WALTER H. SEEGERS 
495 
Die Hiilmchen erhielten mit einer Pipette so viel vom cholesteriu- 
freien Lebertranpraparat, daB dies im Laufe eines Monats einer Menge 
von 15 g Lebertran entsprach, falls kein A-Stoff bei der Behandlung 
verloren gegangen war. Dies entspricht gut 1,5% des Futters. Im 
ganzen erhielten zehn Tiere dieses Futter.y Pie Tiere wollten nicht gut\ 
^edeihen. Nach etwa 3 Wochen zeigten sie verschiedene innere 
Blutungen, und sie starben ungefahr 1 Monat alt. Die Blutungen 
wurden teils im Verdauungskanal, teils subkutan und intramuskular 
an verschiedenen Stellefi gefunden. Einige hatten zugleich Atz- 
wunden im Kropf, andere hatten Wasseransammlungen in der 
Bauchhiihle und in den Brustmuskeln. Die meisten Tiere hatten 
mehr oder weniger krumme Beinknochen und waren zugleich blutarm'. 
Nachdem die Blutungen entstanden waren, erhielten drei Tiere taglich 
10 Tropfen Citronensaft, aber es trat keine Anderung im Zustande 
ein. Die Blutungen bUeben auch nicht aus bei zwei Tieren, welcho 
von Anfang an Citronensaft ( steigend von 5 bis 15 Tropfen im Laufe/ 
jon einem Monat) erhielten.y Ein Erstatten der Salzmischungen mit 
dem Gemisch, welches Hart, Haipin und Steenbock^, sowie Bart, Steenbock 
The animals did not thrive well. After 3 weeks they 
developed internal bleeding at various sights and died 
at about an age of one month. The bleedings were partly 
in the intestinal tract, some were subcutaneous, and at 
various places intramuscular. Several also had ulcerative 
wounds in the gizzard, others accumulated fluid in the 
abdominal cavity and in the breast muscles. Most of the 
animals had more or less bowed leg bones and were also 
anemic. After the hemorrhagic condition developed, three 
animals were given 10 drops of lemon juice daily, but 
there was no change in the condition. The hemorrhages 
also appeared in two animals that received lemon juice 
at the outset (increments from 5 to 15 drops in a period 
of a month). 
Figure 2. — Facsimile and translation of Dam's recorded 
observations on bleeding in chickens due to dietary de- 
ficiency. Later called vitamin K deficiency. 
recognized (Figure 2). He isolated the active 
principle and called it vitamin K. This stimu- 
lated studies in blood coagulation as v^ell as 
work on the importance of quinones. A few 
years later, I was a graduate student at the 
State University of Iowa where I was studying 
Biochemistry and Physiology (1931-1934). I 
can remember details about my living at the 
Alpha Chi Sigma house. At this professional 
fraternity, chemists were educating themselves 
along the lines of what was considered clean 
and respectable chemistry for them. Physiology 
and Biochemistry were tolerated with the atti- 
tude that "rat feeders" would not completely 
degrade the standards of the institution. In this 
fraternity of brilliant scholars, the chickens of 
Heinrik Dam would certainly have had nothing 
to crow about. I notice with great satisfaction 
that the hard preliminary work in the field of 
blood clotting enzymology is now finished. Next, 
we can expect the clean chemistry. I mention 
these prejudices because I believe that narrow 
views of scientists are a part of the perspective 
on animal experimentation as well as other sci- 
entific work. 
Observing diseases in animals has been a 
dominant way to learn about the coagulation of 
blood. Dicumarol and its congeners were found 
in that way. I presume it is well-known that 
this drug is used extensively to deal with 
thrombosis problems and owes its effectiveness 
to reducing the concentration of the plasma 
prothrombin complex. It antagonizes the func- 
tion of vitamin K. Before the latter was discov- 
ered, the effects of Dicumarol were observed in 
cattle that were by chance fed spoiled sweet clo- 
ver hay.^* This forage crop was introduced in 
Ontario, Canada. It was alarming to see herds 
of cattle die of internal hemorrhages. In North 
Dakota, U.S.A., the same was happening and 
the defect in blood coagulation was identified as 
a prothrombin deficiency. In Wisconsin, dairy 
cattle also developed the deficiency. A method 
was found to produce the toxin.^ It was iso- 
lated, synthesized, and introduced for clinical 
use. 
During the isolation work, rabbits were used 
as test animals. Some of these were found to be 
resistant to the drug on a genetic basis. Later, 
such resistance was also found in rats. Once 
many of us hoped that anticoagulants would 
serve the purpose of exterminating the rat as a 
pest. Certainly many have gone to sleep in 
that way, but now it has been discovered that 
large numbers of brown "house" rats (Rattus 
norvegicus) and black "ship" rats (Rattus rattus) 
can eat the anticoagulant and continue to enjoy 
it. New immune strains have developed. Such 
animals are, of course, especially useful for 
studying the synthesis of the prothrombin com- 
plex. It has been found that some human beings 
are also resistant to the drug." In fact, the re- 
port on this subject documents the first instance 
of genetically determined drug resistance in 
man. 
In man, hemophilia was popularly associated 
