ITEM No. 24 
FILE No. X—14 and XII—23 
COPY No.. 
THE NX ORGANON 
PHARMACEUTICAL FACTORY 
COMBINED INTELLIGENCE OBJECTIVES 
SUB-COMMITTEE THE N. V. ORGANON'PHARMACEUTICAL FACTORY 
OSS, HOLLAND 
Report by 
Lt. Colonel H. J. PH2LPS 
CIOS Black List Item 24 
Medical 
COMBINED INTELLIGENCE OBJECTIVES"SUB COMMITTEE 
G-2 DIVISION, SHASF <Rear) APO 413 TABLE OF CONTENTS 
Page No. 
I. Visit to N*V. Organon at Oss. 
Holland (3-11 November 1944) 3 
History of the Organon Factory during 
the Occupat ion.........♦, 3 
Technical Information...... f., ....... • 6 
II. Discussions with Dr. Lenz 9 
Table 1. Requirements for Restarting 
Production.. 12 
Appendix I Developments In the Prep- 
aration of Synthetic 
Hormones... 13 
" II Periston 14 
n III Application of Capain in 
Shock 15 
» IV Vitamin C 18 
»» V Vitamin A 19 
* VI liar fan 11 20 
" VII Dolantln,,... 23 
" VIII Ge sarol ......... 24 
11 IX Penicillin 25 
M X List of Shortages 26 I. VISIT TO N.V. ORGANON at OSS - HOLLAND 
Target No. 24/21 
The Organon pharmaceuticals factory at Oss 
was visited on November 3rd, 9th, 10th and 11th, 
1944* My first visit confirmed our suspicions 
that this factory had been under the control of 
Sobering of Berlin throughout most of the occupa- 
tional period, and had been an important centre 
of manufacture of this concern after the bombing 
of their plants in the Berlin area. It was also 
apparent that the Germans haa left Oss in a 
panic and had left all the installations and many 
records behind. I had the most amazing co-opera- 
tion from Dr. Tausk, Managing Director of the 
plant, who mobilised the whole of his high level 
technical staff to assist me by sorting and trans- 
lating available information on the more important 
items of manufacture. I then spent two days in 
discussing the material available with Dr; Tausk 
and his various specialists, the Organon Company 
providing the services of an English-speaking 
stenographer who took notes on these discussions 
which form the basis of the technical appendices 
to the present report. 
History of the Organon Factory during the Occupation 
The Organon Factory lies a little to the 
east of Oss railway station, adjacent to the Van 
Zwanenberg meat packing factory which Organon 
obtained supplies of animal glands for extraction) 
and the Hartog margarine plant, the three factories 
forming what is.virtually one industrial complex. 
The directors of the company left Oss the 
day after the German invasion of Holland in an 
attempt to reach England with important technical 
information and considerable stocks of some rarer 
drugs, particularly insulin. The party became 
separated and although two of the Dutch directors 
and an English manager, who was visiting the 
factory at the time, eventually reached England, 
Dr. Tausk was unable to do so. He returned to Oss 
on the 15th May 1940 and for some time neither he 
nor the company were interfered with by the Germans, although the controlling interest of the Organon 
factory appears to lie with the Van Zwanenberg 
combine, in which there is a large Jewish inter- 
est. In November 194-0 the occupying authorities 
declared the Organon concern to be confiscated as 
a Jewish business and the shares were vested in 
a German trading company which had been set up in 
Holland to act as a receiver and custodian of 
Jewish property. Dr. Tausk was dismissed from 
the position of Managing Director, but when he 
applied shortly afterwards in his own name for the 
position of Director of Laboratories he was 
promptly engaged and filled fchis position through- 
out' the occupation. A Dr. Duden of the Sobering 
Company was appointed Trustee of the Organon fac- 
tory. Dr. Duden was not a technical man and 
interfered very little in the operations of the 
factory which continued with its pre-war.activi- 
ties but on a greatly reduced scale. 
Early in 194-2 the Sobering concern formally 
took over Organon N.V. by purchasing the shares 
which had been sequested by the German trading 
company acting as Custodian for Jewish property. 
From this time the factory was worked entirely 
as a Sobering concern, and a Dr. Zastrow, one of 
the leading chemists of Sobering A.G., came to 
Oss as technical director of the factory. 
Sobering began immediately to enlarge the factory 
and to install new plant. New buildings were 
erected and the staff was increased. In the R.A.F. 
attacks on Berlin in February 194-4 Sobering !s 
offices, laboratories, and tabletting and ampoul- 
ing plants, were entirely destroyed, and much of 
the other manufacturing capacity severely damaged. 
In consequence Sobering transferred a considerable 
part of their manufacturing activities to Oss and 
the enlargement of the factory was accelerated. 
The installation of h&w plant at Oss continued with- 
out a break during the early days of the Allied 
landing on the Continent, and work was actually 
proceeding on the equipment of a new building up 
to the 4th September 1944* On this day the B.B.C. 
broadcast a false rumour that the British Forces 
advancing from Brussels had reached Breda. The 
Germans in the Organon factory and all German 
civilians in Oss, left the town in a panic and 
never returned, although British forces did not 
reach Oss until the airborne invasion of 17th 
September. The chief activity of the Schering Company 
at Oss centred on the manufacture of hormone 
preparations. The production of insulin, which 
was normally one of the principal activities of 
the Organon factory, was continued on a reduced 
scale but large quantities of oesterone were 
made by a new synthetic method devised by Scher- 
ing, while the production of cortisterone and 
testosterone was also pushed forward and new 
technical methods were employed. A new method 
of the synthesis of Vitamin C was introduced and 
research on the production of a synthetic 
Vitamin A was carried to the point of producing 
a synthetic chemical with about one-tenth of 
the biological activity of natural vitamin A. 
A considerable amount of work was also done on 
the preparation of a synthetic plasma substitute 
known as Capain, which can now be made on a 
commercial scale and which appears to have 
given most satisfactory results in treatment. 
The Schering Company was engaged in active 
research on penicillin, but this work was not 
carried out at Oss. From information which the 
Dutch technical people at Oss had obtained from 
the Germans, it is apparent that Schering had 
not had much success with this work. On the 
other hand, the Dutch experts at Oss, and particu- 
larly Dr. Tausk, had been able to carry out 
some research secretly on pencillin and had dis- 
covered a strain of moulds which gave a high yield 
of very active antibacterial substance. It is not 
as yet certain whether this substance is identical 
with penicillin. The important cultures are 
now believed to be held by Professor Julius of 
Utrecht and when this town is liberated it would 
seem important to contact Professor Julius and 
obtain from him a sample of the mould which had 
been used. 
Throughout the occupational period the 
of the Organon factory:appear to have been very 
active in the resistance movement, and many of 
them certainly displayed remarkable courage. Two 
of the Organon technical managers were, unfortunate 
ly, arrested for their activities. Dr. Boerrigter, 
who was a most courageous leader of the resistance 
group, was arrested in 1941 and sentenced to twelve 
years imprisonment by the local military court. 
This sentence was, however, referred back to the 
local Summary court by Berlin and commuted by them 
to the death sentence. Dr. Boerrigter was executed in 194-2. At the same 
time Dr. Geerling was sentenced to four years 
imprisonment and is still in Germany. 
TechnicalInformation 
The chief points of technical information 
which were obtained from the records left in the 
factory, and from the personal knowledge of the 
Dutch technical staff, were the following:- (tech- 
nical details are set out in appendices to this 
report, numbered as shown below). 
1. New developments in the commercial preparation 
of synthetic hormones. (Appendix I). 
2. The preparation and use of plasma substitutes. 
These were, of two types:- 
(a) An entirely synthetic substitute for 
blood liquid which was a colloidal poly- 
mer of polyvinyl-pyrrolidon, known bv 
the Germans as PERISTON (Appendix II). 
(b) A colloid polypeptide prepared from 
casein and known as CAPAIN (Appendix III) 
which appears to be quite free from any 
toxic effects and which may be regarded 
as a complete protein substitute. Full 
details for the manufacture of this sub- 
stance were obtained. 
3• New Developments in Vitamin Chemistry. A new 
method for the preparation of vitamin C has been 
evolved which avoids the use of potessium perman- 
ganate and of large quantities of acetone, both of 
which substances were in short supply in Germany. 
The new process also evades th« existing patents 
on the production of synthetic Vitamin C.- It is, 
however, admitted tnat the yield of vitamin is less 
good than that obtained by the standard process of 
manufacture (Appendix IV). Research on the prod- 
uction of synthetic Vitamin A was prompted by the 
fact that supplies of Vitamin A were deficient in 
Germany. So far these researches have succeeded 
in producing a substance with about one-tenth of 
the biological activity of natural Vitamin A, but 
prospects for the full synthesis of Vitamin A 
appear to be good. (Appendix V.) 4. Marfaall arid Sulpha Drugs. The Germans have 
done a great deal of work on the preparation and 
use of MARFANID and a similar compound known as 
TIBATIN. Methods for the quantity production of 
Marfanil have been worked out, and it appears 
to have been used particularly in association 
with sulphanilamiae. There appeared to be no 
evidence of the use of Marfaril and pencil Lin in 
combination, but this may be due to the fact 
that the Germans have not apparently succeeded 
in preparing penicillin in considerable quantity. 
(Appendix VI). No other significant developments 
in sulpha drugs were apparent, sulphanilamiae 
and sulphathiazol being the drugs most commonly 
used. 
5. Synthetic Substitutes for Morphine. It was 
confirmed that the Germans were preparing consider- 
able quantities of DOLANTIN, and this substance 
could in fact be purchased in many stores in Bel- 
gium and Holland. Since the preparation of 
Dolantin is known in the U.K. and the U.S.A., 
information was collected only on the applications 
of Dolantin and on the question as to whether or 
not the drug causes adaiction. (Appendix VII). 
6. Anti-louse Powders. The only insecticide 
in which the experts at Oss knew the Germans to be 
interested was GESAROL. This substance is almost 
certainly less effective than D.D.T., and no infor- 
mation was collected on its methods of preparation, 
which are in any case generally known. A short 
note on the toxicity of Gesarol was prepared. 
(Appendix VIII). 
7• Penicillin ana Anti-bacterial Substances 
extracted from Moulds. The Germans, and 
particularly Sobering, has carried out intensive 
research on Penicillin, and haa obtained strains 
of Penicillium notatura from Professor Vvesterdijk, 
who has in her laboratories what is believed to 
be the largest collection of moulds in the world. 
Apparently, however, the particular strain of 
penicillium notatum which Professor Vvesterdijk 
deliverea to Schering was remarkably inactive as 
regards penicillin formation. Whether this 
strange circumstance was an accident or due to 
remarkable ingenuity on the part of Professor 
Mesterdijk could not be ascertained with certainty, 
as tie Organon technicians preferred to keep a dis- 
creet silence on the matter, but it was aamitted jtbat Professor Iftesterdijk had very active penicillin 
Containing cultures on which she had done consider- 
able secret research in association with Professor 
Julius of Utrecht and Dr. Tausk of Organon. 
IX). 
8. Anti-Malarials. No information was available 
at the Organon factory regarding any new develop-, 
raents in the manufacture of synthetic 
Dr. Tausk was of the opinion that there had been 
no advances on atebrin and plasmoquin, and that there 
had been no changes in the methods used to prepare . 
these substances. It was confirmed that there had 
been an increase in the use of the total mixed alka- 
loids of cinchona instead of refined quinine in 
the treatment of malaria in order to conserve as 
far as possible stocks of bark. 
9. Dr. Tausk prepared for me a list of chemicals 
and chemical apparatus which were in short supply 
during the occupation, with comments specifically 
on the experiences of tne Organon factory (Appendix 
X.). I also attach a note on the stocks «of raw 
materials of various products and the requirements 
for the restarting of manufacture in various 
branches of the factory as at the time of my visit. 
(Table I folio-wing Section II). This information 
was also handed to the local civil affairs authori- 
ties who had passed it to 30 Corps, S.C.A.O., under 
reference CA/504/I - 3* 
H.J.PHELPS.Lt.Col. 
E.A.B.6(d). SECRET 
II. Discussions with Dr. Lenz, of 
Organon N.V. Oss. 
In the course of my stay at Oss I had the 
opportunity of several discussions with Dr. Lenz, 
Director of the Chemical Departments of Organon 
N.V., who was employed in the Dutch Chemical War- 
far e Service in 1940* The following is a brief 
summary of the information given by him \ 
Immediately after the occupation of Holland, 
the Germans examined the Dutch chemical warfare 
laboratories at Delft, but although all the records 
had been destroyed the Dutch technicians were 
asked very few questions. Practically all the 
Dutch technicians were allowed to depart, or were 
dismissed, and a limited amount of research was 
continued, mainly by Germans, on the penetration 
of vesicants through different types of protective 
clothing. The people working in these laboratories 
were interested both in mustard and in "nitrogen 
mustard". The Germans were plainly interested 
both in protective clothing against "nitrogen 
mustard" and in finding a suitable decontaminant. 
During the latter part of 1940 and early 1941 they 
did not seem to have had much success.in either 
direction. It is of interest that the German stand- 
ard for protective clothing against both vesicants 
was only two hours1 protection. Most of the experi- 
ments were carried out on various types of canvas 
cloth coated with rubber on both sides. 50$ of 
the samples of this kind of material failed to give 
two hours* protection against ordinary mustard. 
In the Spring of 1941 all work in the Dutch 
laboratories was suddenly suspended and the labora- 
tories, including the remaining Dutch technicians 
of the laboratory assistant grades, were leased to 
the Delft Technical High School and usea as ordinary 
teaching and research chemical laboratories. So 
far as Dr. Lenz was aware, no further work on chem- 
ical warfare was carried out. 
Although no specific work on gas masks was 
carried out by the Germans at Delft, Dr. Lenz knew 
that the Germans were somewhat concerned at the 
high breathing resistance shown by the G.M.4O. Throughout the occupation period the German 
troopr of all ranks, ana uniformed female auxil- 
iaries, in Oss invariably carried gas masks and 
Losantin tablets even v.hen off duty in the town. 
After the midule of 1941 there was practically 
no pressure on the local Dutch population to 
obtain gas masks or to undertake any form of anti- 
gas precautions or exercises. The Dutch State 
Railways continued to give considerable attention 
to the problems and their employees were provided 
with gas masks and instructed in their use. The 
State Railways also had gas decontamination cars 
at every major railway station. These cars were, 
however, either constructed in 1939 or replicas 
of a type introduced at that time. Dr. Lenz 
thought that these activities were an independant 
effort on the part of the Dutch State Railways rat- 
her than the result of German pressure or encourage- 
ment. 
Dr. Lenz knew nothing of any C/VV activities 
by Sobering A.G., although this company had taken 
over Organon factories. This, however, cannot be 
taken as proof that Scherings are not manufacturing 
C/W material in German since they were very 
reticient regarding most of their activities in 
their home country. Dr. Lenz deduced that Sobering 
were doing a certain amount of physiological re- 
search on G/Vv since he knew that their physiolo- 
gists had found that rats less than ten days old 
give no local reaction with "H". After this age 
a normal local reaction is shown. 
The only specific C/W activities by the 
Germans in Holland, of which Dr. Lenz had any know- 
ledge, were the use of a few ten-litre bottles of 
arsine which were dropped from an aeroplane in the 
neighbourhood of Greebe in daylight on 11th May 
1940. I questioned Dr. Lenz closely on this event, 
and he was quite sure that it had occurred and 
said that some of tnese containers had been sent 
to the Dutch C/\V laboratory at Delft for examina- 
tion. This experiment in C/Vv apparently caused no 
harm to anybody and was never repeated. In 1943 
the Germans took over a large laundry at Ubbergen, 
near Nijmegen, in order to convert it to a clothing 
decontamination centre. A small gas testing labora- 
tory was also set up at this laundry. No other information regarding German C/Vv 
activities in Holland could be ascertained from 
Dr. Lenz or any other organisation in Holland. Name of the 
Prod.capac» 
Raw materials 
labou- 
Higher 
kg of 
coal daily 
gas 
Other 
preparation 
per week. 
sufficient 
rers 
staff 
require 
1 in 
per 
requirements 
. 
for 
(men or 
the fora of 
day 
women) 
steam 
electr. 
refrig. 
l.Sulfanila- 
40 kg p.w. 
3 
1 
200 
per week 80 kg of 
mid or 
40 weeks 
lammonia (for nr.2) 
2.Sulfapyri- 
60 kg p.w. 
6 
2 
250 
25 
120 
and from the 10th 
din 
we 600kg chlor sul- 
fonacid and 4001. 
of benzol (weekly) 
3«Liverextr.' 
6000kg liver 
3 weeks 
12 
I 
900 
run 
250 
(Pemaemon) 
p.w. 
4.Vitamin D 
i+0 a 50 g 
6-7 weeks 
1 
2 
20 
50 
5.Vitamin C 
15 kg 
26 weeks 
9 
2 
500 
150 
Methanol and NaOH 
to be stated later 
B.Cholester- 
on 
ol(semi- 
6000kg raw 
1 week 
4 
600 
100 
manuf.) 
material 
7«Nicotinic- 
more than 
25 m^ 
acid 
700 g 
1 year 
1 
1 
25 
8.Pilling of 
45 
all kinds 
10 m3 
of ampoules 
(girls) 
2 
100 
l6o 
i 
9.Pharmaceut 
30 
2 
150 
packing 
3 3* mill 
(girls) 
10.Production 
of tablets 
11•Manufac ture 
- 
of coated 
7 
1 
50 
60 
tabl. 
1 
The capacity of the Departments, mentioned under numbers 8, 9, 
10 and ] 
l1, allows filling, production of 
tablets and packing in charge of third parties. 
0 
Tat>le 1. Requirements for Restarting of Production APPENDIX I. 
SCIENTIFIC AND TECHNICAL DEVELOPMENTS IN THE 
PREPARATION OF SYNTHETIC HORMONES 
Oxidation of Cholesterol: 
The oxidation of cholesterol-acetate dlbromide 
is at present carried out in a homogeneous mixture 
of acetic acid and ethylenedlchlorlde. 
The result of this new procedure is a 50% 
Increased yield. This method is applied now by 
Ciba (Basle), Sobering (Berlin) and Organon. 
Desoxycorticosterone-acetate: 
The preparation of diazomethane is now possible 
on a relatively large scale, and in consequence it 
is possible to prepare desoxycorticosterone-acetate 
on a technical scale. There are no fundamental 
changes from the original Reichsteln procedure for 
the synthesis. 
Progesterone: 
As the new oxidation-process of cholesterol 
(see above) gives no pregnenolone-acetate, it was 
necessary to look out for a new preparation method 
for this substance. In the Sobering works the 
procedure (which has been published by Butenandt 
c.s. in Berlchte) has started on a technical scale. 
With this method it is possible to reach a ZZ% 
yield of progesterone from Dehydro androsterone- 
acetate. 
Ethinyl-testosterone; 
ifi'e preparation of ethlnyl-androstenediol is 
now possible with other alcohols than tertiary butanol. 
Synthetic Oestrone: 
It was very Important for Sobering to prepare 
oestrone from another source than pregnant mares1 
urine. 
The chemists of Sobering, especially Inhdffen, 
have.carried out the synthesis of oestrone starting 
from dehydro androsterone-acetate and as far as we 
know this procedure has been applied on a technical 
scale, (published in Berichte by Inhoffen), 
The most difficult stage is the dehydrogenating 
and demethylatlng of the first ring. Following the 
data received from the German chemists the total yield 
is between 10 and 20%• 
As far as is known the whole procedure is not yet 
carried out regularly in the factory. APPENDIX II. 
PERISTON 
This substitute for blood liouid was prepared 
by Weese and Hecht (pharmacological institute of the 
I. CL Farben), described in the publication : Hecht 
und Weese “Periston, ein neuer Blutflueslgkeitersatzn 
(Munch, med. Wschr. 90, 11 (1943) No.l. 
It consists of a colloid, the polymerisation pro- 
duct polyvinylpyrrolldon (known as’ "Kollldon") In a 
2..$% solution, to'which Is added' NaCl, 0,9042^ 
KOI, CaClo, 0,0005;* MgClg, 0,0024# NaHC03“ and 
ca. 10 vol. % free COo. This solution has a pH 6, 
and after being steritlzed is ready for use and keeps 
indefinitely. Tills product and similar mixtures of 
slightly different composition are described collective- 
ly as "Periston". In the animal it.normalizes the 
blood pressure after an acute loss of blood. Its 
action persists for one or two days; after three to 
four weeks the substance can no longer be detected in 
the blood. 
H Clinical experiences were published by Klees 
(Munch.Med. Wschr. 90, 29 (1943) No.2* According to 
this author Periston is superior to all other known 
plasma substitutes. He tested it in 50 oases of 
haemorrhage w mostly severe - (laparotomies, various 
obstetrical cases); the doses varied from 100 to 700 
cm3. He observed a prompt restoration of normal blood 
pressure without noxious Influences. The main actions 
ares- 
(1) An analeptic action; 
(2) A vasotonic action; 
(3) An improvement of the capillary circulation. 
Dieckhoff and Kunstler (Dtsch.Med.Wschr. 69, 589 (1943) 
No.33/34, obtained favourable results wltHPerlston in 
alimentary intoxication of sucklings. 
Fonio "Blutersatz im Felde" (Sitz.ber.medlz.Bezlrksver- 
ein,' Bern-Stadt, Schweiz.med. Wschr. 73, 1416 (1943) 
No.47, remarks, concerning|f"das an der Ostfront verwend- 
ete Periston": "Die Akten uber die desselben 
sind noch nicht |(abgeschlossen; Armeepathologen machen auf 
Leber—Nlerensohadigungen aufmerksam". 
The last work has not yet been said about its action; 
German army pathologists have called attention to liver 
and kidney damage. APPENDIX III. 
APPLICATION OF CAPAIN IN SHOCK, 
Literature: L. A. Gr. Hisslnk, Ned. TIJdschr. 
v. G-eneesk. 38, 52l (1944); 88, 
824 (1944). 
J. H. P. Jonxis. Maandschr. Kindergew. 
13, 169 (1944) 
Capaln is an aoueous solution of the breakdown 
products of casein, obtained by the action of papain 
on this protein. It is characterised by its high 
colloid©smotic pressure and its freedom from anaphy- 
lactogenic properties. It serves to retain fluid in 
the blood streaA and also provides readily assimil- 
able nitrogen to the body. 
It has been Issued for clinical purposes in 
100 cc. ampoules filled with a 15% solution of the 
combination of these peptones and polypeptides. 
A special type of capain is prepared for intrave- 
nous nitrogen feeding especially *for infants. The 
source of protein in this case consists of two parts 
of casein and one part of lactalbumen, to supply the 
necessary amount of tryptophane and cystein. 
Method of Application: 
The usual dose of capain is from 75 to 150 cc. 
diluted with physiological saline, or 5% glucose solu- 
tion to 1 L. It is Injected intravenously, the rate of 
the injection depending on the condition of the patient. 
In cases of shock, blood pressure is chosen as the 
criterion, severe cases demanding a faster rate amounting 
up to 1 L per hour. 
Results. 
A review is given of twenty cases of more or less 
severe shock. The results of the treatment were satis- 
factory; only three of the patients died in the first 
week after the transfusion. Five of the patients had a 
slight general reaction (shivers). 
With another twenty patients the author claims to 
have obtained similar favourable results, but no 
details are given. APPENDIX III (Continued) 
Jonxis claims favourable results In Infant 
feeding by the intravenous route* It is well 
tolerated and he gains the impression that capaln 
Is a complete protein substitute. 
Method of Preparation 
The following prescription is based on infor- 
mation obtained from Professor Brinkman of Groningen, 
who is the Inventor of capaln, and on limited 
experience in the Organon factory. 
180 grs of sodium caseinate (soluble) are 
dissolved in 900 cc. of cold water. To this solution 
is added a buffer solution of the composition: 
40 vol. of citric acid 21 gr/I. 
60 vo'l. oBaikaline sodium phosphate (NagHP04 2 
aa) 35,6 gr/1. 
To this mixture 900 cc. of boiling water and 
finally 12 gr of papain (l : 80) are added. The cloudy 
solution is stipred for ten hours at a temperature of 
60 to 70° C. The initial pH of the salution is 
approximately 5.8. During the digestion much of the 
casein dissolves but the cloudiness does not disappear 
completely. The solution is left overnight and a 
precipitate of undigested material settles to the bottom. 
It is decanted or filtered. To the filtrate trichloro- 
acetic-acid is added to a final concentration of 3 g/100 
cc. The precipitate is filtered off through folded 
filters and the clear filtrate neutralised with 25# 
NaOH until Just red to Congo red. At this acidity the 
trlchlore-aoetlc-acid is transformed into chloroform 
and sodium carbonate, provided the temperature 1b not too 
low. It is found advantageous to keep the solution at 
60 to 70° C to promote the reaction. In case the 
solution becomes alkaline it is neutralised by means of 
citric acid. 
The solution is then concentrated in vacuo to one- 
third of its original volume. The temperature in the 
original recipe was not specified but apparently 60 to 
70° C will do. At the end of the process the tempera- 
ture is raised to boiling point for a few minutes* 
Finally the solution is kept for two to three days at 
room temperature. A slight precipitate which occasion- 
ally forms is filtered off through asbestos fibre or 
hyflo filters. APPENDIX III (Continued) 
The nitrogen content of the filtrate Is estimated. 
The strength of the solution Is. calculated by 
taking 8 x the N-content. It is adjusted to 13 to 
calculated back to protein. As a preservative 
270 nlpagln (p-oxy-benzolcacld methylester) is added. 
It is Issued in 100 cc. ampoules. Before use 
these ampoules must be carefully cleaned, preferably 
by bichromate-sulphuric acid solution, follov/ed by 
frequent washings with water. The last rinse should 
always be one of freshly distilled apyrogenlc water. 
The filled ampoules are sterilized for one hour by 
live steam. 
Samples of the ampoules ready for issue are 
subjected to a sterility test. 
The toxicity in test animals is quite low; 5 cc' 
are well tolerated if slowly injected in the marginal 
earveln of a rabbit. No anaphylactic reactions are 
apparent in appropriate test on guinea pigs. Organon 
have so far,prepared two batches only and the 
definite tests for. the toxicity have not yet been 
established. Meanwhile the above-mentioned tests are 
used provisionally. Care should be taken to avoid 
the development of micro-organisms during any stage of 
the process as subsequent sterilisation would still 
leave dead bacterlas in the solution liable to cause 
pyrogenic reactions. APPENDIX IV. 
VITAMIN C. 
The shortage of vitamin C in German occupied 
territory and the impossibility of importing 
sufficient ouantlties, made it desirable to manu- 
facture vitamin C in Holland. As Hoffmann-1a-Roche 
were unwilling to grant a licence a new process 
was evolved. This starts from glucose and uses 
the classical steps 
sorbitol - sorbose - ketogulonic acid. 
It avoids the use of potassium-permanganate and of 
large cuantities of acetone, both substances having 
been very scarce in German-occupied countries. As 
an oxidizing agent sodium-chlorate is used. The 
conversion of sodlum-ketogulonate to ascorbic acid 
is performed with the aid of sodium fluoride. The 
whole process falls.cut side the scope of the Swiss 
patents, although this is still being contested 
by Hoffman-la-Hoche. 
The yields of ascorbic acid are considerably 
inferior to those obtained by the Swiss process. 
The Dutch Government has stimulated research through 
an official organisation and they too have found a 
new process ("which, to our mind, is partly dependent 
on the Swiss patents").# Large scale production has 
also been taken up following this "Government- 
process ". 
* Dr. Tauskfs comment. APPENDIX V. 
VITAMIN A. 
In the course of experiments on a synthesis of 
Vitamin A the ketone I was prepared. From this sub- 
stance 1:.he methyl-ester of Vitamin A-acld II Is ob- 
tained by means of methyl-bromo-acetate and zinc in 
benzene. 
This acid possessed about one-tenth of the 
biological activity of vitamin A itself. 
The prospects for the preparation of Vitamin A 
from I, are good. As ester of the iso-vitamin A 
acid II was also prepared. This substance was not 
active. 
ch3 ch3 ch3 0% 
X" GH « CH - C - CH - CH - CH - 0 » 0 
®c„3 
3 I 
ch3 ch3 
CH « CH - C s CH - CH - CH - C « CH - COOH 
II 
CHg CH3 
jj - GH » CH - C = GH - C s GH - CH = CH - -COOK 
III APPENDIX VI. 
HARFANIL HgN-HgO-OaOoNHg 
Kg.rfg.nil (originally named Hesudln) was synthesized 
by Klarer. On the basis of experiments with animals 
It was recommended by Domagk for the clinical treat-, 
ment of infections by anaerobic bacteria (e,g, gas- 
gangrene). In.the'animal the toleration is excellent. 
(Domap’k und Hegler. ‘'Chenotheraple bakterieller 
InfektlonenH 2. Aufl., Leipslz 1942). 
According to Hegler there is as yet (1942) 
little experience concerning the application In man. 
However, several Investigators have recommended the 
preparation, amongst others Konjetzny. who used a 
combination with sulphanilanide (Prontalbin) locally 
against wound Infection. This combination Marfan11- 
Prontalbln (l part M, 9 parts P) is supposed to be 
active both against streptococci (and staphylococci) 
and anaeroblcs. The first publication concerning 
this combination Is probably that by Beyer MDle 
Chemotheraple In der Hand des Chirurgent Marfanll- 
Prontalbln, eln neues WundantlseptikumH (Zbl.Chir. 
68. 1730, 1941; not available In Oss). 
Other References 
it 
Meull. HZur Frage der Fruhbehandlung von Kriegsver- 
let zungen mlt Sulfonamiden M. (Schweiz.med. Wschr. 74, 
23, 1944). M. mentions that Klages (Med.Klin*1943. 
37/38) saw good results in war wounds with Marfanil 
for the treatment and prophylaxis of gasgangrene. 
It is stated further that the combination Marfanll- 
Prontalbln has been recommended for war wounds by 
Domagk. Haferland. Konietzny and others (in local 
and oral application). 
Kirschner is sceptic about the benefit of M.P. In 
the treatment of wounds. 
Florcken stresses the harmlessness of large doses 
of U.P. powder, locally applied. 
G. Herrmannf Marfan 11-Prontaiblnpuder In der'Krleg- 
lchirurgle (Munch. medfWschr. 90, 697 (1943), No. 
48/49). H. reports on his experiences with the 
German army in Russia. He used the preparation for 
many different injuries. According to this author 
the locally,applied M.P. powder gives a chance of 
success in fresh wounds only (up to 12 hours after 
the injury)1 As to fresh wounds, H. advocates 
universal application of M.P. powder (after primary 
wound excision). APPENDIX VI. (continued) 
H. W. Voigt ( SulphpnamIdes in surgery). (Dtsch.med. 
'Ws ;hr. 70, 93 (1944) No. 7/8). V. used, among other 
preparations, II.P. powder locally with very favour- 
able results. 
H, Kr ue H Sulpho n am id e an der Front." (Dtsch.med. 
Wschr. 69, 417 (1943) No.2l/?2. K. saw good effects 
of sulpHpnpmides (locally and orally) in the treat- 
ment of war wounds. He also mentions casually the 
use of M. P. 
Eunike. "Uber die lokale Anwendung (Jes Mar fan 11- 
Prontalbin in der ChlrJLrgle zur Bekampfung der Wund- 
infektion". Fortsohrltte der Theraple 18, 11 (1942) 
(not available in Oss). 
Preparation of Marfanil:- 
Formula HgM-HoG-< > 30,11 Ho 
German Patent 7P.6336 (priority 27.1.39): 
Protection for the reaction RCHg< >30oNHp—>NHp 
CH2<Z>S02NH2, executed in practically every Imaginable 
way. (R* a substituent which can be converted to the 
amino group). Included is also the reduction of / 
%C-<I> S02NH2. 
rman Patent Application I 67614 (priority 8.8.40): 
Halogenation of compounds with the formula 
CH3 S02Hlg (HLg ss halogen) with halogenatlng agents 
at Increased temperatures. 
German Patent Application I 67629 (priority 8.8.40); 
Reaction of compounds with the formula 
SOoHlg (as produced by the preceding patent application) 
with ammonia at temperature below 60°C, thus producing 
HlgCHo S°2NH2 
TIP AT IN (l.G. Farben). 
Formula 0 gHio CC«N- < > S0o-<CZ>- Ng Cg H-| oQ 5 
(digalactoside of dlaralnodiphenvl 
sulfone) 
No particulars about the preparation available. APPENDIX VI (Continued) 
German Patent 694679 (priority 21.10.38): 
Preparation of stable solutions of compounds 
like Tlbatln, by addition of sugars to the solu- 
tion. In an example the addition of Inverted 
lactose to a solution of Tibatin is mentioned. APPENDIX VII 
DOLANTIN. 
Chlorhydrate of l-methyl-4-phenylplperldln-4-carbon- 
icacld-ethyl-ester. Tabl. 25 mg, amp. 100 mg. 
No information was available at Organon regard- 
ing the manufacture of Dolantin. The following 
references to its use had been filed in the Organon 
scientific library 
Schlungbaum (lied.Klin. 35, 1259, 1939). 
Dolantin opuses no addiction, no habituation. 
Skamnakis (Zbl.Gynak. 67, 139.7, 1943). 
Dolantin is frequently used in obstetrics as 
an analgesic. The author has recently replaced 
Dolantin by the "Analgetlcum 446” bayer, the latter 
having a better spasmolytic and analgesic action 
(no details on the latter.preparation).> 
v* Brucke (Wien.kiln. Wschr. 1940 II, 854; ref Klin* 
Wsohr. 22, 59, 1941). 
Dolantin gives rise to addiction in predisposed 
individuals; therefore one has to be cautious in 
prescribing this preparation. 
Kucher. MZwei Falle von Dolantinsucht* (Klin.Wschr. 
19, 688, 1940). 
Describes two cases of pronounced addiction 
(high dosos; up to 25 amp. s 2,5 g pro die.1). 
This should be a warning, as most clinicians 
deny that there can be such a thing as addiction 
to Dolantin. The author emphasizes, the Importance 
of this “ersatz” for morphine, the necessary raw 
material being available in.Germany. 
G-ar ratal et al. (ref. Schweiz, med* Wschr. 73, 83,1943). 
Prolonged use of Dolantin leads to habituation. 
Oelkers and Wanowius (Klin. Wschr. 21, 752, 1942) demon- 
strated in micean increase of'toxicity of various 
substances, among which Dolantln, when the animals were 
treated with eulphonanldes. This might be important 
for therapeutics in man. APPENDIX VIII 
SESAROL. 
H 
CCI3 
The drug Is a poison for all 
kinds of Insects# It works by 
simply contact with the animal. 
It Is scarcely soluble In water 
but to a large extent In lip- 
old solvents. Therefore, It 
Is easily absorbed by the lip- 
oids in the cutlcula of Insects. It reaches the nerve 
endings and because it Is a typical nerve poison 
kills the animals under violent spasms. The skin of 
mammals is not permeable for G-esarol, therefore no 
toxic effects are to be expected In these animals. 
Because contact with the skin is necessary, G-esarol 
is more active against flies, mosquitos, moths, etc# 
than against hairy animals like caterpillars. 
best be applied by making a solution, 
e.g. in‘carbontetrachlorlde, and spraying this on the 
walls of the room, on the floor, on leaves of plants, 
etc. Very small amounts suffice, a stable could be 
kept free from flies for five to six we3kg with an 
amount of five to seven g pro cm2. 
To kill a rat of about 60 grams an amount of 
25 mg given orally is necessary, mice of about 20 
grams body weight can be killed with 20 mg. 
The effect is not immediate, a lag time (for 
resorption) is present, depending on the species of 
animal. 
A good survey of G-esarol and related drugs can 
be found in Helv.chlm.acta. £7, 892, (1944). APPENDIX IX 
PENICILLIN 
The Organon specialists knew nothing of any 
large scale manufacture of penicillin in Germany. 
It will of course be known in England, that Clba 
of Bale has taken up the manufacture of this prod- 
uct. Reports were published in a special issue 
of the Schweiz. Med. Wschr. 74, No.23, (1944). 
From private information they know that 
Sobering were engaged on rather Intensive research 
on penicillin. On various occasions they obtained 
strains of penicillium notatum from Professor 
Westerdijk of Baarn, who is in charge of the HCen- 
traal Bureau voor Schimmelcultures H, having at its 
disposal what is probably the largest collection 
of moulds of the world. From discussions with 
Professor Westerdijk the impression was gathered 
that the strains of penicillium notatum, available 
in Holland and delivered to Sobering, were probably 
Inactive as regards penicillin-formation. It is 
understood that the fluid of their cultures is blue. 
On the other hand Professor Julius, collab- 
orating with Dr. Tausk of Organon and with Professor 
Westerdijk, took up penicillin research secretly. 
Unis has never been brought to the notice of the 
German wartime managers of Organon, A strain of 
moulds was found, giving a high yield of a very 
active anti-bacterial substance. It cannot yet be 
said whether this is identical with penicillin, al- 
though in many respects it behaved exactly like it. 
Other Dutch centres of research have recently 
become actively interested in penicillin and other 
anti-bacterial substances of moulds. It is believed 
that none has got so far as Professor Julius and his 
collaborators. APPENDIX X. 
1st of Shortages 
(alphabetically arranged) 
Acetic Acid; Delivery almost stopped after 
the Amsterdam factory had been 
damaged. In 1944 we received 
three tank loads from Germany. 
Acetone: First years, of the war almost 
unobtainable. Later on a spe- 
cial permit. 
Acetylsalicylic Acid: Limited import from Germany In 
bulk. 
Ethyl Alcohol: Though rather scarce always 
obtainable. 
Aneurlne; Irregular though sufficient 
deliveries from Germany and 
Hungary. 
Asbestos Filters: (Seitz). Almost unobtainable. 
Benzaldehyde; Sporadic supplies. 
Boron Compounds unobtainable. The last batches of 
ampoules received from Germany 
were of boronfree glass of very 
poor ouality. 
Chinydron; Very difficult. Chromium salts 
nad to be handed. In exchange( I. G.) • 
Chloroform; Very limited. 
Chloro-suLohonlc Ac Id: Obtainable though restricted. 
Chromic Acid; Very short. 
Code In: Not available. 
Cod liver oil; Unobtainable. 
Coffeine and its salts: Mot available In.Germany. 
Small stocks in Holland. Germans 
attempted a synthesis. APPENDIX X (Continued) 
Dlchloro-ethylene; In Holland unobtainable. X. G, 
Farben delivered small 
Quantities but Informed us 
Just before the liberation 
that they were unable to 
continue. 
Dimethylsulphate; Unobtainable, 
Glass Apparatus; Orders for laboratory glass- 
ware delivered after several 
years or not at all. 
Particularly funnels ar 
unobtainable. 
Glycerine; Though liable to restrictions, 
available in modest quantities. 
Iodine; Compounds very scarce. 
Iron Ammonium Citrate; Almost unobtainable. 
Manganese sulphate; Not available. 
Papalne; Unobtainable. 
Papavarine; Delivered only once. 
Peanut Oil; Completely exhausted. 
Phenacetln; Unobtainable. 
Potassium Permanganate; Not available. 
Haney metal; After the bombing of the fac- 
tory, unobtainable. 
Sodium Benzoate; Supplied In small Quantities. 
Sodium Fluoride; Not available. 
Sulphuric Acid; Decreasing delivery. 
Semlcarbazlde; We have the impression that 
the last stocks sire exhausted. 
Tartaric Acid; Unobtainable. 
Trlchloro-acetic Acid; Not available. 
All fine chemicals for analytical purposes were very 
difficult to. obtain, or were not delivered at all. 
Iodine; 
Papaine;