Author: Ibon Cancio, UPV/EHU Associated Professor in Cell Biology; researcher in the ‘Cell Biology & Environmental Toxicology’ (CBET) research group of the Plentzia Marine Station (PiE-UPV/EHU); Spanish scientific representative in the EMBRC Committee of Nodes
Jacques Loeb was born in Mayen (Prussia) in 1859 as Isaak Loeb, but in 1880, when he was about to begin medicine studies at university (studies that he carried out in Berlin, Munich and Strasburg), he adopted the French and secular name with which he would gain worldwide fame. His original given name tells us of his Jewish origin, his research and publications tell us about his atheism and mechanistic engineer conception of life. Public celebrity came mainly from his research in parthenogenesis with marine invertebrates. His findings would call the attention of public media, which would present them as a sort of ‘immaculate conception’ result of the general biblical notion around the creation of life. A man of science, considered the highest exponent of experimental research, Loeb always adhered to his philosophical conception of the meaning of and the role of science in the study of living organisms.
Until 1891, Loeb taught and experimented at various German institutions and at the Stazione Zoologica Anton Dorhn (SZN) in Naples in the winters of 1889 and 1890. After his marriage in 1890 to an American philologist whom he met in Zurich, Ann Leonard, Loeb moved to the United States. He was escaping from his not very promising academic prospects in a system with little possibilities to fit in as a Jewish-born, atheist turned ‘antimilitaristic non-nationalistic Prussian’. In the US, he lectured at various institutions from coast to coast, first and for a single year at Bryn Mawr College in Pennsylvania, then at the University of Chicago, University of California, Berkeley, and finally the Rockefeller Institute for Medical Research in New York, from 1910 until his death in 1924. In California, he experimented during the summers in the marine station that was created for him in Pacific Grove, and, while in Chicago and New York, at the Marine Biological Laboratory (MBL) in Woods Hole, Massachusetts.
While in Germany, Loeb focused on degenerative and regenerative problems of brain anatomy and neurophysiology. This took place at a time when neurological disorders in soldiers (who had served in the 1870-71 Franco-Prussian war) were a real problem. He used experimentation to answer questions about development and regeneration rather than observation alone. However, this was not so easy to do with dogs, which were his experimental model while in Strasburg and Wurzburg. Loeb’s influences during that period provided the practical and theoretical foundation for his work philosophy. According to Loeb, the only way to explain biological phenomena was through physiochemically manipulating living organisms. The function of the biologist was not to understand life but to control it, change it so that it could be better used or harvested. For him, a biologist was like an engineer and organisms were machines that biologists manipulated.
It was during the beginnings that his two first trips to SZN took place (he would return a few more times for short stays from the US). These visits translated into his first use of marine animals for experimentation, and led to the development of the three research themes that would bring him public recognition: animal tropisms, organ development and regeneration, and artificial parthenogenesis. In Naples, he used different model animals to conduct experiments on animal orientation and movements in response to light, gravitational or electrical stimuli. These experiments were a means to study animal behavior and neural capacities. Loeb believed that animal instinct followed the same elementary physical and chemical laws which determine plant movements. According to him, a light stimulus (heliotropism) would induce chemical reactions in the retina. The produced chemicals passed directly through the central nervous system to influence the energy production necessary for motion in the locomotor appendages, until a new plane of symmetry was established between the eyes and the source of light. This opposed the anthropomorphic conception that animals responded to light according to voluntary reactions. As such, Loeb reduced instinctive behavior to a series of movements and connected reflexes, proposing that there was no purpose of will in animals and that these are forced mechanically to move in one direction under the influence of their locomotor organs. It is not free will that shapes movement and orientation, but a series of reflexes to external stimuli, and if you can control this external stimuli, you can control behavior (life). In Naples, he performed a series of beautiful experiments, mainly with hydrozoa such as Eudendrium and ascidia, which, over the years, he would repeat in different species from the Atlantic. Playing with light, Loeb was able to redirect the growth of hydrozoan polyps changing their axis of symmetry.
Loeb did also seminal discoveries in regenerative research describing the process that he called heteromorphosis in 1892. While in Naples, he began to explore the regenerative capacity of some animals in response to trauma. He was able to externally induce different developmental outcomes in animals. For instance, after excising one end of tubularian hydroids, he was able to induce the formation of a head instead of a foot at the aboral end, producing animals with two heads and a clear distortion of polarity. Heteromorphosis defines alterations in which an anatomical structure, organ or tissue is formed in the place where another one should be formed. Further experiments, for instance in Campanularia hydrozoans, proved that there was no need of an injury to generate such changes in polarity, and the way in which hydrozoans were placed in an aquarium in relation to gravity affected the growth axis, changing the sites where new polyps sprouted. Many examples of heteromorphosis have been shown in organisms from protozoans to chordates. These studies raised many questions regarding the potentiality and capacity of cells to differentiate during the formation of one organ or another, as well as the reversibility of the differentiated state of a cell to become undifferentiated.
Loeb’s public fame as an engineer biologist was based mainly on his 1899 publication ‘On the Nature of the Process of Fertilization and the Artificial Production of Normal Larvae (Plutei) from the Unfertilized Eggs of the Sea Urchin’ that showed artificial parthenogenesis in Arbacia sea urchins after experiments conducted at MBL. Parthenogenesis is the process by which an egg initiates development into a new organism without participation of a sperm cell. Loeb manipulated unfertilised Arbacia eggs by placing them in hypertonic solutions to see if chemicals could initiate embryo development. He was successful when placing eggs in solutions of NaCl, KCl, CaCl2, and MgCl2. After several minutes, the eggs had to be placed in normal sea water and divisions began properly. His experiments the following year in California were also successful with sea urchins common there, Strongylocentrotus purpuratus and franciscanus, and although the success rate was lower, he obtained early-stage embryos and larvae. Loeb reviewed most of his results on the subject in his book ‘Artificial Parthenogenesis and Fertilization’, published in 1913. He also proved that increasing the osmotic pressure of seawater with non-electrolytes (eg sugar, ethyl acetate, fatty acids) initiated development in unfertilised eggs. Loeb further triggered parthenogenesis by applying different techniques in starfish, annelids, and molluscs. He was also successful with frog eggs, although vertebrate eggs are more impermeable to the chemicals that he normally used. In this case, it was necessary to punctuate the eggs and to introduce the blood of an animal to trigger development.
Thus, sperm was not needed to initiate development of eggs into embryos. This reinforced Loeb’s idea that the chemical nature around the embryos affects their development, so scientists could manipulate materials under laboratory conditions to create the beginning stages of life. Loeb’s findings made it all the way to the popular press, and many viewed him as an engineer, creator of life. Even Mark Twain, considered by some the father of American literature, and who was fascinated with science, wrote an essay titled ‘Dr. Loeb's Incredible Discovery’, with a plea to remain open to new scientific advances. In any case, Loeb did not like the press and always talked very cautiously in public.
Loeb helped transform biology into a mainly experimental science. He made seminal contributions in fields such as stem cell and cell differentiation research as well as regenerative medicine. These are fields in which the marine environment has unbeatable model research organisms to offer. He was, in many senses, a pioneer behind the life-controlling ideal that biotechnology embraces. His science philosophy was published in his 1912 book The Mechanistic Conception of Life that led to his reputation as a researcher who treated organisms as machines. Biologists, in his view, were able to explain natural phenomena only when they were able to control such phenomena. The mechanisms of such physical and chemical phenomena needed definition as the components that form an organism providing its functions, which he published in his book ‘The Organsim as a Whole’ (1916). Once he wrote that book, the moment would arrive in which humans would be defined by a mathematical equation. His commitment to explaining life in physicochemical terms drove him to research in protein chemistry during the final years of his life. Loeb died of an angina in Bermuda in February 1924. He had visited the islands for several years, engaged in research with his beloved ‘marine machines’ at the marine laboratory in Hamilton.
A very prolific author, producing more than 400 papers and books, Loeb received 78 nominations for the Nobel Prize in Physiology and Medicine, the first in 1901 and the last six in the same year as his death. He never received the distinction. Loeb was never successful in creating new forms of life either, if that was indeed his intention. However, he himself came back to life after his death. Loeb inspired the character of the scientist Max Gottlieb in the Pulitzer-winning novel Arrowsmith written by Sinclair Lewis in 1925. Lewis (who declined the Pulitzer award in 1926) had a scientific and medical advisor for the technical aspects of the fiction plot, Paul de Kruif, who was a researcher at the Rockefeller Institute and personally knew Loeb. This is considered the first great fiction story prizing scientists and science. The book was turned into a film in 1931 starring Ronald Colman and Helen Hayes, and received four Oscar nominations (yet did not win). So no prizes for Loeb, but he did win our appreciation for his search for truth through for his search for truth through experimentation, although his approach to living organisms was so ‘mechanistic’ that it deprived life of part of its charm and epic nature.