|On 8 December 1664, while on a visit to Paris, Swammerdam carried out a gruesome but intriguing experiment in front of Olaf Borch, a Danish botanist who left a clear account of the study in his diary .
Swammerdam cut the heart out of a living, unanaesthetized frog and showed that this had no effect on its ability to move: the severely damaged animal would carry on swimming about. On the other hand, if the brain was removed, movement ceased.
Swammerdam concluded that the circulatory system was not necessary for movement at least in a frog (it wouldnt have worked in a dog!) and that the brain was required for co-ordinated movements such as swimming.
But Swammerdam then took the dying frog, its body bloody and gaping, and showed that if he stroked his scalpel on the severed nerve ends around the wound, the muscles contracted.
This result, which he had observed informally in 1662 when dissecting dogs, showed that movement could occur without any connection between the muscle and the brain, thus putting paid to the predominant theory, put forward by Descartes, that movement took place following the transmission of fluid animal spirits from the brain to the muscles, through the nerves.
Furthermore, the fact that what Swammerdam called irritation could lead to movement strongly suggested that animal spirits were not involved in nervous transmission and muscle movement at all.
Over the next three years, Swammerdam perfected his experiment and his vision of its implications, aware that the frog was particularly appropriate for such studies because the nerves are very conspicuous in these animals, and may be easily discovered and laid bare.
He made a brief description of the effects of irritating a nerve, in his anonymous 1665 article In ranis (On the frog), and in his 1667 doctoral thesis he publicly demonstrated that the movement of the dogs diaphragm could also be produced by stimulating the cut nerve.
At the same time, he tried to see whether the same effect could be observed in an isolated nerve-muscle preparation: Another very delicate and useful experiment may be made, if one of the largest muscles be separated from the thigh of a Frog, and, together with its adherent nerve, prepared in such a manner as to remain unhurt.
This instantly recognisable procedure, which has been described as one of the most important experiments of the century , has since become a classic, being widely used in neurobiological studies and also repeated in high schools the world over.
The initial demonstration simply involved holding the muscle then stimulating the nerve :
if [...] you take hold, aa, of each tendon with your hand, and then irritate b the propending nerve with scissors, or any other instrument, the muscle will recover its former motion, which it had lost. You will see that it is immediately contracted, and draws together, as it were, both the hands, which hold the tendons.
Not satisfied with demonstrating the effect only to the person holding the muscle, Swammerdam then proposed a more precise version of the same experiment:
If we have a mind to observe, very exactly, in what degree the muscle thickens in its contraction, and how far its tendons approach towards each other, we must put the muscle into a glass tube, a, and run two fine needles bb through its tendons, where they had been before held by the fingers; and then fix the points of those needles, neither too loose nor too firmly, in a piece of cork. If afterwards you irritate, c, the nerves, you will see the muscle drawing dd the heads of the needles together out of the paces; and that the belly of the muscle itself becomes considerably thicker e in the cavity of the glass tube, and stops up the whole tube, after expelling the air. This continues till the contraction ceases, and the needles then move back into their former places.
In principle, this procedure could have transduced the contractile power of the muscle into a measurable scale one of the key features of the scientific revolution was the mathematization of natural phenomena.
Swammerdam then went on to put the final nail in the coffin of Descartes vision of nerve function when he used the same frog nerve muscle preparation to demonstrate that, against Descartes fundamental prediction, muscles do not increase in volume when they contract. (Click here for more details.)
Swammerdam was acutely aware that he had discovered something vitally important. He had shown that animal spirits, whether they were like water, fire or air, were not involved in movement:
From these experiments, therefore, it may, I think, be fairly concluded, that a simple and natural motion or irritation of the nerve alone is necessary to produce muscular motion, whether it has its origin in the brain, or in the marrow, or elsewhere.
And, as he made quite clear in his later presentation of the results, this was not something that was specific to the frog or to its thigh muscle: these were Experiments on the particular motion of the muscles in the Frog; which may be also, in General, applied to all the motions of the muscles in Men and Brutes.
Although the full details of these experiments were not finally published until over 50 years after his death, they were widely known in the early modern European scientific community. Swammerdam would demonstrate them to the rich and influential visitors who came to see him at work, such as the future Grand Duke Cosimo III of Tuscany, who visited him in Amsterdam in 1668.
Furthermore, Swammerdam was in close contact with some of the most influential figures in science, such as his student friend the Danish anatomist Nicolas Steno, and two of the driving forces that organized early modern science, the Frenchman Melchisedec Thévenot, who was partly at the origin of the foundation of the Académie des Sciences, and the first secretary of the Royal Society, Henry Oldenburg .
By a network of letters, visits and discussions, such contacts ensured that knowledge of Swammerdams findings spread rapidly, even in the immediate absence of detailed experimental descriptions.
Swammerdams experiment was typical of the scientific revolution - not only did it lead to a major discovery, it also showed what was new and powerful about science itself:
It dealt with a phenomenon that was completely unsuspected and which went against centuries of ideas about the natural world. The clinging cobwebs of tradition and authority were blown away by experimental audacity. By turning to the study of the novel, rather than re-hashing the accepted, science provided itself with a vital tool to create a new vision of the world and, ultimately, to change that world.
It showed the power of the reductionist method. Swammerdam literally reduced the frog to its component parts, in this case a nerve and a muscle, and suggested that something could be learned about the behaviour and organisation of the whole frog - indeed of all animals - on the basis of this example.
It showed the relation between biological and mechanical phenomena. Swammerdam effectively transformed the nerve-muscle preparation into an instrument that in principle could provide quantitative information. And within this instrument, the biological component played a simple mechanical role, implying that, in natural movement also, muscles and nerves could be compared to mechanical components.
It was backed up by detailed description that showed the reader how the experiment could be carried out. This was a hallmark of the development of science and its ability to spread across the globe and down the subsequent centuries.
From irritation to stimulus-response
Swammerdams research also set the intellectual stage for the development of more complex theories of behaviour and nerve function, based not on Cartesian hydraulics, but on mechanics. For neuroscience, the most important thing about this series of experiments was that Swammerdam had shown that movement was the due to the external stimulation (irritation) of the nerve.
The decisive connection between stimulus and response conceived of by Swammerdam was part a revolutionary mechanistic view of the organisation of the body and behaviour. Abandoning all talk of spirits, this view stated simply that when something happened to the animal (or to part of it), it responded, much as releasing a brake would set a machine in motion. Descartes view of the body as a machine was applied thoroughly, down to its smallest components.
This view was not only revolutionary in its immediate context, it had continuing reverberations down the centuries: without this view triumphing somewhere and somewhen, modern neuroscience would look very different.
Swammerdams discovery was the basis of all that followed: it led directly to the conception that an organisms behaviour could be understood in terms of the sum of the stimuli that it received, which was in turn the basis of all the theories of learning that appeared in the 20th century, and in particular of Pavlovs conception of conditioned reflexes and J. B. Watsons behaviourism.
All that from a simple experiment on a frog nerve.
The final phase of Swammerdams work on nerve function came in the 1670s, as he sought to understand his results. He had clearly shown that nerves did not function through animal spirits, but he had not found any explanation of how irritation might lead to movement.
Although he felt that the true answer lay buried in impenetrable darkness, he nevertheless rose to the challenge and outlined both a strategy for studying the phenomenon and an analogy. First, he reiterated why the traditional view was wrong:
I would have it seriously considered, that it cannot be demonstrated by any experiments, that any matter of sensible or comprehensible bulk flows through the nerves into the muscles. Nor does any thing else pass through the nerves to the muscles: all is a very quick kind of motion, which is indeed so rapid, that it may be properly called instantaneous.
He then put forward the following analogy:
Therefore the spirit, as it is called, or that subtile (sic) matter, which flies in an instant through the nerves into the muscles, may with the greatest propriety be compared to that most swift motion, which, when one extremity of a long beam or board is struck with the finger, runs with such velocity along the wood, that it is perceived almost at the same instant at the other end.
This statement provides an explanation for nervous transmission which was in keeping with the most radical mechanistic conceptions of the time. In itself, the use of such an analogy is a striking confirmation of Swammerdams status as one of the foremost thinkers of the scientific revolution with regard to physiology and anatomy it is far more novel than Descartes idea of fluid animal spirits.
And tantalizingly, he was not so wide of the mark - the transmission of the action potential down the axon is based on a cascade of biochemical phenomena, just as a vibration travels down a plank by a cascade of interactions between molecules. However, it is not clear what contemporary experiments might have flowed from this analogy, and it is hardly surprizing that neither Swammerdam nor anybody else followed up this insight.
He then went on to suggest that, because it was so difficult to investigate nerve action in animals, a useful approach would be to make a comparative study of movement in plants such as the sensitive plant.
Although it is unlikely that any further insights into nerve function would have arisen. from such a study, because of the different bases of movement in plants and animals, this suggestion was nevertheless important because it formed part of the comparative method that was a key aspect of the development of science.
These are perceptive speculations, based on the most developed contemporary knowledge and the most powerful analogies available. Their immediate impact, however, was relatively limited: the gulf between the knowledge that would be required to fully investigate and exploit them and that which was available to contemporary investigators was too great. They remain as brilliant but inevitably fruitless insights.
Nerve function after Swammerdam
Despite Swammerdams clear demonstration, the animal spirits had a long life ahead of them.
A few years after Swammerdam resolved the problem, Giovanni Borelli (1608-1680), a pupil of Galileo who had been Professor of Mathematics at Pisa and Messina before going to work in the court of Queen Christina of Sweden, began working on the nature of animal movement, focusing on a mathematical interpretation of muscle function.
In his posthumous work De Motu Animali (1680-81), Borelli followed Swammerdams insight by arguing that what moved down the nerve was a commotion or oscillation, but, like Descartes, he maintained that there was a fluid within the nerves a succus nerveus spirituosus that contributed to the inflation of muscles on contraction.
In the first part of the 18th century thinkers continued to invoked animal spirits to explain nerve function, even those who were well aware of Swammerdams work, such as his editor, the great Dutch physician Herman Boerhaave.
For some scientists, and especially for physicians, it was better to pursue a vague but wrong explanation that could at least lead to a spurious diagnosis and treatment than to admit that there was no satisfactory explanation for what the commotion irritation or vibration was, nor how it moved down the nerve.
In 1751, Albrecht von Haller (1708-1777) who knew of Swammerdams work and was extremely admirative of it6, tried to define and study nervous irritability, but was unable to come to any precise explanation, although he did explicitly rule out the role of electricity .
The decisive breakthrough came at the end of the 18th century, when Luigi Galvani (1737-1798), dissected a frog on the same bench as an electric machine and discovered by chance that muscles responded to external electrical stimuli . He went on to reason that it was probable that the internal factor responsible for movement was also electrical.
Even on this point, it is possible that Swammerdam unwittingly got there first .
One of Galvanis decisive experiments was to show that movement could be induced by stroking an iron plate against a brass hook inserted into the frogs spinal column, which generated a small electric current. In one version of Swammerdams nerve muscle experiment, the nerve was suspended in a brass hook, which was then stroked with a silver wire:
It is possible that this induced a small electrical current which gave rise to the subsequent muscular contraction.
This page is excerpted and adapted from an article published in Nature Reviews: Neuroscience, May 2002, Vol 3, pp395-400.
To download the full article, in PDF format, cliclk here.
The Nature Reviews: Neuroscience website can be found here.