319), von Helmholtz (pp. 213 and 319), and Albrecht von Graefe
(1828-70). The last was a professor at Berlin who greatly improved the
operation for cataract and introduced or improved many other important
operations on the eye. He was one of the first to make important
clinical observations with the ophthalmoscope, and he showed how the
instrument may be made to yield information not only of the condition
of the eye itself, but also of the brain and of its membranes, an
application which has become of the greatest value in later medical
developments. Though he died before the most important work of Pasteur
and Lister had become generally accepted, von Graefe was yet practising
a system of surgery which was not far from aseptic.
As with most departments of Medicine, so also with Ophthalmology,
the most significant advances during the last generation have been
in the direction of prevention rather than cure. Prominent among
these measures are, firstly, school inspection with the consequent
early detection and isolation of infectious cases of conjunctivitis;
secondly, maternity welfare accompanied by prompt notification and
treatment of the very dangerous and sight-destroying ‘Ophthalmia of the
New-born’; thirdly, improved light regulation in factories and schools;
and, fourthly, adequate provision of spectacles for school children
with errors of vision.
The recognition of the infectious character of the very chronic
and sight-destroying disease known as _Trachoma_, or ‘Granular
Conjunctivitis,’ has been of great importance for the Public Health.
The disease is common in the near East and in Eastern Europe and by no
means rare in slum quarters in the West. A rigid system of inspection
of immigrants, together with quarantine combined with treatment, has
done much to diminish its ravages in the United States.
§ 20. _Investigation of the Nature and Action of Drugs._
(a) _Entry of Vegetable Drugs into the Pharmacopoeia._
An examination of the list of drugs that are in use at the present
day--apart from those which have been introduced by the scientific
movement of the last generation--yields some surprising results. Some
thirty per cent. of the crude vegetable drugs in the modern official
Pharmacopoeia were known in remote antiquity. The Egyptian medical
papyri mention, among others, Aloes, Caraway, Castor Oil, Coriander,
Dill, Fennel, Juniper, Mint, Myrrh, and Turpentine. Among Egyptian
mineral remedies still in use are salts of copper and of lead. Assyrian
medical tablets refer to most of the Egyptian drugs as well as to a
number of others, among which are Almond Oil, Aniseed, Galbanum, and
Liquorice. Among Assyrian mineral remedies that are used by us to this
day are Alum and Bitumen. Early Indian medicine had a very copious
pharmacopoeia. _Cannabis indica_, known as ‘Hashish’ or ‘Indian hemp’,
Cardamoms, _Cassia fistula_, _Datura stramonium_, and _Nux vomica_ are
among the valuable Indian herbs now in use in scientific medicine,
while Mercury preparations were perhaps ultimately of Indian origin.
The medical herb lore of the Greeks comes to us chiefly from
Dioscorides (p. 43), who mentions about five hundred plants. A large
number of these are still in our own Pharmacopoeia. Among these,
besides those of Egyptian, Assyrian, and Indian origin, are Ammoniacum,
Belladonna, Camomile, Catechu, Cinnamon, Colchicum, Colocynth, Crocus,
Galls, Gentian, Ginger, Hyoscyamus, Lavender, Linseed, Male Fern,
Mallow, Marjoram, Mustard, Poppy, Rhubarb, Sesame, Stavesacre, Storax,
Terebinth, Tragacanth, and Wormwood. About thirty-seven per cent. of
our Pharmacopoeia was known to the later Greeks. From them the Arabs
derived, adding, however, enormously to their drug-lists, so that we
may say that about fifty per cent. of our drugs were in use by the
Arabic-speaking physicians of the Middle Ages. With the discovery of
America further important additions were made. Of these we have already
discussed the introduction of Cinchona, Ipecacuanha, and Tobacco (p.
95). Few important additions were made in the eighteenth century,
though among them was Digitalis (p. 328).
(b) _Active Principles._
One of the things that separate the practice of Medicine of our time
from that of previous ages is our power to give drugs in ‘pure’ form.
This means not only that we can secure drugs without adulteration, but
also that the active substances in drugs can be chemically isolated
and given without admixture. Most drugs used in Medicine are, in fact,
of vegetable origin. The possibility of giving them in chemically pure
form depends upon the discovery, early in the nineteenth century, that
plants owe their poisonous and remedial properties to small quantities
of _Active Principles_, which are susceptible of chemical extraction
and isolation. Thus the science that deals with the action and nature
of drugs, _Pharmacology_, really took its rise about a hundred years
ago, though many had experimented with drugs at an earlier date.
Further progress in the same direction has been made by the so-called
‘synthetic’ preparation of drugs. Certain substances of vegetable
origin do not readily yield their active principles and to extract them
very complex chemical processes may be involved. There are special
obstacles to the complete purification of other drugs, even when they
have been obtained in a relatively pure state. These difficulties can
sometimes be surmounted by the preparation of the drug from inorganic
materials. This synthetic process of preparation is now possible for
many substances that are of medical application. Furthermore, when
a drug can be thus synthetically prepared, it is often possible to
try chemical variants upon it, and thus to obtain a more effective
preparation.
In former times a vast number of drugs were habitually employed
by physicians, and they were often given in very complicated
prescriptions. ‘Polypharmacy’, the giving of many drugs, is a vice
from which Medicine has now in large part freed itself. The number of
drugs given by scientific physicians is far fewer that it was. For
this there are several reasons. Firstly, many drugs were found useless
for the purpose for which they were administered, and were at times
even dangerous. Secondly, since attention has been drawn to the active
principles of drugs rather than to the crude natural drugs, it has been
seen that, in fact, many of the drugs that were being given were merely
duplicates one of another, and that often the administration of the
active principle itself was more effective and more reliable than that
of the source from which it was obtained.
What then is the nature of the drugs now being administered by
scientific physicians? They fall into a number of classes. The nature
and action of some of these is so simple that no prolonged discussion
of them is necessary. There are, for instance, the inorganic acids
and alkalis, the primary action of which, when taken internally,
can be determined by a series of experiments on gastric juice in a
test-tube kept at body temperature. Again, there are soluble inorganic
salts, which are absorbed unchanged from the alimentary canal. These
have the effect of increasing secretions. Their purgative effect is
well known, though the physiological details of their action are not
yet clear. There are yet other substances, such as metallic Mercury
in ‘grey powder’ or Bismuth, which act mechanically, even when
administered internally. Over and above these simpler substances, and
in addition to the traditional vegetable substances which have been in
use as medicines for centuries, there are others which have only been
accessible during the last few generations. We have already discussed
under separate headings the derivatives from animal glands, such as
of the Thyroid (p. 305), of the Adrenals (p. 307), or of the Pancreas
(p. 306), as well as the bacterial Vaccines (p. 261) and Antitoxins
(p. 267). We now turn to pure chemical substances of vegetable origin.
Of these mention may be made especially of the groups known as the
_Alkaloids_ and the _Glucosides_.
(c) _The Alkaloids._
By ‘Alkaloid’ is understood a nitrogenous substance, usually of
vegetable origin, which forms salts with acids. The alkaloids are
mainly obtained from the dicotyledonous plants. Generally they occur
in nature in combination with plant acids such as citric or tartaric
acid. The alkaloid group contains some of the most important drugs that
we possess. Among them are Morphine, Strychnine, Cocaine, Atropine, and
Quinine.
The investigation of the alkaloids began with the nineteenth century.
Morphine was isolated from Opium by the Parisian apothecary Charles
Derosne (1780-1846) in 1803. He failed, however, to recognize its
chemical affinities, which were first grasped by the German apothecary
Adolf Sertürner (1783-1841). Their work, however, attracted but
little notice until attention was drawn to it by the great French
chemist Joseph Gay-Lussac (1778-1850), in 1817. The result was the
concentration of much scientific ability on the alkaloids. Prominent
among the early investigators were the French pharmacologists Pierre
Joseph Pelletier (1788-1842) and Joseph Caventou (1795-1878). Between
1818 and 1820 they isolated from Cinchona (p. 95) certain alkaloids
allied to Quinine, from Nux vomica the alkaloid Strychnine and certain
of its allies, and from Coffee the alkaloid Caffeine. Pelletier
in conjunction with the distinguished chemist Jean-Baptiste Dumas
(1800-84) followed this by a quantitative examination of a number of
alkaloids in 1823. The first alkaloid to be used as such in medicine
was Strychnine. It was introduced in 1821 by the French physiologist
François Magendie (1783-1855), the teacher of Claude Bernard.
In the thirties and forties of the nineteenth century Liebig, who had
developed his doctrine of radicles (p. 206), attempted to determine
the formula of alkaloids. He was followed by Wöhler (p. 206). Since
then an immense amount of work has been done in investigating the
chemical nature and physiological action of alkaloids. The general
result has been to reveal the fact that each alkaloid-yielding plant
contains not one but a number of alkaloids. Those from the same plant
often have similar but not identical action upon the animal body. The
differences in physiological action of allied alkaloids have occupied
much of the attention of pharmacologists. The accurate knowledge of
these differences has made possible a far greater finesse in the
administration of alkaloid drugs than was previously possible. Some
alkaloids can be prepared synthetically, but the process is mostly of
theoretical rather than practical importance.
(d) _The Glucosides._
The Glucosides are an ill-defined group which have in common the
property of yielding a sugar-like substance--usually glucose itself--as
a result of certain chemical processes. They are mostly of vegetable
origin and the history of their investigation has been parallel with
that of the alkaloids. The first glucoside to be isolated was Salicin,
which was obtained from willows in 1819. It is the active principle of
the very ancient remedy for rheumatism, ‘Oil of Wintergreen’. Salicylic
acid was introduced into Internal Medicine in 1873 and its derivative,
Aspirin, in 1899. Both drugs are of great importance, and many other
derivatives of Salicin are in use. Salicin and its derivatives can
be prepared synthetically, and the synthetic products are in use in
Medicine.
Of all the glucoside-yielding plants, perhaps medically the most
important is the Foxglove, _Digitalis purpurea_. The use of the plant
was known to some of the medieval herbalists, and is, moreover,
recommended in the German and English printed herbals of the sixteenth
and seventeenth centuries. Foxglove is mentioned as a folk remedy
in George Eliot’s _Silas Marner_, the story of which refers to a
period round about 1750 before the Industrial Revolution, ‘when the
spinning-wheels still hummed busily in the farm-houses’ (Fig. 89). It
was introduced into scientific Medicine in 1785 by William Withering
(1741-99) of Birmingham in his _Account of the Foxglove_, which gives
details of numerous cases treated with it.
Digitalis long resisted the attempts to extract an active principle,
but since the seventies it has yielded to investigators a whole series
of glucosides. Digitalis and its derivatives have become of much
importance, especially in the treatment of cardiac conditions. Despite
the success in obtaining glucosides from the Foxglove, the extract of
the plant itself continues in wide use.
(e) _The Study of Pharmacology._
Since the middle of the nineteenth century the investigation of the
physiological action of drugs has been mainly in German hands. The
most prominent exponents of the method have been Karl Binz (1832-1912)
and Oswald Schmiedeberg (1834-1921), both professors at Dorpat, where
there has been a pharmacological laboratory since 1849. The first
pharmacological laboratory in America, that at Ann Arbor established in
1893, and the first in England, that at University College, London,
established in 1905, were successively occupied by A. R. Cushny
(1866-1926). The work of these and of other pharmacologists has not
tended to increase but to reduce the number of drugs. Nevertheless,
some new drugs of great importance have been introduced by them. Of
these, among the more valuable is Amyl nitrite, the inhalation of which
was first recommended by T. Lauder Brunton (1844-1916) as early as 1867
as a remedy in certain cases of sudden heart seizure.
Improvements have been made not only in the drugs themselves but
also in modes of administration. The ancient methods of inunction
and inhalation, as well as other older methods, have been greatly
elaborated in modern times, and are now of wider application than
they were. No advance of this order compares in importance with the
introduction of the Hypodermic Syringe by the ingenious French surgeon
Charles Gabriel Pravaz (1791-1853). By means of this instrument various
drugs can be injected directly into the subcutaneous tissues or into
the veins. This mode of administration is more accurate and under
better control than any other, and the action of the drug so injected
is swifter and more sure.
(f) _Chemotherapy._
During the twentieth century the outlook on drug treatment has
been modified by the success obtained in the _specific_ treatment
of certain diseases, that is to say, treatment by remedies which
strike at a particular disease and no other. Until quite recently
scientific Medicine recognized very few specific remedies. It had been
ascertained that Cinchona owes its value in Malaria to the alkaloid
Quinine (p. 326), which acts as a specific exterminator of the malaria
parasites, and not simply as a remedy for fever in general. It had
also been ascertained that Ipecacuanha owes its value in tropical
Dysentery to the alkaloid Emetine, which acts similarly as a specific
exterminator of the protozoal organisms which are the infective agents.
Quinine and its allied alkaloids and Emetine and its allied alkaloids
were practically the only specifics the value of which had been
scientifically proved, except Mercury for Syphilis.
About the beginning of the twentieth century arose the new
‘Chemotherapeutic’ movement as it came to be called. This movement was
initiated by the studies of natural Antibodies (p. 262) by Paul Ehrlich
of Frankfurt (1854-1915). Antibodies are strongly antagonistic to the
parasitic organism the toxin of which has elicited them, but, on the
other hand, they are quite harmless to the animal body in which they
reside. Here are ideal remedies provided by Nature herself. Ehrlich
compared them to magic bullets, constrained by a charm to fly straight
at their objective and to injure no other. No such perfect artificial
drugs have yet been produced. The problem of Chemotherapy is rather how
to poison the parasite as much as possible while poisoning the host as
little as possible.
When Ehrlich began the study of Chemotherapy observers had long known
that certain aniline dyes have a special affinity for certain cells
or organisms. Indeed the affinity of certain of the dyes for certain
bacteria had made possible the work of Koch on Tuberculosis and on
other diseases. As far back as the seventies and eighties much
work had been done on the subject, and the action of these dyes had
interested a large variety of investigators. Ehrlich’s first results
were on a protozoal parasite, which infests dogs. By injecting small
doses of a certain aniline dye into the veins of the infected animal
it was found possible to destroy the parasites while doing very little
injury to the dog.
[Illustration:
FIG. 133. THE ORGANISMS OF SYPHILIS IN A SMEAR FROM THE LOCAL
INFECTION. Highly magnified. They are best seen by means of a special
optical arrangement in which the outlines of the objects appear
glistening white and the background black. The round objects are pus
corpuscles, the two spiral objects the organisms of syphilis. ]
At this point Ehrlich turned aside from the aniline dyes to study
the effects of much more toxic substances. He selected the compounds
of arsenic for the purpose. After prolonged research, he obtained an
arsenical derivative which proved very toxic to parasitic protozoa and
little toxic to their animal hosts. When a vast number of experiments
had been made, this substance was tried in 1910 in cases of human
Syphilis. This disease had been shown by Fritz Schaudinn (1871-1906)
in 1905 to be due to a protozoal parasite, the _Spirochaeta pallida_
(Fig. 133). The results obtained by the new remedy were very
satisfactory and a valuable specific was thus added to the medical
armory. The drug became widely known as 606, since this is its number
in the series of the arsenic derivatives with which Ehrlich had
experimented. In the meantime others had been at work along lines
suggested by the aniline experiments. Their investigations led in 1920
to the discovery of a specific against the deadly _Sleeping Sickness_
or _Negro Lethargy_. This drug is known as _Bayer 205_ from the firm
that prepared it and the number in the series of substances that were
tested.
Since the first preparation of 606 and 205 some interesting facts have
emerged concerning their action as well as the action of Quinine,
Emetine, and other specific remedies. It has been found that the
toxicity of these substances to the parasites against which they are
aimed is much greater when the parasites are within the body than when
the drugs are applied to the organisms outside the body. In other
words, the drugs do something to the body, or the body does something
to the drugs, that is inimical to the parasite. The nature of that
something is still under discussion. In the case of Quinine it seems
that the Quinine so affects the red blood corpuscles that the malarial
parasites cannot enter them and so cannot go through their sexual
cycle (Fig. 123). Thus the Quinine does not act as a direct poison
but attacks the parasite in a much more subtle manner. In the case
of other parasites the action of the specifics is more difficult to
understand. It should be pointed out, however, that the chief victories
of Chemotherapy have been in dealing with the protozoal rather
than the bacterial diseases. A main task of future Medicine will be
the discovery of means of eliciting antibodies against the various
bacterial infections. For this there is more immediate hope from the
use of remedies of vital origin than from those synthetically produced.
§ 21. _Interpretation of Collective Medical Data._
The drawing of a deduction of scientific value from experience is
by no means a simple process. In many sciences the investigator has
the power to control experience; in other words he can _experiment_.
But even the interpretation of experiment needs special precautions.
The physical experimenter must, for instance, make sure that he has
but one ‘variable’. Thus, if examining the effects of pressure on
a gas, he must see that in raising or lowering pressure he is not
altering temperature, or if recording the effects of temperature he
must satisfy himself that he is eliminating those of pressure. In
experiments upon living things the limitation of the field of action to
one simple factor is often--perhaps always--impossible. The biological
investigator is therefore accustomed to accompany his experiment with
‘controls.’ Thus, if he wishes to ascertain the effect on the growth
of animals of feeding with milk that has been boiled, he must feed one
series of animals on unboiled milk while he is experimenting with a
series fed with the boiled milk. He must take steps to ensure that the
two series are similar as regards age, strength, size, &c., and that
the conditions under which they live are identical, except as regards
the one factor the results of which he seeks to ascertain.
When the observer is dealing with human material, it is very seldom
that he can either restrict the number of variables to one or secure an
adequate series of controls. Physicians are habitually in a position in
which action of some kind is demanded. They cannot await the conclusion
of laboratory researches, which may extend over years, for the patient
must be relieved at once or die. Being often unable to use those most
reliable instruments of science, experiment or observation under
control conditions, physicians have come to rely on what is called ‘a
general experience of disease’.
One of the commonest fallacies of such general experience is assignment
of causative relationship between two conditions, simply on the ground
that they frequently occur in association. Thus it is a fact--and one
to which attention has been drawn by medical observers--that rheumatic
affections and red-headedness are often found together. But both
conditions are common and it has not been satisfactorily demonstrated
that the association of the two is any commoner than their frequency
in the population at large would render probable. Such general
experience is therefore very fallible and is incapable of scientific
expression, though it is often very valuable and sometimes indeed
entirely indispensable. To give such experience scientific expression,
to place it in terms of the ‘primary qualities’ of the founders of
modern Science (pp. 106-7), it is necessary to put it into statistical
form. Statistical statement thus becomes of the highest importance
for medical progress. Medical statistics, when prepared from proper
material and drawn up with the requisite skill, are at once the most
exact and the most generalized expression of medical experience.
[Illustration:
FIG. 134. DIAGRAM ILLUSTRATING THE ALTERATION IN THE PERCENTAGE OF
AGE-DISTRIBUTION OF THE POPULATION OF ENGLAND AND WALES FROM 1891 TO
1926. It will be observed that the people of England and Wales have
been getting steadily older. ]
Statistical statements, however, vary greatly in their value and ease
of interpretation. The simplest statistical statements with which the
medical man has to deal are perhaps those which relate to surgical
operations. The categories in which the patient may be placed are here
limited; he may die, recover, improve, or get worse. If the operation
is a quite simple one, and if the surgeon is perfectly honest, and
also--which is rarer--quite unbiased, a small body of statistics
may carry immediate conviction as to the value of an operation.
Thus, Lister’s first results with amputation, as obtained under
his antiseptic conditions, at once satisfy the mind, although the
conclusions are based on only forty cases (p. 240). No surgeon at once
both able and willing to appreciate these results would hesitate to
adopt the new method.