Basal medium development for serum-free culture: a historical perspective

The evolution of basal synthetic formulations to support mammalian cell culture applications has been facilitated by the contributions of many investigators. Definition of minimally-required nutrient categories by Harry Eagle in the 1950's spawned an iterative process of continuous modification and refinement of the exogenous environment to cultivate new cell types and to support emerging applications of cultured mammalian cells. Key historical elements are traced, leading to the development of high potency, basal nutrient formulations capable of sustaining serum-free proliferation and biological production. Emerging techniques for alimentation of fed batch and continuous perfusion bioreactors, using partial nutrient concentrates deduced from spent medium analysis, can enhance medium utilization and bioreactor productivity.     

The Tinel sign: a historical perspective

The Tinel sign is one of the most well-known and widely used clinical diagnostic tools in medicine. Aside from Jules Tinel, after whom the sign is named, several authors have described the famous "tingling" sign seen in regenerating injured nerves. In fact, Tinel was not the first to present the sign to the scientific community. The clinical value and utility of the Tinel sign have remained in question since its introduction; many may misinterpret the sign as a prelude to complete functional recovery of injured nerves, when in fact it only signals the progress of nerve regeneration. Today the Tinel sign is widely associated with the diagnosis of carpal tunnel syndrome and in the evaluation of regenerating peripherally injured nerves. Knowledge of the history and misconceptions surrounding the sign provides clinicians today with a greater appreciation of current debates on the use of the Tinel sign.     

Somatostatin: a historical perspective

Following the discovery and biochemical characterization of natural somatostatin its action profile has been thoroughly investigated. Although the name somatostatin was coined in virtue of its growth hormone release-inhibiting properties, a number of central and peripheral endocrine and paracrine actions have been ascribed to this peptide. Its inhibitory effect on a series of pituitary and gastrointestinal hormones has characterized somatostatin as a classical brain-gut hormone. Circulating and tissue levels of somatostatin and its possible physiological role are analyzed and clinical implications are drawn.     

The impact of cell culture on stem cell research

Induced pluripotent stem cell research has broadened possibilities for regenerative medicine and captured the world's attention in a way that science rarely does. However, clinical applications utilizing cultured stem cells have existed for >30 years and can assist benchers and bedsiders in identifying and expediting promising avenues for future therapies.     

The acceptability of continuous cell lines: A personal & historical perspective

In the 1950s, only primary cell cultures were acceptable for the production of human biological products. This position was challenged in the late 1960s by human diploid cells (HDCs), and again in the 1980s by continuous cell lines (CCLs). The history of the HDC controversy is reviewed and lessons from that era that are relevant to the use of CCLs are pointed out. It became apparent in the early days of recombinant DNA technology in the 1980s that CCLs were needed for the development of some products. CCL acceptability therefore became more urgent, and several attempts were made to reach a consensus on regulatory issues. In 1986, the World Health Organization convened a Study Group to review the safety issues related to products derived from CCLs. The Study Group made a clear recommendation to pursue CCLs in product development because of the demonstrated capability of modern manufacturing processes to cope with contaminants. Issues such as acceptable levels of cellular DNA in products and the relationship of purity to safety are discussed in the context of the need for regulatory authorities, industry, and the general biomedical community to cooperate in addressing problems in a rational scientific manner.     

Neutral theory: a historical perspective

To resolve a panselectionist paradox, the population geneticist Kimura invented a neutral theory, where each gene is equally likely to enter the next generation whatever its allelic type. To learn what could be explained without invoking Darwinian adaptive divergence, Hubbell devised a similar neutral theory for forest ecology, assuming each tree is equally likely to reproduce whatever its species. In both theories, some predictions worked; neither theory proved universally true. Simple assumptions allow neutral theorists to treat many subjects still immune to more realistic theory. Ecologists exploit far fewer of these possibilities than population geneticists, focussing instead on species abundance distributions, where their predictions work best, but most closely match non-neutral predictions. Neutral theory cannot explain adaptive divergence or ecosystem function, which ecologists must understand. By addressing new topics and predicting changes in time, however, ecological neutral theory can provide probing null hypotheses and stimulate more realistic theory.     

Intermediate filaments: a historical perspective

Intracellular protein filaments intermediate in size between actin microfilaments and microtubules are composed of a surprising variety of tissue specific proteins commonly interconnected with other filamentous systems for mechanical stability and decorated by a variety of proteins that provide specialized functions. The sequence conservation of the coiled-coil, alpha-helical structure responsible for polymerization into individual 10 nm filaments defines the classification of intermediate filament proteins into a large gene family. Individual filaments further assemble into bundles and branched cytoskeletons visible in the light microscope. However, it is the diversity of the variable terminal domains that likely contributes most to different functions. The search for the functions of intermediate filament proteins has led to discoveries of roles in diseases of the skin, heart, muscle, liver, brain, adipose tissues and even premature aging. The diversity of uses of intermediate filaments as structural elements and scaffolds for organizing the distribution of decorating molecules contrasts with other cytoskeletal elements. This review is an attempt to provide some recollection of how such a diverse field emerged and changed over about 30 years.     

The pathophysiology of stress urinary incontinence: a historical perspective

This article provides a historical perspective on the evolution of theories regarding the pathophysiology of stress urinary incontinence (SUI). The progression of these theories has followed the development of the diagnostic technologies that have provided insight into different aspects of urethral dysfunction. The earliest theories tied SUI to anatomic failure of urethral support. Recognition that anatomic failure impacted the interplay of intra-abdominal pressure and the bladder and urethra led to theories focused on the dynamic interaction between the bladder and urethral pressures. Investigators then began to recognize the importance of urethral sphincteric dysfunction. More recently, investigators have attempted to combine the anatomic and functional etiologies into a consolidated theory. These efforts point to a multi-factorial etiology of SUI. Continuing research has provided new insight into the neurophysiology of urethral function, opening new avenues for tailoring therapy for SUI.     

The tachykinin tale: molecular recognition in a historical perspective

Crystallography, mutational mapping and crosslinking are but a few of the experimental techniques that have helped to elucidate the underlying principles of molecular recognition between macromolecules and to improve our understanding of the evolution of the structure-activity relationship (SAR). While this development has been particularly successful for small and rigid ligands and substrates that bind to larger hydrophilic biomolecules, our understanding of membrane-embedded proteins is still rather limited. This review uses the example of the neuropeptide family of tachykinins and their G-protein coupled receptors (GPCR) to present how complementary experimental strategies over the past decades have nourished and modified conceptual models of the structural requisites of molecular recognition and function. Given the little we know, the pertinent question is how we proceed from here.     

BioMetals: a historical and personal perspective

Understanding of BioMetals developed basically from a starting point about 60 years ago to current mechanistic understanding of the biological behavior of many metal ions from protein structural and functional studies. Figure 1 shows a Biochemical Periodic Table, element by element, with requirements, roles and biochemistry of the specific ions indicated. With few exceptions, the biology is of the ions formed and not of the elemental state of each. Early BioMetals efforts defined nutritional growth needs for animals, plants and microbes for inorganic “macro-nutrients” such as magnesium, calcium, potassium, sodium, and phosphate and of “micronutrients” such as copper, iron, manganese and zinc. Surprises came early with regard to microbes, for example the finding that Escherichia coli (then and now the standard microbial model) grows happily in the apparent total absence of calcium, sodium, and chloride, which are certainly major animal nutrients. Some elements such as mercury and arsenic are never required by living cells, but are always toxic, often at very low levels. Therefore, the division into nutrient elements and toxic elements came soon. For most inorganic nutrients, excessive amounts can be toxic as well, for example for copper and iron.     

Class,culture, and the Miskito Indians: A historical perspective

Conclusion In this paper I have endeavored to outline a dialectical analysis of the Miskito Indian historical experience of the last 350 years. This history has been divided into three periods, in each of which class processes have been integrally tied to particular ethnic configurations. In the first, pre-contact period, a series of autonomous egalitarian hunting, gathering and horticultural groups, linked in a network of mutual trading and raiding, inhabited the various river basins of the coastal region. In the second period, beginning roughly in the early 17th century, integration as a periphery in the British mercantile empire engendered a political economic transformation in which local headmen emerged as focal points in the articulation of coastal production with British exchange networks. The new level of power over the allocation of social surpluses assumed by these headmen was validated through the symbolic framework of British monarchy. This also served the geopolitical interests of the British. The rise of this incipient tributary mode of production was a central force in the emergence of the Miskito as a new ethnic entity.The decline of mercantilism and the rise of the second phase of the Industrial Revolution saw a shift in British interests in the periphery from commodities to sources of labor and loci for investment. This brought about a second transformation in which the incipient tributary kingship was undermined both from within, by the demise of the slave trade, and from without, by increasing foreign contact coupled with population expansion and the large-scale introduction of wage labor. The Miskito were now integrated fairly uniformly as an underclass in the new coastal class hierarchy. However, wage labor took its place beside kin-ordered production and exchange in a dualistic system, which alternated with continual booms and busts in the local economy. Ethnic groupings now both defined, and were rooted in, class differentiation.As we have seen, due to its theoretically fragmented and inconsistent nature, our received anthropological history of the Miskito also serves us poorly, if we want to develop a critical understanding of the Atlantic coast of Nicaragua and its dilemmas within the revolution. Focusing on the intersection of class and ethnic processes through history gives us a more coherent and analytically convincing picture. It provides us, as well, with a basis for a deeper understanding of the roots of the Miskito/Sandinista conflict. While politics conceived in terms of class or in terms of ethnicity have given rise to ostensibly different social agendas, it is clear that historically the two have never been separate aspects of existence. Miskito culture is an historical creation — evolved in response to the ongoing pressures of integration into a world political economy whose center lay in Europe or the United States and expressive of the class processes set off by these encounters.Yet it is more than just an expression of these processes, for the way in which the Miskito defined and articulated themselves as a cultural unit played a central role in the shaping of those processes themselves. Thus, a Marxist analysis that downplays the importance of ethnic identity in favor of class identity will miss fundamental aspects of what it is to be Miskito, culturally and politically, as well as economically. By the same token, ethnic movements that eschew class analysis in favor of a strictly cultural interpretation will fall into a similar trap, becoming perhaps more vulnerable to acting in ways that go against their own interests. Whatever the outcome of this particular situation, given the size and importance of the indigenous peoples through the Americas, the left's ability to deal with culture as a basis of resistance will have a deep impact on the course of progressive social change throughout the region.Daniel Noveck received his BA degree in anthropology, from the University of Massachusetts, Amherst.