History Comp Final

8/2/2019 History Comp Final

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Word Count: 7467

Title

Why Joseph Erlanger rejected the local circuit theory of nerve impulse propagation

Author name and affiliation

Greg Gandenberger

University of Pittsburgh, Department of History and Philosophy of Science, 1017 Cathedral of

Learning, Pittsburgh, PA 15260.

[email protected]

Corresponding author

Greg Gandenberger

Work phone: 412-624-5896

Cell phone: 217-828-0932

Fax: 412-624-6825.


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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. Hodgkins experiments are well known, but

the nature and sources of Erlangers 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.

Keywords

Joseph Erlanger; Alan Hodgkin; local circuit theory; membrane theory; St. Louis School;

electrophysiology


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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

Hodgkins work. This paper begins to address that gap by discussing Joseph Erlangers 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 Erlangers claim that the local circuit theory seemed to

him teleologicallyqueer (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

1The 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.


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around the same time are quite important for understanding Erlangers 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 Erlangers claim that the local circuit theory is problematic teleologically.

Erlangers opposition to the local circuit theory diminished between 1936 and 1939. The

details of exactly how and when Erlangers 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


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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

Erlangers opposition to the local circuit theory that took place between 1936 and 1939.

2. Erlangers 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 Strmchen theory Ludimar Hermann


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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 nerves 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


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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 Lillies 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

2This 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


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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.

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

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.


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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 Lillies 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


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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. Erlangers 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

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

3This source is a published version of Erlanger and Gassers 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.)


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currents are without physiological significance of any kindincluding 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.


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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 benarrower 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 Erlangers 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 Erlangers 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.


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3). Erlangers 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 Gassers 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 Erlangers 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


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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 Erlangers 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

4By 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.


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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 Erlangers 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

Erlangers fundamental reason for rejecting the local circuit theory between 1932 and 1936.

4. Erlangers opposition to the local circuit theory declines (1936-1939)

Erlangers opposition to the local circuit theory declined between 1936 and 1939, largely

because of Hodgkins 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 Hodgkins 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

Hodgkins 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).


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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 Hodgkins 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 Hodgkins 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 Hodgkins demonstration that external resistance affects conduction

velocity persuaded Erlanger to accept the local circuit theory, but the available evidence on this

5The one point Erlanger regarded the thesis as failing to confirm was Blair and Erlangers

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. Thisdiscrepancy was later traced to differences between Blair and Erlangers method of recording

from single fibers and Hodgkins method of recording from multiple fibers in a single nerve

trunk (Erlanger, 1947, p. 65).6This range of dates for when Erlanger saw Hodgkins 1938 results comes from (Blair & Erlanger, 1939): Blair and

Erlanger wrote on page 105 of this paper that they saw Hodgkins 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

Hodgkins 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.


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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 Hodgkins thesis, and early

1939, when he saw Hodgkins 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 Katos 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 Erlangers scepticism about

the theory had already been substantially diminished before he saw Hodgkins 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 theorys 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.


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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 Blairs 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).


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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 innerve 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


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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 tobe 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 Hodgkins exchange regarding Hodgkins 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


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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 Hodgkins 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 Erlangers objections

(Erlanger, J., 1910-1965, Hodgkin to Erlanger, February 1, 1937). In response to Erlangers

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 Erlangers appeal to

teleology.

Hodgkin also argued that propagation by eddy currents is compatible with Erlanger and

Blairs 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


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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 Erlangers 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 Hodgkins 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 Hodgkins letterdirectly, but he did write to Hodgkins 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


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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 Erlangers challenge

Gasser, who had in 1935 become director of the Rockefeller Institute, was sufficiently

impressed by Hodgkins work that he arranged for Hodgkin to come to America in September

1937 to spend a year primarily working in Gassers 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).

Hodgkins innovation was to change the resistance of the surrounding medium while leaving the

nerves 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


24/33

the fiber decreased, but the chemical and ionic composition of the nerves 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)

Hodgkins diagram of the experimental setup he used to show that conduction velocitydecreases 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.


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Fig. 4. (Hodgkin, p. 564)

Record taken from one of Hodgkins experiments with crab nerve in sea water and oil.Thex axis is time in minutes from the start of the experiment, the y axis conductionvelocity. The open circles represent velocities taken with the nerve in sea water, the

closed circles in oil.

Erlanger and Blair saw Hodgkins results sometime between late January and April 30,

1939.7 Two other developments from around the same time also weakened Erlangers

opposition to the local circuit theory. In April 1938, Jasper and Monnier undercut Erlangers

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

7See Footnote 5.

8This possibility came up in Erlanger and Hodgkins exchange regarding Hodgkins thesis, when Erlanger warned

Hodgkin about the dangerous of relying on but a single axon spike, evidently with this result in mind (Erlanger, J.,


26/33

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 Erlangers 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

Erlangers opposition to the local circuit theory helped inspire Hodgkins 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).


27/33

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.

Erlangers 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. Hodgkins

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 Hodgkins 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.


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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.


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