Thanks to modern technology, man can see the inky depths of the sea in great detail and can study plants and animals living in a world of their own.
In their task of studying the human physiological system scientists have been aided to a large extent by their knowledge of the internal structure and vital organs of various animals. One such animal that can provide a wealth of information so as to enable them to understand the human nervous system is the common squid, a creature which is about 1.5 feet long and which lives in the sea. Every year, when summer begins in June, the Atlantic squid known as Lohgo Pealei begins its annual migration to the seaside town of Woodshole, Massachusetts (in the United States) from the edge of the continental shelf. There it turns up in large numbers to mate and spawn in the protected bays nearby.
About the same time, a group of about 50 scientists from all over the United States come to Woodshole to study these animals. The squid has very big nerve fibres that are much larger than any found in mammals including humans. Its brain is well developed and its visual and motor systems are the most advanced of the invertebrates. The scientists study a 5 inch long bit of nerve fibre (called axon) dissected from thousands of these animals. Every day 200 axons are collected.
The entire work ultimately involves the meticulous examination of the axons of 15,000 squids under electronic microscopes and the recording of their electrical activity. Their interiors are flushed with fluids and drugs. The data gathered by the scientists are processed by computers. The main purpose of this extremely complex analysis is to learn more about how the nerves of the squids, and by inference human nerves, function and how different drugs act on the nervous system.
It is hoped that an analysis of the processes taking place in the axons of squids would help scientists to get a better understanding of such degenerative disorders of the human nervous systems as Alzheimer’s disease and amyotrophic lateral sclerosis (Lou Gehrig’s disease). Rita Hayworth, once regarded as Hollywood’s most beautiful actresses later in life became a helpless victim of the former and the renowned English physicist Stephen Hawking was confined to a wheelchair because of the latter affliction.
One of the reasons why the squid is so dynamic and, hence useful in the study of neurobiology and neurophysiology is the unique syphon system that this creature employs as a ‘flight jet’ to flee from predators, sometimes behind a cloud of black inky fluid. In order to go into the reverse direction, the squid draws seawater into a special chamber situated between the long flattened cylinder of its body and an envelope-like outer mantle. By ejecting water forcibly the squid can propel itself backwards trailing its tentacles. The squid’s aquatic propulsion mechanism is indeed a marvel of hydrodynamics.
The entire power springs from the squid’s mantle which contracts violently using strong muscles to eject seawater out of the chamber. What interests the scientists most is the mantle’s ignition system that is fed by the long nerve cell extensions or axons. In human beings also, this system has its counterpart. Peripheral nerves in human beings contain thousands of minuscule axons each a fraction of the size of the squid’s stretching out from the nerve cells in or near the central nervous system.
In the human spinal cord, axons connect nerve cells to leg muscles. When impulses from the brain activate the nerve cells a message goes along the axons to the leg muscle making them contract. In the squid messages are first beamed from the brain to a pair of relay stations called the stellate ganglia, in the front portion of the animal’s body. Two long axons each having the dimensions of a pencil lead, pick up the nerve impulses from the stellate ganglia, and send them at lightning speed to the mantle muscles.When they reach the mantle muscles, they stimulate contraction of the muscles enabling the squid to jet its way out of danger.
By studying this unique escape system, scientists have discovered much about how the so-called excitable cells such as neurones and muscle fibres generate and conduct electrical messages. By implanting electrodes in the axons of squids, scientists have determined that the tiny impulses that activate a nerve are generated by a quick exchange of sodium and potassium ions across the nerve cell membrane. Moreover, they now know that the flow of ions depends on a class of molecules called channels embedded in excitable cell membranes. These are holes in the membranes have gates that are opened and closed by change in membrane voltage.
William Adelman, physiologist and chief of the National Institute of Health Laboratory of Biophysics at Woodshole, is of the opinion that the mechanism that produces nerve impulses in squids is similar to that in higher animals including human beings. The similarity in the axons of squid and man extends to the neurofilaments and microtubules inside and even to the exoplasm, a viscous substance through which nutrients and essential particles flow. This vital cellular freight includes vesicles containing the chemicals that are released at nerve endings to carry messages from one cell to another.
Apart from the similarities, it is the sheer size and abundant supply of axoplasm that fascinate biologists.They are collecting information which they hope will enable them to develop new drugs such as analgesics, hypnotics and anaesthetics that will act on the central nervous system. In order to determine where and how these powerful drugs work, scientists squeeze the axoplasm out of the axon and replace it with a miniature plumbing system through which they can pump drugs and chemical solutions.
One pharmacologist at Biological Marine Laboratory, Toshio Narahashi, has shown that the local anaesthetic, xylocaine, blocks nerve conduction by closing the channels that vary the flow of potassium and sodium ions through the membrane of the nerve cells. Narahashi feels that the effect of this anaesthetic is exerted inside the nerve fibre. Research is on to analyse the mechanisms of a member of heart drugs.
Many other scientists at the Woodshole Marine Biological Laboratory (MBL) are studying the squid axon to ascertain the causes of degenerative diseases in which the transport of cellular particles appears to be hampered. Victims of Alzheimer’s disease experience degeneration of nerve cells in the brain which hampers the passage of signals from one cell to another resulting in memory loss and ultimately death. In Lou Gehrig’s disease, there is deterioration of the motor nerve cells that serve the body’s major muscles. At present, these two diseases are fatal and untreatable.
It is believed that the study of the squid axon, especially the movement of transmitter chemicals through it, will lead to a better understanding of the basic mechanism of nerve functions, and perhaps may lead to the treatment for some of the neurological diseases. In the brains of victims of Alzheimer’s disease several peculiarities are noticed. Nerve cells are filled with a tangle of neurofilaments and twisted microtubules that normally serve as tracks along which essential cellular materials move. This abnormal skein prevents the movement and release of chemicals that transport messages between cells. If the tracks are fouled up the transport would also be fouled up, leading to a breakdown of the nervous system.
A neurologist named Anthony Brever has used a technique that allows the cellular particles that make up the axon’s traffic to be video-taped in motion under a microscope and tracked by a computer. He has studied the transport in the axons of squids as well as normal people. He plans to examine nerves from patients with Lou Gehrig’s disease. The squid enables scientists to get at molecular mechanisms that they cannot get at in human axons.
Scientists are planning to study and compare that information with what they see in normal and abnormal human nerve traffic behaviour. If one begins to understand just how axonal transport is affected in people with degenerative diseases then it might be possible for them to find some specific molecular therapy or some drug of choice. This may lead to a major breakthrough in finding a cure for degenerative diseases.
In the meantime, a new optimism has been generated by the discovery of Prion (Proteinaceous infectious particle) by Stanley Prusiner who won the Nobel Prize in 1997 for his hypothesis. It is beginning to be suspected that the degenerative diseases may all be perhaps caused only by Prion after all! If so, much more research has to be conducted in the field as well before a permanent cure for these diseases is found.