The Chemical Languages of the Nervous System: History of Scientists and Substances
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《新英格兰医药杂志》
This book recalls the discovery of the way in which impulses are transmitted from one nerve cell to another. By 1900, it had become clear that the nervous system consists of separate nerve cells rather than having a syncytial structure. The next problem was determining how nerve cells communicate: by the transmission of electrical signals across the synapse (the theory supported by the faction known as the "sparks") or through transmitter molecules (the theory supported by the group known as the "soups").
In 1914, Henry Hallett Dale (1875–1968), working in the Wellcome Laboratories in London, showed that the actions of acetylcholine could be separated. One consisted of effects on smooth muscle, the heart, and endocrine glands; these effects were similar to those of muscarine and were blocked by atropine. The other effect of acetylcholine was stimulation of the adrenal medulla and ganglia of the autonomous nervous system, which resembled the action of low doses of nicotine. Dale surmised that acetylcholine might well be a chemical transmitter, but the actual transmitter remained unknown.
Enter Otto Loewi (1873–1961), who in 1909 was appointed head of the pharmacology department at the University of Graz in Austria. His research spanned many subjects, including the effect of digitalis on the frog's heart and the ways in which calcium influences this effect. In 1921, he awoke during the night from a dream with an idea for an important experiment. He scrawled something on a piece of paper but the next morning found that it was illegible. On the following night, he had the same dream, and this time he recorded the idea carefully. The next day — even that very night, according to some sources — he carried out the experiment.
(Figure)
Henry Dale and Otto Loewi in Stockholm, 1936.
Dale and Loewi were in Stockholm to receive the Nobel Prize in Physiology or Medicine.
From the Wellcome Library, London.
Loewi isolated the hearts of two frogs, the first with its nerves, the second without nerves. He placed them in Ringer's solution and stimulated the vagus nerve of the first heart for a few minutes. The Ringer's solution bathing the first heart was transferred to the second heart, and its rate of contractions slowed, just as if its vagus nerve had been stimulated. In the same way, when the "accelerator nerve" was stimulated and the Ringer's solution bathing the first heart was transferred, the contractions of the second heart speeded up. Chemical transmission of nerve impulses had been proved beyond doubt.
In 1936, Dale and Loewi were awarded the Nobel Prize in Physiology or Medicine for their work. Loewi was forced by the Nazis to emigrate in 1939; he eventually became an American citizen.
The Chemical Languages of the Nervous System, written by two pharmacologists, does not succeed in recounting these events in a straightforward fashion. It is a collection of essays, some of which are biographical: eight about Loewi, three about Dale, and one about Wilhelm Feldberg, another refugee, from Nazi Germany, who discovered the action of acetylcholine on striated muscle. The introductory remarks about each scientist are somewhat confusing, and it is not always clear who wrote what. The book also seems to have missed the hand of a good editor. The biographical accounts are followed, in the last part of the book, by a section on a variety of transmitter substances. In short, the subject is fascinating, but the book does not quite measure up.
J. van Gijn, M.D., F.R.C.P.
University Medical Center Utrecht
3584 CX Utrecht, the Netherlands
j.vangijn@umcutrecht.nl(By Josef Donnerer and Fre)
In 1914, Henry Hallett Dale (1875–1968), working in the Wellcome Laboratories in London, showed that the actions of acetylcholine could be separated. One consisted of effects on smooth muscle, the heart, and endocrine glands; these effects were similar to those of muscarine and were blocked by atropine. The other effect of acetylcholine was stimulation of the adrenal medulla and ganglia of the autonomous nervous system, which resembled the action of low doses of nicotine. Dale surmised that acetylcholine might well be a chemical transmitter, but the actual transmitter remained unknown.
Enter Otto Loewi (1873–1961), who in 1909 was appointed head of the pharmacology department at the University of Graz in Austria. His research spanned many subjects, including the effect of digitalis on the frog's heart and the ways in which calcium influences this effect. In 1921, he awoke during the night from a dream with an idea for an important experiment. He scrawled something on a piece of paper but the next morning found that it was illegible. On the following night, he had the same dream, and this time he recorded the idea carefully. The next day — even that very night, according to some sources — he carried out the experiment.
(Figure)
Henry Dale and Otto Loewi in Stockholm, 1936.
Dale and Loewi were in Stockholm to receive the Nobel Prize in Physiology or Medicine.
From the Wellcome Library, London.
Loewi isolated the hearts of two frogs, the first with its nerves, the second without nerves. He placed them in Ringer's solution and stimulated the vagus nerve of the first heart for a few minutes. The Ringer's solution bathing the first heart was transferred to the second heart, and its rate of contractions slowed, just as if its vagus nerve had been stimulated. In the same way, when the "accelerator nerve" was stimulated and the Ringer's solution bathing the first heart was transferred, the contractions of the second heart speeded up. Chemical transmission of nerve impulses had been proved beyond doubt.
In 1936, Dale and Loewi were awarded the Nobel Prize in Physiology or Medicine for their work. Loewi was forced by the Nazis to emigrate in 1939; he eventually became an American citizen.
The Chemical Languages of the Nervous System, written by two pharmacologists, does not succeed in recounting these events in a straightforward fashion. It is a collection of essays, some of which are biographical: eight about Loewi, three about Dale, and one about Wilhelm Feldberg, another refugee, from Nazi Germany, who discovered the action of acetylcholine on striated muscle. The introductory remarks about each scientist are somewhat confusing, and it is not always clear who wrote what. The book also seems to have missed the hand of a good editor. The biographical accounts are followed, in the last part of the book, by a section on a variety of transmitter substances. In short, the subject is fascinating, but the book does not quite measure up.
J. van Gijn, M.D., F.R.C.P.
University Medical Center Utrecht
3584 CX Utrecht, the Netherlands
j.vangijn@umcutrecht.nl(By Josef Donnerer and Fre)