Philadelphia and the Delaware Valley: A Geographically Distributed and Expanding Life Science Ecosystem

Philadelphia has been considered by many to be the birthplace of the modern US pharmaceutical industry with Merck & Co. Inc.’s research division Merck Research Labs [originally called MSDRL] based in West Point and GSK’s primary US labs [originally SKF] now based in Collegeville. The City of Philadelphia is also home to two of the oldest medical schools in the US: Perelman School of Medicine at the University of Pennsylvania founded in 1765 and the Sydney Kimmel Medical College [formerly Jefferson Medical College] founded in 1824. The conjunction of those two touchpoints along with the other big pharma players, e.g., Johnson & Johnson/Janssen and emerging biotech entities in the wider Delaware Valley region is significant. Also noteworthy is the presence of other research intensive universities such as Drexel University, Temple University, Jefferson University and research institutes such as the Wistar Institute, Fox Chase Cancer Center [associated with Temple University School of Medicine], Lankenau Institute, Monell Chemical Senses Center and the Coriell Institute in Southern New Jersey.

A história do rato de laboratório: do ódio ao amor

ResumoO rato está na base de importantes descobertas na área da medicina. Contudo, nem sempre foi bem visto pela sociedade. No século XIV abateu-se sobre a Europa uma pandemia, a Peste Negra, causada por uma bactéria (Yersinia pestis) transmitida ao Homem por uma pulga (Xenopsylla cheopis), cujo hospedeiro era o rato (Rattus rattus). Esta doença vitimou aproximadamente 150 milhões de pessoas. Estava-se longe de imaginar o contributo que o rato viria a ter na saúde humana.No século XVII o rato proliferou descontroladamente, surgindo uma nova profissão: os caçadores de ratos. Estes indivíduos ganhavam dinheiro com a captura e venda destes animais para alimentação. Nessa época apareceu um desporto novo e as apostas a ele associadas: as lutas de ratos. Como resultado desse desporto, aumentaram os acasalamentos consanguíneos e surgiram variações na pelagem do rato, aparecendo os primeiros ratos albinos. Em 1828 foram utilizados os primeiros ratos albinos num ensaio experimental sobre o estudo do efeito do jejum. Mais tarde, em 1906, no Instituto Wistar, Helen Dean King desenvolveu uma estirpe a partir dos ratos albinos, designada de Wistar, para uso na investigação biomédica.Ainda no século XX o uso do rato de laboratório alargou-se a estudos de aprendizagem em labirinto, nutrição, reprodução, genética e cancro, e consequentemente mais estirpes de animais foram desenvolvidas, passando a existir empresas com o propósito de os vender para investigação. A importância desta espécie pode comprovar-se pela análise do número de artigos publicados anualmente com recurso à sua utilização. Neste trabalho apresenta-se uma revisão histórica do uso do rato na investigação, evidenciando-se as caraterísticas que fizeram deste animal um modelo único na pesquisa biomédica. Palavras-chave: Investigação, Peste Negra, Rattus rattus, Wistar Abstract The rat is the basis of important findings in Medicine. However, it was not always well-seen by the society. In the 14th century, the Europe was affected by a pandemic disease, Black Pestis, caused by a bacterium (Yersinia pestis) transmitted to the Man by a flea (Xenopsylla cheopis), whose host was the rat (Rattus rattus). This disease victimized approximately 150 million people. It was far from imaging the contribution that the rat would have for human health. In the 17th century, the rat proliferated wildly, emerging a new job: the rat hunters. These people earnt money with the capture and selling of these animals for food. At that time appeared a new sport and the bets associated to it: the rat fights. Because of this new hobby, the consanguineous mating increased and appeared variations on rat coat, appearing the first albino rats. In 1828 the albino rats were used by the first time in an experimental assay about the fasting effects. Later, in 1906, in the Wistar Institute, Helen Dean King developed a strain from albino rats, called Wistar, for use in biomedical research. Still in the 20th century, the use of laboratory rats was expanded to studies of learning, nutrition, reproduction, genetics and cancer, and consequently more strains were developed by companies with the purpose to sell them for research. The importance of this specie may be evidenced by the analysis of the number of scientific works published annually using it. In this work, a historical review of the use of the rat in the investigation is provided, evidencing the characteristics that made it a unique model in biomedical research. Keywords: Black Pestis, Investigation, Rattus rattus, Wistar

Commercial Rodents in America: Standard Animals, Model Animals, and Biological Diversity

Rodents as standardized test animals were developed for commercial distribution in the USA between 1910 and the 1930s. The selective breeding of rats (Rattus norvegicus) and pure-bred mice (Mus musculus) at the Wistar Institute and the Jackson Memorial Laboratories eventually led to a decline in the diversity of species used in American medical and life sciences. The early driving figures, science administrator Milton Greenman and the scientists Henry Donaldson and Clarence Little, sought to standardize animals to render science and its application to humanity more precise. But their efforts were exaggerated in the USA through an expanding industrial and engineering ideal, culminating in a preference for Big Science. I explore the nineteenth century origins of this ideal in Emil Du Bois-Reymond’s neurophysiology. This foundation later merged with increasing standardization, American commercialism, and the success of Big Science to transform animal laboratory “standards” into “model animals.” Recent accounts of research with commercially bred mice reveal how findings can be co-constructed using human clinical data, as animal research is applied to humans. The neglect of evolutionary perspectives and the dominance of “models” may even have begun with the government’s post-war emphasis on funding greater species access for large-scale biomedical research.

17β-Estradiol Stimulates Arachidonate Release from Human Amnion-Like WISH Cells through a Rapid Mechanism Involving a Membrane Receptor

17β-Estradiol (17β-E2) greatly and dose-dependently stimulates [3H]arachidonic acid (AA) release from the human amnion-like Wistar Institute Susan Hayflick (WISH) cells. This action is abolished by the phospholipase A2 inhibitor AACOCF3, significantly reduced by the estrogen receptor (ER) antagonist ICI 182,780, and uninfluenced by cycloheximide. The estradiol-BSA conjugate E2coBSA, which binds putative membrane ERs and is unable to enter the cell, also highly stimulates [3H]AA release from WISH cells, although to a lesser extent compared with 17β-E2. The fluorescent conjugate E2coBSA-FITC specifically binds to the surface of a subset of intact WISH cells, and labeling intensity appears dose and time dependent. Cell permeabilization results in a dense intracellular staining, mainly in the peripheral cytoplasm. H-150, an antibody against the N terminus of human ERβ, also labels the plasma membrane of intact WISH cells and the cytoplasm of permeabilized cells. Almost no labeling is observed using ER-21, an antibody against the N terminus of human ERα. RT-PCR evidences the presence of mRNA for ERβ, not for ERα. Our data suggest that 17β-E2 stimulates [3H]AA release from WISH cells through an apparently nongenomic pathway and interaction with membrane binding sites. These last are, at least in part, similar if not identical to ERβ.

Hypotheses and facts

The book, The river , is based on assumptions and not facts. Oral polio vaccine was produced entirely in rhesus monkey kidney cell cultures. Allegations that it was produced in chimpanzee kidneys at the Wistar Institute in Philadelphia or, alternatively, that the vaccine was made in the then Belgian Congo in chimpanzee kidney has no basis in fact. As the only witness to the historical events leading to the development of oral polio vaccine, I have demonstrated in this paper the truthful facts excluding any link between oral polio vaccine and human immunodeficiency virus.