MODERN TEXTBOOKS ON anesthesiology run to the thousands of pages, yet for all the minute understanding that has accumulated, no one really knows why anesthetics work. The first serious theory was postulated in 1847, just months after ether had been introduced for use in surgery. A pair of scientists named von Bibra and Harless noticed that anesthetic gases were strongly drawn to fat-like molecules (lipoids) in the human body but required some water to be present as well. Von Bibra and Harless drew unlikely conclusions, but their basic research led to the recognition that of all the systems in the body, nerve tissue has the ratio of lipids to water most attractive to anesthetic substances.
In 1909 R. S. Lillie suggested that since the membrane of a nerve cell is made up of lipoids (along with protein molecules), anesthetic molecules attaching themselves to those lipoids could block up the membrane and interfere with cell flow and function. An earlier scientist, thinking along these same lines of anesthesia-by-clogging, had made note of the fact that the interior portions of cells that are affected by anesthetics—either by drugs or by such natural phenomena as heat, cold, and electric shock—become slightly “gelatinized” and slow to send or respond to impulses. By 1912 attention had turned from the lipoids at the cell membrane to the proteins there. According to a new theory, anesthetics attached themselves to the amino acids that compose the proteins, temporarily denying them oxygen and so energy.
All the theories concluded that anesthetics interfered with something in the cell: lipids, the interior matter, or proteins. A theory developed by Linus Pauling in 1961 concluded that anesthetics worked on water molecules in the brain instead. The brain is 78 percent water, and when anesthetic molecules are introduced, water molecules cluster around them in hydrate crystals and “cause the level of electric activity of the brain to be restricted.” The primary argument against Pauling was that such a phenomenon may occur at low temperatures but not in the body, where the temperature of 98.6°F keeps any such crystals from appearing.
Dr. Vincent J. Collins, author of the massive text Principles of Anesthesiology , reviewed these and other conclusions regarding the effect of anesthetics on body functions and drew his own firm conclusion: “None of the theories answers all the various factors of the problem.”
Anesthesia—so elusive for such a long time—still has its secrets.
—J.M.F.
