When Italy entered into the First World War, Reinhard Dohrn, son of Anton and at the time Director of the Station, and the German assistants had to leave the country. The station, as private entity belonging to a German citizen, was placed under national control. In 1916 the station was solemnly inaugurated as an 'Italian Institute' and placed under the direction of a national committee.
At the end of the war, after a period of uncertainty, Benedetto Croce, then Minister of Education, in a speech to the Senate on December 9, 1920, suggested placing the Zoological Station again under the responsibility of the Dohrn family, the only way, according to the Neapolitan philosopher, to guarantee the institution its scientific links and its functionality. In October of 1923 its legal status was redefined and the Stazione Zoologica became an 'Ente Morale' (a semi-private institution), under the surveillance of the Ministry of Public Instruction and directed by a Board of Directors, chaired by the Mayor of Naples. Reinhard Dohrn was nominated ‘managing director and administrator’.
The new institutional structure maintains the international status of the Stazione Zoologica, fostering contacts among researchers of different countries and encouraging their presence in Naples, thanks to a total freedom of research and a technical structure effective, able to create ideal working conditions and providing all the research material needed.
The scientific activities of the Stazione Zoologica in the interwar period show a great continuity with the previous period. Systematics remains a priority. The physiology of the embryo, the regeneration, research of biochemical components in marine organisms and their quantitative changes during embryonic development, the study of embryonic gradients, research on bioluminescence and photogenesis, hereditary symbiosis continue to be points of aggregation, while the wealth of the Gulf of Naples, with its flora and diversity of animals both superficial and abyssal forms, favored the development of a new ecological approach, centered on alimentary chains, the complex of organisms, in connection with the biological and physical-chemical environment. And, as in previous periods, the Stazione Zoologica is the ideal place for experimentation of new technologies applied to research, such as the use of cinema for the study of experimental embryology, the first experience of scientific cinematography (Istituto Luce) and research supported by Kodak on gels of animal origin for film.
Once again, however, the main thrust to scientific innovation comes from embryology. The turning point in this kind of research can be identified in a classic article of 1924 in which Hans Spemann and Hilde Mangold had begun to study the morphogenetic processes leading to the formation of the eye in amphibians. This research program is developed further in the following years, through a very complex series of experiments in tissue transplants, many of which are made in Naples, where Spemann worked quite often, accompanied by a substantial group of assistants.
In the 20s and 30s the physiological and biochemical research continues to play a major role in the scientific life of the Stazione Zoologica. Albrecht Kossel and the Svedberg, founders of nucleic acid chemistry, work equally to the Zoological Station, as Jean Brachet, that at this time develops the cytochemical techniques for localization of nucleic acids into cells and embryo. Otto Meyerhoff (a future Nobel laureate) studying muscle metabolism, focusing interest on chemical stimulation of the muscle fiber. In 1935, Zénon-Marcel Bacq and Francesco Paolo Mazza demonstrate the presence of acetylcholine in the ganglia of the optical octopus (Octopus), and identify the substance chemically. The contribution of Bacq and Mazza is a milestone in the history of chemistry of nerve transmission, the first direct proof of its existence in the nervous tissues. Bacq, a pharmacologist from Belgium, in collaboration with Francesco Ghiretti employed cephalopods to develop endocrinology, using adrenaline-like agents.
The Zoological favored another important progress in neurobiology, the discovery of Ernst Scharrer of the phenomenon of what has become known "neurosecretion," the elaboration and secretion of hormones from by nerve cells.
What may be called the modern era of research on cephalopod research begun in Naples with the research of Enrico Sereni, who conducted major experiments on the chromatophores and salivary hormonal secretion. Sereni also works on the peripheral nervous system of cephalopods, in collaboration with the young British researcher John Z. Young, who founded another line of research, that will become characteristic of the Stazione Zoologica, pursued for decades and almost uninterrupted. Working with Sereni on the Octopus, Young discovered by chance the giant axon this became a fundamental tool in exploring nerve conduction. The sections of the brain and giant fibers of octopus and cuttlefish, created by Young at the Stazione Zoologica in 1936 showed the possibility of studying higher nervous activities, such as learning and memory.
The Stazione Zoologica remains virtually closed between 1943 and 1945, with a very small number of researchers and technicians. The Aquarium reopened to the allied troops in December 1943. The Villa Comunale was left by Allied troops on May 1, 1944 and the activity of the station can begin again. The Library was relocated to its place at the end of 1944. After the liberation of Rome, June 4, 1944, contacts are established with the Ministry of Education and the National Research Council, who supported the station consistently. This will create a "Center for Biological Studies", under the direction of Joseph Reverberi, whose main purpose is to create training grants for young biologists. After 1950, the National Science Foundation, newly created, the Lilly Endowment and the Rockefeller Foundation increase considerably their engagement with the Stazione Zoologica. The scientific prestige of the Stazione Zoologica and its location in the postwar period made it rapidly a privileged place for the realization of conferences and scientific meetings. This was also an opportunity for Italian scientists to enter the international circuit. The station hosts important conferences on embryology and genetics, mutagenesis, on neurosecretion. In 1951 the Stazione Zoologica held a conference on the application of X-rays to the study of biological problems, in particular the study of the submicroscopic structure of protoplasm. In this conference, Wilkins shows a figure of X-ray diffraction of the crystalline DNA and this stimulates JD Watson, who attended the meeting, to start its work on nucleic acids, that will take him with Francis Crick's discovery of the double helix.