JZ Young

In 1930, Young was working at the Stazione Zoologica (Zoological Station) in Naples, Italy, as the visiting Oxford scholar. A collaborator of his there, Enrico Sereni, was interested in the chromatophore musculature of octopuses; it was Sereni who first introduced Young to cephalopods as experimental animals. A chromatophore is a cell or a group of cells that contain pigment, and octopuses and other cephalopods can manipulate the chromatophore cells embedded in their skin by muscular contractions of various kinds. Sereni and Young were interested in how the nervous system of the octopus wired into its chromatophore musculature and skin, and together they published a few papers on the topic. However, Young did not stay long at the Stazione Zoologica, and Sereni, an outspoken anti-fascist, was killed in suspicious circumstances on 1 March 1931, a few short months after Young left Naples.

Working with Sereni, Young found an odd structure at the end of a ganglion in the mantle of a lightly pigmented octopus, Eledone. He decided to see if the squid Loligo pealeii had a similar structure, but was surprised to find that they did not. Instead, attached to an analogous ganglion were long radiating nerve cells and a large tubular group of fused cells which at first Young suspected were blood vessels. Young returned to Oxford and over the next few years he continued to study this long tubular structure in the squid, mostly at the Plymouth Marine Laboratory, in Plymouth, UK. By careful examination he found no blood cells in the fiber. Eventually he discovered that when it was galvanized by a simple electrode, it caused the mantle of the squid to contract. Smith College has collected parts of a now out of print documentary titled The Squid and its Giant Nerve Fiber, one part of which shows Young at work dissecting the squid and enervating it with electrodes. The video clips from this documentary are well worth the interested reader’s attention.

Young remarked in autobiographical notes that there was no one moment in which he understood that these fused nerve cells were one giant axon. His first paper on the topic was published in ’36, a year after he moved to Chicago, Illinois, on a Rockefeller Fellowship to work on unrelated issues in anatomy. At Chicago he made a number of important contacts who encouraged Young to visit the marine laboratory at Cold Spring Harbor in New York, where he would announce his rediscovery of the squid giant axon. These contacts also encouraged Young to spend a summer at the Marine Biological Laboratory (MBL) in Woods Hole.

I say that Young announced his “rediscovery” of the giant axon because it was actually first described by Leonard Worcester (L.W.) Williams while working at the MBL in 1909. However, Williams’s discovery was promptly forgotten, perhaps because Williams himself died in an elevator accident at Harvard, where he was an instructor of comparative anatomy, just three years after his anatomical description of Loligo pealeii.

At the MBL, Young had access to some of the newest technological innovations in cellular physiology research. For example, the MBL had to an oscilloscope, a device that allows an experimenter to track the change in an electrical signal over time. The broad strokes of the oscilloscope as applied to the squid axon are these: if you attached part of the oscilloscope to an axon you can characterize the dynamics of the electrical activity of the surface membrane of the axon over time. Using this technology, and in collaboration with MBL luminaries like Haldan Keffer Hartline (the Nobel prize winner in physiology or medicine in 1967), Young made the first successful recordings of the giant axon’s action potential from the surface of the axon. However, it wasn’t until 1939 that Cole and Curtis, and apparently independently at Plymouth, Hodgkin and Huxley, were able to get readings from inside the axon, by using a more sophisticated microelectrode and a voltage clamp.

In these early phases of looking at the electrical activity of neurons, scientists described the resting potential of an axon, which is the electrical charge an axon has when it isn’t sending signals. Remember, this story is about how scientists discovered the mechanism by which neurons communicate with other neurons. This signaling is accomplished through a complex cascade of chemistry within the axon that changes the voltage carried by the axon. The change in voltage has several effects. It opens small gates along the axon, which allow in ions (charged atoms or molecules) of various kinds. The voltage change also opens small gates at the synapse (the junction between two neurons), which allows chemicals to flow from between neurons across the synaptic gap. This flow of released chemicals, causes the channels in the next neuron in the communication chain to open, causing the next neuron to undergo a complex cascade of chemical and electrical activity, and so on. What Young and Hartline recorded, when they put the squid giant axon in a solution of sodium citrate, was a change in the voltage of the nerve fiber, but not a change from resting to some non-resting state alone. Rather there was a spike in activity, and then a return to the resting state. This indicated that whatever the chemical-electrical mechanism of an action potential was, it also automatically reversed itself.

To a cellular physiologist, these were incredibly provocative data. They suggested that sodium in the medium surrounding the axon in some way caused the action potential produced when a nerve fiber was artificially shocked or stimulated. The neuron had an equilibrium state, the resting potential, and so some part of the chemical-electrical system had to be responsible for bringing it back to its resting potential. Fully understanding this data required detailing how sodium and potassium ions interact with the neuron’s cellular structure to generate the action potential, and then bring it back to its resting potential.

If the reader is interested in the details there is no end of introductions freely available online, some of the best are recordings of lectures given at the MBL.

What matters here is that the summer of ’36 was an eventful one at the MBL. Young’s results and methods, his preparation of the squid giant axon, preoccupied many MBL researchers, like Kenneth Stewart Cole and Howard J. Curtis. The MBL is, because of some local oceanographic conditions, an ideal place for collecting and experimenting on squid during the summer. For this reason, researchers interested in this experimental animal often still travel to the MBL in the summers to do their work. Researchers like Cole spent much of their working life on the giant axon at the MBL.

Oddly enough, JZ Young bows out of our story here. He continued on doing experimental physiological and zoological work at Cambridge. However, he did not return to the squid giant axon, nor did he play a major role in detailing the chemical-electrical signals which work on the squid giant axon made possible. He left the topic apparently just as exciting progress was being made. Where he left off, however, others continued.