00:44:18 Over here is my hand.
00:44:20 My hand was bigger.
00:44:22 It was the whole length from here to here.
00:44:24 In other words, he was about this length.
00:44:27 That's how big he was.
00:44:29 And this is what he looked like
00:44:33 at 1 pound 9 ounces at birth.
00:44:37 At one year.
00:44:40 That's not the same patient.
00:44:42 It's the same idea.
00:44:44 May I have the next slide, please?
00:44:49 That caused an explosion in the United States.
00:44:52 A meeting was held...
00:44:54 Can you put the lights on, please?
00:44:56 I better get it on because this is taking longer than I thought.
00:45:01 I'll be finished in about 5 or 10 minutes.
00:45:05 What do you mean?
00:45:07 A meeting was held of the leading pediatricians in the country,
00:45:11 and they had a symposium in the Corps of Review of Pediatrics,
00:45:14 each one saying vile things,
00:45:18 saying that the soldiers were wasting for prematures,
00:45:20 and they were led by Clement Smith
00:45:23 and also by a guy I never worked for,
00:45:26 and also by Charles Levine.
00:45:28 And they ripped me apart,
00:45:30 and this is the answer to it later on that I gave at that time.
00:45:35 I have here the name of 12 of the institutions.
00:45:39 You name a famous institution,
00:45:41 there was somebody there writing a criticism.
00:45:44 The criticism all through was,
00:45:46 if you give salt, they'll get retrolethal fibroplasia.
00:45:49 Of course, retrolethal fibroplasia has nothing.
00:45:51 This afternoon, this evening,
00:45:53 I'm going to put up the statements they made,
00:45:56 and I'm not putting their names down
00:45:58 because they'd be ashamed of it if they were here.
00:46:00 May I? Put the lights on.
00:46:05 I'll just pick one here.
00:46:07 The authors present such data finding, in many instances,
00:46:09 low sodium chloride levels,
00:46:11 elevated fats, and extreme atherosclerosis.
00:46:13 Methods employed use finger-picked blood.
00:46:16 Since these authors are much more intimately familiar than I was
00:46:19 at their galleries of all the microtechniques,
00:46:22 they wanted to set a certain hesitation
00:46:24 to accept their usual findings of pre-confirmed medicine.
00:46:27 I said to myself, déjà vu.
00:46:29 That's what they wrote about Benjamin's crampus.
00:46:33 The crampus is now a micro-method for calcium.
00:46:35 May I have the next slide, please?
00:46:40 For the next 20 years,
00:46:43 papers from Mayo Clinic,
00:46:45 from Clement Smith's laboratory,
00:46:47 from Hopkins, came out,
00:46:49 and everyone said the same thing.
00:46:51 It's remarkable the way prematures
00:46:54 are able to tolerate salt
00:46:58 and how they lose it so easily.
00:47:01 But nobody referred to males.
00:47:04 This is a summary.
00:47:05 A pediatric clinic in February 1979.
00:47:08 These data suggest that the daily sodium requirement
00:47:11 of immature sick infants,
00:47:13 and notice he uses the word I used,
00:47:15 immature instead of premature,
00:47:17 may be much higher than was previously thought.
00:47:20 In such infants, the investigators say
00:47:22 urinary sodium should be monitored,
00:47:24 and sodium intake adjusted to prevent
00:47:26 hyponatremia in the first place.
00:47:28 May I have the next slide?
00:47:29 And they refer to this paper in general again.
00:47:32 I said that in 1951,
00:47:35 and this is 1979.
00:47:37 In the interim, there were at least 20 or 30 papers.
00:47:40 Not one of them referred to the original work
00:47:43 which we have done.
00:47:45 May I have the next slide, please?
00:47:50 Now, I didn't ignore the methodology.
00:47:54 I kept looking for a convenient way
00:47:57 of doing what everybody wants.
00:47:58 Some method way, you put the blood on the presser pump,
00:48:00 and I developed this tape system.
00:48:02 I call it an analysis,
00:48:04 which is now called the Kodak Ektachrome system.
00:48:07 And this is my patent, which says,
00:48:10 and I want to read it so that you will understand it.
00:48:12 An arrangement of chemical analysis
00:48:15 comprises the combination of three flat strips,
00:48:18 mediums, two peripherals, one on the other,
00:48:20 the outer medium on the one side being absorbent,
00:48:24 and the side can receive a sample.
00:48:26 The intermediate medium being non-reactive,
00:48:28 as far as the pore size,
00:48:30 such that it's bundled together with molecules
00:48:32 with a molecular weight higher than proteins
00:48:34 cannot pass through.
00:48:36 The outer medium on the other side being a test tube
00:48:39 which the samples can take.
00:48:41 Obviously, these were Kodak systems while I sat back.
00:48:47 But in 1980, I was looking at the Ektachrome system,
00:48:51 and I didn't have my name on here,
00:48:53 and I said to the kid who was there,
00:48:56 he said, where can we buy this machine?
00:49:01 And he said, well, we're waiting for Nagelson's patents to expire.
00:49:04 And that is the Ektachrome system.
00:49:06 May I have the next slide, please?
00:49:10 And here, I propose that it be used in space.
00:49:13 And I went down to NASA to demonstrate it.
00:49:15 Contracts are now for biological tools
00:49:18 in a gravity-free environment using that tape system.
00:49:21 May I have the next slide, please?
00:49:23 They said that these are the objectives.
00:49:26 A receiving tape, a porous tape, and a reagent tape.
00:49:31 May I have the next slide?
00:49:34 And this shows that this is by reflection,
00:49:37 and this is by transmission, showing that reflection.
00:49:40 All of these things were available to Eastman,
00:49:43 and they had the advantage of being able to use it.
00:49:46 May I have the final slide?
00:49:49 This is the machine that I delivered to them.
00:49:52 This is schematic.
00:49:54 The specimen's put here, 10 microliters, goes around.
00:49:57 This is a piece of cellophane.
00:49:59 This is reagent tape.
00:50:01 It comes out here.
00:50:02 They're separated here.
00:50:04 And this goes on to the recorder.
00:50:07 Today, it's a little card.
00:50:09 Do you have the instrument here?
00:50:11 Dr. Pesci, do you have an Eastman core instrument?
00:50:13 No, no. We don't have that.
00:50:15 We have them at the VA.
00:50:16 What?
00:50:17 Veterans Hospital has it.
00:50:19 Well, it's now the fastest-growing system.
00:50:23 Whitehead of Technicon, at the time that I showed this, said to me,
00:50:26 I'm not afraid of any of these other systems,
00:50:29 but if this thing ever goes on the market, we close shop.
00:50:32 And it's true, they're closing shop.
00:50:34 As a matter of fact, you can't buy a Technicon anymore.
00:50:36 May I have the next slide?
00:50:39 And this is what the machine looked like.
00:50:41 It was built large because, after all, it was homemade.
00:50:45 And the specimen comes in.
00:50:47 This is the tape that's going to receive the specimen.
00:50:50 This is a complicated machine where you put the specimen in the capillary,
00:50:54 and the capillary dumps it on.
00:50:56 I was too complicated.
00:50:57 But finally, here, it goes through this heater, and it's red.
00:51:01 And it's red in the colorimeter.
00:51:03 And I had to develop a colorimeter.
00:51:06 And don't forget, I didn't have the modern system.
00:51:10 But this entire machine was hand-built by you.
00:51:12 Pardon me?
00:51:13 You said this entire instrument was hand-built by you.
00:51:16 That's right.
00:51:17 May I have the next slide?
00:51:18 And this is Eastman's patent.
00:51:24 Eastman caught it.
00:51:25 And let's read what they say in their patent.
00:51:27 They finally got a patent for it.
00:51:29 But mine is in 1961, and theirs is 1976.
00:51:35 An integral element for analysis of liquid-sit element
00:51:39 an isotropically porous spreading layer.
00:51:42 That's the paper.
00:51:44 Surprisingly, a non-fibrin material.
00:51:46 This is the invention.
00:51:48 They said you could do it without paper.
00:51:50 Incidentally, what they're using is paper.
00:51:54 And a reagent layer permeable to a substance spreadable within the spreading layer
00:51:59 or a reaction process.
00:52:00 So they got what you call a dependent patent,
00:52:04 saying that they could do it without using paper on the receiving end.
00:52:08 And they finally could.
00:52:10 But they introduced one layer that was very good.
00:52:12 They introduced dictating dioxide, which is a better reflector.
00:52:15 And that's essentially it.
00:52:16 May I have the next slide, please?
00:52:19 It's all over now.
00:52:21 Again, I will say this.
00:52:23 Prematures of full-term infants are now monitored in signs of dehydration.
00:52:27 And just go up to the P-DAC floor.
00:52:30 And one of the people who reviewed in this criticism said that I would hate to see every kid
00:52:35 with a polyethylene tube in his nose.
00:52:38 Well, I can tell you this.
00:52:39 Every kid in your previous assembly has a polyethylene tube in his nose.
00:52:46 As a result of our reduction in mortality statistics,
00:52:50 and I just pointed out the fact that this was a greater benefit.
00:52:54 I don't know of any invention, including penicillin,
00:52:58 that had a greater impact on the mortality statistics than this.
00:53:02 Milk formulas are now designed to stimulate the composition of breast milk.
00:53:06 And sludge hydrolysis have completely replaced lactose.
00:53:09 Calcium administration is now carried out exclusively with chelated calcium.
00:53:13 And these were the contributions that I made at that time.
00:53:17 Put the light on.
00:53:19 Now, I made this paper specifically for his benefit.
00:53:25 You know why?
00:53:26 Because when I asked him if he knew what I had done in pediatrics, he didn't know.
00:53:29 He knew that I had made a micro-gasometer.
00:53:32 He knew that I had developed methodology.
00:53:34 But he didn't realize that the clinical chemist was not interested in the methodology.
00:53:38 He was interested in using it.
00:53:41 And that was what Liebig was a clinical chemist.
00:53:46 And he was studying urine, and he synthesized urea.
00:53:50 Verla was the MD.
00:53:52 And Louis Pasteur was a clinical chemist.
00:53:56 Berzelius was a clinical chemist.
00:53:58 He used the word organic chemist.
00:54:00 And he was responsible for isolating uric acid from urine, and so on.
00:54:07 So the profession of clinical chemistry has been an honored profession
00:54:13 since the days when the word chemistry was invented.
00:54:15 Chemistry was invented by clinical chemists.
00:54:18 The clinical chemists were the people who were able to take silver
00:54:24 and make it black with sulfur.
00:54:26 And that's what the word chemist means.
00:54:28 The blackeners, the people who make things black.
00:54:30 And therefore, if you could take silver and make it black,
00:54:33 obviously you could cure a disease.
00:54:39 Once again, the alchemist used to say the purpose of alchemy
00:54:46 is not to make anyone rich, but to cure disease.
00:54:51 And we have to find cures for disease.
00:54:53 Von Helmont was a clinical chemist who invented the balance
00:54:58 that was used for many, many years, the gravity balance.
00:55:01 And he was also a clinical chemist.
00:55:03 He called himself an iatrochemist.
00:55:06 The word iatro means medicine.
00:55:09 So the clinical chemist was called an organic chemist, an iatrochemist,
00:55:14 a biochemist.
00:55:15 When the biochemists first formed a society, there was clinical chemistry.
00:55:19 The early years of the general biological chemistry were all clinical chemistry.
00:55:23 But today we have a new class of clinical chemists,
00:55:26 the analytical clinical chemists, who have replaced,
00:55:30 and it has nothing to do with the physician.
00:55:33 He's not cooperating with them.
00:55:36 The clinical chemistry lab used to be the center of the hospital.
00:55:39 All the research that went on in that hospital.
00:55:41 I remember what was true in every single hospital.
00:55:44 Thank you.
00:55:46 Incidentally, one thing I would like to point out.
00:55:52 These methods were spread all over the world.
00:55:57 Abbott wrote them up here in what's new.
00:56:01 Then they wrote it up in a mosque on medicine, a Spanish thing.
00:56:06 Take a look at this.
00:56:08 And here's one in Italian.
00:56:10 And this is in the 60s in Abbott's magazine.
00:56:15 These methods are messed up.
00:56:17 But they all feature the methodology, not what was done.
00:56:20 Very interesting.
00:56:22 Thank you.
00:56:24 This is Abbott Gilbert.
00:56:31 They were made in 1951 or so.
00:56:35 And the visibility is not very good.
00:56:38 They're small.
00:56:40 And the way the organs are disposed is going to be very difficult to see that,
00:56:44 unless you have a telescopic vision.
00:56:47 So I'll read this.
00:56:49 It says, outcome of Nielsen's pediatric studies.
00:56:52 Prematures and full-time infants are now monitored by signs of dehydration.
00:56:56 Okay.
00:56:57 Are we on?
00:56:58 More signs of dehydration.
00:57:01 Especially in the life of a life-like condition on a routine basis.
00:57:06 I went up to the third floor where there was a neonatal intensive care unit.
00:57:13 Yeah.
00:57:15 I'm the grandfather of that unit, you might say.
00:57:19 Because prior to my activities in this field, there was no such thing.
00:57:24 As a result of what I call a mass reduction of mortality rates as a result,
00:57:29 people don't realize that in 1951,
00:57:32 the baby was born, weighed about four pounds,
00:57:35 and only had one or two chances of survival.
00:57:38 It was weighed less than 1,000 grams.
00:57:41 It had no chance of survival.
00:57:45 The milk formulas are now designed to simulate the composition of breast milk,
00:57:51 1% protein.
00:57:54 The reason I put that up there was because a pediatrician by the name of Charles Levine in Hopkins
00:58:02 had written a paper in which he advocated high-protein milks.
00:58:07 And in working on pediatric form, and I'll tell you about that,
00:58:12 I noticed that these children became severely acidotic on high-protein milks
00:58:18 and had very high ureas, as you would expect.
00:58:21 So I did studies comparing breast milk versus high-protein milks
00:58:29 and showed that the high-protein milks were a disaster.
00:58:32 As a result, if you go and look around, you'll see the advertisements for things like infant milk,
00:58:37 which are milks which imitate human breast milk.
00:58:44 And starch hydrolysis has completely replaced lactose as a source of calories.
00:58:49 I was given the job to find out why lactose was such a horrible thing to put into a formula.
00:58:56 Children had foul-smelling stools and would not survive, do very well.
00:59:03 When I examined the stools, I found that the lactose that had gone in and came right out unchanged,
00:59:09 most of it, some of it came out in the urine, but none of it, or very little of it,
00:59:13 was changed to lactose glucose, which was quite surprising.
00:59:20 And therefore, lactose was no good for infants.
00:59:25 And then, of course, lactose is milk sugar. That didn't make any sense.
00:59:29 I'll show you what the problem was.
00:59:31 Calcium administration is now carried out exclusively with chelated calcium carbonate,
00:59:35 especially with hexose phosphate.
00:59:37 When I came into this field in the 30s, the major problem in pediatrics was Ricketts.
00:59:43 I told this morning groups that I had two older brothers, twins, both of whom died of the English disease.
00:59:50 The English conkite, or the English disease, was Ricketts.
00:59:54 And all over Europe, all over England, all over the United States,
00:59:58 the floor at the Brooklyn Jewish Hospital had 70 children with Ricketts at the same time.
01:00:04 There was no vitamin D milk.
01:00:07 And even with cod liver oil, it didn't work on all children.
01:00:12 I was given the job of finding a way of getting calcium into these children.
01:00:17 There was a gentleman who ran an epileptic clinic.
01:00:21 Ninety percent of the patients ran calciums of five.
01:00:25 They were children who had hypocalcemia.
01:00:30 May I have that slide, please?
01:00:33 And at that time, I don't see this slide here.
01:00:40 If you turn the page on this chart, you'll see what happened.
01:00:46 There are three slides that I'm not showing, apparently.
01:00:50 These three slides show that calcium fructose diphosphate,
01:00:54 calcium phosphate was not absorbed, calcium carbonate was not absorbed,
01:00:58 or calcium citrate was not absorbed.
01:01:00 We tried everything.
01:01:01 And finally, I found calcium fructose diphosphate was absorbed quantitatively
01:01:06 and could cure Ricketts without any vitamin D.
01:01:10 And that was an interesting thing.
01:01:11 And Dr. Benjamin Kramer, at that time, who was head of the pediatric department,
01:01:16 said, Nelson, you'd have gotten your name in headlines if not for the discovery of vitamin D
01:01:22 because we had a cure for Ricketts, but it was useless.
01:01:26 People using cod liver oil were fed.
01:01:29 Now, if you used cod liver oil with milk, you were just as well off.
01:01:32 But basically, what I showed was that calcium could not be absorbed very well
01:01:37 unless it was chelated with a hexose phosphate.
01:01:40 And that's essentially what water is in milk.
01:01:47 Now, at that time, when I came to Rockford in 1949,
01:01:57 I had had 16 years of experience doing research in pediatrics.
01:02:04 I had developed a galaxy of micro-methods because I was originally trained as a micro-analyst.
01:02:11 And I was given certain problems.
01:02:15 One of the problems was, what are we going to do about this mortality statistics with premature deaths?
01:02:23 Could I borrow one of those books, please?
01:02:26 Those green ones are green books.
01:02:39 These are the kind of things you'll read in here.
01:02:42 Bunderson, who was made the Surgeon General of the United States at that time,
01:02:49 said the mortality statistics of neonates, and particularly premature ones,
01:02:56 is a disgrace in the United States.
01:02:59 If a child weighed 4 pounds, which is a pretty big infant,
01:03:05 it only had a 50% chance of survival.
01:03:08 If it weighed 1,000 grams or less, it had less than one chance in 20 of survival.
01:03:15 Now, I knew certain facts before I came to Rockford.
01:03:22 I knew there was such a thing as immaturity.
01:03:26 And the way I knew that was because of the fact that, worried with calcium,
01:03:33 there were some children who were born that would have low calciums.
01:03:37 You would give them calcium, and I used calcium fructose by phosphate,
01:03:41 and give them AT10, which is a relative of vitamin D,
01:03:46 and which was available long before vitamin D was available,
01:03:49 and was made from a gospel.
01:03:51 And their calcium would come up.
01:03:54 You'd stop the treatment and down it, drop to 5.
01:03:59 You would then repeat the treatment.
01:04:01 And you went up and down for about a week, two weeks, sometimes three weeks,
01:04:05 sometimes once in a month, when suddenly, one morning,
01:04:08 you'd come in and the youngster had a calcium of 10, and it stayed there.
01:04:13 And you didn't have to give them any more treatment.
01:04:15 So Dr. Patras, who was head of these children, said,
01:04:19 this shows that their calcium balance, their parathormone,
01:04:25 of course, they didn't know anything about calcitonin,
01:04:27 their system is inadequate, ineffective,
01:04:31 and that they're immature in the sense that it has to mature.
01:04:34 Now that it's matured, they have grown out of it.
01:04:36 You know that expression?
01:04:37 Grows out of it means it's matured.
01:04:40 Now, I say here, certain infants are born with an inherent inability to respond
01:04:49 with normal growth and development,
01:04:51 and conditions of treatment under which the vast majority of infants flourish.
01:04:56 The smaller infants are at a disadvantage,
01:04:58 and the point here is they tend to become dehydrated most easily.
01:05:03 And it's for this reason that the smallest infants present an acute
01:05:06 and urgent problem in fluid therapy.
01:05:11 Now, in the purpose of this report, to which this is our focus,
01:05:19 we discuss illustrative cases of the various findings common to the immature
01:05:24 which can be successfully treated.
01:05:26 Now, there was another type of immaturity that was very common among premature.
01:05:30 They would be born, premature were born with high hematocrits.
01:05:34 And then you would, and there could be a big one,
01:05:38 a 1,500-gram one or a 2,000-gram one,
01:05:41 and you'd notice if you measured the hematocrit drop steadily
01:05:44 over a period of maybe a month, two months,
01:05:47 so you'd give them hematinics, you would give them iron, B12,
01:05:53 everything that you could think of, including folic acid,
01:05:56 and they would not respond, nothing.
01:05:59 If you gave them blood, that was fine.
01:06:01 You could raise the hematocrit.
01:06:03 And then you came back two weeks later, and they were back to a hematocrit of 20.
01:06:08 We'd give them some blood and kick them up to 40 or 45,
01:06:11 and then two weeks later they were down to 20.
01:06:14 All of a sudden, one day the mother would bring them in,
01:06:16 and the hematocrit had stayed up.
01:06:18 Their reticular endothelial system had matured,
01:06:21 and they didn't need any more treatment.
01:06:23 I knew that there were many systems in the body which were not mature at birth,
01:06:29 and I was not surprised to find that the system which controls sodium
01:06:34 and fluoride balance in the body could be immature.
01:06:39 And not only that, but it was immature in every low-weight premature infant.
01:06:44 That was the remarkable discovery that we made at that time.
01:06:48 May I have the next slide, please?
01:06:54 Oh, this is a big one, 1398 grams.
01:06:58 And what does this show?
01:07:00 Oh, this shows—he's got the top chopped off.
01:07:04 This shows one of those children with an immature reticular endothelial system.
01:07:10 There were some physicians who would not go along with us,
01:07:14 and therefore I used their patients as controls.
01:07:17 The child starts out at 58, and at 41 days is down to 25,
01:07:24 and 110 days is 128, and is now an idiot.
01:07:28 The child now falls way below normal, because nowhere—
01:07:34 now this child was given every hematinic that you could think of, repeatedly, and no response.
01:07:41 In other words, this child had an immature reticular endothelial system.
01:07:45 Had he been given blood earlier, I believe he would have been able to mature.
01:07:50 Maybe every time we gave him blood, we gave him similar to a poet, and I don't know.
01:07:54 But one thing is clear, that this child was mistreated,
01:07:58 in the sense that the pediatrician did not recognize that he had an immature infant,
01:08:04 immature in the sense that he didn't have a mature reticular endothelial system.
01:08:09 May I have the next slide, please?
01:08:12 This is another child who had the same problem, but has one difference.
01:08:16 This child got repeated transfusions, all the way through.
01:08:21 At the end of 59 days—
01:08:26 notice here he's not being treated—
01:08:29 at the end of 53 days, his hematomas have taken flight, and it seems to stay up.
01:08:38 He went on, and we left him alone, and he was discharged,
01:08:42 because for about, oh, 10 or 15 days in a row, there were no dropped hematomas.
01:08:48 But all along, he had gotten slight shots of blood, 5 cc, 10 cc, 15 cc,
01:08:57 so that we recommended that blood be given every week.
01:09:01 This was a heresy.
01:09:03 Under no circumstance should you ever give blood to a newborn infant.
01:09:06 That was the feeling at that time.
01:09:08 There was too much danger of hepatitis.
01:09:10 But there was no choice.
01:09:12 You either ended up with an idiot, or you gave him blood.
01:09:15 May I have the next slide, please?
01:09:25 One of the interesting things was this.
01:09:27 I was one of the few people in the country who had a Ph.D.
01:09:30 that worked on small quantities.
01:09:34 And this child was on high-protein milk.
01:09:39 And as expected, on schedule, the Ph dropped down to 7.1.
01:09:47 At this point, there were little numbers here, which told me what would happen.
01:09:52 At this point, notice over here, his total CO2 is down to 1, and 7 over here, Ph 7.1.
01:10:01 At this point, we gave the child sodium lactate at the advice of the physician.
01:10:07 Now, sodium lactate is an acid solution.
01:10:10 It has excess lactic acid added as a preservative, and the Ph is around 6,
01:10:17 so that this child was not able to metabolize the lactic acid.
01:10:22 As a result, his Ph got even lower.
01:10:25 Sodium lactate is not an alkalizing solution for a child in severe acid health.
01:10:31 Now, everybody was afraid of sodium bicarbonate.
01:10:34 They were afraid that you'd over-treat them easily, and sodium bicarbonate was a little not so.
01:10:39 Therefore, I had a Ph meter, and I didn't have to worry about that, so I titrated these kids.
01:10:45 And here he gets sodium bicarbonate, I bring it up to 7.21.
01:10:49 He then goes back on that same milk, and the Ph drops to 7.1.
01:10:53 Then, of course, I keep giving him sodium bicarbonate, bring him to 7.2,
01:11:00 and then he goes on, and he can even handle a high-protein milk.
01:11:04 May I have the next slide, please?
01:11:10 And this is what happens to the growth rate of a child.
01:11:13 When you bring him out of the acid Ph, of course, to normal Ph, he just takes right off.
01:11:18 May I have the next slide?
01:11:24 I'll show that slide. That's important.
01:11:39 In order to give fluid to this, you have to understand that I'm not a physician,
01:11:43 and I have to find an easy way of getting the fluid out of his body.
01:11:48 You understand that I'm not a physician, and I have to find an easy way of giving fluid.
01:11:54 I didn't know, I was not skilled in cutting down on a scalp vein or anything like that.
01:11:59 So here in Cincinnati, by Dr. Jones, and what's the other fellow's name, I forgot, two pediatricians,
01:12:06 had started using polyethylene tubes in newborns.
01:12:11 So I used a finer one, about one-fifth what they used, and put it down this infant's stomach.
01:12:18 I measured the infant's stomach, and I'll show you how small they were,
01:12:22 and started giving fluids through the nose.
01:12:25 Why bother giving sodium bicarbonate solution through a vein, or if you can give it by mouth?
01:12:32 As a matter of fact, the use of bicarbonate rectally and orally
01:12:38 was very common at the turn of the century.
01:12:42 It was a standard form of treatment, because then you didn't have to worry about over-treatment.
01:12:47 On the other hand, when they started using sodium bicarbonate,
01:12:50 they started killing children with alkalosis, because if you follow the titration curve,
01:12:55 if you give just a little bit too much, the pH just jumps up to about one.
01:13:00 So if you walk on the third floor, you'll find all the kids,
01:13:05 every one of them has one of these tubes in his nose, and they have all kinds of equipment on them.
01:13:10 And that's important, because I'm going to tell you about that in a few minutes, why it's important.
01:13:15 And the next slide.
01:13:17 Now, the first thing I found was that if you give these kids salt, they lose it.
01:13:24 You start out with chloride of, let's say, 80, and you say,
01:13:28 I'm going to add 250 milligrams of salt to their formula, and that should raise the sodium chloride level.
01:13:36 You calculate out how much you give them.
01:13:38 You have to calculate it out, because there are very small volumes you're dealing with.
01:13:43 And you give them the salt, and it goes up for a short time,
01:13:48 and then the next thing you know, the next morning, the salt's gone.
01:13:51 You find it all in the urine.
01:13:53 So that this happened repeatedly, particularly in the very small premature.
01:13:58 They were very hard to keep hydrated.
01:14:02 So I came to the conclusion that they were suffering from immaturity of the adrenal system.
01:14:12 In other words, they didn't have the necessary salt-mutating hormones.
01:14:18 I put it in quotation marks, and I say down here,
01:14:22 the term adrenal immaturity is used here to designate conditions resulting in the inability of the infant to hold water,
01:14:30 sodium, iron, and chloride, in the face of the administration of these substances
01:14:37 in what would be more than adequate for a normal infant of equal weight.
01:14:42 There was no unequivocal histological or pathological evidence to support the thesis that the adrenal is involved.
01:14:51 That statement is not true.
01:14:53 Because subsequent to this, we did get autopsy reports, and the adrenal was involved.
01:14:59 We showed some children had adrenals that were something like one-tenth the normal weight of the other children.
01:15:05 And I have the next slide.
01:15:08 So I decided to do an experiment.
01:15:12 The books which came out of Harvard and Yale and places like that and Hopkins,
01:15:17 there were books called The Premature, and it said,
01:15:21 if a child weighs less than 1,000 grams, leave him alone for 72 hours.
01:15:26 If he weighs less than 2,000 grams, then leave him alone for 24 hours.
01:15:31 So I took a child who was born, a white female, who weighed 754 grams,
01:15:39 and I said, let's follow this procedure.
01:15:41 Only one difference. I put him on a scale.
01:15:44 And every hour or so, I took the weight.
01:15:47 At the end of 24 hours, the kid was dead, and he had lost 20% of his body weight.
01:15:53 Therefore, what did that tell me?
01:15:55 That told me that you had to hydrate the child.
01:15:59 You had to somehow or other find some way of getting fluids in him.
01:16:02 The only way I knew was to use clysus, you know, just stick a needle in the blood,
01:16:07 and the other was through the polyethylene tube.
01:16:10 And I used both.
01:16:11 I have the next slide, please.
01:16:14 And here I'm showing a paradigm of this technique, how I went about it.
01:16:20 This was the first one that I took for 80 days, and this one is alive.
01:16:28 And I told the group this morning he's a butcher,
01:16:31 and when I go to Chicago at the ACS meeting, at the AACC meeting,
01:16:37 I'm going to go on to Rockford and get my free steak dinner that he gives me
01:16:41 every time I come to Rockford.
01:16:44 He weighed 861 grams, and I want you to read this, or I don't think you can.
01:16:50 That's the way you are.
01:16:51 Stomach capacity, 4 milliliters, empty time, 3 milliliters per hour.
01:16:55 Who would guess that?
01:16:57 The stomach capacity, how do we determine that?
01:17:00 Well, I took a syringe and saw how much I could put into the stomach,
01:17:04 and all I could get in was 4 milliliters.
01:17:06 Then I waited and sat there and tried to put more in
01:17:10 and plotted how much I could get into the stomach, 3 milliliters per hour.
01:17:14 I sat down with a pencil and paper, multiplied by 24,
01:17:18 and I said that I can't put more than 72 milliliters into this child,
01:17:22 and he needs at least 120 milliliters to survive.
01:17:26 So I said the rest has to go by twice.
01:17:29 So I stuck the needle in him.
01:17:34 I put into my mouth 1 milliliter of water at 8 hours.
01:17:38 You see, I didn't wait 24 hours.
01:17:42 1 milliliter of water until 5 milliliters,
01:17:45 then 2.5 milliliters, 2.5 percent of it was in water,
01:17:48 per hour for 24 hours.
01:17:52 I was afraid, 24 hours, I didn't use any salt at all.
01:17:56 I was afraid, because the book said,
01:17:58 if you give salt to children, they get retroactive fibroplasia.
01:18:02 That's exactly what they said, and I'll show you that.
01:18:05 Now, of course, it's nonsense, but that's what the book said.
01:18:09 A crisis, by 15 days, I got the crisis up to 30 milliliters,
01:18:14 2.5 percent was 72 milliliters, 2.5 percent glucose,
01:18:19 and I also had some salt in there, it doesn't seem to say.
01:18:22 Now, I added cortisone, because by that time,
01:18:26 from autopsy reports, I knew that they needed cortical support.
01:18:30 Cortisone was useless.
01:18:32 Four times a day, 1 milligram of slug,
01:18:35 and by the seventh day,
01:18:41 the driver was called in and told that the child wasn't breathing
01:18:46 and that it wouldn't live much longer.
01:18:48 But I wouldn't give up, and I called the anesthesiologist to work with me,
01:18:52 and he pumped the kid, and somehow or other,
01:18:55 I increased the amount of fluid that he got in,
01:18:59 and by the 13th day, we held him,
01:19:02 and I was able to get 84 milliliters by the 30th day of human breast milk.
01:19:07 His mother started giving milk, and I was able to do that.
01:19:11 By the 17th day, notice he hasn't gained very much.
01:19:14 Breast milk is up to 120 milliliters,
01:19:17 and I kept putting a little salt in it all the time.
01:19:20 By the 18th day, up to 130 milliliters.
01:19:23 I've got him now.
01:19:25 With this amount, I can keep him alive indefinitely.
01:19:28 And then, by the 24th day,
01:19:30 he had four-tenths of a gram of sodium chloride in breast milk,
01:19:33 and 150 milliliters of breast milk.
01:19:35 This sodium chloride was in all of these fluids,
01:19:38 and it's all that's messed up now.
01:19:41 On the 26th day, I noticed the following.
01:19:45 You come over here, and you see the sodium 110.
01:19:48 You're not very happy about it.
01:19:50 And the chloride is 75.
01:19:52 There's adrenal immaturity.
01:19:54 I said, I've got to do something and get the chloride up.
01:19:59 So I didn't know what to do, so I gave him 5 milliliters of blood.
01:20:02 Why 5 milliliters of blood?
01:20:04 Because you're dealing with a 950-gram baby,
01:20:07 and that's like, in an adult, giving him 3 units of blood.
01:20:12 So I noticed that, without increasing anything,
01:20:18 that it didn't do very much.
01:20:20 But on the other hand, let's turn to the next page.
01:20:22 I kept adding salt, hoping that I would get it up.
01:20:25 What I noticed is this.
01:20:28 Sodium 135.
01:20:30 I was giving 5 cc of blood each day.
01:20:32 And all of a sudden, the sodium jumped to 135 and 100.
01:20:37 Let's have the next page.
01:20:39 I came to the conclusion, at that time,
01:20:42 that there's something in blood that helps him hold the sodium.
01:20:46 In other words, I discovered aldosterone, but didn't know it.
01:20:50 Now, I said, what hormone could possibly be in blood that's helping him hold it?
01:20:55 It has to be something in the adrenal.
01:20:58 There was a lot of talk of a salt-retaining hormone.
01:21:00 It didn't have a name yet.
01:21:02 But desoxychorticosterone had been isolated from animals.
01:21:06 So I took desoxychorticosterone and started to use that.
01:21:09 And in that way, I was able to maintain the sodium at the chloride level.
01:21:15 You notice, here I have trouble again.
01:21:17 So I went back to the blood.
01:21:19 See there.
01:21:21 Where's the next slide?
01:21:26 There's another second slide that's missing there.
01:21:33 It should say 30th day and so on.
01:21:35 But actually, on the 80th day, he went home.
01:21:40 The slide had gotten longer.
01:21:42 Let's have the next one.
01:21:45 Subsequent to that, Dr. Crawford, who is chief, put back the sentiment.
01:21:54 If this works this way, and these children need salt and some clinical support,
01:22:03 then let's try salt in the heavier infant and see whether that cuts down this hospital state.
01:22:11 These are the hospital states.
01:22:13 A child weighing 2,000 grams.
01:22:16 This is 1,620 grams.
01:22:19 1,630 grams.
01:22:21 Should go home in 40 days.
01:22:28 So we gave this child.
01:22:30 We found two of them at the same time.
01:22:32 This one at one gram a day.
01:22:34 Mind you, right from the first day, we're giving them a gram of salt.
01:22:41 We found a loss of weight, normal to every child, and this one went home at the end of 20 days.
01:22:48 50% savings.
01:22:50 This one, we gave two grams.
01:22:52 We just said we're going to push it.
01:22:54 We got them at Debenhams, and then we cut it back to one gram, and he went home about the same time.
01:22:59 This child was in good condition on the 20th day.
01:23:02 So we discovered that if you gave salt and Tazoxycorticosterone,
01:23:08 and we didn't give Tazoxycorticosterone in an infant that big, we just used plain salt,
01:23:13 then they went home early.
01:23:17 May I have the next slide, please?
01:23:26 About 47 cases were not chosen at random,
01:23:33 but represent those cases in which the physician chose to allow that case to be studied.
01:23:38 I was working in all the hospitals, and as soon as they got in trouble with a premature,
01:23:42 I get a phone call, we've got a case for you.
01:23:45 And out of these cases, there were five deaths.
01:23:51 Out of a total of, I think there were 47 survivors and five deaths.
01:23:58 Out of a total of over 50.
01:24:01 Now, four of them were dead on arrival.
01:24:03 One of them we killed.
01:24:05 You saw the one we killed, which we didn't do anything for.
01:24:09 We used watchful waiting as recommended by the professors from Harvard.
01:24:16 And so this was impossible.
01:24:22 As a result, when these statistics, and of course you add up all the other 200 and so infants that lived,
01:24:30 our statistics were incredible.
01:24:32 In other words, Rockford, Illinois, now has the lowest mortality rate in the world,
01:24:38 in any city, in prematures, regardless of weight.
01:24:43 The state of Illinois decided that we were falsifying the records.
01:24:48 So they sent a representative down to Rockford to inspect.
01:24:52 And he wrote the foreword to this, and you can read the foreword in here.
01:24:56 All I said to him was go to the charts and read them.
01:25:00 And he came out shaking his head, and he said, I have to report to people.
01:25:05 And he said, make a report to the state.
01:25:07 And that's how this report was made.
01:25:09 Originally, the state then asked that the methodology and the normal value be put in the back,
01:25:16 and that gave rise eventually to the book called Microtechniques of Clinical Chemistry.
01:25:21 But the conclusion here was this.
01:25:25 It is hoped, and I want to read this very carefully for what I'm going to say next.
01:25:29 It is hoped that this report will stimulate others interested in the problem of prematurely
01:25:34 to undertake similar studies to prove or disprove our contention that the solution to the problem
01:25:40 of successful management of prematurely lies in making available promptly to the physician
01:25:46 quantitative chemical data so that he can use similar principles of floor therapy
01:25:52 which have been successfully used in older children.
01:25:55 That was the conclusion of the report.
01:25:57 Now, as a result of this,
01:26:01 there was an explosion.
01:26:03 I'll have to save this slide.
01:26:06 The Quarterly Review of Pediatrics collected 12 leading pediatricians in the country,
01:26:12 and each one gave his opinion of the book, and they were all bad.
01:26:17 They all said that I was crazy, that you can't give salt to prematures,
01:26:21 and that this is utter nonsense because what I was doing was challenging them.
01:26:27 They were all leaving the prematures alone, and if the premature couldn't take the bottle by mouth,
01:26:32 he was dead.
01:26:34 And what I was suggesting is one said, all these injections that he had to get,
01:26:41 go over to the third floor and take a look, and you'll see every crib has a nurse,
01:26:48 and they're taking care of the kid on a 24-hour basis, these prematures,
01:26:53 and I'm sure I'm saying over here that he's doing a tremendous job in prematurity because he's following me.
01:27:01 This was the title, Doesn't a Premature Infant Need Adrenal-Cortical Support?
01:27:06 Now, this was a yellow dog title because I had never said that every premature infant needed adrenal-cortical support.
01:27:14 I said the low-weight premature needed it,
01:27:18 and you could do it with salt alone if you wanted to, but it was easier to do it with.
01:27:23 So, nevertheless, this is what they wrote.
01:27:26 Now, in retrospect, after 40 years, this was correct.
01:27:32 The premature needs adrenal-cortical support.
01:27:37 That is a fact.
01:27:38 And I have the next slide, whether you use salt or hormones.
01:27:42 Now, let me read you.
01:27:43 I'm taking it.
01:27:44 The editor wrote this statement.
01:27:47 He's describing what I recommended.
01:27:49 Blood levels of electrolytes, CO2, protein, and matter, pH, sugar, and urea,
01:27:54 are followed at frequent irregular intervals by study of fingertip or heel blood.
01:27:58 That's being done routinely in practically every hospital in the United States.
01:28:04 An attempt is made to maintain facilities on an around-the-clock basis.
01:28:08 That's the case in the hospital in Cincinnati here.
01:28:12 Microchemical methods and micro-bacteriological procedures.
01:28:18 Corrective fluid therapy is attempted on a quantitative basis.
01:28:22 I calculated in the back of the book how to calculate fluid for a 2-pound premature.
01:28:27 An illustrated appendix describes the laboratory processes in detail.
01:28:32 In other words, at the request of the state of Illinois, I gave the procedures in the back.
01:28:38 And here's a typical page showing how to draw the blood.
01:28:41 I'm sure looking around at the same setup here that that's what they're doing.
01:28:46 And I have the next slide, please.
01:28:49 Now, this is one of the statements of one of the critics.
01:28:53 And there were 12 of them, and each one was worse than the other.
01:28:57 Our feeling in contrast to that of the authors,
01:28:59 that prematures generally handle salt poorly.
01:29:02 They never gave the premature salt, so they didn't know.
01:29:06 And are just as likely to retain salt and become indeed as to become dehydrated.
01:29:10 This is the reason why some of the pharmaceutical companies
01:29:13 omit salt from their proprietary feeding products.
01:29:17 In other words, how can an infant live without salt?
01:29:21 The argument concerning early feeding equipment still goes on.
01:29:24 We have had more satisfactory results in normal ability.
01:29:27 I was holding all peripheral edema, so all fluids, until peripheral edema disappears.
01:29:33 He's talking about the full-time infant, because the premature infant is not born with edema.
01:29:38 The water in a newborn baby is put in in the last month, in the ninth month.
01:29:43 And the children are born again.
01:29:45 This is the assumption that the milk in the mother will not flow for at least two or three days.
01:29:50 But the premature infant is born that way.
01:29:52 He's born dehydrated.
01:29:54 As recommended by Clifford and Smith.
01:29:59 Clifford Smith is Clement Smith, who had written a book called The Premature.
01:30:03 I can say categorically that there isn't a single page of any truth in his book.
01:30:09 I think that these infants vomit and aspirate most frequently with moderately dehydrated.
01:30:15 In other words, he said, that's one of the statements.
01:30:20 Now let's have the next one.
01:30:22 Oh, shoot.
01:30:25 The information deriving the study may be valuable.
01:30:28 Before adopting such a complex regime with all those injections of fluid, etc.,
01:30:32 which is going on right now in this hospital,
01:30:35 one would wish to be sure that such a program of management offers real advantage
01:30:39 over the threat of all methods of current use in large communities,
01:30:43 including every infant born alive.
01:30:55 The gross mortality rates in most centers now approximate the following.
01:30:59 1,000 grams or less.
01:31:01 He says 90 to 100 percent die.
01:31:05 In my study, 9 out of 10 survived.
01:31:09 I had one lady, 500 grams who survived.
01:31:12 Out of the 10, the heaviest one was the woman you saw, weighing about 800 grams.
01:31:18 And that was what brought the state of Illinois down to my level.
01:31:23 45 to 55 percent died.
01:31:25 You take 1,500 grams, you've got well over 3 pounds.
01:31:30 And 1,500 to 2,000 grams, you've got 5 to 15 percent.
01:31:37 And that's his place.
01:31:40 But, you see, they were here with cheating.
01:31:43 Because if a child was born dead, they didn't count them.
01:31:46 If a child was, like in my case, 5 deaths, 4 were delivered dead to the hospital.
01:31:52 I counted them.
01:31:54 May I have the next slide, please?
01:31:58 This is another one.
01:32:00 One interesting statement is that the premature infant has an unusual susceptibility to dehydration,
01:32:06 and a dehydration, in some cases, irreversibly in the first place.
01:32:09 We have yet to observe this in five years.
01:32:11 They didn't observe it for a very good reason.
01:32:14 Because when the child died, they threw him in the trash basket or something.
01:32:17 They never really discovered the fact.
01:32:20 Why did he die?
01:32:21 They say, well, he was a premature.
01:32:23 And they write prematurity on his testicle.
01:32:26 As a matter of fact, most prematures seem to have damage at birth.
01:32:31 That's maybe so, but I've never seen one.
01:32:34 This, indeed, remains for several hours and seems to slowly disappear on the success of 24 to 72 hours.
01:32:41 Rarely have we found it necessary to administer fluids within the first few days of life.
01:32:45 Indeed, most observers probably vote against the administration of fluids for a deadly premature.
01:32:50 Most, they say, for a deadly premature.
01:32:52 If the premature was a deadly, it would be the exception, and I also would not give him fluids.
01:32:59 For fear of further fluid retention.
01:33:01 May I have the next slide, please?
01:33:04 Each one is different.
01:33:06 One is the Philadelphia Lyon Hospital, Hopkins, Harvard, Yale.
01:33:11 An important contribution to this study seems to be the publication of microchemical methods to determine the various fluctuations.
01:33:17 We are, however, not necessarily in agreement with the clinical study.
01:33:20 The evidence can help us work.
01:33:22 An increase in sodium intake is apt to increase the danger of recurrent and final plague.
01:33:26 There's also evidence that premature infusions add to the danger of retroactive final plagues.
01:33:31 That's the nonsense that they wrote in this article, in these articles.
01:33:36 May I have the next slide?
01:33:37 Of course, retroactive final plagues have nothing to do with blood and have nothing to do with salt.
01:33:42 We do not find that a small premature is dehydrated.
01:33:46 You understand that a woman who has an abortion hasn't had fluids for 48 hours sometimes.
01:33:52 Obviously, the infant is born dehydrated.
01:33:55 Nor do they tend to dehydrate sufficiently.
01:33:59 They need peripheral fluids, except in rare instances.
01:34:01 The loss of chlorides is not the usual finding in small premature.
01:34:06 I want to read that again.
01:34:07 The loss of chlorides is not the usual finding in small premature.
01:34:10 Because I'm going to read a rebuttal to that by some of these people.
01:34:15 On the contrary, I suspect normal saline will give them an excess of chloride, which they do not have.
01:34:21 Well, I never used normal saline at any time in my studies.
01:34:26 I was only diluting it with 2.5% salt solution, and it says so up here.
01:34:31 May I have the next slide?
01:34:32 This is another one.
01:34:34 The work of Heckler regarding the relationship between retro-level and high-sodium chlorinated,
01:34:38 as well as blood transfusion of premature,
01:34:40 has an observation that feeding a formula of low-sodium content may be associated with regression of the vascular length of the ER.
01:34:47 That's utter nonsense.
01:34:49 Demands careful evaluation.
01:34:51 The regimen recommended by the present authors is in disagreement with Heckler,
01:34:55 and, of course, it allows them to disagree.
01:34:57 Unless a definite reduction in mortality can be demonstrated,
01:35:00 it should not be encouraged unless we find out how we can decide between two alternatives,
01:35:05 more blind survivors versus poor-looking brain tumors.
01:35:08 And, of course, he was making fun of the fact that I was saying that if you hydrate prematures
01:35:12 and keep them at normal pH, they go home sooner.
01:35:16 May I have the next slide, please?
01:35:20 Considerable emphasis is placed on the so-called responsive interest to the administration of short-employed gazoxy-corticosterone.
01:35:26 However, Weber was at the lowest value for serum-carbonated content,
01:35:30 so we're observing what we get.
01:35:33 The observations in this sample might almost be considered as evidence against the idea of adrenal immaturity.
01:35:40 May I have the next slide?
01:35:41 At that time, after reading all of this, I was a little nervous.
01:35:45 I said, I chose the wrong words.
01:35:47 I should have used loss-solving, salt-losing syndrome, or something like that,
01:35:52 or inability to hold water.
01:35:55 But now, today, 40 years later, there's no question.
01:35:58 It's adrenal immaturity.
01:36:01 Now, this was the only man, and this was Daryl.
01:36:05 Daryl was a very intelligent pediatrician.
01:36:10 He was a friend of Benjamin Kramer.
01:36:12 He knew me, and he knew that I would not publish something that I hadn't proven thoroughly.
01:36:19 So he wrote this.
01:36:20 He's one of the kindest ones.
01:36:22 The views of this article seem obviously heretical.
01:36:25 But since the two prophets appear to be a heretic when he introduces new ideas,
01:36:29 I do not believe in throwing stones at heretics, although many are false prophets.
01:36:34 See, he doesn't know what to make of what I'm saying.
01:36:37 The first and worst heresy is the thought that the premature infants can readily handle large loads of salt
01:36:43 and think that they need extra salt to survive.
01:36:46 That is true.
01:36:47 That statement is true.
01:36:48 I'll soon prove it.
01:36:49 May I have the next slide, please?
01:36:54 I went down with Dr. Crawford, and I was rather apologetic.
01:37:00 Not Dr. Crawford.
01:37:01 He worked with these prematures.
01:37:03 He has had 40 years of experience, and he said there's no question about it, that we are right.
01:37:10 And, of course, in answering them in action, and some of you have gotten a copy of a reprint of this article in which I answer them,
01:37:20 the authors rephrase their work on the problem.
01:37:22 There's a premature infant need that we don't call it a prescription.
01:37:25 That was not the heading.
01:37:27 The heading was something about the maintenance of electrolyte valves in infants.
01:37:34 They changed the heading to read this to make me look bad.
01:37:37 But they didn't, because it turns out that they were doing me a favor.
01:37:42 And we say, was the stimuli of interest in the application of the principle of forward therapy,
01:37:48 which has been successful in older children.
01:37:51 This was taken, according to him, directly out of the book.
01:37:56 Going in, especially in those low-rate ways where mortality statistics are high, and so on.
01:38:02 We go on and answer that.
01:38:04 May I have the next slide, please?
01:38:07 This is still more.
01:38:08 In many cases, after a 24-hour delay, the condition is irreversible, even when fluids were administered intravenously.
01:38:17 We couldn't resuscitate them after 24 hours, so we gave up on that.
01:38:22 This is from the answer to that.
01:38:24 May I have the next slide, please?
01:38:26 The next answer to that came from Burke.
01:38:29 He was the leading critic of this study, and he got a $50,000 grant to prove I was wrong.
01:38:35 He got on the phone one day, and he called me.
01:38:38 He says, Nelson, I have only one thing to say.
01:38:40 You're absolutely right.
01:38:42 And he referred to this paper, which he published in the proceedings of the staff meeting of Mayo Clinic.
01:38:49 Reports of a failure of a premature infant began on a low-salt diet.
01:38:56 That's a big one, 1,600 grams.
01:38:59 After he turned to adequate salt, the brief period of waking was remarkable.
01:39:04 That 1,000 grams was gained in 20 days, giving him salt.
01:39:09 So he supported the idea that salt was necessary.
01:39:12 Now let's get to the next one.
01:39:14 This is the best one of all.
01:39:18 Brian Smith, who was the archenemy and who was being attacked by me,
01:39:24 got a $100,000 grant from the NIH to prove that I was wrong.
01:39:29 And here's what he wrote.
01:39:32 O'Brien, Anson, and Smith have again shown hemoconcentration associated with obvious physical signs
01:39:41 in premature infants not treated with fluids and a rising chloride level.
01:39:46 He observed an infant whose hydration was maintained.
01:39:50 Can you push this over?
01:39:53 By mists.
01:39:55 And he introduced, he now admitted in the article that they were dehydrated for the first time.
01:40:01 In his book, which he wrote, he said that premature infants are born overhydrated.
01:40:05 But now he admitted they were dehydrated and they needed fluids.
01:40:09 So I said to Crawford, I said, now that he's using mists, we will get him.
01:40:16 So I gave Crawford the ammunition.
01:40:19 You know why?
01:40:20 Because in the mists they were using aloe vera.
01:40:23 And the fellow who made aloe vera was me, you see.
01:40:26 And what I used in aloe vera was the sodium salt of octophenol sulfate,
01:40:32 which I made from my doctorate thesis, and I knew it was awful as hell.
01:40:36 So let me have the next slide, please.
01:40:41 I gave this slide to Crawford, who was the pediatrician.
01:40:46 And this was, he took a child and he took the chemistry, sodium, potassium, chloride, pH.
01:40:54 This was the child to begin with.
01:40:56 He did this with a normal child.
01:40:58 He then used mists, and he used a full-term child because he didn't want to kill him.
01:41:03 At six hours, sodium had gone to 143, and the chloride had dropped.
01:41:09 And you can see that the pH, of course, didn't show.
01:41:12 It started to show a little alkalosis.
01:41:14 At 12 hours, the child was in bright alkalosis, 148 sodium and 90 chloride.
01:41:21 And at 24 hours, he had 152 sodium and 85 chloride.
01:41:27 This killed mists.
01:41:29 All over the country, you saw them spraying mists.
01:41:32 After this slide was shown at the pediatric meeting in Chicago,
01:41:37 the parent ran home with his tail between his legs, and that was the end of mists.
01:41:43 May I have the next slide?
01:41:46 Now, since that time, every year, a paper comes out, at least one a year, sometimes two,
01:41:53 claiming that premature needs salt.
01:41:56 And a paper appeared by these people here in 1978,
01:42:02 and it was reviewed in Pediatric Currents.
01:42:06 It said, these data suggest that the daily sodium requirement of premature sick infants
01:42:11 will be much higher than was previously thought.
01:42:14 Each one makes a discovery.
01:42:16 None of them refer to nails.
01:42:18 In such cases, the investigations say urinary sodium should be monitored
01:42:22 and sodium intake adjusted to prevent hyponatremia in the first days of life.
01:42:27 And if you read it carefully through, they're saying the same thing that I said in 1951.
01:42:33 May I have the next slide, please?
01:42:36 Nothing has been so documented.
01:42:38 Now, I bring this slide out to show what effect these people had.
01:42:44 I have an assistant by the name of Sidney Godfrey.
01:42:47 Sidney Godfrey said he needed a paper.
01:42:50 He wanted to apply for a job.
01:42:52 So I said, you can make an easy paper.
01:42:55 Just take a nails and blood collecting tube and go up on the floor
01:42:59 and collect the blood of over 50 or so newborn infants and do the hematocrit.
01:43:06 But there was no data on hematocrit, but he did that.
01:43:09 And he showed, of course, 60, 50, 60, and 90.
01:43:13 So he sent the paper into the Journal of Pediatrics.
01:43:18 It should be edited, but Charles Levine,
01:43:21 the fellow whom I had castigated because of his high-protein milks.
01:43:26 So he rejected the paper and said,
01:43:28 if you take out the reference to Nielsen, I'll publish it.
01:43:31 The paper was published without a reference to Nielsen.
01:43:34 That's why for the last 40 years there's been a blockade in the literature.
01:43:38 Nobody refers to Nielsen when it comes to this subject.
01:43:43 Now, the result of this work was this child was born not adrenally immature,
01:43:50 but adrenally insufficient.
01:43:53 In other words, the child was born with practically no adrenals.
01:43:57 The result was that the child had two siblings that had died,
01:44:02 full-term children had died, and this one finally was born.
01:44:05 And I made the diagnosis by analyzing the blood.
01:44:10 And I said the sodium chloride is low.
01:44:12 They have 65 chloride and 105 sodium.
01:44:17 The kid needs salt.
01:44:18 So the kid was given salt, and then was given some didoxycorticofluorone,
01:44:22 but basically was, since it could suck so many grams of salt over,
01:44:28 I don't know how much he was giving a day,
01:44:31 but he was giving them enough salt to maintain the level.
01:44:34 The child then went home,
01:44:36 and this is what the child looked like at about two years of age.
01:44:41 The child moved to Chicago, and who should his doctor be but Dr. F.,
01:44:46 who was head of the pediatric division at Michael Reese Hospital.
01:44:51 Dr. Nielsen's crazy, and he took away the salt from the kid
01:44:55 and put her on a low-salt diet.
01:44:58 She was readmitted 48 hours later, maybe three days later, to Rockford.
01:45:04 They drove her to Rockford at 2 o'clock in the morning,
01:45:06 and with a circulatory collapse, the veins were all white.
01:45:10 I managed to get a little blood, and she had 65 chloride.
01:45:14 Before Dr. Crawford could get there and give the child a transfusion,
01:45:19 the child expired.
01:45:20 So this child was executed because of the fact that they refused to believe
01:45:25 that these children needed salt.
01:45:27 May I have the next slide, please?
01:45:33 Now, I took this picture not too long ago in the hospital.
01:45:36 I don't remember where, but if you go up on the third floor here,
01:45:39 that's what you'll see.
01:45:41 They were talking about all these fluids.
01:45:44 The kids up on the floor here have twice as many as me.
01:45:47 They have attachments all over the body.
01:45:50 Dr. Meininger was talking about getting data without invading the body
01:45:54 and getting blood.
01:45:55 The premature nurses were doing that all the time.
01:45:58 They're getting PCO2, PO2, and other data by various types of electrodes.
01:46:04 This is what a premature looks like.
01:46:06 This is a pretty big one.
01:46:08 I would say that this is pretty close to maybe 2,000 grams or more.
01:46:16 The child has a polyethylene tube in him, and he has everything else.
01:46:22 May I have the next slide, please?
01:46:26 I'm going to show this slide again.
01:46:28 Can you raise your phone?
01:46:31 It didn't drop.
01:46:32 It didn't drop.
01:46:33 Let me try again.
01:46:34 We're going to go backwards and then forwards.
01:46:38 The outcome of the Nielsen studies were those same points that I made before,
01:46:43 and I believe that I have shown two facts at least.
01:46:47 I've shown that the general feeling at that time was that salt
01:46:51 and water treatment to prematures was not an acceptable procedure
01:46:57 and that I was the first one to introduce that idea
01:47:00 and that that idea has now been shown to be the general practice.
01:47:04 You can't walk into a hospital anywhere in the United States
01:47:07 where they have an acute program for infants without seeing children look just like that
01:47:17 with polyethylene tubes and so on.
01:47:19 One of the critics said,
01:47:21 I would hate to put polyethylene tubes in all the children's noses.
01:47:25 They would develop rhinitis, infection,
01:47:27 and they gave a whole list of diseases that they would get with polyethylene tubes.
01:47:32 Well, it just isn't true.
01:47:34 You see, if you remove the tube periodically,
01:47:37 now you wash it and clean it and put it back in there.
01:47:40 So I went upstairs and I said to the kid there,
01:47:47 I said, you see this floor here that Sangeet has set up?
01:47:51 They said, yeah.
01:47:52 I said, I'm the grandfather of that.
01:47:55 But you have to tell them who taught Reggie Sange how to do calciums.
01:47:58 Pardon me?
01:47:59 You have to explain to everybody who taught Reggie Sange how to do calciums.
01:48:03 How to do calciums?
01:48:05 Remember he was at Michael Rees Hospital?
01:48:07 Well.
01:48:09 I was not the inventor of the calcium procedure.
01:48:18 No, no, but you showed Reggie Sange at Michael Rees Hospital how to do calciums.
01:48:23 Wasn't Reggie Sange a resident at Michael Rees?
01:48:26 Sange was at Michael Rees.
01:48:28 But we were doing it by atomic absorption by that time.
01:48:33 Incidentally, in that book that I had,
01:48:37 there isn't a single method that's used today.
01:48:40 And therefore, what I'm saying is the clinical chemist is not known for the methodology.
01:48:45 Because the methodology of today is obsolete tomorrow.
01:48:49 The clinical chemist is known for what he does in connection with developing new and better ways of treating disease
01:48:55 and working with a physician in solving these problems.
01:48:59 And I pride myself not on the methodology because that's all obsolete.
01:49:04 I pride myself on the fact that I was able to contribute to the treatment of hypercalcemia,
01:49:11 to the treatment of, in this particular case, in this area,
01:49:16 to the maintenance of the premature and to the general maintenance of the newborn infants.
01:49:22 And that is the most important thing.
01:49:24 And I couldn't have done it without the help of about 25 or 30 doctors.
01:49:29 And that's what the clinical chemist's job is,
01:49:33 to work with the medical staff in seeing that the patient gets a better care.
01:49:39 Thank you.
01:49:41 Thank you.
01:50:03 Thank you very much, Dr. Nadelson.
01:50:05 It was certainly a stimulating presentation.
01:50:08 Dr. O'Rourke and almost all of our hospitals, I don't mind, have a very active neonatal unit,
01:50:13 with all of this testing done continually.
01:50:17 And I suppose in the next five or six years, we're not going to have to use raw blood to do all that.
01:50:22 The basic principles will still be there.
01:50:24 Thank you for doing this.
01:50:26 I think Mikey's going to be right this time.