Carl and Gerty Cori: A collaboration that changed the face of biochemistry.

Carl Cori and Gerty Cori elucidated basic biochemical mechanisms involved in the utilization of energy by muscle and liver, first at Roswell Park Cancer Institute and then at Washington University. In 1929, they formulated the Cori cycle, the process by which glycogen is converted to glucose in liver and is then reconverted to glycogen in muscle. They later found that glycogen breakdown yielded glucose-1-phosphate (Cori ester) and lactate, key intermediates in the cycle; they also established that lactic acid provided the energy employed in muscle contraction. They later discovered phosphorylase, the enzyme that catalyzed glycogen breakdown. After purifiying and crystallizing muscle phosphorylase, they identified two forms of the enzyme and defined their respective roles in metabolic regulation. These studies emboldened other scientists to advance our knowledge of fundamental regulatory processes such as the adenylate cyclase-cyclic AMP system and enzyme phosphorylation. The Coris also built a world-renowned Department of Biochemistry at Washington University, which included seven future Nobelists. In 1947, the Coris were awarded the Nobel Prize, with Gerty Cori being the first American woman to win this prestigious honor.

Robert Furchgott (1916-2009): A scientist with a mission.

Robert Furchgott was first noted for research on drug-receptor theory, autonomic neuroeffector mechanisms, and vascular pharmacology/physiology. His studies on drug-receptor interactions provided important knowledge about the properties of drug receptors long before methodologies were developed to study them directly. However, Furchgott achieved an enduring legacy for recognizing the importance of endothelial cells for the relaxation of vascular smooth muscle. On the basis of his own experiments and those of others, he proposed that acetylcholine interacted with muscarinic receptors at the surface of endothelial cells to release a substance called endothelium relaxing factor. Endothelium relaxing factor was later identified as nitric oxide, a colorless, odorless gas. Furchgott's discovery of an entirely new mechanism by which blood vessels dilate revolutionized studies on the physiology of the vascular system. His work also suggested new treatments for hypertension and heart disease, and was a key factor in the development of the anti-impotence drug sildenafil. In 1998, Robert Furchgott shared the Nobel Prize in Physiology or Medicine with Ferid Murad and Louis Ignarro.

Hermann (Hugh) Blaschko (1900-1993): His fundamental contributions to biochemical pharmacology and clinical medicine.

Hermann (Hugh) Blaschko was a biochemical pharmacologist best known for discovering how adrenaline (epinephrine), noradrenaline (norepinephrine), and dopamine were synthesized, stored, and metabolized in adrenomedullary cells and sympathetic nerves. Blaschko's work not only supported the validity of the concept of neurochemical synaptic transmission but he also made fundamental contributions to the development of drugs used in clinical medicine to treat diseases such as depression, hypertension, and Parkinson's Disease.

Joshua Harold Burn (1892-1981): A visionary during the evolution of pharmacology as a biomedical discipline.

This article encapsulates the career of Joshua Burn, whose work encouraged new lines of experimentation and paved the way for fundamental advances in our knowledge of the autonomic nervous system. His legacy also endures in his efforts as Department Chairman to oversee a very supportive environment which led to the development of many successful scientists. By producing a body of work that enabled the discipline of pharmacology to contribute in a major way to the advancement of clinical medicine, Joshua Burn stands out as a unique figure in the annals of true scientific pioneers.

The enduring legacy of Alfred Gilman senior (1908-1984) to pharmacology and clinical medicine.

Alfred Gilman was best known for his co-authorship with Louis Goodman of the seminal textbook on pharmacology The Pharmacological Basis of Therapeutics in 1941. The book made the discipline of pharmacology relevant to clinical medicine by providing a link between the basic medical sciences and the practice of medicine. Gilman was also instrumental in establishing the use of chemotherapy in the treatment of cancer and made important contributions in areas related to renal function, acid-base balance, and diuretics. During the 1960s, he created a first rate department at the newly formed Albert Einstein College of Medicine. A superb lecturer, he commented incisively on issues related to pharmacology, therapeutics, and pathophysiology. Dr Gilman also provided a key link between academia and the pharmaceutical industry by serving as a consultant to several drug firms. The legacy of Alfred Gilman senior was continued by his son, Alfred Goodman Gilman, who became a Nobel Laureate.

The Vogt family: Creators of diverse paths for women in biological research.

The life and careers of Cecile, Marthe and Marguerite Vogt are chronicled in this article during an era where women were not readily accepted in the upper echelons of academia. By exploring important questions, these women made major contributions to the broad base of scientific knowledge which impacted the fields of neurobiology in both the central and peripheral nervous systems, infectious disease, and oncogenesis. As a result, each was considered the elite of her respective field and achieved an enduring legacy.

The ascension of women in the biomedical sciences during the twentieth century.

While scientists were always cognizant of the fact that they must be objective about the questions they ask of nature, there was a time when they were less willing to consider the diverse views that could be contributed by female participation. Undervalued in terms of their intellect, ambition, and curiosity, women found it difficult to compete for and/or retain a research post, particularly when they married. As a result, many women undaunted by existing convention had to work without remuneration or were financially supported by colleagues and/ or relatives. But eventually, the time became right for a change in culture-bound attitudes. The present work revisits the inestimable accomplishments of five unique women in creating a positive environment for those scientists who have succeeded them.

The evolution of the discipline of pharmacology amid an era of global turbulence: the unique contributions of Otto Krayer (1899-1982).

This article revisits the life and times of Otto Krayer, a gifted scientist, teacher and administrator. His unique contributions to the discipline of pharmacology and to the biomedical sciences are chronicled in the wake of the political upheaval that crippled German science during the 1930s. The anti-scientific attitude that pervaded Germany at the time led to the exile of Krayer and many other eminent scientists. Their fate is recounted, as well as the negative impact on science caused by a National Socialist regime that blatantly disregarded basic scientific principles. The threat of intolerance and unethical behaviour still remains a key obstacle to scientific creativity.

Role of nerve growth factor in the regulation of parotid cell differentiation induced by rat serum.

The present study was undertaken to examine the factors that regulate rat serum (RS)- and nerve growth factor (NGF)-induced differentiation in a rat parotid acinar cell line. RS elicited extracellular signal-regulated kinase (ERK1/ERK2) activation within 5min, while cyclic AMP (cAMP) levels transiently rose after 6hr. RS also elicited a rise in amylase mRNA levels within 30min, which preceded the rise in amylase protein levels. A possible role for NGF was suggested by the findings that parotid cells express both TrkA and p75 receptors. The immunoreactivity of these NGF receptors was reduced during exposure to RS. Following prolonged incubation in RS when ERK activity subsided to near basal levels, NGF restored ERK1/ERK2 activity to the elevated level initially observed in RS. NGF was ineffective when cells were incubated in fetal bovine serum. NGF, when incubated in combination with the cAMP-generating neuropeptides, calcitonin gene-related peptide and vasoactive intestinal peptide, markedly enhanced the cellular amylase content produced by RS. We conclude that parotid cell differentiation arises from an activation of cell surface receptors by humoral factors in combination with NGF and cAMP-generating neuropeptides.