„Substances capable of self-reproduction“ as cellular targets of chemical carcinogens.In the course of studies on chemical carcinogenesis, which included animal experiments with a carcinogenic azo dye and a mathematical analysis of the observed effects, Hermann Druckrey and Karl Küpfmüller showed in 1948 that carcinogens induce heritable changes by targeting cellular „substances capable of self-reproduction“. The authors did not discuss the chemical nature of these substances which remained unclear for a long time thereafter. It was not until 1964 that deoxyribonucleic acid (...) (DNA) was recognized, by Peter Brookes and Philip Lawley, as a target for the genotoxic action of chemical carcinogens. In retrospect, the results of Druckrey and Küpfmüller gave an early, indirect and until now not considered hint to an important role of DNA (the „substance“) malfunction in the development of cancer, since DNA is the only molecule capable of self-reproduction.The results are now appreciated in light of the scientific knowledge available at the time. (shrink)

In this paper I consider Kenneth Schaffner''s(1998) rendition of ''''developmentalism'''' from the point of viewof bacteriophage biology. I argue that the fact that a viablephage can be produced from purified DNA and host cellularcomponents lends some support to the anti-developmentalist, ifthey first show that one can draw a principled distinctionbetween genetic and environmental effects. The existence ofhost-controlled phage host range restriction supports thedevelopmentalist''s insistence on the parity of DNA andenvironment. However, in the case of bacteriophage, thedevelopmentalist stands on less firm (...) ground than when organismswith nervous systems, such as Schaffner''s C. elegans, areconsidered. (shrink)

Scientific hypotheses may either predict particular unknown facts or accommodate previously-known data. Although affirmed predictions are intuitively more rewarding than accommodations of established facts, opinions divide whether predictive hypotheses are also epistemically superior to accommodation hypotheses. This paper examines the contribution of predictive hypotheses to discoveries of several bio-molecular systems. Having all the necessary elements of the system known beforehand, an abstract predictive hypothesis of semiconservative mode of DNA replication was successfully affirmed. However, in defining the genetic code whose biochemical (...) basis was unclear, hypotheses were only partially effective and supplementary experimentation was required for its conclusive definition. Markedly, hypotheses were entirely inept in predicting workings of complex systems that included unknown elements. Thus, hypotheses did not predict the existence and function of mRNA, the multiple unidentified components of the protein biosynthesis machinery, or the manifold unknown constituents of the ubiquitin–proteasome system of protein breakdown. Consequently, because of their inability to envision unknown entities, predictive hypotheses did not contribute to the elucidation of cation theories remained the sole instrument to explain complex bio-molecular systems, the philosophical question of alleged advantage of predictive over accommodative hypotheses became inconsequential. (shrink)

The introductory personal remarks refer to my motivations for choosing research projects, and for moving from physics to molecular biology and then to development, with Hydra as a model system. Historically, Trembley’s discovery of Hydra regeneration in 1744 was the begin¬ning of developmental biology as we understand it, with passionate debates about preformation versus de novo generation, mechanisms versus organisms. In fact, seemingly conflicting bottom-up and top-down concepts are both required in combination to understand development. In modern terms, this means (...) analysing the molecules involved, as well as searching for physical principles underlying development within systems of molecules, cells and tissues. During the last decade, molecular biology has provided surprising and impressive evidence that the same types of mol¬ecules and molecular systems are involved in pattern formation in a wide range of organisms, including coelenterates like Hydra, and thus appear to have been “invented” early in evolution. Likewise, the features of certain systems, especially those of developmental regulation, are found in many different organisms. This includes the generation of spatial structures by the interplay of self-enhancing activation and “lateral” inhibitory effects of wider range, which is a main topic of my essay. Hydra regeneration is a particularly clear model for the formation of defined patterns within initially near-uniform tissues. In conclusion, this essay emphasizes the analysis of development in terms of physical laws, including the application of mathematics, and insists that Hydra was, and will continue to be, a rewarding model for understanding general features of embryogenesis and regeneration. -/- -/- . (shrink)