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PubMed1995

Much ado about me.

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Genetics, Medical↗
PubMed2005

The biography of psychiatric genetics: from early achievements to historical burden, from an anxious society to critical geneticists.

When the study of human inheritance became a topic of scientific interest more than 100 years ago, brain function and mental disease immediately attracted the interest of researchers. Psychiatric genetics was dominated from its early beginnings by the question of nature and nurture. Today this problem can be quantitatively approached with odds ratios and attributable risks for certain genotypes. The false doctrine of eugenics and its practical application by the Nazi regime paved the way for the development of a prevailing anxiety in society that psychiatric genetics might lead to stigmatisation or even a revitalization of eugenics. The major challenge for the field, however, stems from the attitudes of fellow geneticists who doubt that genetics can ever contribute to an understanding of brain function and mental disease. Whereas genetically complex traits are being successfully pinned down to the molecular level in other fields of medicine, psychiatric genetics still awaits a major breakthrough. Although mental disorders are harder to tackle than any other complex disease the concepts developed and the methods available today are powerful enough to predict a bright future of the field.

Eugenics↗
PubMed2003

The wonders of magnetism.

In this acceptance address for the Bioelectromagnetics Society's 2001 d'Arsonval Award, Dr. Tenforde reviews the highlights of the nonionizing field aspects of his research and scientific service career. These are focused in four areas: (a). development and application of microelectrophoretic methods to probe the surface chemistry of normal and cancerous cells; (b). research on the biophysical mechanisms of interaction and the dosimetry of static and extremely low frequency magnetic fields; (c). application of extremely high intensity magnetic fields in several spectroscopic methods for probing the detailed structures of large biological macromolecules; and (d). development of national and international guidelines for the exposure of workers and members of the general public to electromagnetic fields with frequencies spanning the entire nonionizing electromagnetic spectrum.

DNA↗
PubMed1992

Use of the HPRT gene and the HAT selection technique in DNA-mediated transformation of mammalian cells: first steps toward developing hybridoma techniques and gene therapy.

In 1956, I decided to apply my experience in microbial genetics to developing analogous systems for human cell lines, including the selection of mutants with either a loss or gain of a biochemical function. For instance, mutants resistant to azahypoxanthine showed a loss of the HPRT enzyme (hypoxanthine phosphoribosyl transferase), whereas gain of the same enzyme was accomplished by blocking de novo purine biosynthesis with aminopterin, while supplying hypoxanthine and thymine (HAT selection). Using HAT selection, we: (i) genetically transformed HPRT- mutant cells to HPRT+ wild type by using DNA extracted from HPRT+ cells, and (ii) selected HPRT+ hybrid cells by fusing HPRT- D98/AH2 cells with skin cells. These approaches, which we dubbed in 1962 as a 'first step toward gene therapy', contributed to the later development of (i) cell fusion techniques, (ii) the development of monoclonal antibodies, (iii) routine transformation of mammalian cells with cloned genes, and (iv) methods for creating transgenic organisms.

Animals↗
PubMed1992

Thy-1, the enigmatic extrovert on the neuronal surface.

Thy-1 is a small glycoprotein of 110 amino acids which, folded in the characteristic structure of an immunoglobulin variable domain, are enchored to the plasma membrane via a glycophosphatidylinositol (GPI) tail (Fig. 1). It is a major component of the surface of various cell types, including neurons, at certain stages of their development. These qualities doubtlessly appeal to certain cognoscenti, but it is not clear why they would raise Thy-1 to the status of a favourite molecule. Indeed, few scientists readily admit to having a favourite. We study individual molecules because science is rooted in specific observations; but we do so in order to discover mechanisms of general importance. A molecule's appeal is dependent on its ability to reveal novel aspects of how nature works. Thy-1 has been unusual in this respect. It was the first lymphocyte surface antigen shown to be restricted to a functional subset of lymphocytes (T cells in the mouse), a finding crucial to the development of cellular immunology; it was one of the first cell surface molecules to be sequenced and indicated the importance of immunoglobulin domains and GPI anchors as structural motifs; it has been pivotal in studies demonstrating that GPI-anchored molecules are able to signal across the membrane they do not span. Thy-1 has revealed this much, however, with the charm of an adroit stripper: it has always promised glimpses of things more exciting than that displayed. In particular, the function of this molecule has never emerged.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗