Czech roots in the discovery of the molecular mechanisms by which cells sense and respond to oxygen concentration
Abstract
This work was inspired by the seminal lecture of Nobel prize winner Sir Peter J. Ratcliffe in which he discussed various approaches to generating new knowledge in physiology.
This report reflects and summarizes our efforts 50 years ago to reveal the molecular mechanisms involved in hypoxia-induced erythropoietin production. In this work, we demonstrated the unique role of oxygen in the activation of erythropoietin production and demonstrated that erythropoietin production is independent of oxygen consumption linked with ATP generation.
The Symposium Erythropoieticum held in Prague in 1970 played a significant role in the acceptance of these results. This research is also an example of the significance of publishing negative results in cases where the research question is correctly defined.
Circumstances influencing the acceptance and elaboration of research results by the broader scientific community are considered, as are the timing and external conditions that restrict the achievement of research goals and their acceptance. This report also demonstrates that even a deep understanding of the molecular and cellular mechanisms that underlie physiological functions is not necessarily sufficient to explain their role in vivo where they are modified by complex control mechanisms.