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trypsin was shown by S. Martin.^ The proteids in the juice are a globulin
very like serum globulin, small quantities of an albumin, and proteoses of
two kinds, with one of which the ferment appears to be closely associated
(Martin). i*>

Bromelin. — This is the proteolytic ferment in pine-apple juice. Its
existence was first noted by Marcano of Venezuela. It is made use of
extensively in South America for the preparation of artificially digested

^ Am. Chcm. Journ., Baltimore, vol. xiv. No. .3.

- Ihid., vol. xiii. Nos. 7, 8, and 9 ; vol. xiv. No. 1. ^ Ibid., vol. xiv. No. 8.

'^ Ibid., vol. XV. No. 6; "Seventeenth Ann. Rep. Conneeticut Agric. Expt. Station,"
Newhaven, 1893.

^ Ann. Botany, Oxford, 1895, vol. ix. pp. 171, 503.

'' Journ. Am. C'hem. Soc, N. Y., 1894, vol. xvi. p. 633.

'' Ibid., 1895, vol. xvii. p. 539. See also Osborne and Campbell on proteids of potato
on congUitin and vitellin, on legiimin and other jjvoteids of the pea and vetch, ibid., 1896
vol. xviii. No. 7.

>* Comjyt. rend. Acad. d. sc, Paris, 1879, p. 425 ; 1880, p. 1379.

^ Journ. Ihysiol., Cambridge and London, vol. v. p. 213.
1" Ibid., vol. vi. p. 336.


foods. 1 Its action has been studied by Chittenden - and his pupils. It is a
ferment of intense activity, and acts well in neutral, acid, and alkaline
solutions, especially at 60° C. The ferment itself is associated or identical
with a proteose-like substance in the juice. The products of its action
(proteoses and peptone) are like those of other proteolytic ferments.

I have alluded to these two ferments because they have formed the basis
of very thorough investigations, not because they are in any way exceptional
occurrences in the vegetable kingdom; as already stated, such ferments
probably play an important part in all plants, by converting the insoluble
proteid of the seed into the soluble nitrogenous substances of the sap.'

Proteids as Poisons.

The line between food and poison is easily crossed. When, a few
years ago, the idea was first mooted that proteids may act as poisons, it
was received with incredulity in many quarters ; but there can now be
no doubt that it is a fact.^

The best known of the vegetable proteid poisons are : —

1. Those contained in the seeds of jequirity (Ahrus precatorius).
Warden and Waddell ^ named the poisonous substance abrin. S. Martin ^
separated the two proteids — a globuhn and a proteose — of which it is
composed. The material is used as a drug to produce conjuncti\dtis.

2. The proteid associated with or identical with papain (S. Martin).

3. Pdcin, the poisonous proteid in castor-oil beans.'''

4. Lujpino-toxin from Lujjinus luteus?

The most important of the animal proteid poisons are —

1. Snake poison.

2. Proteids in the serum of certain fishes (conger eel, murtena, etc.).^

3. Proteid poisons found in certain spiders,^*^ and in the stinging
apparatus of many insects.

4. Ordinary peptones and proteoses ; 0'3 gr. of commercial peptone
per kilog. of body weight is in dogs usually fatal, when injected into
the blood.

5. Nucleo - proteids. — These were called tissue fibrinogens by
Wooldridge, and cause intravascular clottmg when injected into the
blood (see " Coagulation of Blood ").

6. Poisonous proteids produced by bacterial action. This subject
has recently received much attention, and opens up the whole subject
of toxins and antitoxins. To go into this matter thoroughly would

1 Bidl. Plmrm., Detroit, 1891, vol. v. p. 77.

■2 Trans. Connect. Acad. Arts and 6'c., New Haven, 1891, vol. viii. ; Journ. Physiol., Cam-
bridge and London, vol. xv. p. 249.

^ See further Green's papers ah'eady quoted ; also J. E. Green, " On the presence of
vegetable trypsin in the fruit of C'ucumis utilis and other plants," A7in. agronomiqucs,
Paris, tome xix. p. 508 ; ISTeumeister, Ztschr. f. Biol., Miinchen, Bd. xxx. Another recent
paper on the subject (J. Hjort, Ccntralhl. f. Physiol., Leipzig, 1896, Bd. x. S. 192) shows
that there are similar ferments in fungi.

* Nencki's opinion that poisonous proteids are more labile than other proteids can
hardly be considered an explanation of this fact (" Ueber die labile Eiweissstofte, " Jf'chnschr.
f. Pharm., 1891, ISTo. 29).

" "Non-Bacillar ISTature oi Ahrus Poison," Calcutta, 1884.

'^ Brit. Med. Journ., London, 1889, vol. ii. p. 184.

■^ Stillmark, Pharm. Centr.-BL, Leipzig, 1890, Bd. xxx. S. 650.

^ Schmidt's Jahrb., Leipzig, 1SS8, Bd. cciv. S. 10.

" Mosso, Jahresh. il. d. Fortschr. d. Thier-Chem., Wiesbaden, Bd. xviii. S. 92.

1" Robert, Sitzungsb. d. Doiyater naturforscli. Gcscllsch., 1888 ; Centralhl. f. d. med.
Wisscnsch., Berlin, 1888, S. 544.


lead us too far into pathological regions. The exact nature of the
toxalbumoses and their antitoxins is by no means settled, but has
already been followed l;)y important practical results in the way of

Snake poison. — The first group of proteid poisons in the foregoing
list will furnish us with a typical example of the class, and it appears
probable that, as the nature of the poison has been more thoroughly
worked out in this than in most of the other cases, this will also form
an important field of research in furnishing the key to the question of
the nature of antitoxins ; for protective inoculation has here been
followed with considerable success (Calmette,^ Eraser ^ ).

The first investigation into the chemistry of snake poison of any
importance was by Prince Lucien Buonaparte, on the poison of an adder,
in 1843.^ He found that the activity of the poison was associated with
the portion precipitable by alcohol ; and he gave the name vi-parine to
this precipitate.

About 1860, Weir Mitchell* turned his attention to the subject, and
he was the first to recognise that the toxic principle of the venom is
albuminous in nature. He termed it crotalin in the case of the rattle-
snake. From that time till 1886 (in conjunction with Eeichert) he
continued his work, and confirmed his general conclusion in the case
of the North American snakes. About 1871 the Indian snakes received
their share of attention, and the names of Sir Joseph Fayrer^ and
Lauder Brunton® are associated with valuable researches concerning
the venom of the cobra, krait, and Indian viper. These observers dealt,
however, with the object mainly from the point of view of the physio-
logical action of the venom.

In 1883 Wall,7 in 1886 Wolfenden,^ and in 1892 Kanthack,^
published important contributions to our knowledge of cobra poison,
the improved methods of chemical physiology enabling them not only
to identify the poison as a proteid, but to show that the variety of
proteid present is principally proteose. Two observers have described
poisons other than proteid in snake venom, viz. Gautier,^*^ who regarded
the venomous principle as alkaloidal ; and Wynter Blyth,^^ who gave the
name cobric acid to a crystalline substance which he separated from
cobra venom, and which he asserted to be highly poisonous. Eecent
work has failed to substantiate these results, and such alkaloids as are
present (and they are generally absent) are non-poisonous ones.

In their researches on the venom of the Australian black snake, C.
J. Martin and M'G. Smith '^^ determined positively the nature of the

^ " Le Venin des Serpents," Paris, 1896.

^ Brit. Med. Journ., London, 1895, vol. i. p. 1309. Tlie name given to the antitoxin
contained in the serum of immnnised animals is antivenine.

^ See Sir J. Fayrer, Proc. Med. Soc. London, 1884.

•* N. Am. Med.-Ghir. Rev., vol. v. p. 269 ; Med. News, Philadelphia, 1883 ; "Researches
Tipon tlie Venoms of Poisonons Ser]ients," Smithsonian Contributions to Knowledge, 1886.

■'' Rep. on sail, improrement-'i in India, London, 1873, 1874.

''Rep. on i^an. measures in India, London, 1874; Proc. Roy. Soc. London, 1872-3.
1873-4, 1875 and 1878; Sir J. Fayrer, " Thanatophidia of India," London, 1872, and
numerous papers by same author in Edin. Med. Journ., and Indian Med. Ga~., Calcutta,
between 1868 and 1874.

"^ " Indian Snake Poisons, their Nature and Effects."

" Journ. Physiol., Cambridge and London, vol. vii. pp. 327, 357, 365.

" Ibid., vol.'xiii. p. 372. "' Ball. Acad, dc mM., Paris, 1881.

" Analyst, London, 1876, vol. i.

^" Proc. Roy. Soc. New South JFales, Sydney, July 3, Aug. 3, 1892 ; Journ. Physiol.,
Cambridge and London, 1893, vol. xv. p. 380.


venom. By appropriate experiments they excluded micro-organisms,
ferments, alkaloids, ptomaines, and crystalline acids.^ They next showed
that there are three proteids in the secretion ; one, an albumin, is not
irulent ; but the other two, which are proteoses (proto- and hetero-pro-
teose), are extremely poisonous. Their action is the same as that of the
venom itself. They, like the venom, can be momentarily l^oiled without
impairing their activity, but prolonged boiling for days destroys their

The action of the poison is local and general. The most marked
local effect is oedema ; the general symptoms in non-lethal doses consist
of twitching and convulsions. A fatal dose kills within a few seconds
or minutes. There is also a peculiar effect on the blood. More than a
century ago, the Abbe Fontana ^ noticed that the blood of animals
killed by viper bite remained fluid. Brainard,^ writing more than forty
years ago, states that when death occurs immediately, in animals bitten by
rattlesnakes, the blood is found at the post-mortem examination to be
clotted ; but if some time elapses before the animal succuml^s, the blood
remains fluid in the vessels. The continued fluidity of the blood has
since then been noted by numerous observers in the case of various
snakes. These observations are explained by C. J. Martin's researches.
He found that different doses produce different results. Immediately after
the introduction of the venom, the coagulability of the blood increases,
and this increase in the case of moderate or large doses (more than
O'OOOl grm. per kilog. of body weight) culminates in intravascular
clotting of greater or less extent. The injection of smaller doses
produces a transient phase of increased coagulability, but after two
minutes this is succeeded by a negative phase ; the blood when drawn
either fails to clot at all, or does so only after the lapse of several hours.
The thrombosis occurs more readily in venous than arterial blood, and is
frequently confined to the portal area. These results show a great
resemblance between the action of the venom and that of nucleo-proteid.
The effect of diminished coagulability is not unexpected, seeing that the
principal substance in the venom is proteose, but the minuteness of the
dose necessary is very striking and distinctive. The smallness of the dose
suggests that the injected material does not itself contribute to fibrin-
formation. It probably acts by producing disintegration of the cells of
the endothelium of the blood vessels, or, according to Martin's later
observations, of the red corpuscles ; in either case the result would be
liberation of nucleo-proteid material.

With regard to the question of how these poisonous proteoses are
formed, Martin puts forward the following hypothesis : the cells of
the venom gland exercise a hydrolysing agency on the albumins supphed
them by the blood, the results of which influence are the poisonous
proteoses found in the venom. A difference between the process and
digestion by pepsin, or by anthrax bacilli, is that the hydration stops
short at the proteose stage, and is not continued so as to form peptone,
or simpler nitrogenous materials, like leucine, tyrosine, or alkaloids.
Gland epithelium is certainly capable of exercising such a hydrolysing
influence; the conversion of glycogen into sugar in the liver cells is
one of the best known examples.

^ A questionable trace of organic acid found did not possess toxic properties.
^Fontana, "Poisons," Trans, by J. Skinner, London, 1787.
^ Ref. Smithson. Inst., Washington, 1854.


The following table, somewhat altered from Sidney Martin,^ illustrates
the analogy between various hydrolysing processes, proteid being in all cases
the material acted on.

Primary Agents.




Nitrogenous but not

1. Epithelial cell of gastric


2. Epithelial cell of pancreas

3. Bacillus anthracis

4. B. diphtheria

5. Epithelial cell of snake's




None yet

Ferment not

None yet

Proteoses, peptone.
Proteoses, peptone.

Proteoses, peptone.


Brieger's pepto-

toxin ; a very

doubtful basic

Leucine, tyrosine,

lysine, argiuine,

aspartic acid,

Leiicine, tyrosine,

and an anthrax

Organic acid of

doubtful nature.
Trace of organic


Calmette"-^ has worked out a table of the relative toxicity of venoms, as
Roux and Vaillard have done for tetanus toxins, based on the ratio of
lethal dose weight, subcutaneously injected, to body weight. He found the
toxic value to be represented by the following numbers : —

Cobra 4,000,000

Hoplocephalus curtus ..... 3,450,000

Pseudechis 800,000

Pelias berus 250,000

Martin places the toxic power of the two Australian venoms at —

Hoplocephalus 4,000,000

Pseudecis 2,000,000

This is a very high virulence ; put in another way, it means that 0-00025
gr. of the one, and 0*0005 gr. of the other poison is sufficient to kill a rabbit
weighing a kilogramme. The virulence of snake poison much exceeds that of
most of the poisonous proteids of zymotic diseases, though it is about the
same as the diphtheria toxin of Roux and Yersin.^ The following table also
gives the toxic value of anthrax toxin, "^ and toxopeptone ^ from cholera
cultures calculated in the same way : —

Diphtheria toxin 4,000,000 (about)

Anthrax albumoses ...... 80

Toxo-peptone ...... 3,000

Animal Alkaloids.

Ptomaines and leucomaines. — The word ytomaine was originally
employed to designate those putrefactive products of animal substances which

which are more or less
metabolic activity, either

give the reactions of vegetable alkaloids, and
poisonous. The similar substances formed by
from lecithin or proteids,*^ are called leucomaines.

1 Published in Brit. Med. Journ., London, March 1892.
- Ann. de I'Inst. Pasteur, Paris, 1894, tome viii.

2 Quoted by Sims Woodhead, "Bacteria and their Products," p. 307.
■" Sidney Martin, Rep. Med. Off. Local Gov. Bd., London, 1890-91.

'' Petri, quoted by Vaughan and Novy, "Ptomaines and Leucomaines," p. 109.
" A discussion of the chemistry of the origin of alkaloids from proteids will be found
in a paper liy Latham, fjcim-cl, London, 1888, vol. ii. p. 751.


The importance of the animal alkaloids was first brought into prominence
in courts of law ; the defence urged in certain notorious trials for murder, was
that the alkaloid alleged to have been administered to the victim, or found in
his stomach, really arose as the result of putrefactive changes occurring after
death. It has, moreover, been demonstrated that alkaloids existing in
different forms of putrefying food, produce poisonous symptoms. Sausages
made with bad meat, certain forms of stale milk and cheese,^ mussels and
other shell fish,- at certain seasons of the year, produce serious symptoms
in those who partake of them.

It has further been supposed that, in many cases of disease, the poison
formed by bacteria in the body, and which produces the symptoms of the
disease, is of an alkaloidal nature. The probability that cholera is caused by
an alkaloid was first pointed out by Lauder Brunton,^ from the similarity of
the symptoms to those produced by muscarine poisoning. Two alkaloids at
least have, in fact, been discovered in cholera, and in cultures of Koch's
comma bacillus, and have been named cadaverine and putrescine, but they
cannot be the actual poisons in cholera, because they are not markedly
toxic. The same two alkaloids are found in the urine and faeces in
totally different pathological conditions, namely, cystinuria,* and pernicious

Alkaloids in animal tissues were first described by Dupr6 and Bence
Jones j*^ the substance they separated they called "animal quinoidine";
about the same time, Marquardt' obtained an alkaloid from a corpse, and
named it "septicine." Schmidt^ and Panum'-' obtained a substance they
named sepsine from septic fluids, and they considered that it was the cause of
septicsemia. Later, prominent workers at the subject have been, Selmi,^"
Gautier," and Brieger;^'' to Brieger we owe the best methods of obtaining
these substances in a state of purity. Brieger separated some alkaloids with
such powerfully toxic properties, that he named them toxins ; these include
typhotoxine (from cases of typhoid fever), and tetanine ^^ (from cases of

All poisons produced by bacteria are, however, not necessarily ptomaines.
In fact, many of the toxins and antitoxins have been shown to owe their
power, at one time ascribed to ptomaines, to the tox-albumoses or poisonous
proteids (see "Proteids as Poisons," p. 55).

A few details concerning the principal animal alkaloids may be added.

Parvoline (CqHjoN). — This was first separated from the putrid flesh of the
mackerel and horse. It is an oily base, but its chloroaurate and chloro-
platinate are crystalline (Gautier).^*

Hydroeollidine (CgHjoiSr, boiling point 210° C), and

Collidine (CgH^^N) have been obtained from flesh, from putrid ox pancreas,
and from gelatin. isTencki considers collidine to be isophenylethylamine,

CgH- — CH"/ ^xr- These three bases are all highly toxic.

^ Vaiighan separated an alkaloid, which he named tyrotoxicon, from certain forms of
bad cheese, Zischr. f. physiol. Chem., Strassburg, Bd. x. S. 146.

- Mytilotoxin is the alkaloid separated from mussels by Brieger.

'^ Flc^j. Brit. Ass. Adv. Sc, London, 1873.

** Baumann and Udranszky, Zlschr. f. jihysiol. Chem., Strassbnrg, Bd. xiii. S. 562.

^ Hunter, Lancet, London, 1888, vol. ii. p. 654.

•^ Proc. Roy. Soc. London, vol. xv. p. 73 ; Ztschr. f. Chem. 1866, S. 348.

' Schuchardt in Maschka's " Handb. f. ger. Med.," Bd. ii. S. 60.

* Inaug. Diss., Dorpat, 1869.

^ Virchows Archiv, Bde. xxvii., xxviii., and xxix.
^° £e7'. d. deutseh. chem. Gesellsch., Berlin, Bd. xi. S. 808.
^1 Numerous papers; see especially ^iJ^. Soc. chim., Paris, tome xi. p. 6.
^- Brieger, "Die Ptomaine," 1885, ])art i. ; 1885, part ii. ; 1886, part iii.
1=* Brieger, Berl. Uin. Wchnschr., 1888, No. 17. " Loc. cit.


Neuridine (C5H^_^jSr2) is a constant product of putrefaction of proteids. It
is broken up by sodium hydrate into dimethylamine and trimethylamine
(Brieger). Isomeric with this, though diifering from it in the solubihty of its
salts, is saprine.

Gadaverine, a third isomeride, belongs to the diamine group, and in consti-
tution is pentamethylenediamine (Ladenberg).^

Putrescine [G^y-^^ is also a diamine, iDeing tetramethylenediamine. It
usually accompanies cadaverine, but as a rule makes its appearance later."

All the above are free from oxygen ; the remainder are oxygenated.

Neurine (CjH^^gNO) and choline (C-H^jNO^) are constant products of
cadaveric putrefaction, and their constitution has been described on p. 21.
They are toxic, and derive additional interest from their close relationship to
muscarine (C^HjoNOo), the alkaloid of the poisonous mushroom, Agaricus
muscariusJ'' Muscarine was discovered by Schmiedeberg and Koppe.'^
Schmiedeberg and Harnack ^ obtained it also by oxidising choline Avith nitric
acid. Brieger found it in putrid fish, and it occurs in several vegetables."

The natural alkaloid is probably not identical, but isomeric with that
prepared by the oxidation of choline ; '' more recently an alkaloid, Avith all the
properties of the muscarine of plants, has been prepared artificially from mono-
chloracetal and trimethylamine.^ The constitutional formula of muscarine
is —


N I CH2— Cq


and it is the aldehyde of the non-toxic betaine (trimethylglycocine).^

Choline, neurine, and muscarine are all toxic ; and are antagonistic to
atropine, so far as relates to their action on the heart and glandular system.^''

Gadiiiine (C-H^^ISrOg) is a less toxic alkaloid, which is mixed with the
muscarine obtained by Brieger from putrefying cod-fish.

Mytilotoxine (CgH^^^NOo) is the active agent in mussel poisoning.

Typliotoxiiie (CyH^^JSTOg) is obtained from cultures of the typhoid bacillus,
and was regarded by Brieger as the chemical poison in typhoid fever.

Tetanine {G-^^2-2^ - >^d ^^j 0^ ^^^^ supposed to be, the toxin in cases of
tetanus (Brieger).

Gautier completes his list of animal alkaloids by including a number of
substances of the uric acid group (adenine, guanine, xanthine, hypoxanthine,
«tc.), and of the creatinine group (creatinine itself, and certain sub-
stances separated from muscle, which are termed xanthocreatinine, C5H;^QIS^40,

^ Bcr. d. cleutsch. chem. Gesellsch., Berlin, Bd. xix. S. 2585.

" Brieger, Bcrl. Tdin. TFchnschr., 1887, No. 44 ; Boekliscli, Ber. d. deutscli. diem.
Gesellsch., Berlin, Bd. xx. S. 1441 ; Baumann and Udranszky, ibid., Bd. xxi. S. 2938 ;
Ztsclir. f. physiol. Chem., Strassburg, Bd. xiii. S. 562; Brieger and Stadtliagen, Virchoiv's
Archiv, Bd. cxv. Heft 3.

^ The ^r/ari«6-s vutscarius also co\\taix\^ a considerable amount of a non-toxic alkaloid,
amawrtwie, Neu7neister, "Physiol. Chem.,"Bd. i. S. 71. ■* "Das Mnscarin," Leipzig, 1869.

^ Arch. f. cxper. Path. u. Pharmahol., Leipzig, 1876, Bd. vi. S. 101.

** Such as Beta vulgaris, and the seeds of vetches and cotton. E. Schnlze, Zlschr. f.
physiol. Chem., Strassburg, 1891, Bd. xv. S. 140; ami 1892, Bd. xvi. S. 205.

"^ Boehm, Arch. f. exper. Path. u. Pharmalcol., Leipzig, 1885, Bd. xix. S. 87.

^ Berlinerblau, Bcr. d. deiUsch. chem. Geselheh., Berlin, 1884, Bd. xvii. S. 1139.

•'Found in Beta vulgaris; betaine has been also sjaithetically prepared from niono-
chloracetic acid and trimethylamine : —

CHoCl.C00H-l-N(CH3)3-f-H„0=:NJCH„— COOH + HCl.


'" Tlic fall of blood pressure produced by choline and neurine is of cardiac origin
(Mott and Halliburton, " Proc. Physiol. Soc," Feb. 1897, p. xviii., in Jourii. Physiol.,
Camljridge and London, vol. xxi.).


crusocreatinine, C^HgN^O, and ampliicreatinine, CiH^jNyO^). These leuco-
maines are regarded by Gautier, Loucliard, Pouchet, and others, as feebly toxic
products of metabolism, from which tlie organism is normally freed by excretion,
or by destructive oxidation ; it has been suggested that their retention in
the body may be the cause of certain obscure pathological conditions. The
poisonous properties of normal urine are regarded by some as due to
alkaloids of this nature, while others (Stadthagen) look upon the inorganic,
especially the potassium, salts of urine, as the toxic agents.^

Compound Proteids.

The compound proteids are compounds of albuminous substances
with other materials, which are as a rule also of a complex nature.
They may be divided into the following groups : —

1. Respiratory pigments. — The most important of these are
hcomoglobin and its compounds, chlorocruorin'^ (found in the blood
of certain worms), and hmmocyanin^ (found in the blood of many
molluscs and Crustacea). Haemoglobin and chlorocruorin are compounds
of proteids, with an iron-containing pigment. Hfemocyanin contains
copper in its molecule. Turacin, the red pigment in the feathers of
certain birds (plantain-eaters), also contains copper, and though not
respiratory in function, should probably be included in the same group
of substances.^ Hcemoglobin with its derivatives and allies will be
considered in a separate article.

2. Gluco ~ p)roteids. — Compounds of proteids with members of the
carbohydrate group. This class includes mucins, mucoids, hyalogens
and phospho-gluco-proteids.

3. NiLclein. — Compounds of proteid with phosphoric acid, or with
nucleic acid.

4. Nucleo-proteicls. — Compounds of proteid with nuclein.

5. Zecith-alb'mnins. — Compounds of proteid with lecithin.
We may consider the last four groups in detail.

The gluco - proteids. — The gluco-proteids are mostly free from
phosphorus (mucins, mucoids, and hyalogens), but some contain phos-
phorus (phospho-gluco-proteids).

Mucins. — The mucins are colloid, viscous substances of acid nature,

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