aminoacid nitrogen excretion emerged when the urines her observations should be considered with others on the effect of citrate on the solubility of calcium. Furtherof the patients were subdivided according to whether or were sterile infected Means 12 remarked more her work was concerned with single twenty-four(53) (57). they on the fact that in thyrotoxicosis hypercalcuria with hour collections of urine. Repeated tests might show an the overall deficiency of urinary aminoacids. of skeleton and calculi gross depletion may occur, yet are not associated with this disease. Nor do calculi develop in Fanconi’s syndrome, in which there is excessive WILLIAM HARVEY, NEUROLOGIST excretion of both calcium and aminoacids.13 Lehmann William Harvey’s place among the immortals of mediand Pollak 14 15 at Cambridge found in in-vitro expericine was secured by his description of the circulation of ments that aminoacids increased the solubility of calcium the blood; but he made other important, though less and magnesium phosphates. The most effective aminorevolutionary, observations. He devoted much time to acids proved to be cysteine, glycine, glutamic acid, obstetrics and gynaecology; and, as Sir Russell Brain arginine, citrulline, alanine, ornithine, lysine, and leucine; pointed out in his Harveian Oration, delivered to the cysteine was about twice as effective as glycine and lysine, Royal College of Physicians of London on Oct. 19, he and thiolacetic acid was also effective. The work of was no mean neurologist. He made no major original Lehmann and Pollak suggested that cystine, on the other observations concerning the functioning of the nervous hand, might form an insoluble complex with calcium system, nor were his descriptions of nervous disease as salts; and Dr. McGeown found that 31% of the calculus comprehensive and definitive as those of later physicians; patients had an increased excretion of cystine. In some but scattered through his writings are many fragmentary of the patients the excessive excretion of cystine may observations which attest to his clinical acumen, to his have been due to tubular damage, but many of them had perseverance, and to his spirit of critical inquiry. From no evidence of impaired distal tubular function. Damage Harvey’s De Motu Locali Animalium,l translated by Dr. to the proximal tubules is seldom accompanied by Gweneth Whitteridge and now published for the first excessive excretion of aminoacids. The excessive excretion time, and from the De generatione2 and Prelectiones,3 Sir of cystine seen by Dr. McGeown seems therefore to Russell had collected material showing that Harvey, for represent a specific defect in the handling of one the times in which he lived, was exceptionally interested aminoacid. in the functions of the nervous system and had a remarkThe Cambridge workers studied the effect of protein able grasp of the problems of clinical neurology. intake on the absorption of calcium and magnesium,16 17 Clearly Harvey, unlike his contemporaries, believed and concluded that very little calcium would be absorbed that the fleshy part of a muscle was particularly concerned if the diet contained no protein or aminoacids. Mellanby 18 with contraction; and from his study of insects, birds, had previously observed that casein had some antiand animals he distinguished between tonic or sustained rachitic effect over and above that due to its calcium contractions (anticipating in a sense the concept of poscontent, and McCance et al. 16 pointed to the interesting tural tone) and the intermittent contractions concerned position of meat in the diet: this substance, itself with movement or propulsion. He also made some acute rather poor in calcium, may so promote calcium observations on the role of synergists and antagonists in absorption by providing a plentiful supply of amino- muscular activity. In considering the organisation of acids that it becomes the equivalent of a food rich in movement he decried those theories which demanded a calcium. 18 Lehmann 19 remarked that the two organs motivation from the soul, and distinguished clearly bemost commonly showing pathological calcium deposits tween movements that were largely autonomous and in their excretory channels are liver and kidney. Besides those controlled by the will. His conclusions on the sigremoving water from biological fluids, these are particu- nificance of involuntary movements were also remarkably larly rich in aminoacid oxidases. In model experiments modern in many respects, and he was aware that the he showed calcium deposition when water-soluble organisation of movement depended largely on forms of enzyme from pig’s kidney was added to a supersaturated sensation which did not enter consciousness. Harvey’s solution of calcium phosphate in 20% alanine. 20 Such a experience of cases of apoplexy and of other brain diseases high concentration of aminoacid is hardly physiological, convinced him that the cerebral substance was itself alland conditions in vivo might have been imitated more important, despite the contemporary view that the spirits closely by using a much lower concentration of amino- or humours within the ventricles controlled nervous acid and by observing precipitation of calcium over a activity. Of Harvey’s clinical observations-his descripperiod of days rather than over a period of an hour. tions of pupillary changes, of exophthalmos, of abnormaliUnder the conditions chosen there was a considerable ties of gait, of muscular fasciculation, of hysteria, and of time lag between deamination of alanine and precipitaa probable case of syringomyelia-Sir Russell had much tion of calcium, and deposition of calcium continued for more to say. These amply sustain Sir Russell’s view that some time after the enzyme had been inactivated. The was Harvey by no means a physician of limited interest, chelating effect of protein and its breakdown products but that he belonged to that rare genus of geniuses-the has been held responsible for decalcification of teeth.21 comprehensive man. Not all of the 110 patients examined by Dr. McGeown showed a lowered urinary aminoacid excretion; possibly Prof. A. L. HODGKIN and Prof. R. MILNES WALKER have 12. Means, J. H. The Thyroid and its Diseases; p. 330. London, 1948. 13. Dent, C. E., Harris, H. J. Bone Jt Surg. 1956, 38B, 204. 14. Lehmann, H., Pollak, L. J. Physiol. 1942, 100, 17P. 15. Lehmann. H., Pollak, L. Biochem. J. 1942, 36, 672. 16. McCance, R. A., Widdowson, E. M., Lehmann, H. Biochem. J. 1942,
36, 686. 17. Hall, T. C., Lehmann, H. ibid. 1944, 38, 117. 18. Mellanby, E. Spec. Rep. Ser. med. Res. Coun., Lond. 1925, no. 93. 19. Lehmann, H. Biochemical Society Symposia, 1948, no. 1. 20. Lehmann, H. Nature, Lond. 1942, 150, 603. 21. Schatz, A., Karlson, K. E., Martin, J. J., Schatz, V. Ann. Dentist. 1957, 16, 37.
been appointed members of the Medical Research Council in succession to Prof. R. C. GARRY and Mr. H. J. SEDDON, who are retiring. Sir HUGH LINSTEAD has been appointed as the House of Commons member of the Council in succession to the late RICHARD FORT. 1. Harvey, W. De Motu Locali Animalium. Edited and translated by G. Whitteridge. Cambridge, 1959. See Lancet, 1955, i, 971. 2. Harvey, W. Exercitationes de Generatione Animalium. London, 1847. 3. Harvey, W. Prelectiones Anatomiæ Universalis. London, 1886.