"The Logic of Monsters:" Pere Alberch and the Evolutionary Significance of Experimental Teratology.

This paper offers an historical introduction to Pere Alberch's evolutionary thought and his contributions to Evo-Devo, based on his unique approach to experimental teratology. We will take as our point of reference the teratogenic experiments developed by Alberch and Emily A. Gale during the 1980s, aimed at producing monstrous variants of frogs and salamanders. We will analyze his interpretation of the results of these experiments within the framework of the emergence of evolutionary developmental biology (or "Evo-Devo"). The aim is understand how Alberch interpreted teratological anomalies as highly revealing objects of study for understanding the development of organic form, not only in an ontogenetic sense-throughout embryonic development-but also phylogenetically-throughout the evolution of species. Alberch's interpretation of monsters reflects the influence of a long tradition of non-Darwinian evolutionary thought, which began in the nineteenth century and was continued in the twentieth century by people such as Richard Goldschmidt, Conrad H. Waddington, and Stephen Jay Gould. They all proposed various non-gradualist models of evolution, in which embryonic development played a central role. Following this tradition, Alberch argued that, in order to attain a correct understanding of the role of embryological development in evolution, it was necessary to renounce the gradualist paradigm associated with the Darwinian interpretation of evolution, which understood nature as a continuum. According to Alberch, the study of monstrous abnormalities was of great value in understanding how certain epigenetic restrictions in development could give rise to discontinuities and directionality in morphological transformations throughout evolution.

History and highlights of the teratological collection in the Museum Anatomicum of Leiden University, The Netherlands.

The anatomical collection of the Anatomical Museum of Leiden University Medical Center (historically referred to as Museum Anatomicum Academiae Lugduno-Batavae) houses and maintains more than 13,000 unique anatomical, pathological and zoological specimens, and include the oldest teratological specimens of The Netherlands. Throughout four centuries hundreds of teratological specimens were acquired by more than a dozen collectors. Due to the rich history of this vast collection, teratological specimens can be investigated in a unique retrospective sight going back almost four centuries. The entire 19th century collection was described in full detail by Eduard Sandifort (1742-1814) and his son Gerard Sandifort (1779-1848). Efforts were made to re-describe, re-diagnose and re-categorize all present human teratological specimens, and to match them with historical descriptions. In the extant collection a total of 642 human teratological specimens were identified, including exceptional conditions such as faciocranioschisis and conjoined twins discordant for cyclopia, and sirenomelia. Both father and son Sandifort differed in their opinion regarding the causative explanation of congenital anomalies. Whereas, their contemporaries Wouter Van Doeveren (1730-1783) and Andreas Bonn (1738-1817) both presented an interesting view on how congenital anomalies were perceived and explained during the 18th and 19th centuries; the golden age of descriptive teratology. Although this enormous collection is almost 400 years old, it still impresses scientists, (bio)medical students, and laymen visiting and exploring the collections of the Museum Anatomicum in Leiden, The Netherlands.

Thomas H. Shepard, M.D., pioneer in embryology and teratology.

Dr. Thomas H. Shepard died on October 3, 2016 at the age of 93. He was a major figure in the fields of teratology, embryonic and fetal pathology, and pediatrics. He was beloved by his colleagues as he was by the many students and fellows whom he taught, mentored and befriended. His contributions to teratology are extraordinary and he is greatly missed. © 2017 Wiley Periodicals, Inc.

Teratology on the crossroads: historical aspects and modern approaches.

Teratology is the science of congenital developmental disorders (CDDs), overt or latent defects of the organism resulting from the effect of internal and external factors on developmental processes. In this article the significance and position of present-day teratology is discussed in the context of development of this branch of science and related disciplines. The authors present an updated overview of the most important milestones and stages of the development of teratology. Based on the analysis of the historical development of theses and theories that represent a decisive contribution to this field, we present a survey of the fundamental principles of experimental and clinical teratology. The aim of observing these principles is to get insight into developmental relations and to understand mechanisms of action on the level of cell populations (elementary morphogenetic processes), tissues and organs. It is important to realize that any negative intervention into the normal course of these processes, either on genetic or non-genetic basis, inevitably leads to a sequence of subsequent changes resulting in the development of congenital developmental disorders. Despite modern approaches of molecular biology and genetics, along with top diagnostic techniques, we are still not able to identify the actual cause in more than 50% of all congenital defects. One-half of the unidentified cases are referred to as "multifactorial", a term that is rather ambiguous. It either means that some of the basic principles of teratogenesis still escape our attention, or the interpretation of some of the well known principles might be misleading. A third possibility is rather pessimistic. The development of the individual is so sophisticated and dependent on a delicate network of a multitude of factors mutually affecting each other that it is extremely prone to give rise to a plethora of spontaneous errors which are unpredictable and impossible to prevent. Nevertheless, the long and complicated history of scientific endeavour has yielded considerable present-day knowledge on causes and mechanisms of CDDs, a history whose beginnings date back to antiquity.

[Wouter van Doeveren (1730-1783) professor of practical medicine, obstetrics and pathology]. / Wouter van Doeveren (1730-1783) professeur de médecine pratique, d'obstétrique et d'anatomie pathologique.

Between September 1752 and July 1753, Wouter van Doeveren, a student of Gaubius, Albinus and Winter at Leyden University, studied, together with a couple of friends at various Paris hospitals in order to improve his skills in the fields of surgery and obstetrics. After his return to Leyden, he took his doctor's degree in medicine and started his practice in that town. In 1754 he was appointed professor of medicine at Groningen University. In 1770 he was appointed professor of theoretical and practical medicine at Leyden University. He held that office until his death on 31 December 1783. He was a most appreciated foreign member of the Société Royale de Médecine (Paris) and of the Royal Society of Medicine (Edinburgh). He succeeded in improving his medical skills, by doing thorough research in the fields of pathological anatomy and teratology. He laid the foundations for national healthcare regulations for the United Provinces.

In honor of the Teratology Society's 50th anniversary: The role of Teratology Society members in the development and evolution of in vivo developmental toxicity test guidelines.

Members of the Teratology Society (established in 1960) were involved in the first governmental developmental and reproductive toxicity testing guidelines (1966) by FDA following the thalidomide epidemic, followed by other national and international governmental testing guidelines. The Segment II (developmental toxicity) study design, described in rodents and rabbits, has evolved with additional enhanced endpoints and better descriptions, mechanistic insights, range-finding studies, and toxico/pharmacokinetic ADME information (especially for pharmaceuticals). Society members were also involved in the development of the current screening assays and tests for endocrine disruptors (beginning in 1996) and are now involved with developing new testing guidelines (e.g., the extended one-generation protocol), and evaluating the current test guidelines and new initiatives under ILSI/HESI sponsorship. New initiatives include ToxCast from the U.S. EPA to screen, prioritize, and predict toxic chemicals by high throughput and high-content in vitro assays, bioinformation, and modeling to reduce (or eliminate) in vivo whole animal studies. Our Society and its journal have played vital roles in the scientific and regulatory accomplishments in birth defects research over the past 50 years and will continue to do so in the future. Happy 50th anniversary!

Holoprosencephaly: A mythologic and teratologic distillate.

This review of holoprosencephaly provides a mythologic and teratologic distillate of the subject under the following headings: Babylonian tablets; Greek mythology; pictures from the 16th through the 20th Centuries; 19th Century teratology; history of more modern concepts and their terminologies; and ocean-going ships named "Cyclops."

The principles of teratology: are they still true?

James Wilson originally proposed a set of "Principles of Teratology" in 1959, the year before he helped to found the Teratology Society. By 1977, when these Principles were presented in a more definitive form in Wilson and Fraser's Handbook of Teratology, they had become a standard formulation of the basic tenets of the field. Wilson's Principles have continued to guide scientific research in teratology, and they are widely used in teaching. Recent advances in our knowledge of the molecular and cellular bases of embryogenesis serve only to provide a deeper understanding of the fundamental developmental mechanisms that underlie Wilson's Principles of Teratology.

The neurobehavioral teratology of retinoids: a 50-year history.

This review of the central nervous system (CNS) and behavioral teratology of the retinoids over the last 50 years is a commemorative retrospective organized by decade to show the prominent research focus within each period and the most salient findings. In the 1960s, research focused on the gross CNS malformations associated with exposure and the delineation of dose-response and stage-specific responses in rodent models. Relevant scientific events before and during the 1960s are also discussed to provide the zeitgeist in which the field of neurobehavioral teratology emerged in the 1970s. During this period, studies demonstrated that adverse effects on postnatal behavior could be produced in animals exposed to doses of vitamin A lower than those that were teratogenic or impacted growth. Work during the 1980s showed an overrepresentation of behavioral studies focused on the reliability of screening methods, while the marked effects of human exposure were illustrated in children born to women treated with isotretinoin during pregnancy. The human catastrophe invigorated research during the 1990s, a period when technological advances allowed more elegant examinations of the developing CNS, of biochemical, cellular, and molecular developmental events and regulatory actions, and of the effects of direct genetic manipulations. Likewise, research in the 1990s reflected a reinvigoration of research in neurobehavioral teratology evinced in studies that used animal models to try to better understand human vulnerability. These foci continued in the 2000-2010 period while examinations of the role of retinoids in brain development and lifelong functioning became increasingly sophisticated and broader in scope. This review of the work on retinoids also provides a lens on the more general ontogeny of the field of neurobehavioral teratology. Birth Defects Research (Part A), 2010. © 2010 Wiley-Liss, Inc.

The arrogance of teratology: A brief chronology of attitudes throughout history.

While the discipline of Teratology has existed for about 60 years, there has been a deep interest in the causes of human malformations for millennia. Absent the scientific method and acting on fervent beliefs that made sense to ancient/medieval populations, "mechanisms" were described and prognostications of future events were assigned to terata resulting in tragic (and unwarranted) sequelae. This article examines the collective beliefs and thinking within various eras in the hope of providing lessons to inform future behavior. The eugenics movement is an informative, recent example. Science of the 19th century had unraveled some of the mysteries of development and the role of genetics in determining birth outcomes. There was, however, a deep misunderstanding about the enormous amount of information that had yet to be uncovered. Based on immature science and faulty assumptions, it was suggested that "unfit" individuals be euthanized and their parents sterilized. Such "solutions" would be considered deplorable today. Surprisingly, such a reprehensible program was supported (at least in part) by many intelligent and highly regarded individuals. Today, it is imperative that we enter into the era of molecular biology and gene editing cautiously and perspicaciously. The history of teratology has elucidated our inability to understand where our new technologies and actions might take us and how unintended consequences could disrupt even our most carefully thought-out plans.

A hitchhiker's guide to the older literature of descriptive teratology.

Though relatively neglected in the age of molecular biology, the older literature of teratology includes superb illustrations and descriptions of malformations, and other information of permanent value to science and medicine. Accessing that literature can be challenging, as most is in works that are rare, published in languages other than English, and not available in digital form. This article describes some valuable sources of information concerning the antiquarian literature of descriptive teratology.

Blind ambition: Geoffroy St-Hilaire's theory of everything.

When Napoléon Bonaparte invaded Egypt in 1798, he took with him a group of savants to study the natural history, architecture, ancient history and society of Egypt. One young naturalist, Etienne Geoffroy Saint-Hilaire, went along and made his mark in the study of living and mummified animals, setting the course for his future successes and fame when he returned to Paris in 1801. But during his time in Egypt, when he was free to roam physically and intellectually, he formulated a radical, all-encompassing theory, which he claimed could explain all natural forces and processes in the world.

L'Ecole de Nogent: the contributions of Etienne Wolff and Nicole Le Douarin.

We retrace here the foundation of the "Nogent School". What were its main scientific orientations? Two fields of research dominated Etienne Wolff's work: Experimental Teratology and Intersexuality. Nicole Le Douarin's work , in one sense, started with a remarkable tool which is the quail / chick marker system. She applied this system to the study of in vivo migration of cells during embryonic life, i.e.neural crest cells and lymphoid progenitors. This article revisits some of these fundamental aspects.