50 
that iodine (or rather an iodine containing substance) is an important 
constituent of the thyroid was the fact that the removal of thyroids 
which contain no iodine is followed by as severe symptoms as the 
removal of those which do contain iodine. Such a result would be 
inexplicable on the view that an iodine compound is an essential 
constituent of the thyroid; it would, however, be intelligible on the 
hypothesis that thyroid free of iodine alone has a certain degree of 
physiological activity. We may suppose that this iodine free or 
iodine poor thyreoglobulin is sufficient, as a rule, for the ordinary 
purposes of the organism. Much of the iodine usually found in the 
thyroid may be considered as one of those “factors of safety” dis- 
cussed by Meltzer . 0 That the iodine free or iodine poor thyreoglob- 
ulin is not, however, always adequate to meet the demands of the body 
is shown, for example, by the losses suffered by sheep breeders on 
account of cretin lambs before the extensive use of iodine containing 
salt . * 6 
Another indication that the iodine serves a useful purpose is that 
there is in general an inverse ratio between the size of the thyroid 
and the amount of iodine it contains. 
U. COMPARATIVE PHYSIOLOGICAL ACTIVITY OF COMMERCIAL SHEEP 
THYROIDS. 
Inasmuch as most of the commercial thyroid preparations are 
obtained from the sheep, and as these are official in the United 
States and several other pharmacopoeias, especial attention was 
given to the comparison of their iodine content and physiological 
activity. There is a widespread belief among clinicians that com- 
mercial thyroid preparations differ considerably in activity; we 
believe that this opinion is fully justified. 
Before describing the results of our experiments a few remarks 
may be made as to the character of quantitative results which may 
be expected in a study of the physiological action of drugs. When 
the great importance, both theoretical and practical, of dosage in 
medicine is considered, it is remarkable that so little work has been 
done on the scientific principles underlying it. c Not many phy- 
sicians would assume that by doubling the dose of a drug twice the 
effect would be produced, yet the relation between successive incre- 
ments of the dose and the physiological effects is unknown in the 
case of nearly all drugs. With some drugs, in certain doses, double 
the amount will produce twice the physiological effect. In other 
a S. J. Meltzer, J. Am. M. Ass., Chicago, 1907, 48, p. 655. 
& cf. D. Marine, Johns Hopkins Hosp. Bull., 1907, 18, p. 359. 
c cf. Juckuff, Versuche zur Auffindung eines Dosierungsgesetztes, Leipzig, 1895; 
E. Harnack, Mtinchen med. Wchnschr., 1896, 43, p. 1065; J. T. Cash, Brit. Med. 
J., Lond., 1908, i, p. 1213. 
