Physiology on the sub-way map of science

By way of Chad Orzel and Derek Lowe I came upon Crispian Jago's wonderful sub-way map of science. While he actually presents his quite fantastic map as : "500 Years of Science, Reason & Critical Thinking via the medium of gross over simplification, dodgy demarcation, glaring omission and a very tiny font," I have to take umbrage for physicians and physiologists everywhere. Albrecht von Haller wasn't the only physiologist who did anything in the 18th century, and I think we existed, at least partially separate from "Natural History" in the 16th and 17th centuries. Above all, the science of Medicine certainly did not turn into "21st Century Microbiology!"

How, then, should this be put right?

Well, with a blog-post obviously. But first microbiologists deserve a line of their own, even if it will intersect with the line of medicine in quite a number of places. This is their problem. The medicine-line should be renamed "Medicine and Physiology", neurology is either a medical speciality or a branch of physiology. It could, of course, be argued that neuroscience/neurology/psychology should have a line of its own, but I leave that to the neuroscientists.

The freed-up line called "Medicine and Physiology" should start at Vesalius. Unless you want to go back to earlier times. Given the extent of the map, it may be wise to stop at the 16th century.

Hooke, Harvey, Malpighi and some others should be included on this new line. Now to the additions:

16th Century

• Paracelsus (founding father of toxicology and early enlightened surgeon who suggested that wounds shouldn't be cauterised).
• Bartolomeo Eustachi (One of the first anatomists, although his work wasn't published until 1714: Tabulae Anatomicae).
• Ambroise Paré (1545: Wrote the first non-Latin/Greek textbook in surgery and was one of the original great experimentalists in surgery).

17th Century

• Olof Rudbeck (1651: described the lymphatic circulation).
• Lorenzo Bellini (1662: Exercitatio Anatomica de Structura Usu Renu).

18th Century

• F. Pourfois du Petit (1727: shows vasodilation in the eye following denervation).
• Stephen Hales (1733: Haemastatics).
• Giovanni Mrogagni (1761: The seats and causes of disease).
• John Hunter (1794: A treatise on blood, inflammation and gun-shot wounds).
• Alexander Schulmansky (1783: De structura renum).

19th Century

• Hanaoka Seishu (1804: first known use of anaesthesia).
• Charles Bell (1811: sensory and motor nerves).
• Richard Bright (1827: renal disease and oedema).
• Jean Louis Marie Poiseulle (1828: measures blood pressure, 1841: fluid dynamics in small tubes).
• William Bowman (1842: On the structure and use of the Malpighian body of the kidney).
• Carl Ludwig (1842: describes glomerular filtration as physical forces).
• Emil du Bois-Raymond (discovers the neural action-potential).
• Adolf Fick (1855: describes law of diffusion that bears his name, and later used it to measure cardiac-output).
• Karl von Vierordt (1855: measures the arterial pulse pressure).
• Jakob Henle (1862:Described the loop of Henle's, and together with Robert Koch formulated the "Henle-Koch postulates").
• William Gull (1872: microvascular disease).
• Camillo Golgi (Described large parts of the nervous system and received the Nobel Prize in 1906. In addition he described how the distal tubule returns to the originating glomerulus, an important finding in kidney physiology).
• Scipione Riva-Rocci (1896: Presented his method for measuring blood pressure, which is still used today).
• Robert Tigerstedt (1898: showed the existence of Renin the first identified hormone).

20th Century

• Victor Henri (1901: Describes the Henri-Michaelis-Menten equation for enzyme kinetics).
• Leonor Michaelis and Maud Menten (1913: provides their insight on enzyme kinetics).
• Ernest Starling (Describes the exchange of fluid over the capillary membrane in the Starling equation, then goes on to describe the Frank-Starling law of the heart, and then goes on to describe the idea of hormones).
• Otto Frank (Describes the Frank-Starling law of the heart).
• August Krogh (Treated diabetes with insulin).
• Ewald Hering (1924: Discovered the baro-receptor and their role in blood pressure regulation).
• Joseph Wearn & Alfred Richards(Establishes glomerular ultrafiltration as described by Carl Ludwig by micropuncture).
• Werner Forssman (1929: performs the first human heart catheterisation, on himself).
• Homer Smith (Describes the nephrons as autonomous working units in the kidney, and much more).
• Harry Goldblatt (1934: Establishes the first experimental model of hypertension).
• Arthur C. Guyton (1955: proposes that cardiac out-put is governed by periferal resistance, measures interstitial pressure and shows that it is negative, and goes on to show how the kidney regulates blood pressure).
• Carl Gottschalk (1959: shows that the concentrating mechanism in the kidney is dependent on a counter-current system).
• Edward D. Freis (1960: presents the first ever double blinded, controlled clinical trial).
• Robert Furchgott (1980: Discovers the endothelial derived relaxing factor, and goes on to show that this is nitric oxide in 1986).

And then there are any number of still living physicians and physiologists who could be included.

Before it, in the end, turns into "21st Century Medicine and Physiology" and nothing else.

At least, that is the view of a nephrophysiologist. I know. There are physiologists and physicians who aren't into kidneys, but I always try to have hope: They will convert in the end.

Experimental Biology - first morning

It is conference time for physiologists. Experimental Biology is by far the largest meeting for physiologists, and this year it's in Anaheim, California, right beside Disney Land. Now it's the morning of the second day. It is 5.30am and I can't sleep.

It started yesterday with the traditional refresher course. I feel a little bad for them, because I just couldn't take four hours of sitting down, so I only stayed for the first two and a half - even though the last talk looked like lots of fun. Of course, now in the days of the internet, I can just go and listen to the recording at www.the-aps.org/education/refresher.

The first two were really good, Donna Korzick talked about how:

"The Heart Develops Pressure, And Pressure Makes the Blood 'Go Round"

Which turned out to be mostly charge excitation coupling and pacemaker activity, including some exciting new data on how local calcium releases actually drives the slow depolarisation (see Lakatta et al, Circ Res, 106: 659-673, 2010).

Then Philip Clifford talked about "Local control of blood flow." He showed some really nifty confocal images of vascular structure and then talked about autoregulation. Not proper, renal autoregulation, but the sloppy kind you find in other organs. Most interestingly he pointed out that the myogenic response is a quite slow mechanism in muscle tissue, for example. Taking somewhere around two minutes to return blood flow to normal after a perturbation. In the kidney, bloodflow quickly stabilizes (20-30 seconds) following a perturbation. Although some of this is probably because of interactions between the myogenic response and the tubuloglomerular feedback, I think I brought home that myogenic response is faster in the kidney.

The afternoon brought a guest appearance of renal circulatory physiology at the micro circulatory society. You might call it a refresher course in renal autoregulation and afferent arteriolar function provided by the usual suspects, Arendshorst, Peti-Peterdi, Inscho. There was a small detour to the medulla. Pallone presented some very interesting data on how water shunting from the descending vasa recta to the ascending helps increase the concentrating capacity.

Last of the days lectures was the Walter B. Cannon memorial award lecture. This year it was awarded to JJ. Fredberd of the Harvard School of Public Health, an engineer who works in pulmonary physiology and probably wil receive the Nobel Prize in medicine for his evolutionary findings. A fantastic lecture, where he presented more novel ideas (with supporting data) in less time than anyone I have met in recent memory. In short, cells are soft as shaving foam because it makes them capable of eating their neighbours and/or crawling around. This explains the development of the eucaryote. I will have to study this for years before I understand it, maybe I will attempt a post on the implications for renal physiology at some later time.

Finally it was time for the free food and free beer, i.e. the opening reception.

The time when the breakfast buffet opens is approaching and I have to go.

/M

First recorded nephrology experiment?

I like finding original documentation for the facts in science that are generally accepted, and for which experimental evidence is seldom or never given. I hope to write a series of these small notes concerning the history of experimental renal physiology.

One can assume that the association between the kidneys and urine production has been known since the first time pre-historic man, or woman, killed an animal and ate the kidneys. There has however been considerable discussion through the ages what the relative roles of the kidneys, the urethers and the bladder actually are.

Around 360 B.C. Plato wrote in "Timaeus" that:

“The outlet for drink by which liquids pass through the lung under the kidneys and into the bladder, which receives and then by the pressure of the air emits them...” (from the Internet Classics Archive at MIT, translated by Benjamin Jowett.)

He then goes on to describe the use of the actual outlet in sexual intercourse.

Somewhere around the same time Aristotle has a surprisingly correct description in "On the parts of animals":

"A pair of stout ducts, void of blood, run, one from the cavity of each kidney, to the bladder; and other ducts, strong and continuous, lead into the kidneys from the aorta.

The purpose of this arrangement is to allow the superfluous fluid to pass from the blood-vessel into the kidney, and the resulting renal excretion to collect by the percolation of the fluid through the solid substance of the organ, in its center, where as a general rule there is a cavity.

From the central cavity the fluid is discharged into the bladder by the ducts that have been mentioned, having already assumed in great degree the character of excremental residue." (Part 9. Also from the Internet Classics Archive, translated by William Ogle.)

However, even though some dissection must have taken place, neither Plato nor Aristotle describe the methods behind their conclusions. I have read somewhere that it was not fashionable to refer too closely to the real world at the time. The world of ideas (platonic) was thought to exist independently of the real world and all important conclusions could be arrived at through contemplation and deduction.

Quite a bit later Galen or Claudius Galenus describes what I believe is the oldest surviving description of a scientific experiement in renal physiology. Seeking to show that the urine is produced in the kidneys and passed through the urethers to the bladder, Galen writes:

"Now the method of demonstration is as follows. One has to divide the peritoneum in front of the ureters, then secure these with ligatures, and next, having bandaged up the animal, let him go (for he will not continue to urinate). After this one loosens the external bandages and shows the bladder empty and the ureters quite full and distended- in fact almost on the point of rupturing; on removing the ligature from them, one then plainly sees the bladder becoming filled with urine." ("On the Natural Faculties", book 1, chapter 13, from the Internet Classics Archive, translated by Arthur John Brock).

It is ofcourse not a very humane experiment given that anaesthesia was not developed for another 1600 years or so. I have not found any date of publication, but given that he lived from year 129 to year 200 it is the oldest fairly solid experimental description in nephrology I have been able to find.

Do you know of any older records?

Please chime in,

Michael