Why Joseph Erlanger Rejected the Local Circuit Theory of Nerve Impulse Propagation
Greg Gandenberger
University of Pittsburgh, Department of History and Philosophy of Science
1017 Cathedral of Learning, Pittsburgh, PA 15260.
Abstract
In the 1920s and 1930s, Joseph Erlanger and his colleagues expressed doubts about the local circuit theory of nerve impulse propagation in some of their publications. In 1934, their scepticism inspired Alan Hodgkin to begin a series of experiments that are generally regarded as providing strong support for the local circuit theory. Hodgkin’s experiments are well known, but the nature and sources of Erlanger’s scepticism are not. In the mid-1920s, Erlanger believed that oscillograph recordings indicated that the eddy currents generated by action currents are too small to propagate the nerve impulse as the local circuit theory proposes. In the 1930s, his fundamental objection to the local circuit theory was his belief that eddy currents large enough to propagate nerve impulses would dissipate a large amount of energy and produce uncontrolled stray effects. However, a 1936 discovery led him to admit that eddy currents do at least increase the excitability of an active fiber ahead of the action current wave. His opposition to the local circuit theory diminished further as a result of several developments between late 1938 and early
1939, including most notably Hodgkin demonstration that the resistance of the medium outside the active nerve affects propagation velocity.
Word Count: 7467
Keywords
Joseph Erlanger; Alan Hodgkin; local circuit theory; membrane theory; St. Louis School; electrophysiology
1. Introduction
Early in his 1934-1935 year as a Cambridge undergraduate, Alan Hodgkin discovered that a blocked nerve impulse increases the excitability of the nerve beyond the block. He realized that it would be easy to explain this increase in excitability as the effect of eddy currents flowing ahead of the propagated action current in accordance with the local circuit theory of nerve impulse propagation (Hodgkin, 1976, pp. 3-4). Later in that school year he realized while reading the papers of the “St. Louis School” that many leading physiologists were, as he put it,
“thoroughly sceptical both of the membrane theory in general and of the local circuit theory in particular” (Hodgkin, p. 4). Spurred on by their doubts, he decided to investigate whether the increase in excitability beyond a block was in fact an electrical effect as the local circuit theory suggested.
Key experiments Hodgkin performed during his investigation of the local circuit theory are now regarded as classics in the history of physiology.1 However, little is known about the views of the St. Louis School that lay behind the expressions of scepticism that helped inspired
1 The most notable of these experiments are presented in Hodgkin (1937a), (1937b), (1939). These experiments are often cited in elementary physiology textbooks, such as Aidley (1998), pp. 46-47.
Hodgkin’s work. This paper begins to address that gap by discussing Joseph Erlanger’s views about the local circuit theory. Erlanger was the senior member of the St. Louis School. Hodgkin quotes his objections to the local circuit theory in his autobiography (Hodgkin, 1994, pp. 74-75), but those objections are difficult to understand without more historical context than Hodgkin provides. For instance, Hodgkin quotes Erlanger’s claim that the local circuit theory seemed to him “teleologically…queer” (Hodgkin, p. 74; the original quote is from Erlanger, J., 1910-1965,
Erlanger to Hodgkin, January 6, 1937). This statement and others like it that Erlanger made around the same time are quite important for understanding Erlanger’s opposition to the local circuit theory, but they are rather obscure by themselves.
An examination of both published and unpublished writings by Erlanger and his colleagues reveals that Erlanger had two fundamental objections to the local circuit theory. First, he believed that the eddy currents flowing in front of an action current wave are too small to re- excite the nerve fiber. Second, he believed that if eddy currents were large enough to re-excite the nerve fiber, then they would produce substantial current leaks away from the active fiber, dissipating energy and producing stray effects. The first objection crystallized between 1924 and
1926, while the second manifested itself between 1932 and 1936. This second objection underlay Erlanger’s claim that the local circuit theory is problematic teleologically.
Erlanger’s opposition to the local circuit theory diminished between 1936 and 1939. The details of exactly how and when Erlanger’s opinions changed are not entirely clear from the available documents, but some broad conclusions can be drawn. Erlanger did not argue against the local circuit theory after his January 6, 1937 letter to Hodgkin, either in print or in any of his correspondence that I have examined. However, Hodgkin reported that Erlanger was still “very sceptical” of the local circuit theory when Hodgkin visited Erlanger in St. Louis in April 1938
(Hodgkin, 1994, p. 113). Soon after that meeting Hodgkin met a challenge Erlanger had posed to show that changing the resistance outside the active fiber changes its conduction velocity. It seems that even after he learned about that result, Erlanger continued to entertain the possibility that chemical as well as electrical processes are involved in propagating nerve impulses.
However, he no longer questioned that claim that eddy currents are essential to that process.
This paper is organized as follows. §2 concerns the period between 1924 and 1926, during which Erlanger argued privately that oscillograph records indicate that eddy currents are too small to be responsible for propagation. §3 concerns the objections to the local circuit theory that Erlanger presented between 1932 and 1936, which were based on the assumption that propagation by eddy currents would be messy and inefficient. §4 concerns the decline of
Erlanger’s opposition to the local circuit theory that took place between 1936 and 1939.
2. Erlanger’s first objection: eddy currents are too small to account for propagation (1924-
1926)
In 1922, Erlanger and his colleague Herbert Gasser introduced the cathode-ray oscillograph into electrophysiology (Erlanger & Gasser, 1922). George Bishop was brought on as a collaborator in 1923 (Bishop, 1965, p. 1), when Gasser went to Europe for a two-year research leave (Gasser, 1964, p. 10). Their oscillograph could follow the rapid voltage changes that occur during a nerve impulse with far greater fidelity than previous recording techniques.
Among other contributions, it promised to provide evidence relevant to the local circuit theory by revealing the size of the eddy currents that flow ahead of the action current wave. However,
Erlanger, Gasser, and Bishop disagreed among themselves about the size of the “foot” their
action current records contained. That is, they disagreed about how much of their action current records should be attributed to eddy currents rather than to the action current proper. Erlanger and Gasser believed that the foot was negligible, which led them to doubt the local circuit theory.
Bishop maintained that the foot was large enough that its size did not provide a strong objection to the local circuit theory.
The theoretical context within which this debate took place extends back into nineteenth century. The local circuit theory has its roots in the “Strömchen theory” Ludimar Hermann proposed in the 1872 edition of his Grundriss der Physiologie des Menschen (pp. 323-324; see also Hermann, 1879, pp. 193-194). In that work, Hermann pointed out that the travelling wave of electronegativity associated with the nerve impulse should cause eddy currents to flow into the excited region from neighboring unexcited regions. Such currents would repolarize the excited region and depolarize the unexcited regions. They would thereby tend to restore the excited region to its resting state while exciting the neighboring regions. Hermann proposed that the nerve impulse could propagate itself electrically in this way.
Hermann combined this electrical theory of nerve impulse propagation with a chemical theory of the impulse itself (e.g. Hermann, 1867). In the early twentieth century, Bernstein developed the “membrane theory” as an alternative account of the nerve impulse (e.g. Bernstein
1902, 1912). According to the membrane theory, chemical transformations do not play a central role in the nerve impulse. The electrical phenomena associated with the nerve impulse arise from the separation of already existing ions across the nerve’s semipermeable membrane, and the electrical changes during activity arise from a partial breakdown of that membrane.
Erlanger, Gasser, and Bishop were influenced by Ralph Lillie (see e.g. Gasser 1924, p.
117; Erlanger & Bishop, 1926, p. 631), who accepted many of the central claims of the
membrane theory but argued that the theory was inadequate in the form in which Bernstein presented it (Lillie, 1923, pp. 302-303). Lillie accepted that the demarcation current between injured and uninjured nerve surfaces arises from the separation of ions across the semipermeable membrane and that the membrane at least partially breaks down during activity. However, he argued that Bernstein neglects metabolic processes involved in maintaining the cell membrane and in repairing it after breakdown. He claimed that the chemical composition of the cell membrane changes as a result of these processes and that those changes in membrane composition manifest themselves electrically along with changes in ion concentration (Lillie, p.
311).
Lillie also attributed propagation to “local bio-electric circuits” like those postulated by
Hermann (Lillie, pp. 322-323, 379-410). The local circuit theory requires that eddy currents extend far enough ahead of the nerve impulse at high enough intensity to be able to produce excitation at a given point ahead of the action current wave in the time it takes the wave to reach that point. Lillie claimed that eddy currents extend three centimeters in advance of the action current wave front at an intensity sufficient to excite (Lillie, p. 389). For an action current traveling at a typical rate of about thirty meters per second, this extension would give the eddy currents about a millisecond to act.
Erlanger, Gasser, and Bishop followed Lillie in expressing scepticism about whether the membrane theory is adequate in its simplest form (Bishop & Erlanger, 1926, pp. 653-655). Like
Lillie, they did not question that the central claims of the theory are true, but only that the theory accounts for all of the factors that are relevant to the electrical phenomena that nerves exhibit.
They argued that cellular activity plays a large role in creating and maintaining membrane polarization (Bishop & Erlanger, 1926, p. 631; Gasser, 1933, p. 144) and that chemical
transformations precede and initiate the breakdown of the membrane during activity (Bishop,
1927, p. 475; Erlanger & Gasser, 1930, pp. 273-275). But while they accepted Lillie’s theory of the local processes involved in the nerve impulse, all three of them initially rejected his local circuit theory of nerve impulse propagation (Bishop, G. H., 1915-1978, Bishop to Gasser, [ca.
1925]2). They rejected it primarily because, whereas Lillie assumed that eddy currents have about a millisecond to act, their oscillograph records indicated that they in fact had a tenth of a millisecond or less (Erlanger, Gasser, & Bishop, 1926, pp. 566-567). This finding raised the question whether eddy currents are large enough to account for propagation.
While Erlanger, Gasser, and Bishop agreed that the foot of the action current is smaller than Lillie assumed, they disagreed about its exact size (Bishop, G. H., 1915-1978, Bishop to
Gasser, [1924]; Bishop, G. H., 1915-1978, Bishop to Gasser, [ca. 1925]). There was room for debate about its size because the potential changes due to eddy currents overlap with the changes due to the action current proper. Thus, recording techniques such as the use of the cathode ray oscillograph do not yield clear, objective measurements of the size of the foot. Erlanger, Gasser, and Bishop attempted to get around this problem by using the time between the start of the rise of the action current record at a point and the start of the absolutely refractory period at that point as an estimate of the duration of the foot, assuming that the start of the absolutely refractory period coincides with the start of the local response (Erlanger et al., 1926, pp. 566-567).
However, because this method was indirect and inexact it did not resolve the debate entirely.
2 This letter must be from either 1925 or early 1926. Bishop writes about “the Xmas paper” in a way that makes clear that the paper had already been delivered. That paper was presented at Thirty-Seventh Meeting of the American Physiological Society, which took place December 29-31, 1924 (Bishop et al. 1925), so the letter cannot have been from before 1925. It cannot have been written after June of 1926 because Bishop wrote in it that two papers that would be received for publication on June 9, 1926 (Erlanger et al. (1926)) and July 2, 1926 (Bishop & Erlanger (1926)) were not yet in the proof stage. There are a few reasons to prefer a 1925 date, but nothing hangs on this point.
Based on the results they obtained by this method, Erlanger, Gasser, and Bishop presented a value of 0.07 milliseconds as a rough upper bound on the duration of the foot
(Erlanger et al., 1926, p. 567). This duration indicated that a significant eddy current was flowing at most 2.9 millimeters ahead of the action current, about an order of magnitude smaller than the extension Lillie had assumed. They noted that for the local circuit theory to be correct in light of this result, it would have to be the case that a potential with intensity less than one- fifth that of the action current lasting for significantly less than a tenth of a millisecond suffices to stimulate a nerve fiber (Erlanger et al., p. 568). On these matters Erlanger, Gasser, and Bishop were in agreement. However, they disagreed about how close the size of the foot is to their upper bound and about whether the Lillie theory is plausible in light of that size (Bishop, G. H.,
1915-1978, Bishop to Gasser, [ca. 1925]; Gasser, H. S., 1933-1961, Gasser to Hill, December 22,
1936). Erlanger and Gasser believed that the actual size of the foot was probably much smaller than their upper bound and that the local circuit theory was unlikely to be correct in light of that size. Gasser went so far as to argue that the errors of measurement in their experiments were so large that there might be no foot at all (Gasser, H. S., 1933-1961, Gasser to Hill, December 22,
1936), and Erlanger agreed with him (Bishop, G. H., 1915-1978, Bishop to Gasser, [1924]). By contrast, Bishop believed that the foot was nearly as large as their upper bound and that its size did not constitute strong evidence against Lillie’s theory. He argued that eddy currents are “a physically necessary consequence of the conditions in nerve” and that whatever the size of the foot it certainly is at least present in their recordings (Bishop, G. H., 1915-1978, Bishop to
Gasser, [ca. 1925-1926]).
As well as arguing that the foot is larger than Erlanger and Gasser supposed, Bishop cautioned against concluding that the local circuit theory is false from the fact that the foot is
small. Bishop argued that they simply did not know how much current is needed to excite a single nerve fiber. They knew how much current is needed to excite at least one fiber in a nerve trunk, but because stimulating currents applied to nerve trunks pass through individual fibers in series, Bishop wrote, “We have no knowledge of what the effective stimulating potential really is.” This fact “does not prove the [local circuit] theory,” he wrote, “but it disposes of our objections to it” (Bishop, G. H., 1915-1978, Bishop to Gasser, [ca. 1925-1926]).
In subsequent papers, Gasser took a cautiously agnostic stance toward the local circuit theory (e.g. Gasser, 1928), while Bishop continued to assert that it was consistent with all of the evidence that had yet been obtained (e.g. Gilson & Bishop, 1929). Erlanger did not write about the theory again until 1932, when he published new results from joint work with Edgar Blair that he took to cast further doubt on the role of eddy currents in propagation.
3. Erlanger’s second objection: eddy currents large enough to re-excite would dissipate energy and produce stray effects (1932-1936)
Erlanger presented the same two arguments against the local circuit theory on three occasions between 1934 and January 1937 (Erlanger & Blair, 1934; Erlanger, J., 1910-1965,
Erlanger to Hodgkin, January 6, 1937; Erlanger & Gasser, 19373). The first of these arguments cited a set of results he and Blair reported in 1932, in which they failed to find any sign of eddy currents leaking from fiber to fiber in experiments designed to detect such leaks if they exist
(Blair & Erlanger, 1932). Erlanger claimed that those results indicated that eddy currents are without physiological significance. His second argument was that propagation by eddy currents
3 This source is a published version of Erlanger and Gasser’s Eldridge Reeve Johnson Foundation lectures. The book was published in 1937, but the lectures took place in March 1936 (Erlanger, J. Bishop to Erlanger, October 10, 1935.)
is implausible on teleological grounds. We will see that both of these arguments rely on the same underlying assumption: eddy currents large enough to propagate the nerve impulse would leak away from the active fiber, dissipating energy and producing stray effects.
In their (1932), Blair and Erlanger reported uniformly negative results from several experiments designed to reveal effects of eddy currents flowing through active fibers on the excitabilities of other fibers in the same nerve trunk. They ended that paper with the conclusion,
“Such current as leaks from fiber to fiber in normal nerve is without physiological significance”
(p. 567). In subsequent writings, however, they cited those results to support the claim that eddy currents are without physiological significance of any kind—including the ability to propagate an action current in accordance with the local-circuit theory.
As an example, one of the experiments Blair and Erlanger reported in their (1932) involved timing shocks on two branches of a nerve trunk so that the fibers in one branch would conduct an action current that was slightly out of phase with an action current flowing through the fibers from the other branch. Eddy currents leaking from fiber to fiber would act as subthreshold shocks, which Erlanger and Blair had shown in a previous paper (Erlanger & Blair,
1931) first increase irritability, then decrease it. As a result, to the extent that eddy currents leaked from fiber to fiber, they would tend to bring the action currents originating in the two branches into phase. Erlanger and Blair compared records of the two action currents running through the phrenic nerve together to the algebraic sum of records of the currents running separately. The comparison revealed no tendency for the currents running together to come into phase, indicating that eddy currents do not leak from fiber to fiber substantially. This experiment produced a negative result even when Erlanger and Blair created favorable circumstances for leaking eddy currents to manifest themselves by raising the excitabilities of the fibers by various
means. Several similar experiments that were also performed under favorable circumstances for leaks to reveal themselves also yielded negative results.
Fig. 1. (Blair & Erlanger, 1932, p. 561)
A + B is the algebraic sum of two action currents running through two sets of fibers in the same nerve trunk at different times. C is the action current generated by these action currents running through the fiber simultaneously but slightly out of phase. C would be narrower than A + B if the action currents running slightly out of phase had any tendency to synchronize with one another, as one would expect if eddy currents leaked from fiber to fiber.
Although Blair and Erlanger did not use these results to argue against the local circuit theory in their (1932), they did do so on three later occasions (Erlanger & Blair, 1934; Erlanger
& Gasser, 1937; Erlanger, J., 1910-1965, Erlanger to Hodgkin, January 6, 1937). In his 1936
Johnson Foundation lectures, Erlanger went so far as to question whether eddy currents exist at all. In comments on Erlanger’s manuscript as it was being adapted for publication, Gasser objected strongly to this suggestion: “‘If eddy currents exist at all’ !!!!” he wrote. “What does one measure with a galvanometer?” (Gasser, H. S., 1933-1961, Gasser to Erlanger, July 20,
1936, p. 3). Erlanger seems to have realized that he had gone too far, writing back simply, “The statement has been deleted” (Gasser, H. S., 1933-1961, Erlanger to Gasser, August 4, 1936, p. 3).
Gasser also objected to Erlanger’s claim that his 1932 results with Blair showed that eddy
currents lack any kind of physiological significance, writing, “You must mean without physiological significance to adjacent fibers” (Gasser, H. S., Gasser to Erlanger, July 20, 1936, p.
3). Erlanger’s response to this comment is strange: “Yes,” he wrote, “and the passage has been changed to read, ‘Evidence indicating that outside eddy currents generated by fiber activity are not strong enough to be of physiological significance’” (Gasser, H. S., Erlanger to Gasser,
August 4, 1936, p. 3). He seems at first to agree with Gasser’s correction, but he then fails to restrict his claim to adjacent fibers as Gasser wanted. Perhaps he thought it was sufficiently weak to claim only that the 1932 results were evidence that eddy currents lack physiological significance.
Erlanger did not attempt to justify the inference from the fact that eddy currents do not leak substantially from fiber to fiber to the claim that they do not re-excite an active fiber ahead of the action current wave on any of the occasions on which he presented that argument,. He evidently took it to be obvious that eddy currents sufficient to propagate an action current would inevitably leak away from the active fiber and affect other fibers nearby. That same assumption underlay Erlanger’s claim that the local circuit theory is problematic teleologically, which he presented on the same three occasions. In fact that, on all three occasions he presented the teleological argument before the 1932 results, treating the latter as merely bolstering the former, indicating that the teleological objection carried significant weight in his mind.
Erlanger presented his teleological objection to the local circuit theory at greatest length in his Johnson Foundation lectures:
But if progression in nerve is from node to node, and in the manner just described, it
would have to be accomplished through restimulation by eddy currents flowing from
node to node outside of the segments….4 In other words the process that determines
impulse propagation in a fiber would have to operate through structures that are foreign
to the fiber. From the standpoint of teleology it is hard to believe that this is the case. It
seems much more reasonable to suppose that a nerve fiber conducts by means of a self-
contained mechanism; that it contains within itself everything that is necessary for the
performance of its own proper function. (Erlanger & Gasser, 1937, pp. 126-127)
Erlanger seems to have been suggesting in this passage that propagation by eddy currents would be a suboptimal process and that this fact makes the local circuit theory implausible. He may have had in mind the idea that natural selection would not allow such a mechanism to evolve and persist, but to my knowledge he never elaborated any such view.
On the other hand, Erlanger did reveal in his Johnson Foundation lectures why he thought that propagation by eddy currents would be suboptimal when he presented his alternative theory of nerve impulse propagation in myelinated fibers (Erlanger & Gasser, 1937, p. 127). According to that theory, each internodal segment acts as an isopotential cell. During activity, a chemical reaction is initiated somewhere in the cell, which changes the potential of the entire cell nearly instantaneously, even as the chemical reaction remains relatively localized. The energy associated with this change propagates across hypothetical nodal barriers by some means, perhaps electrical, and the process repeats in the next internode.
According to this alternative to the local circuit theory, the function of the myelin sheath is, in Erlanger’s words, “not the direction of currents to the outside, but rather the prevention of leakage of current from the axon, with its consequent dissipation of energy and risk of stray
4 By this time Erlanger had adopted the view that nerve impulses propagate in a saltatory manner in myelinated fibers (Erlanger & Blair, 1934), with the jumps corresponding to nodal segments. Thus, he was considering a modified version of the local circuit theory in which eddy currents flow from node to node.
effects” (Erlanger&Gasser, 1937, p. 127). Here Erlanger is clearly contrasting his alternative theory with the local circuit theory, revealing his belief that eddy currents would dissipate energy and produce stray effects. This passage shows that Erlanger’s teleological objection, like his objection based on the 1932 results, is driven by the assumption that propagation by means of eddy currents flowing outside the nerve fiber would be a messy process in which the eddy currents would inevitably spread away from the active fiber. This assumption was evidently
Erlanger’s fundamental reason for rejecting the local circuit theory between 1932 and 1936.
4. Erlanger’s opposition to the local circuit theory declines (1936-1939)
Erlanger’s opposition to the local circuit theory declined between 1936 and 1939, largely because of Hodgkin’s work. I will briefly sketch the changes in his opinion that occurred during this period before discussing in more detail the findings that brought about those changes.
Hodgkin showed in his Cambridge fellowship thesis that impulses blocked by cold or pressure produce both an electrical potential and an increase in excitability beyond the block.
Erlanger read Hodgkin’s thesis in December 1936 (Erlanger, J., 1910-1965, Gasser to Erlanger,
December 23, 1936; Erlanger, J., 1910-1965, Erlanger to Gasser, December 29, 1936). Although
Hodgkin’s results appeared to support the local-circuit theory, they did not catch Erlanger by surprise. Erlanger and Blair had produced similar results the previous May, and had already admitted that those results could only be account for by eddy currents flowing ahead of the blocked impulse (Blair & Erlanger, 1936, p. 364). Nevertheless, he continued to doubt that eddy currents are essential for propagation as the local circuit theory proposes (Erlanger, J., 1910-
1965, Erlanger to Hodgkin, January 7, 1936).
Although Hodgkin went further than Erlanger and Blair in showing that the electrical potential has the same spatial and temporal characteristics as the increase in excitability, Erlanger wrote to Gasser that he “could see nothing wrong with [the thesis]” and that “it confirms every point save one” that he and Blair had made in their (1936) (Erlanger, J., 1910-1965, Erlanger to
Gasser, December 29, 1936).5 Thus, Erlanger saw Hodgkin’s thesis as essentially confirming the results he and Blair had produced earlier that year, rather than as providing substantial new evidence for the local circuit theory.
Erlanger and Hodgkin exchanged letters about Hodgkin’s thesis, in which Erlanger presented to Hodgkin the objections to the local circuit theory described in §3 and Hodgkin addressed those objections (Erlanger, J., 1910-1965, Erlanger to Hodgkin, January 6, 1937;
Erlanger, J., 1910-1965, Hodgkin to Erlanger, February 1, 1937). According to Hodgkin,
Erlanger remained “very sceptical” of the theory as late as April 1938 (Hodgkin, 1994, p. 113).
At that time Erlanger told Hodgkin that he would take the local circuit theory seriously if
Hodgkin could demonstrate that changing the resistance of the medium outside the active fiber changes the conduction velocity. Hodgkin met that challenge in May, and Erlanger saw the result between February and April 1939.6
It seems likely that Hodgkin’s demonstration that external resistance affects conduction velocity persuaded Erlanger to accept the local circuit theory, but the available evidence on this
5 The one point Erlanger regarded the thesis as failing to confirm was Blair and Erlanger’s finding that the increase in excitability beyond the block may persist for as long as 100 milliseconds. Hodgkin had found a corresponding value of about 20 milliseconds. This discrepancy was later traced to differences between Blair and Erlanger’s method of recording from single fibers and Hodgkin’s method of recording from multiple fibers in a single nerve trunk (Erlanger, 1947, p. 65). 6 This range of dates for when Erlanger saw Hodgkin’s 1938 results comes from (Blair & Erlanger, 1939): Blair and Erlanger wrote on page 105 of this paper that they saw Hodgkin’s results after submitted the paper for publication. Page 97 reveals that the paper was received for publication on February 4, 1939, so they cannot have seen Hodgkin’s paper more than a few days before that date. The paper was published on April 30, 1939, so they must have seen it somewhat before that date.
point is unclear in two ways. First, it is not clear how strongly Erlanger opposed the local circuit theory between January 1937, when he sent Hodgkin his response to Hodgkin’s thesis, and early
1939, when he saw Hodgkin’s demonstration. Erlanger discussed the local circuit theory in print twice during that period, and he did not present his usual arguments or any other arguments against it on either occasion (Erlanger & Blair, 1938a, p. 451-452; Erlanger & Blair, 1938b). On the second of these occasions, he and Blair even defended the theory against Kato’s claim to have falsified it experimentally (Erlanger & Blair, 1938b, pp. 355-356). Perhaps Hodgkin had already persuaded Erlanger to drop his objections to the theory, and Erlanger’s scepticism about the theory had already been substantially diminished before he saw Hodgkin’s results on external resistance and conduction velocity. On the other hand, it is also possible that Erlanger chose not to present his objections to the local circuit theory between late 1936 and early 1939 for other reasons, and during that period he remained as opposed to the theory as he had been when he wrote to Hodgkin about this thesis.
The evidence is also somewhat unclear about the extent to which Erlanger accepted the local circuit theory after 1939. He only discussed the theory once more in print before his 1946 retirement, and again in his 1947 Nobel lecture. On the first of those occasions he made a brief comment about the theory’s consequences without commenting on its correctness (Erlanger &
Blair, 1940, p. 107). He discussed the local circuit theory fairly extensively in his Nobel lecture in a largely neutral or favorable way (Erlanger, 1947, pp. 63-72). However, he also treated the idea that propagation involves chemical processes as well as eddy currents as a live option, albeit one that had not been adequately substantiated (p. 64). Despite these caveats, it is clear that
Erlanger was much more favorably disposed toward the local circuit theory after 1939 than he had been before 1936.
4.1 Erlanger admits that eddy currents can raise excitability
Erlanger and Blair discovered in May 1936 that a blocked action current can increase the excitability of a myelinated nerve beyond the block (Blair & Erlanger, 1936). Moreover, they produced one observation in which this effect appeared to extend across two nonresponding internodes (Blair & Erlanger, p. 357). In that case especially, the increase in excitability occurrs too rapidly too far from the block to account for with a chemical hypothesis. In addition, the fact that it occurrs across nonresponding internodes ruled out Erlanger and Blair’s alternative theory, which involved propagation across hypothetical transverse barriers at the nodes. The effect,
Erlanger and Blair concluded, could only be due to eddy currents (Blair & Erlanger, p. 364).
Erlanger and Blair discovered that an action current can increase excitability beyond a block as a result of their investigations into a phenomenon they called temporal summation. In temporal summation, a block that suffices to stop a single impulse sometimes fails to stop a second impulse that is sufficiently close to the first in time. Erlanger and Blair realized that temporal summation could be due either to an increase in the stimulating power of the impulse at the segment prior to the block or to an increase in the excitability of the segment just beyond the block (Blair & Erlanger, p. 361). They argued against the first of these possibilities, claiming that an increase in stimulating power would be associated with an increase in the spike height, which was not observed, even if the action current spike is not the cause of propagation. They tested the second possibility by stimulating the nerve just past the block upon the arrival of an impulse and comparing its response under these conditions to its response under the same conditions in the absence of an impinging impulse (Blair & Erlanger, pp. 361-362).
Fig. 2. (Blair & Erlanger, p. 358.)
This figure displays records of temporal summation. A1 is a record of a single impulse (R2) that fails to conduct through an anodal block. A2 shows a pair of impulses, the first of which (R1) is blocked in the same way but the second of which propagates through the block (R2). A3 shows a case with the same setup in which both R1 and R2 fail to propagate, as can happen occasionally because of apparently spontaneous variations in nerve fiber excitability. B1 through B3 show the same phenomena occurring with impulses that are closer together in time. C1 through C3 show temporal summation occurring when the anodal block extends across two nodes in front of the recording lead. C1, like A1 and B1, shows a single impulse being blocked. C2 shows a second impulse that passes through the first blocked node but not the second. C3 shows a second impulse passing through both blocked nodes.
The results of this test were consistent with the hypothesis that temporal summation acts by increasing the excitability of the segment beyond the block. In addition, Erlanger and Blair showed that the increase in the effectiveness of the second shock was greatest when the delay between the first and the second shocks was equal to the time needed for the initial impulse to reach the block. That is, there is essentially no delay between the initial impulse reaching the block and the increase in excitability one to two millimeters beyond the block. Because electrical forces are capable of travelling nearly instantaneously while chemical substances are not, Erlanger and Blair state that these results “signify that propagation in nerve is accomplished
by a mechanism that is in part, at least electrical. It does not seem possible to attribute the summation to a mechanism involving the liberation of neurohumors [chemical substances that were hypothesized to be involved in impulse propagation].” (Blair & Erlanger, p. 364). By accepting that eddy currents can measurably increase the excitability of an active nerve ahead of the action current wave, Erlanger took a major step toward accepting the local circuit theory.
4.2 Erlanger and Hodgkin’s exchange regarding Hodgkin’s thesis
Like Blair and Erlanger in their (1936), Hodgkin in his fellowship thesis reported observations on the ability of blocked impulses to increase excitability beyond the block.
Hodgkin used cold and pressure blocks rather than blocks induced by anodal polarization and reported that the increase in excitability beyond a block is invariably accompanied by a spread of electrical potential that closely resembles the “electrotonic” phenomena associated with currents that are used to stimulate nerve artificially. Moreover, he showed that the temporal and spatial properties of the change in excitability parallel closely those of the electrical potential. In a pair of papers based on his thesis work (1937a, 1937b), Hodgkin concluded from this close parallelism that local circuits set up by the blocked impulse are likely to be responsible for both the electrical potential and the increase in excitability. The blocked impulse decreased the threshold of excitation by as much as ninety percent, so it appeared that eddy currents in the absence of a block would be more than sufficient to re-excite the nerve ahead of the nerve impulse as the local circuit theory supposes. In his (1937b), Hodgkin noted cautiously that these results do not prove that eddy currents are solely responsible for propagation. However, he
claimed that there was no need to posit additional (e.g. chemical) mechanisms to account for his results (Hodgkin, p. 227).
In his letter responding to Hodgkin’s thesis, Erlanger wrote, “I find it hard to believe that nerve impulses are propagating by currents eddying outside of the conducting structure”
(Erlanger, J., 1910-1965, Erlanger to Hodgkin, January 6, 1937, p. 1). He then briefly rehearsed the two objections to the local circuit theory he had been presenting since 1934 (see §3). In early
February, Hodgkin sent a reply to Erlanger in which he addressed Erlanger’s objections
(Erlanger, J., 1910-1965, Hodgkin to Erlanger, February 1, 1937). In response to Erlanger’s concern that propagation by eddy currents would be problematic teleologically, he claimed that
“this concept seems to me to fit in with the general implications of cell physiology” (Erlanger, J.,
1910-1965, Hodgkin to Erlanger, p. 1) He argued for this claim as follows: there is ample evidence that excitation depends on a change at the cell surface; such changes can be produced electrically; the only way for such changes to be produced electrically is for current to flow through it; the only way for current to flow is in a circuit, flowing one direction inside the cell membrane and the opposite direction outside the cell membrane; given that there does not seem to be a gap between the cell membrane and the myelin sheath, there is nowhere for these currents to flow except in the interstitial fluid. For Hodgkin, this argument trumped Erlanger’s appeal to teleology.
Hodgkin also argued that propagation by eddy currents is compatible with Erlanger and
Blair’s failure to find evidence of eddy currents travelling between parallel fibers during activity
(Erlanger, J., 1910-1965, Hodgkin to Erlanger, pp. 1-2). That result would be easy to account for within the local circuit theory if it were known that the resistivity of the interstitial fluid is significantly higher than that of the axon cores; under those conditions, eddy currents would
naturally remain close to the fiber that produced them. It is more difficult, Hodgkin wrote, to discern what would happen on the assumption that the interstitial fluid and the axon curves are roughly similar in resistivity. Hodgkin attempted to calculate what would happen in such circumstances and estimated that in the most favorable case a fiber could have its excitability increased by at most 25% due to eddy currents in nearby fibers. Hodgkin wrote that he did not know whether to count this result as in his favor or in Erlanger’s and acknowledged that in any case it would be dangerous to rely on such an argument without more knowledge of the current distribution in nerves.
Hodgkin ended his response to Erlanger by writing that although he was quite confident that the increase in excitability he had observed beyond a block is due to the spread of eddy currents, he was not confident that this mechanism is the only one involved in impulse propagation (Erlanger, J., 1910-1965, Hodgkin to Erlanger, p. 5). At this level of generality,
Erlanger and Hodgkin were in agreement; but whereas Erlanger was inclined to believe that eddy currents are a minor factor in propagation, Hodgkin regarded them as essential and probably sufficient to propagate an impulse by themselves under normal conditions.
It is unclear how much of an impression Hodgkin’s arguments made on Erlanger. On the one hand, after his letter to Hodgkin Erlanger never again presented his two standard objections to the local circuit theory in print or in any correspondence that I have examined. He seems not to have responded to Hodgkin’s letter directly, but he did write to Hodgkin’s advisor A. V. Hill,
“[Hodgkin] evidently had been giving very thoughtful and experimental consideration to the questions I had raised” (Erlanger, J., 1910-1965, Erlanger to Hill, February 11, 1937). On the other hand, Hodgkin reported in his autobiography that Erlanger was still “very sceptical” of the local circuit theory when Hodgkin visited him in April 1938 (Hodgkin, 1994, p. 113). At the
very least, Erlanger was sceptical enough at that time to challenge Hodgkin to show that the resistance of the medium outside an active fiber affects its conduction velocity.
4.3 Erlanger’s challenge
Gasser, who had in 1935 become director of the Rockefeller Institute, was sufficiently impressed by Hodgkin’s work that he arranged for Hodgkin to come to America in September
1937 to spend a year primarily working in Gasser’s laboratory (Hodgkin, 1994, pp. 78, 89). In the spring of 1938, Hodgkin visited Erlanger and Blair in St. Louis (Hodgkin, 1994, p. 113). It was on that occasion that Erlanger told Hodgkin he would take the local circuit theory seriously if Hodgkin could show that changing the resistance outside a nerve fiber affects conduction velocity. Of course, provided adequate controls, one would expect to find such an effect if propagation is by eddy currents flowing outside the nerve fiber but not otherwise.
Others had attempted to show that changing the resistance outside the active fiber changes its conduction velocity (e.g. Pond, 1921). However, they had changed the resistance outside the fiber by changing the chemical composition of the surrounding medium. Thus, they faced the objection that any changes in conduction velocity they observed might be due to chemical or ionic effects rather than to the change in resistance (Hodgkin, 1939, p. 569).
Hodgkin’s innovation was to change the resistance of the surrounding medium while leaving the nerve’s immediate environment unchanged. He did so by submerging a crab nerve in a layer of sea water (a conductor) underneath a layer of paraffin oil (an insulator) (see Fig. 3). When he lifted the nerve out of the water and into the oil, it was still surrounded by a thin layer of water.
The resistance outside the nerve increased because the area of the conducting sea water around
the fiber decreased, but the chemical and ionic composition of the nerve’s immediate environment remained unchanged. Hodgkin found that conduction was more than thirty percent faster in sea water alone than in a thin layer of sea water surrounded by oil and that this change was completely reversible, in accordance with the predictions of the local circuit theory
(Hodgkin, p. 561; see Fig. 4).
Fig. 3. (Hodgkin, p. 561)
Hodgkin’s diagram of the experimental setup he used to show that conduction velocity decreases when the resistance of the surrounding medium increases. A, F, and G held the nerve fiber in place. B-E are electrodes. The entire arrangement could be lifted out of the seat water and into the oil.
Fig. 4. (Hodgkin, p. 564)
Record taken from one of Hodgkin’s experiments with crab nerve in sea water and oil. The x axis is time in minutes from the start of the experiment, the y axis conduction velocity. The open circles represent velocities taken with the nerve in sea water, the closed circles in oil.
Erlanger and Blair saw Hodgkin’s results sometime between late January and April 30,
1939.7 Two other developments from around the same time also weakened Erlanger’s opposition to the local circuit theory. In April 1938, Jasper and Monnier undercut Erlanger’s primary experimental argument against the theory by showing that activity in one fiber does affect the excitabilities of adjacent fibers for unmedullated fibers in close proximity with one another (Jasper & Monnier, 1938). In April 1939, Blair and Erlanger reported that they had been able to reproduce reliably their lone 1936 observation showing temporal summation across two nonresponding internodes, which could only be accounted for by eddy currents (Blair &
Erlanger, 1939). Their ability to reproduce that result eliminated the lingering possibility that it had been an artifact.8
7 See Footnote 5. 8This possibility came up in Erlanger and Hodgkin’s exchange regarding Hodgkin’s thesis, when Erlanger warned Hodgkin about the dangerous of relying on “but a single axon spike,” evidently with this result in mind (Erlanger, J.,
While it is not clear that Erlanger ever accepted the local circuit theory whole-heartedly, he certainly became more favorably inclined toward it as a result of the developments discussed in this section. At a minimum, he fully accepted the claim that eddy currents play a major role in nerve impulses propagation, though he held open the possibility that other processes are involved as well. But perhaps Erlanger’s willingness to consider the possibility that other mechanisms were involved as well as eddy currents should not count against the claim that Erlanger accepted the local circuit theory. After all, in this respect, as we have seen, he was no different from
Hodgkin (Erlanger, J., 1910-1965, Hodgkin to Erlanger, p. 5).
5. Conclusion
Erlanger’s opposition to the local circuit theory helped inspire Hodgkin’s early experiments that provided strong support for that theory. Despite the important role that
Erlanger played in this major episode in the history of physiology, the nature and sources of his scepticism are not widely understood. His doubts about the local circuit theory date back at least to the period between 1924 and 1926 when he and Gasser argued against their colleague Bishop that their oscillograph records showed that the eddy currents flowing ahead of the action current wave are too small to produce excitation. His fundamental objection to the theory in the 1930s was his belief that eddy currents large enough to account for nerve impulse propagation would leak away from the active fiber substantially, dissipating energy and producing stray effects.
This assumption underlay both his teleological objection to the theory and his claim that the fact
1910-1965, Erlanger to Hodgkin, January 6, 1937, p. 2; Erlanger, J., 1910-1965, Hodgkin to Erlanger, February 1, 1937, p. 4).
that he and Blair had failed to find effects from eddy currents leaking from fiber to fiber indicated that eddy currents are not physiologically significant.
Erlanger’s opposition to the local circuit theory began to wane in 1936, when he and
Blair discovered that a nerve impulse blocked by anodal polarization can increase the excitability of the nerve beyond the block at a speed for which only eddy currents could account. Hodgkin’s thesis reported the same result for blocks produced by cold or pressure and showed that the spatial and temporal course of the increase in excitability mirrored closely those of the electrical potential. Erlanger did not argue against the local circuit theory publicly after 1936, but Hodgkin reported that he was still very sceptical of the theory in April 1938. Within a year, Erlanger learned about Hodgkin’s success in meeting his challenge to show that changing the resistance of the medium outside an active nerve fiber would change its conduction velocity. He continued to entertain the possibility that chemical processes also play a role in impulse propagation after this point, but he seems to have accepted the claim that eddy currents are at least the primary means by which the action current wave traverses a nerve fiber.
Acknowledgments
I wish to thank Carl Craver for suggesting the topic of this paper and for providing advice about how to pursue it; Jim Bogen, Ken Schaffner, Marcus Adams, and Kathryn Tabb for feedback on earlier drafts; Joseph McCaffery for suggesting sources; and Philip Skroska,
Stephen Logsdon, Martha Riley, Lee Hiltzik, the staffs of the Rockefeller Archive Center and the
Wisconsin Historical Society Library and Archives for research assistance.
References
Aidley, D. (1998). The physiology of excitable cells (4th ed.). Cambridge: Cambridge
University Press.
Bernstein, J. (1902). Untersuchungen zur Thermodynamik der biolektrischen Ströme. Erster
Theil. Pflügers Archiv European Journal of Physiology, 92, 521-562.
Bernstein, J. (1912). Elektrobiologie: die Lehre von den elektrischen Vorgängen im
Organismus auf moderner Grundlage dargestellt. Braunschweig, Germany: Druck und
verlag von Friedrich Vieweg & Sohn.
Binet, L., & Minz, B. (1934). Sur un corps du type de l’acétylcholine, present dans le tronc du
nerf vague. Comptes Rendus des Séances de la Société de Biologie et de ses Filiales,
117, 1029.
Bishop, G. (1915-1978). Correspondence. George H. Bishop Papers (FC033). Archives,
Bernard Becker Medical Library, St. Louis, MO.
Bishop, G. (1927). The form of the record of the action current of vertebrate nerve at the
stimulated region. The American Journal of Physiology, 82, 462-477.
Bishop, G. (1965). My life among the axons. Annual Reviews of Physiology, 27, 1-20.
Bishop, G., & Erlanger, J. (1926). The effects of polarization upon the activity of vertebrate
nerve. The American Journal of Physiology, 78, 630-657.
Bishop, G., & Gilson, A. (1929). Action currents from skeletal muscle. The American Journal
of Physiology, 89, 135-151.
Bishop, G., Erlanger, J., & Gasser, H. (1925). Data on the nature of propagation in nerve. The
American Journal of Physiology, 72, 199.
Blair, E., & Erlanger, J. (1932). On the effects of polarization of nerve fibers by extrinsic action
currents. The American Journal of Physiology, 101, 559-564.
Blair, E., & Erlanger, J. (1934). Manifestations of segmentation in myelinated axons. The
American Journal of Physiology, 110, 287-311.
Blair, E., & Erlanger, J. (1936). Temporal summation in peripheral nerve fibers. The American
Journal of Physiology, 117, 355-365.
Blair, E. & Erlanger, J. (1939). Propagation, and extension of excitatory effects, of the nerve
action current across nonresponding internodes. The American Journal of Physiology,
126, 97-108.
Erlanger, J. (1910-1966). Correspondence. Joseph Erlanger Papers (FC001). Archives,
Bernard Becker Medical Library, St. Louis, MO.
Erlanger, J. (1939). The initiation of impulses in axons. The Journal of Neurophysiology, 2(5),
370-379.
Erlanger, J. (1947). Some observations on the responses of single nerve fibers. In
Nobelstiftelsen World Scientific. (1999). Nobel lectures, physiology or medicine, 1942-
1962. Amsterdam: Elsevier Publishing Company.
Erlanger, J., & Blair, E. (1931). The irritability changes in nerve in response to subthreshold
Induction shocks, and related phenomena including the relatively refractory phase. The
American Journal of Physiology, 99, 108-128.
Erlanger, J., & Blair, E. (1934). Manifestations of segmentation in myelinated axons. The
American Journal of Physiology, 110, 287-311.
Erlanger, J., & Blair, E. (1938a). Comparative observations on motor and sensory fibers with
special reference to repetitiousness. The American Journal of Physiology, 121, 431-453.
Erlanger, J., & Blair, E. (1938b). The action of isotonic, salt-free solutions on conduction in
medullated nerve fibers. The American Journal of Physiology, 124, 341-359.
Erlanger, J., & Blair, E. (1940). Facilitation and difficilitation effected by nerve impulses in
peripheral fibers. The Journal of Physiology, 3, 107-127.
Erlanger, J., and Gasser, H. (1922). A study of the action currents of nerve with the cathode ray
oscillograph. The American Journal of Physiology, 62, 496-524.
Erlanger, J., & Gasser, H. (1930). The ending of the axon action current, and its relation to
other events in nerve activity. The American Journal of Physiology, 94, 247-277.
Erlanger, J., & Gasser, H. (1937). Electrical signs of nervous activity. Philadelphia: University
of Pennsylvania Press.
Erlanger, J., Bishop, G., & Gasser, H. (1926). Experimental analysis of the simple action
current wave in nerve by the cathode ray oscillograph. The American Journal of
Physiology, 78, 537-573.
Gasser, H. (1924). The methods of recording the electrical potential change in nerve, with
special references to the use of the Braun tube oscillograph. British Journal of Radiology
Röntgen Society Section, 20, 105.
Gasser, H. (1928). The relation of the shape of the action current of nerve to the conduction
velocity. The American Journal of Physiology, 84, 699-711.
Gasser, H. (1933). Axon action currents in nerve. Cold Spring Harbor Symposia on
Quantitative Biology, 1, 138-145.
Gasser, H. (1933-1961). Correspondence. Herbert S. Gasser Papers (RG 302). Rockefeller
University Archives, Rockefeller Archive Center, Tarrytown, NY.
Gasser, H. (1964). Herbert Spencer Gasser, 1888-1963. Biographical Memoirs of the Fellows
of the Royal Society, 10, 1-38.
Hermann, L. (1867). Untersuchungen über den stoffwechsel der muskeln ausgehend von des
gaswechsel derselben. Berlin: August Hirschwald.
Hermann, L. (1872). Grundriss der physiologie des menschen (4th ed.). Berlin: August
Hischwald.
Hermann, L. (1879). Handbuch der Physiologie (vol. 2). Berlin: August Hirschwald.
Hodgkin, A. (1937a). Evidence for electrical transmission in nerve: Part I. The Journal of
Physiology, 90, 183-210.
Hodgkin, A. (1937b). Evidence for electrical transmission in nerve: Part II. The Journal of
Physiology, 90, 211-232.
Hodgkin, A. (1939). The relation between conduction velocity and the electrical resistance
outside a nerve fibre. The Journal of Physiology, 94, 560-570.
Hodgkin, A. (1976). Chance and design in electrophysiology—an informal account of certain
experiments on nerve carried out between 1934 and 1952. The Journal of Physiology,
263, 1-21.
Hodgkin, A. (1994). Chance & design: reminiscences of science in peace and war. Cambridge:
Cambridge University Press.
Jasper, H., & Monnier, A. (1938). Transmission of excitation between excised non-myelinated
nerves. An artificial synapse. Journal of Cellular and Comparative Physiology, 11, 259-
277.
Lillie, R. (1923). Protoplasmic action and nervous action (1st ed.). New York: The Baker and
Taylor Company.
Muralt, A. von (1937). Observations on chemical wave transmission in excited nerve.
Proceedings of the Royal Society of London. Series B, Biological Sciences, 123, 397-421.
Pond, S. (1921). Correlation of the propagation-velocity of the contraction-wave in muscle with
the electrical conductivity of the surrounding medium. The Journal of General
Physiology, 3, 807-826.