TWO YEARS AT THE VITAMIN INSTITUTE IN LENINGRAD
(1936-1937)

Edgar LEDERER

Having obtained my PhD in July 1930 in my native city, Vienna (Austria), on the synthesis of indole alkaloids, I had done postdoctoral research on chromatography and carotenoids with Prof. Richard Kuhn, at the Kaiser Wilhelm Institute in Heidelberg (Germany).

In June 1932 I married in Paris Helene Frechet, the daughter of the famous French mathematician Maurice Frechet¹. In March 1933 we had to leave Heidelberg because of the increasing danger of being arrested by the nazis.

We went to Paris, where I could continue some research on carotenoids, but I had to look for a stable position. My sympathies were very strongly in favour of socialism which I thought was being realised in the USSR. I had learnt Russian and was looking forward to participate in the fascinating experiment going on in the East.

In March 1935 I learnt from the International organisation that a position was offered in Odessa. I took the train through Europe and was the only passenger crossing the frontier at Podvolotschisk, on the Bessarabian border; a sleeper car took me to Odessa.

The position there was not tempting so I went to Kiev where Prof. A.Palladin promised me a position as "Docent" at the University. This, however, never materialised.

Finally, I got a recommendation to the cultural attachй of the Soviet Embassy in Paris, through Professor Paul Langevin, renowned physicist. Fortunately, just at that time the Vitamin Institute in Leningrad needed a chemist. I went there, first by plane to Berlin, then with another small plane to Tallinn; the Leningrad airport was flooded at that time., so I had to take the train from Tallinn to Leningrad.

The Vitamin Institute belonged to the Ministry of Food Industry, the head of which was Anastase Mikoyan. I was offered the directorship of a newly founded laboratory of synthesis, a good salary, a nice new 3-room flat overlooking the Fontanka (Fontanka 25, Kb. 32) and a rather well-equipped lab with 5 or 6 co-workers. Transportation of my family, furniture etc... from Paris to Leningrad and back would be paid by the Institute. The 3-year contract was quickly signed and in October 1935 I took the train from Paris to Moscow with my wife and our two daughters, the youngest just 4 months old. At the frontier station, Negoreloie, a cable from the Institute was waiting for me and I received one month salary in advance.

We first stopped for a few days in Moscow at the hotel Metropole. At that occasion I met Prof. V.Engelhardt, the famous biochemist who had discovered the ATP-ase activity of myosin².

The Krasnaia Strela took us then to Leningrad where a big container with our furniture was waiting for us after arriving by ship from Le Havre.

Amongst the senior staff of the Vitamin Institute I remember Prof. N.N.Ivanov, Prof. Sadikov, Dr. Boukin, Dr. V.Lebedev, Dr. N.V.Novotelnov, Dr. Krestinskaia and of course the Director Prof. A.A.Schmidt. Prof. Ivanov was very competent in Plant Biochemistry. Prof. Sadikov had his own "cyclol" theory of protein structure; Dr. Boukin, whom I later met after the war, was a vitaminologist and Prof. Schmidt with his pince-nez and a very stern look was an energetic and efficient director³.

Amongst the collaborators of the laboratory of synthesis I only remember Valentina Alexandrovna Rosanova⁴, A.G.Pesina, Ya.S.Slobodin and Kristallinskaia. Two young American chemists had joined me in 1936: Franz Rathmann who later followed me to Paris and Sulo Karjala (from Finnish parents). They both came to work in the Soviet Union, to help building socialism. They left the country after my departure and later found jobs in the USA.

I had been asked to help with the development of various vitamin preparations; we started synthetic studies vitamin C following the fundamental work of Professor Thaddeus Reichstein (Basle).

That was indeed an urgent task because, at that time there were no vitamin C preparation available in the USSR and scurvy was still a very serious problem, especially in Siberia. Once I was taken to a hospital to see some cases of scurvy. I still remember one pretty, very pale girl lying in bed; when she was asked to open her mouth it was full of blood⁵.

Somewhat later a vitamin C preparation from conifer needles became available, but its taste was very bad and it contained a large proportion of more or less noxious terpenoids.

Then, at the Vitamin Institute, extracts of rose-hips were developed as source of vitamin C.

With Sulo Karjala a synthesis of vitamin B₁ was started, but then abandoned when Alexander Todd in England published his first results.

In spring 1937, we started some work on preparation of vitamin E (tocopherol) from wheat germ oil. This was to be used for the treatment of abortion in cows infected by Bacillus abortus Bang.

My interest in vitamin A⁶ brought me once to Murmansk in company of N.V.Novotelnov; we there visited a brand new installation for the production of cod liver oil; then I wondered, whether the livers of the big Volga fishes (sturgeons, beluga, etc.) could be used as source of vitamin A. At my request, I received tinned samples of such livers from all over the USSR, even from the Far East. We then analysed extracts of these liver samples by the well-known Carr-Price reaction⁷, using a small spectrometer I had bought for 25Ł in London. To my astonishment, all extracts gave a green-blue colour (l _max 690) instead of the blue colour typical for vitamin A (l _max 620); this led me, with Valentina Alexandrovna Rosanova, to publish a paper in Biokhimia on "Studies on vitamin A of fish liver oil. I. An abnormal reaction of Carr and Price"⁸.

Then, for further characterisation of the new compound, which we had found to be active as vitamin A in mice and which seemed to be typical for freshwater fish, I got into contact with Prof. I.M.Heilbron⁹, who had first described a minor "chromogen 690" in some fish liver oils.

As a result of this collaboration we published a Letter to Nature¹⁰ reporting also the ultraviolet spectrum of freshwater fish liver oil concentrates, indicating that their "chromogen 693" had six conjugated double bonds instead of five for the classical vitamin A of the marine fish liver oils.

A more detailed paper¹¹ published later contains two sections. The first, Section A, Occurrence and spectrometric characterization of the 693 mm chromogen, together with Valentina Rosanova, describes the ultraviolet spectra and absorption bands in the Carr-Price reaction of 12 marine fish liver oils and 36 freshwater fish liver oils. Biological experiments are also reported; in conclusion it is stated: "It is reasonable to suppose, therefore, that the 693 mm chromogen is vitamin A active. More extensive investigations will, however, be necessary before it can be regarded with certainty as vitamin A₂".

The term vitamin A₂ had indeed first been coined by A.R.Morton (Liverpool) who had found this "chromogen" in gold fish livers; simultaneously George Wald (Harvard) had found it in the retina of pike.

In part B of the above mentioned paper¹¹ oxidation experiments are recorded and two formulae considered for vitamin A₂. An incorrect interpretation of the degradation experiments led us to prefer the second formula, but it was shown later by Shantz in the USA that the first formula of a 3,4-dehydro-vitamin A is the correct one¹².

Vitamin A₂ was later also found to exist in tadpoles, whereas frogs have only vitamin A₁.

On returning to Paris I continued some work on vitamin A₂ with F.Rathman who had joned me after leaving Leningrad¹³.

We must now consider the problem of the possible use of vitamin A₂ preparations in medicine.

Vitamin A was primary considered to be necessary for growth and for normal functioning of epithelial cells. However, at Harvard, George Wald had shown in 1937 that vitamin A (retinol) was dehydrogenated in the retina to the corresponding aldehyde (retinal), which then combined with a specific protein, opsine, to the visual pigment rhodopsine. On exposure to light rhodopsine is split into retinal and opsine; retinal then be reduced to retinol.

Working with retina of freshwater fish, Wald then found that they contained a different visual pigment, porphyropsine absorbing at longer wavelengths than rhodopsine; on exposure to light porphyropsine gave an aldehyde (retinal₂) and then vitamin A₂ (retinol₂).

These important observation suggest that vitamin A₂ containing preparations fed to mammals (or to human) would result in the formation of porphyropsine instead of rhodopsine, thus possibly disturbing the normal perception of colours. One can thus conclude that liver oils from freshwater fish are not suitable as source of vitamin A for man.

In autumn 1936 I received a part-time appointment as lecturer at the Faculty of Medicine. There, I gave a course on Vitamins and Hormons and organised some practical works with the students (on chromatography, extraction of carotenoids, etc.). One of them, Sergei Evstafevich Manoilov was particularly bright and became professor at the Chemical-Pharmaceutical Institute in Leningrad. I later met him several times after the war; he had been in the town during the terrible blockade of Leningrad and had produced under very difficult conditions carotene preparations used for wound healing. He is proud to wear the many decorations he received for his courage during the war.

I had a three years contract, but after two most interesting years in Leningrad the political situation became difficult, especially for foreigners; this was the period sadly known as "Yeshowchina" during which many intellectuals were arrested, to be liberated a few months later, when Yeshow, the head of the GPU was found to be "saboteur".

In November 1937 the renewal of my permit was refused by the local agents of the Ministry of Interior, but the director, Professor A.A.Schmidt wanted me to stay and proposed to go with me to Moscow to see Molotov, the Minister of Foreign Affairs. However, considering the general atmosphere at that time I thought it wiser to return to Paris. I left the USSR via Moscow on December 1^st 1937, full of sad feelings.

It so happened that our delegation was in Moscow on July 14^th, 1955 and there was a reception at the French Embassy. All of a sudden there was a complete silence and everybody looked at the big staircase leading up to the hall where we were: and low and behold here they came: Kroutchtchev, first, then Molotov, Mikoyan, Malenkov, Kaganovitch and many generals with their breasts loaden with decorations. This is quite unexpected, because it was the first time that members of the Soviet Government came to a reception at the French Embassy. I got very excited; it was like a dream and so as to be sure that the chap there in the middle of the hall was really Molotov, I approached him and touched his sleeve; immediately a big chap behind him reached into his pocket and pointed something in my direction. I moved on and thought I could try to talk to Mikoyan who had been my boss during my stay in Leningrad. He was in conversation with Malenkov, but I finally caught his attention and told him that I had worked for two years at the Vitamin Institute. He seemed even to remember my activity there and added: "You know, Stalin always said vitamins are very important".

1 He had many friends among Russian mathematicians, such as Alexandrov, Kolmogorov, Finnikov, etc.

2 We later met several times after the war mostly at congresses and two years before his death we had the great pleasure of his visit at home, with his daughter Alina.

3 He later became member of the Latvian Academy of Sciences.

4 She was killed by a bomb during the siege of Leningrad in 1943.

5 Gingival haemorrhages are one of the serious manifestations of scurvy.

6 In 1931 I had first separated a - and b -carotene, the two major provitamins A by column chromatography and in 1935 in Paris, I had isolated echinenone, a new provitamin A, from sea urchin eggs.

7 Antimony trichloride in chloroform gives a blue colour with vitamin A.

8 E.Lederer, V.A.Rosanova. Studies on vitamin A of fish liver oils. I. An abnormal reaction of Carr and Price. Biokhimiia, 2 (2), 293-303, 1937.

9 At that time at the Chemistry Department of Manchester University.

10 E.Lederer, V.Rosanova, A.E.Gillam, I.M.Heilbron. Differences in the chromogenic properties of fresh-water and marine fish liver oils. Nature, 140, 233, 1937.

11 A.E.Gillam, I.M.Heilbron, W.E.Jones, E.Lederer. On the occurrence and constitution of the 693 mm chromogen (vitamin A₂ ?) of fish liver oils. Biochem. J., 32, 405-416, 1938.

12 The biosynthesis of vitamin A₂ could be due to a dehydration of a 3-hydroxylated carotenoid or to dehydrogenation of vitamin A₁.

13 E.Lederer, F.H.Rathmann. Sur les vitamines A₁ et A₂. Compt. Rendus Acad. Sci. Paris, 206, 781, 1938; E.Lederer, F.H.Rathmann. A physico-chemical and biochemical study of vitamin A₂. Biochem. J., 32, 1252-1261, 1938.

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