From Darkness to Light

Not so long ago I happened to treat a Jewish eighth-grade gymnasium student brought to Petrograd from a province. It was fall and the following spring he was to take his qualifying examinations. The young man, who belonged to a prosperous family, had brilliant abilities and graduated from each class with excellent grades—what would you think his illness was? He suffered—in his own words—from the throes of creative writing. Days and nights he poured over a notebook with his compositions in search of the best form to express his thoughts. Only after applying incredible efforts could one tear him away from his note-books and send him to bed at five or six o'clock in the morning, and this happened on a daily basis. With each day his mental health grew worse. It was clear that the young man undermined his health by overstudying, and that he had reached the point where he needed to worry about his health, not his studies, because a serious mental illness was descending upon him. The young man was well liked by everyone in his high-school. The teachers considered him the best student, and having learned about his illness, they promised to petition to grant him the right to graduate from school without the final examination and with a certificate of excellent. But none of that helped. The young man could not relax, spending days and nights over his compositions and constantly tormenting himself with his "throes of creative writing."     

Hans Zinsser: a tale of two cultures

Hans Zinsser, president of the Society of American Bacteriologists in 1926, was known as much for his literary and textbook writing as for his scientific contributions. He was a widely known scientist and person of letters. His early interests in poetry and other forms of literature were maintained and developed during his career as a microbiologist, and his most enduring legacy is based on his writing about microbiology for a general readership as well as his reflective and philosophical autobiography.     

Osler and the Jewish people

In his writings and actions, Sir William Osler betrayed no evidence of anti-Semitism. In his era, this trait was unusual. Two of his articles, "Letter from Berlin" and "Israel and medicine," dealt directly with his thoughts on the Jewish people. In both he spoke out against anti-Semitism. Osler had friendships with Jewish colleagues--an example is the great regard in which he held US pediatrician Dr. Abraham Jacobi. Osler was not a saint, and he had his "rough side," but in his relationships with Jewish colleagues his example remains relevant.     

pMB9 plasmids bearing the Salmonella typhimurium his operon and gnd gene

A plasmid containing the entire Salmonella typhimurium his operon was constructed from plasmid pM89 and an EcoRI fragment of phi 80 his imm lambda DNA. The recombinant pST41 also includes the glucose 6-phosphate dehydrogenase (gnd) gene and has one EcoRI endonuclease cleavage site in the integrated fragment. This plasmid served as a source for the construction of two additional plasmids, one carrying the OGDC-region of the his operon and the other a CBHAFIE segment of the his gene along with the gnd gene. The presence of the his operon in the constructed plasmids was confirmed by hybridization to S. typhimurium his RNA. The location of the gnd gene in the CBHAFIE fragment of the his gene was confirmed genetically: after transfection with the plasmid bearing the gnd gene, a gnd recipient gained the capacity to utilize gluconate as a sole carbon source. The DNAs of the three hybrid plasmids were analyzed by gel electrophoresis. By comparing the EcoRI endonuclease cleavage pattern of these three hybrid plasmids with the DNA cleavage pattern of phi 80 his imm lambda, phi 80 imm lambda and lambda phages, the EcoRI cleavage map of phi 80 his imm lambda was obtained.     

Philip R. White (1901–1968)—a tribute

The groundbreaking research carried out by Philip R. White in the 1930s and 1940s played a critical early role in the development of modern plant biotechnology and the production of biotech crops. He gained instant fame and became a historical figure early in his career by becoming the first person to attain unlimited growth of cultured plant tissues. White was one of the best known and most influential figures of his generation in plant cell culture research. His tireless and lifelong efforts to promote the use of plant cell culture systems inspired a generation of scientists and stimulated much scientific activity. White was not only a brilliant and visionary scientist but also a highly principled man who spoke courageously about the great moral and political issues of his day. He was admired as much for his science as for his humanity. His belief that plant cell culture research was not well represented at national and international meetings, and his deeply held conviction that science had to be international and without borders in order to be of service to humankind led to the founding of the International Association for Plant Biotechnology in 1963, currently the largest forum for the international plant biotechnology community. This tribute honors and celebrates Philip R. White for his inspiring science, for his kind and generous mentoring of young scientists, for his advocacy of plant cell culture research and its applications, for his promotion of international scientific exchange and cooperation, and for his leadership in the founding of the International Association for Plant Biotechnology.     

The Philosophical Origins of Mitchell's Chemiosmotic Concepts

Mitchell's formulation of the chemiosmotic theory of oxidative phosphorylation in 1961 lacked any experimental support for its three central postulates. The path by which Mitchell reached this theory is explored. A major factor was the role of Mitchell's philosophical system conceived in his student days at Cambridge. This system appears to have become a tacit influence on his work in the sense that Polanyi understood all knowledge to be generated by an interaction between tacit and explicit knowing. Early in his life Mitchell had evolved a simple philosophy based on fluctoids, fluctids and statids which was developed in a thesis submitted for the z at the University of Cambridge, England. This aspect of his work was rejected by the examiners and became a tacit element in his intellectual development. It is argued from his various publications that this philosophy can be traced as an underlying theme behind much of Mitchell's theoretical writing in the 50's leading, through his notion of vectorial metabolism, to the formulation and amplification of the chemiosmotic theory in the sixties. This philosophy formed the basis for Mitchell of his understanding of biological systems and gave him his unique approach to cell biology. This revised version was published online in July 2006 with corrections to the Cover Date.     

Interactions among adult males and females before and after the death of the alpha male in a free-ranging troop of Japanese macaques

This report documents the social interactions among adult Japanese macaques in a free-ranging troop before and after the death of the alpha male, who died at 28 years of age after occupying his rank position for 17 years. The alpha male’s physical condition had deteriorated due to his extreme age for several months before his death. However, he maintained his alpha position. When he was attacked by the second-ranking adult male, he was rescued by the alpha female. Thereafter, whenever the second-ranking male approached him, the alpha male screamed for the alpha female’s support. The number of adult females to whom the alpha male maintained proximity during his last four months was similar to that during the same period of the previous year. Prior to his death, the alpha male was observed in close proximity to the alpha female much more frequently than was the second-ranking male. These results indicate that the alpha male maintained his position by depending on female support and particularly that of the alpha female.     

Endocrine and developmental correlates of unilateral cryptorchidism in a wild baboon

A wild, group-living 8.5-year-old adult baboon was found to have only a single palpable testicle, the only case of cryptorchidism found among more than 200 males that we have examined. This young adult had an unusually small body size for his age, one that was comparable to that of immature males two years younger, and during maturation his body mass was increasingly small for his age. As a young adult, he also had very low testosterone concentrations, which, in combination with his small size, history of impaired growth, and the absence of any obvious scars around the scrotum, suggest that this is a case of spontaneous unilateral cryptorchidism of unknown cause rather than one of monorchidism arising from injury. Despite striking differences in his growth, adult body size, and testosterone levels, the male's cryptorchidism seemed to have relatively little effect on his social and sexual maturation in his natal group. Nonetheless, it may be related to his inability to gain entry into another group after dispersal.     

Treatment with a dietary fat substitute decreased Arochlor 1254 contamination in an obese diabetic male

A case manifesting symptoms due to organochlorine toxicity was treated with the fat substitute olestra in his diet. Before treatment, the patient was obese, with severe type 2 diabetes mellitus and mixed hyperlipidemia, chloracne, frequent headaches, and numbness and paraesthesias of his trunk and lower limbs. Earlier attempts at weight loss had been unsuccessful due to worsening of his symptoms. After inclusion of olestra in his diet for 2 years, weight loss was successful without aggravation of his symptoms, and the patient reverted to normoglycemia and normolipidemia. Olestra may have assisted weight loss and amelioration of his diabetes by increasing fecal elimination of organochlorines, rather than by preventing the partitioning of these pollutants into tissues, where they have been reported to exert antimetabolic effects on substrate oxidation.     

Pavlov and integrative physiology

Ivan Petrovich Pavlov was the first physiologist to win the Nobel Prize. The Prize was given in 1904 for his research on the neural control of salivary, gastric, and pancreatic secretion. A major reason for the success and novelty of his research was the use of unanesthetized dogs surgically prepared with chronic fistulas or gastric pouches that permitted repeated experiments in the same animal for months. Pavlov invented this chronic method because of the limitations he perceived in the use of acute anesthetized animals for investigating physiological systems. By introducing the chronic method and by showing its experimental advantages, Pavlov founded modern integrative physiology. This paper reviews Pavlov's journey from his birthplace in a provincial village in Russia to Stockholm to receive the Prize. It begins with childhood influences, describes his training and mentors, summarizes the major points of his research by reviewing his book Lectures on the Work of the Digestive Glands, and discusses his views on the relationship between physiology and medicine.     

Abraham Flexner and the development of the Yale School of Medicine

Abraham Flexner first toured the Yale University School of Medicine in preparation for his report of 1910, but it was just the beginning of his relationship with the school. While his review of Yale in his report was generally favorable, he mentioned several shortfalls that needed to be improved to make the school acceptable. Throughout the next twenty-five years, Flexner worked with Deans George Blumer and Milton C. Winternitz to improve the school's finances, infrastructure, and quality of education through his work with the Carnegie Foundation and General Education Board Flexner has been given great accolades for his work on medical education for the country, but little mention is made of him at Yale, even though he was one of the most influential figures in the development of Yale in the last century.     

Abraham Flexner and the development of the Yale School of Medicine. 1999

Abraham Flexner first toured the Yale University School of Medicine in preparation for his report of 1910, but it was just the beginning of his relationship with the school. While his review of Yale in his report was generally favorable, he mentioned several shortfalls that needed to be improved to make the school acceptable. Throughout the next twenty-five years, Flexner worked with Deans George Blumer and Milton C. Winternitz to improve the school's finances, infrastructure, and quality of education through his work with the Carnegie Foundation and General Education Board. Flexner has been given great accolades for his work on medical education for the country, but little mention is made of him at Yale, even though he was one of the most influential figures in the development of Yale in the last century.     

Diversity of the trifunctional histidine biosynthesis gene (his) in cereal Phaeosphaeria species.

Phaeosphaeria species are important causal agents of Stagonospora leaf blotch diseases in cereals. In this study, the nucleotide sequence and deduced polypeptide of the trifunctional histidine biosynthesis gene (his) are used to investigate the phylogenetic relationships and provide molecular identification among cereal Phaeosphaeria species. The full-length sequences of the his gene were obtained by PCR amplification and compared among cereal Phaeosphaeria species. The coding sequence of the his gene in wheat-biotype P. nodorum (PN-w) was 2697 bp. The his genes in barley-biotype P. nodorum (PN-b), two P. avenaria f. sp. triticea isolates (homothallic Pat1 and Pat3), and Phaeosphaeria species from Polish rye and dallis grass were 2694 bp. The his gene in heterothallic isolate Pat2, however, was 2693 bp because the intron had one fewer base. In P. avenaria f. sp. avenaria (Paa), the his gene was only 2670 bp long. The differences in the size of the his gene contributed to the variation in amino acid sequences in the gap region located between the phosphoribosyl-ATP pyrophosphohydrolase and histidinol dehydrogenase sub-domains. Based on nucleotide and deduced amino acid sequences of the his gene, Pat1 was not closely related to either PN-w or the Paa clade. It appears that rates of evolution of the his gene were fast in cereal Phaeosphaeria species. The possible involvement of meiotic recombination in genetic diversity of the his gene in P. nodorum is discussed.     

From molecules to the biosphere: Nikolai V. Timoféeff-Ressovsky’s (1900–1981) research program within a totalitarian landscape

Nikolai Vladimirovich Timoféeff-Ressovsky was one of the key figures in the Synthetic Theory of Evolution. Living and researching under what was arguably the two most powerful and cruel totalitarian regimes in human history, the Third Reich and the Soviet Union, Timoféeff-Ressovsky succeeded in developing an ambitious research program aiming to explain evolution on all major levels, from the molecular-genetic, the populational, and the biogeocenotic to the level of the entire Biosphere. Yet his scientific biography remains largely unwritten and his role under totalitarianism, especially in Nazi Germany, remains highly controversial. Here we approach the problem of his hypothetical cooperation with Nazi authorities examining both the crucial episodes of his biography and summarizing the development of his research program. We conclude that the key decisions he made reflected the specificity of his research program that was focused on the fundamental questions of evolutionary biology.     

The genius of Wilhelm Hofmeister: the origin of causal-analytical research in plant development

Friederich Wilhelm Benedikt Hofmeister (1824-1877) stands as one of the true giants in the history of biology and belongs in the same pantheon as Darwin and Mendel. Yet by comparison, he is virtually unknown. If he is known at all, it is for his early work on flowering plant embryology and his ground-breaking discovery of the alternation of generations in plants, which he published at age 27 in 1851. Remarkable as the latter study was, it was but a prelude to the more fundamental contributions he was to make in the study of plant growth and development expressed in his books on plant cell biology (Die Lehre von der Pfanzenzelle, 1867) and plant morphology (Allgemeine Morphologie der Gewächse, 1868). In this article we review his remarkable life and career, highlighting the fact that his scientific accomplishments were based largely on self-education in all areas of biology, physics, and chemistry. We describe his research accomplishments, including his early embryological studies and their influence on Mendel's genetic studies as well as his elucidation of the alternation of generations, and we review in detail his cell biology and morphology books. It is in the latter two works that Hofmeister the experimentalist and biophysicist is most manifest. Not only did Hofmeister explore the mechanisms of cytoplasmic streaming, plant morphogenesis, and the effects of gravity and light on their development, but in each instance he developed a biophysical model to integrate and interpret his wealth of observational and experimental data. Because of the lack of attention to the cell and morphology books, Hofmeister's true genius has not been recognized. After studying several evaluations of Hofmeister by contemporary and later workers, we conclude that his reputation became eclipsed because he was so far ahead of his contemporaries that no one could understand or appreciate his work. In addition, his basically organismic framework was out of step with the more reductionistic cytogenetic work that later came in vogue. We suggest that the translation of the cell and morphology books in English would help re-establish him as one of the most notable scientists in the history of plant biology.     

Elihu Yale and the medicine he promoted: the government general hospital and Madras Medical College, India

Much has been written about the philanthropist Elihu Yale and his life in the Americas and England, where he spent his beginnings and end. Less publicized is his life in India, where he spent the majority of his adult life and where he raised his family. A major contribution of Elihu Yale to medicine in India was his promotion of a local hospital in the major Indian trading port city of Madras. This essay briefly describes the history of that hospital and the medical college that grew out of it.     

Sir William Osler revisited.

The basis of Sir William Osler''s fame is elusive to almost all and the appropriateness of such recognition is questioned by many. His many contributions as a practitioner, teacher, writer, and scientist in medicine do not adequately explain his prominence 60 years following his death. It was his participation in the covenant of medicine and the special components of that relationship that may account for his hold on his followers today.     

Bradycardiac Angina: Haemodynamic Aspects and Treatment

A patient with a sinus bradycardia and angina is described who was unable to increase his heart rate on vigorous exercise by more than a few beats. His severe angina was attributed to the bradycardia. Atrial pacing of his heart abolished his angina and increased his exercise tolerance. Circulatory changes at rest, on exertion, and with atrial pacing are described. The cause of angina in this patient is discussed.     

Hugh Ross's curious lymphocyte experiments

It is now almost 100 years since Hugh Campbell Ross began his experiments on white blood cells and cancer. By suspending peripheral blood cells in a solution of agar gel, he was able to observe changes in them provoked by various natural and artificial substances, which he named auxetics, kinetics, or augmentors, depending on the effects they produced. After his early experience he focused his attention particularly on lymphocytes in peripheral blood samples; he claimed to have observed rapid division in them, although at that time they were looked upon as end cells without a future. He contended that his results challenged what had become the orthodox view of the role of the nucleus in mitosis, asserting that cytologists had been led astray by relying on examination of fixed, dead structures. When doubt was cast on his claim to have induced cell division, his brother Ronald, Nobel laureate in physiology or medicine, came to his defense, but to no avail, and although he continued his experiments for a number of years they were quietly forgotten. Fifty years later the occurrence of mitotic division of peripheral blood lymphocytes was established beyond any doubt by Nowell and Hirschhorn.