treno-immagine-animata-0046

 

We get off the train in Liepāja, where we meet

Lina Solomonova Stern (Shtern)

 

 

Lina Stern conducted innovative research in biochemistry and neurophysiology. She made important contributions to the early history of the blood-brain barrier and was the first scientist to introduce the term “barrier” to the exchange mechanism in brain.

“nous avons constaté que les substances introduites dans la circulation générale ne pouvaient pas toutes être décelées dans le liquide CR. [céphalo-rachidien] et que, par contre, toutes les substances introduites dans le liquide CR. se retrouvaient au bout d’un temps plus ou moins long dans la circulation générale. Nous avons conclu à l’existence d’une espèce de cloison s’opposant à I’entrée de certaines substances dans le liquide CR., mais permettant la sortie dans le sang de toute substance introduite dans le liquide CR. A cette cloison, nous avons donné le nom de barrière hèmatoencéphalique…”.
[“we found that substances introduced into the general circulation could not all be detected in the CR. [cerebrospinal fluid] and that, on the other hand, all the substances introduced into the CR liquid were found at the end of a more or less long time in the general circulation. We have concluded that there is a kind of partitioning preventing the entry of certain substances into the CR, but allowing the release into the blood of any substance introduced into CR. At this partitioning, we have given the name of a hematoencephalic barrier…”]. (Stern & Gautier 1922).

In 1917, Stern was the first woman to be appointed professor at the University of Geneva. In 1926-1928 she was head of the Department of Biochemistry of the Institute of Infectious Diseases in Moscow. In 1929, she founded the Physiological Institute of the People’s Commissariat for Education and the People’s Commissariat for Health in Moscow and headed it until 1948, when she was discredited as a scientist. In the 1930s, she was the editor-in-chief of The Bulletin of Experimental Physiology and Medicine. In 1932, she became a member of the German Academy of Science Leopoldina but soon was deleted because of Nazi antisemitism, and was reinstated as member after 1945. In 1939, Stern was the first woman scientist to be elected a full member of the Academy of Science of the USSR, and in 1944 she was elected a member of the Academy of Medical Sciences of the USSR. Her scientific career was interrupted for five years by the arrest and exile. From 1954 to 1968, Stern headed the physiological laboratory of the Institute of Biophysics of the USSR Academy of Sciences and continued her research on blood-brain barrier, published a review on the topic, and resumed contacts with her Western colleagues.

Lina Solomonovna was fluent in French, German, English and Italian. Before moving to the USSR her works were published in French and German.

Her outstanding contributions to the field of blood-brain barrier biology have been largely ignored.

 

 

 

Stern and her collaborators performed detailed studies of penetration of a wide range of molecules from blood into cerebrospinal fluid into brain and within the subarachnoid and ventricular cerebrospinal fluid of adult animals. She also contributed to the study of brain barriers in developing animals of different species.

In the work of Stern and Rapoport it was hypothesized the existence of two routes of entry from blood into brain: one directly across the blood vessels (endothelial blood-brain barrier) and the other via the choroid plexuses (the epithelial blood-cerebrospinal fluid-barrier). These studies have been ignored or miss-cited, as reported by Saunders and coll. (2014), that have traced the history of the blood-brain barrier studies.

Stern also introduced the concepts of barrier selectivity and barrier resistance. In her 1934 paper, “which was one of the last published in French, Stern makes a very clear statement about the importance of the blood-brain barrier in not only providing protection for the brain but also an appropriate physico-chemical environment for normal brain function. […] The concept of the blood-brain barrier providing mechanisms that control the internal environment of the brain is a major physiological concept that was decades ahead of its time and really only began to be properly accepted and investigated with the advent of radioactive tracers in the 2nd half of the 20th Century” (Saunders and coll., 2014).

“Partant de l’idée que le liquide céphalorachidien represénte le milieu nutritif immédiat des éléments nerveux cérébro-spinaux et que la constance relative de la composition chimique et de l’état physico-chimique de ce milieu est une condition sine qua non du fonctionnment normal des centers nerveux, nous avons attributé un rôle de premier plan à l’activité de cet appareil régulateur que représente la barrière hématoencéphalique.”
[Starting with the idea that the CSF represents the immediate nutritive medium for the cells of the brain and spinal cord and that the relative constancy of the chemical composition and physico-chemical state of this medium is the sine qua non for normal function of the CNS we have attributed a primary role for this regulatory activity to the blood-brain barrier] (as translated in Saunders and coll., 2014).

The problem of the regulation of the physiological and biochemical composition of the environment of organs, tissues and cells had theoretical and clinical implications, particularly for the treatment of diseases of the central nervous system.. The blood-brain barrier, which provides protection from the noxious effects of substances that penetrate into the blood, can play a negative role under certain pathological conditions representing a major obstacle to the delivery of drugs to the central nervous system. To overcome the impenetrability of barriers, Stern proposed a method of injecting drugs directly into the cerebellomedullary cistern situated beneath the occipital lobes of the brain (suboccipital method).

In 1939 she applied her new method for the treatment of traumatic shock, consisting in the suboccipital injection of potassium to increase its content in the intraventricular cerebrospinal fluid. She used this method during World War II, regardless of criticism for the lack of evidence, and later she recommended it as a treatment for a number of different pathological conditions.

Since 1943, she began to apply the suboccipital injections of the antibiotic streptomycin in the treatment of tuberculosis meningitis. Streptomycin was available in the United States only, and Stern obtained it directly from her brother who lived there. She had the monopoly of streptomycin in the USSR and subordinated its availability to the application of her method of invasive injections. For some clinical specialists, there was no need to inject streptomycin directly in the cerebrospinal fluid: a less invasive treatment could have been carried out by intramuscular injections. In many scientists’ opinion Stern lacked lacked objectivity, had excessive faith in her method and did not take into account the adverse effects.

As reported by Rapoport (1991): “At one time, Stalin’s daughter Svetlana Alliluyeva-Stalin approached her to request some streptomycin for a child of close friends. Stern flatly refused, saying that she received streptomycin not for treating tuberculosis in general but strictly for purposes of research.”

In 1953 she came back to the academic life: conducted experimental studies, ordered what was left of the scientific archive and deepened the research published over the past five years regarding her topics. At the age of over 70, she reacquired a role as eminent scientist with a series of research of great theoretical and clinical importance for medicine.

 

 

Biography. Lina Solomonovna Stern (Shtern) was born on August 26, 1878 in Liepāja, a province of Kurland, now Latvia. Her father, Solomon Shtern, was a merchant who dealt export of bread, and her mother, Elena, was a housewife. Lina was the eldest of seven children. After secondary school, she tried for two years to get admission to Moscow University without success even if she spoke German, French, English and Italian: indeed it was impossible for a Jewish woman to pursue studies in Russia. In 1898, Stern moved to Switzerland and began her career as a medical student at the University of Geneva, that was famous for its openness to foreigners. During her studies, she worked at the department of biochemistry and physiology under the supervision of Jean-Louis Prévost, and published her first research on internal secretions of the liver in 1902. In 1904 she defended her doctoral thesis on ureteric contractions and was awarded a university prize. Then, she became an assistant of Prevost and started her teaching career. In 1917, Stern was appointed professor of physiological chemistry and continued her original research, acquiring a considerable reputation in her field. She headed her department, established her own school of physiologists, and was also a consultant to pharmaceutical manufacturers. In Geneva, Stern worked together with Federico Battelli (1867-1941, Italian physiologist and biochemist, studied at Turin, emigrated for political reasons and worked in Geneva), Prevost’s successor, on oxidative metabolism, on respiratory enzymes, on the physiology of heart, blood, central and autonomous nervous systems. From 1918 to 1925 she conducted in collaboration with R. Gautier a series of experiments on tissue barriers and in 1921 she introduced the term “blood-brain barrier” at the Medical Society of Geneva. Stern continued this pioneering research studying the maturation of the hematoencephalic barrier in the developing brain. Because of her work, she came into close contact with the brain researchers Cécile and Oskar Vogt at the Kaiser Wilhelm Institute for Brain Research in Berlin. In 1924, Aleksei Nikolaevich Bach offered her to take the vacant position of head of the Department of Physiology at the Second Moscow State University. In March 1925, at the age of 48, the eminent scientist Lina Stern arrived in Moscow, where the physiology of Ivan Petrovič Pavlov was dominant. In the following four years she continued her research, published numerous articles in Russian, French and German journals, taught physiology and biochemistry, and tried to adjust to the new life and to the Soviet environment. From 1929 to 1948, she was the director of the new Institute of Physiology in Moscow and surrounded herself with a highly qualified research staff. In the following years, Stern invited the most eminent international scientists to visit her institute and many of them donated new equipment to her laboratories. She maintained contacts with her Western colleagues and attended  international conferences held abroad. She was engaged with a British colleague but the marriage never took place, because once married she was expected to interrupt her scientific career. She sacrificed her personal life, devoting entirely to science. In 1942, Lina Stern joined the Jewish Anti-Fascist Committee organized at the initiative of the Soviet Union in order to mobilize world Jewish support for the USSR’s war effort against Nazi Germany. At the end of World War II, Stalin changed his view and promoted antisemitism: this was the beginning of a series of actions against the members of the Committee. A moral and professional discrediting was directed to Stern. In 1948 she was expelled from all medicine and science positions and was also accused of “pseudo-teaching” and of “anti-Pavlovian” ideas. The main members of the Jewish Anti-Fascist Committee were arrested. Lina Stern was arrested on January 1949, at the age of 70, and remained in prison for almost four years, experiencing humiliation and physical strain. In 1952, the members of the Committee were tried in secret and, except for Stern, were executed. She was exiled in Dzhambul, Kazakhstan. In 1953, three months after Stalin’s death, Stern returned to Moscow. She regained her scientific status: she was still a member of the Academy of Sciences. She was allowed to establish a laboratory, at 76 years old, and headed it until her death.

Lina Solomonovna Stern died on March 7, 1968 and she was buried at the Novodevichij cemetery in Moscow.

 

 

 

Prizes and awards

  • 1934: Honoured worker of science
  • 1943: Stalin Prize for outstanding achievements in the study of the blood-brain barrier
  • 1944: Order of the Red Banner of Labour
  • 1945: Order of the Red Star
  • 1960: Honoris causa from the University of Geneva

 

 

Credit

To cite this profile, please use the following format:

Metitieri, T. and Mele, S. (2018). Profile of Lina Solomonova Stern (Shtern). In WiNEu, European Women in Neuroscience, Untold stories: the Women Pioneers of Neuroscience in Europe. Retrieved from http://wineurope.eu/stern/

 

Selected work

  • Battelli F, Stern L (1912). Die Oxydationsfermente. Ergeb Physiol 12: 96–268.
  • Stern L (1921): Le liquide céfalo-rachidien au point de vue de ses rapports avec la circulation sanguine et avec les éléments nerveux de l’axe cérébrospinal. Schweiz. Arch. Neurol. und Psychiatr., 8(2): 215–232.
  • Stern L, Gautier R (1921): Recherches sur le liquide céphalo-rachidien. Arch. Int. Physiol., 17(2): 138–192.
  • Stern L, Gautier R (1922): Recherches sur le liquide céphalo-rachidien. Les rapports entre le liquide céphalo-rachidien et les éléments nerveux de l’axe cérébrospinal. Arch. Int. Physiol. 17(4): 391–448.
  • Stern L, Peyrot R (1927): Le fonctionnement de la barrière hématoencéphalique aux divers stades de développement chez diverses espèces animales. C.R. Soc. Biol. (Paris), 96: 1124–1126.
  • Stern L, Rapoport J, Lokschina ES (1929): Le fonctionnement de la barrière hématoencéphalique chez les nouveaunés. Soc. Biol., 100: 231–233.
  • Stern LS (1958): Present state of the problem of hematoencephalic barrier. Usp Sovrem Biol., 45(3): 328–348.

 

 

References

  • Some aspects of shock therapy. British Medical Journal 1942, Nov. 7: 546.
  • Prof. Lina Stern. The Lancet, 1942, Nov. 14, 580
  • Dreifuss JJ, Tikhonov N (2007) Une etoile a la Belle Epoque: Lina Stern, professeur de medecine a Geneve. Rev Med Suisse 3(2306): 2308–2309
  • НА. Григорьян (2003). Первая женщина-академик. К 125-летию со дня рождения Л.С. Штерн. Вестник Российской Aкадемии Hаук [Grigoryan NA (2003). First woman-academician. To the 125th Anniversary of the Birthday L.S. Stern. Bulletin of the Russian Academy of Sciences], 73, 8: 735-743.
  • Grigorian NA (2017) Lina Solomonovna Stern (Shtern) 1878– 1968. https://jwa.org/encyclopedia/article/stern-shtern-linasolomonova (accessed on 3 March 2018)
  • Rapoport, Yakov. “Lina Stern. Persecution of an Academician.” In The Doctors’ Plot of 1953. Cambridge, MA: Harvard University Press, 1991, pp. 234–253.
  • Sarikcioglu L. (2017). Lina Stern (1878–1968): an outstanding scientist of her time. Childs Nerv Syst, 33:1027–1029
  • Saunders NR, Dreifuss JJ, Dziegielewska KM, Johansson PA, Habgood MD, Møllgård K, Bauer HC. (2014). The rights and wrongs of blood-brain barrier permeability studies: a walk through 100 years of history. Front Neurosci, Dec 16;8:404.
  • Vein AA (2008) Science and fate: Lina Stern (1878–1968), a neurophysiologist and biochemist. J Hist Neurosci 17:195–206
  • Vogt, Annette B. Lina S. Shtern. In: Apotheker JH, Sarkadi LS (eds). European Women in Chemistry. Weinheim: Wiley-VCH, 2011, pp. 59-63.