Wilhelm Feldberg was renowned both for his research and teaching. A
research career of more than sixty years produced a prodigious output of
354 scientific papers. His first work was on the pharmacology of
histamine, particularly its effects on the circulation. As a young
researcher in Berlin, Feldberg succeeded in identifying histamine in
perfusates from isolated guinea pig lungs challenged with antigen, as
well as a second substance called ‘slow-releasing substance of
anaphylaxis’, later identified with the leukotrienes. These observations
were crucial to the understanding and treatment of antigen-antibody
reactions in asthma.
Feldberg is best known for his an outstanding contributions to one of
the most fundamental concepts in physiology and pharmacology – that a
nerve impulse is transmitted from the nerve endings of a nerve cell or
neurone to a second neurone or an effector organ, such as a muscle, by
the release of a chemical substance or ‘neurotransmitter’ into the
intervening gap or ‘synapse’. This is the theory of neurohumoral
transmission. The problem was to detect and identify the transmitter. As
a young researcher in Berlin, Feldberg devised a method for perfusing
organs through their arterial blood supply, and measuring acetylcholine
in the perfusate collected during electrical stimulation of the nerve.
In Berlin, and in later work with Dale and his colleagues at the
National institute for Medical Research (NIMR) at Hampstead, Feldberg
used this technique to establish acetylcholine as a neurotransmitter at
several important sites in the peripheral nervous system and at skeletal
muscle. Feldberg and his colleagues were even able to measure the actual
number of molecules of acetylcholine released by a single nerve impulse.
Feldberg also studied the enzymes involved in the synthesis of
acetylcholine (‘cholineacetylase’) and its breakdown in the tissues (‘cholineasterase’).
Cholineacetylase was detected in extracts of brain and gut, and the
distribution of this enzyme in the central nervous system was used to
define ‘cholinergic’ and ‘non-cholinergic’ neural pathways. During World
War II, Feldberg demonstrated that the toxic effects of war gases were
caused by an action that suppressed some cholinesterase action.
One of Feldberg’s favourite aphorisms was ‘die Methode ist alles’ (the
method is everything), and nowhere is this better exemplified than by
his ‘pharmacological approach to the brain’. To circumvent the
‘blood-brain barrier’ which prevents access of many drugs to the brain
and to exclude peripheral systemic effects, he perfected a method for
injecting drugs directly into the ventricles. Using this technique, he
defined the site and mode of action of several important drugs in the
CNS. With his co-workers, he was able to show that prostaglandins
produce fever by acting on a temperature-regulating centre in the
hypothalamus; and demonstrated that drugs such as paracetamol, which
reduce fever, do so by lowering the level of prostaglandins in the
In other important work, he elucidated aspects of the control of blood
sugar, blood pressure, and the release of the hypothalamic hormone,
vasopressin, which is important for the control of fluid balance in the
Feldberg’s research gained international recognition. He was elected to
the fellowship of several scientific societies and awarded a number of
honorary degrees both at home and abroad. His final accolade was the
award of the Wellcome Gold Medal of the British Pharmacological Society.
Feldberg was an inspired teacher. During the tenure of his Readership in
Physiology at Cambridge from 1938 to 1949, his lectures, and
particularly his practical class demonstrations, were highly acclaimed
by his undergraduate students. He had a genius for collaborative work.
In 1949 he became Head of the Division of Physiology and Pharmacology at
NIMR which had then moved to Mill Hill. It attracted a succession of
aspiring young postgraduates from all parts of the world. Each would in
turn be recruited to Feldberg’s newest research project and gain
enormously from his teaching.
For a fuller account of Wilhelm Feldberg’s life and work, see Wilhelm
Feldberg 1900-1993 (Memoirs of Fellows Royal Society Lond 43, 143-170,
1997, by G. Bisset and T.V.P. Bliss).