,Though the number of schools in which Chemistry is taught as an isolated subject is much less than it was, there are stili between forty and fifty centres of this type with between 600 and 700 students in attendance. They are usually found in small towns, and their students are very. varied in attainment and purpose.

AGES OF STUDENTS.

Of the students attending full-time courses rather more than 70 per cent. are under 21 years of age. In part-time courses the percentage of students under 21 is just a trifle higher, being nearly 72 per cent. As a rule the minimum age of admission to both full- and part-time courses is 16. Since only a limited number of schools provide a course of longer duration than three years, a preponderance of younger students is to be expected. But it is obvious from these figures that a number of students are either entering late or spending more than the minimum number of years required to complete the course. Observation shows that both of these factors exist.

PRELIMINARY EDUCATION OF STUDENTS.

a

For admission to a full-time course student is expected to have received a secondary school education, though he need not have matriculated. For admission to a part-time course a student who has not been to a secondary school is expected to have passed through a junior technical course consisting of Mathematics, Science, Drawing, and English ,or to show that he he has some knowledge of these subjects. Though no statistics have been obtained, it is certain that a large and increasing proportion of th students have been to a secondary school or some other type of fulltime school which provides education of a higher standard than that attained in public elementary schools. This improvement has been encouraged not only by the wider provision of secondary and central schools, but also by the growing practice of employers in requiring that candidates for junior positions in their laboratories shall have received a superior type of education. In some towns, too, the evening junior technical courses are very well organised, and Principals of schools in these towns are able to insist upon an adequate standard of preliminary training as a condition of admission. As a consequence, a higher standard of attainment is now secured ni respect of an increasing number of part-time students.

(To be Continued.)

By F. H. CARR, F.I.C.

(President of the Society of Chemical
Industry.)

(Before the Royal Society of Arts,
February 23, 1927.)

The discovery of insulin has held the imagination of the general public in a greater degree than perhaps any other discovery in pharmacology and chemistry. It is a tribute to the keen interest that is taken in scientific advances which promise relief to suffering humanity that you should come here to-night to listen to an address on technical aspects of this subject.

At this distance of time, five years after the event, it is possible to appraise with some accuracy the value of the work of Banting and Best in discovering insulin. Time has not only justified the dramatic reception accorded to it but has proved the utility of insulin to be perhaps even greater than was anticipated, both in the relief of suffering and in opening out the avenues to new knowledge.

The time has passed when it was novel to regard the living body as the source of therapeutic substances, and there are now a number of natural remedies produced within the animal which are utilised as external agents to supplement and reinforce the activity of the body. Insulin was not, of course, the first of these; adrenalin and thyroxine are examples of substances possessing remarkable potency which had previously been isolated from the animal body in a pure crystalline form.

It was seven years after the physiological importance of the secretion of the suprarenal gland had been first realised that the active principle was isolated as the result of much experimental work. Three years later its chemical constitution was known, and four years after that there had been made artificially adrenalin which was quite indistinguishable from the natural product.

Such is a typical record of scientific achievement. To-day our knowledge in regard to insulin has only proceeded to the point at which we are able to prepare it in a purified form from natural sources. The physiologist has discovered much about its properties, but the chemist has learnt but little of its nature.

Perhaps I may be allowed to refer briefly to one other example of progress in this field. During the past year, Dr. C. R. Harington, a young English chemist, has succeeded not only in determining the structure of thyroxine--the active principle secreted by the thyroid gland-but has

crowned this achievement by building it up in the laboratory from very simple chemical substances.

Thyroxine, like insulin, is produced within the healthy animal, but a lack of it causes well recognised symptoms of disease, which can be removed with dramatic success by the administration of thyroxine. In a norma individual the oxidative metabolism of the body is fundamentally controlled by the continual release of thyroxine from this gland in quantity which must be very minute, for as little as ten milligrams of it injected into a normal individual increases the rate of metabolism to 45 per cent. above the normal-an effect which does not completely subside until a fortnight after the injection.

Adrenalin, the active principle of the suprarenal gland, has a chemical constitution not unrelated to that now found to represent thyroxine, the active principle of the thyroid gland.

Thanks to Harington, then, we have a thoroughly chemical understanding of these substances. As already explained, our knowledge of insulin has not yet advanced to that point, and we know very little of its chemical character. Our information as to its properties has resulted chiefly from the study of the effects produced when it is injected into the blood stream of a living animal. When so injected it causes the removal of sugar. As to what happens to that sugar we shall learn more presently. When added to sugar in a test-tube it effects no change.

Physiologists have led us to regard the human body as an engine which derives its heat and muscle energy for the most part from glucose during its oxidation in the tissues. The alimentary canal functions by partially rendering the useful constituents. of our diet soluble or capable of emulsification so that they may pass into the interior, the intestine being regarded in this sense as exterior. Those constituents which pass thus to the interior are in a large proportion converted to sugar.

Our food consists as to 60 per cent. of carbohydrate, which is converted by the body into sugar; also the remaining 40 per cent. of the diet is largel yconverted into sugar by the body activities, so that by far the greater part of our food is utilised in the form of sugar. The chief sugar occurring in blood is glucose; the other assimilable mono-saccharides, mannose, galactose and fructose, are converted into it before utilisation, probably being first built into glycogen and then broken down into glucose. A few

hours after the taking of food the percentage of sugar in the blood of a healthy individual becomes constant at about 0.1 per cent., but when a meal is given it may rise in about 30-40 minutes to 0.15 per cent. In the course of one or two hours it will again return to normal.

Long before the discovery of insulin, experiment had shown that, if the pancreas be removed from an animal, the body loses control so to speak of its sugar, and the percentage in the blood and tissues increases until the whole body is flooded with sugar. This naturally causes serious disturbances to the general health, and this is the condition present in diabetes. When the blood sugar reaches about 0.18 per cent., sugar begins to overflow into the urine.

Such observations led scientific workers to regard the pancreas as the probable source of a substance which controls the amount of sugar in the blood stream. Time does not permit me to deal at length with the history of the researches which after many years led to the isolation of insulin by Banting and Best in 1922. Suffice it here to say that these workers were the first to isolate from the pancreas a stable substance which had these properties in an extraordinarily high degree. They would be the first to recognise that their achievement was rendered possible by the work of their predecessors.

Now the pancreas has another wellknown function, namely that of secreting digestive enzymes, including a proteolytic ferment. This ferment passes from the pancreas by a duct into the alimentary canal. Insulin, on the other hand, does not pass down this duct but finds its way from the ancreas to the blood stream internally without being ejected externally down a duct.

It may be regarded as an unlucky juxtaposition that insulin and these digestive secretions should occur in close proximity in the pancreas. Unlucky, because the

chemical nature of insulin is such that it is rapidly destroyed by these very digestive substances. It was mainly due to this fact that previous investigators had failed to isolate insulin; this was the difficulty which Banting and Best overcame with so great

success.

Their method of investigating the problem was to inject extracts of pancreas into living animals and to determine the effect upon the sugar content of the blood. For this they required to use living animals, for insulin does not produce its effects in blood which has been removed from an animal.

in

They required, too, delicate methods of determining minute amounts of sugar blood. These had been recently evolved by biochemists, and the work of Banting and Best was in no small measure dependent upon these delicate methods of analysis which others had elaborated before them.

It had been shown that the foetal pancreas does not up to the fourth month of development secrete an active proteolytic ferment, or trypsin, as it is called, and Banting and Best found that an extract of foetal pancreas, though free from trypsin, had a powerful effect in reducing the blood sugar. This gave them the key to unlock the secret which had for so long baffled experimenters. They set out to devise methods of extracting the pancreas which would give an extract rich in insulin and poor in trypsinogen. As trypsinogen is insoluble in strong alcohol, they employed this solvent and soon arrived at a method of preparing a fairly stable and very active extract. There remained the problem of purifying this extract and perfecting the method of preparation so that the destructive action of the enzymes might be entirely eliminated, and in this success was ultimately achieved.

Among those taking part in this work whose names should especially be mentioned are Collip, Doisy, Somogyi and Shaffer, and Dudley.

Insulin then is a substance prepared from the pancreas. It can be purified and obtained as a solid substance. I will not enter into details of the methods of purification, but will content myself with summarising the characteristics of insulin on which these methods depend.

Precipitated by ammonium sulphate.
Precipitated by sodium oxalate.
Precipitated by picric acid.
Precipitated by trichloracetic acid.
Precipitated by naphthol yellow S.
Readily adsorbed at pH 5 on to charcoal
and kieselguhr.

The most characteristic property which is used for separating it from accompanying impurities is precipitation by exactly adjusting the acidity of the solution to a point in the neighbourhood of pH 5. By reason of their amino groups polypeptides are alkaline and by reason of their carboxyl groups they are acid. There is a point in the process of neutralisation when neither the amino group nor the carboxyl group is bound by acid or alkali respectively. This is the iso-electric point and may be represented thus :

By precipitating with absolute alcohol and then re-precipitating from dilute solution with picric acid and finally taking advantage of this iso-electric precipitation, repeating the process if necessary, a white powder may be obtained which has an activity such that a unit is represented by 1/20 mg. Abel has, however, carried the purification further by precipitating with pyridine from acetic acid solution, and he claims to have produced a substance of which 1/100 mg. represents a unit. Moreover, his product was a crystalline substance melting at 233° C.

Purification cannot be carried out by Abel's process without considerable loss, and for every gram of Abel's material probably one ton of pancreas would be required; consequently questions of expense are apt to deter those wishing to repeat his work on a larger scale. Abel's insulin still gives the Biuret, Millon, Pauly and Ninhydrin reactions.

If we base our opinion of the chemical character of insulin upon this evidence, we must class insulin as a proteose or polypeptide. Polypeptides differ chemically in the number of different amino nuclei they contain, and on his showing insulin is a complex one. Others claim to have produced insulin which gives negative reactions for tryptophane and tyrosine.

Casimir Funk has purified insulin by forming a compound with naphthol yellow S, and he claims thus to have prepared a substance of constant composition to which

he assigns the formula C.,H102022N18S. He considers that it is a polypeptide in which fifteen amino acids are coupled. One hesitates to accept these remarkable conclusions without more detailed information than has hitherto been provided as to the experimental evidence on which they are based.

Abel has observed that with increasing purification there is an increase in the sulphur content of insulin, and he says that that portion of the sulphur which is easily split off is an index of the physiologically active hormone present in impure insulin. He takes the view that sulphur is an integral constituent of the molecule. There is one well-known amino acid of the body which contains sulphur; this is cystine, a substance readily obtained from hair or wool. Will the insulin molecule be found to possess similar grouping? Cystine is represented by the following formula :

Our knowledge of its chemical characteristics being so small and uncertain, let us consider a little more in detail the effect which insulin produces in the living animal. We have already seen that within the body much of the food is converted to glucose. Although this glucose passes into the blood stream, the level of sugar in the blood is constant except immediately after a meal. The sugar is laid down or stored in the liver and muscles as glycogen, and this process of storing takes place under the influence of insulin. This store of glycogen provides the source from which the blood continually derives sugar to maintain the normal level below which health suffers. If the percentage of sugar in the blood falls to the minimum, serious symptoms result. The condition when the percentage of sugar is below normal is known as hypoglycaemia. When the blood sugar reaches 0.18, the kidneys, which otherwise do not allow sugar to pass, can no longer prevent it overflowing, and so sugar is excreted in the urine as in the case of diabetes.

Under normal conditions the body produces insulin in the pancreas and stores it, and there is continually discharged into the blood stream that amount of insulin which maintains the blood sugar at the usual level. By some wonderful adjustment the supply

of insulin is increased when the blood sugar rises above and cut off when it falls below

normal. In a person suffering from diabetes the supply of insulin fails, either from lack of insulin or from a defect in this process of releasing it.

It is only within the past year that by a clever and interesting piece of work by Best, Dale, Hoet and Marks it has been shown what happens to the sugar when it disappears from the blood under the influence of insulin.

The sugar is not entirely used up, since the increase in the amount of carbon dioxide given off by the body or of oxygen taken up by it is not sufficient to account for all the sugar which disappears. Where then does it go?

Best, Dale, Hoet and Marks showed that the loss of sugar is completely accounted for by conversion into glycogen and by combustion. In a series of experiments which called for the highest skill and ingenuity, they were able to construct a balance sheet based on actual chemical analysis which accounted for the whole of the sugar passed into the animal together with that originally present before the administration of insulin.

X-RAY ISOCHROMATS OF COPPER TAKEN IN DIFFERENT DIRECTIONS RELATIVE TO THE CACTHODE STREAM.

By WARREN W. NICHOLAS.

Abstracted from the Physical Review.)

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Variation with potential of the intensity of monochromatic X-rays of wave-lengths 0.823 to 0.247A for directions making angles of 36°, 90° and 144° with the cathode stream.-X-ray isochromats of copper were taken in three different directions relative to the cathode stream, for a target face making an angle of 25° with the cathode stream. Corrections were made for stray radiation in the neighbourhood of the measured beam, for radiation due to secondary hits of cathode electrons which had been reflected backward from the focal spot at large angles, and for absorption in the target. It is established that, within experimental error, an isochromat of frequency varies linearly with the potential from potentials about (5/4) Hv to 2Hv, where Hv is the quantum voltage for excitation of frequency v. The linear portions of the graphs were extrapolated to find the intercept on the intensity axis at IIv. This intercept depended on Iv, and also on 0, the angle between the measured X-rays and the cathode stream. For 0 = 90° the intercepts varied between 0.062 I' (for Hv 50 kv.) and 0.085 I' (for Hv = 15 kv.) with 36° the rean average of 0.072 I'; for 0 spective values were 0.076 I', 0.096 I', 0.086 I'; for 0.035 I', 0.010 I', 0.017 I'. I' is the intensity of the isochromat at 2Hv. Values of II used were 15, 20, 30, 40,50 kv. The intercept decreased in general, for increasing Hv, but for @= 36° and 90° the change was within the experimental error of 0.01 I'. Energy distribution in the X-ray continuous spectrum from a thick target.-Kulenkampff's formula for the energy distribution in the X-ray continuous spectrum for 0 = 90° does not hold in detail for the higher voltages and different target face inclination used in the present work. Assuming total energy in the continuous spectrum proportional to the square of the voltage on the tube, and assuming suitable modifications of this law, for the forward and backward angles, from Sommerfeld's space distribution of energy as a function of cathode ray velocity, it is shown that the spectrum for the forward angle contains relatively more high frequency rays than the spectrum at 90°, and the spectrum at the backward angle contains relatively more low frequency

rays.

=

144°,

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Energy distribution in the X-ray continuous spectrum from a thin target.-On similar assumptions as to total energy, the spectra which would have been obtained from a very thin foil of copper are derived from the isochromats by Webster's method. The thin target spectra on a frequency scale, for = 90°, are horizontal except for a sharp rise in intensity as v approaches s the high frequency limit. For 36° the energy is approximately directly proportional to v except for the region near 1, where there is again the sharp increase. For 144° the energy is approximately inversely proportional to v except near vo where there is a decrease for high voltages.

=

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Theories by Kramers and Wentzel for 0 = 90° are in fair agreement with the experiments as to thick target spectra, but if certain assumptions made in this paper are correct, Kramer's predicted thin target spectra are much more nearly in accord with the facts than are Wentzel's.

General Notes.

SAFEGUARDING OF KEY

INDUSTRIES.

The Board of Trade give notice that the Treasury, by order dated 23 June, have exempted under the provisions of Section 10(5) of the Finance Act, 1926, for the period from 27 June, 1927, to 6 March, 1928, the following articles from the duty imposed by Section 1 of the Safeguarding of Industries Act, 1921, as amended by the Finance Act, 1926:

Ammonium perchlorate; Dial (acid diallyl barbituric); Elbon (cinnamoyl para oxyphenyl urea); Hydroquinone; Integrators (planimeter type); R Lead acetate; Lipoiodin; Phytin; Planimeters; Potassium guaiacol sulphonate (thiocol); Urea (carbamide).

ONTARIO HYDRO-ELECTRIC COMMISSION PLANS EXPANSION OF NIPIGON POWER DEVELOPMENTS.

Engineering plans are now being put into effect by the Hydro-electric Power Commission of Ontario whereby the water-powers of the Nipigon River will be developed to their full capacity of 260,000 horse-power in a comparatively short time. At present the Cameron Falls station has a capacity of 75,000 horse-power and is feeding the