Medical hypotheses
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This article complements Dr. Charlton's follow-up of David Horrobin's suggestion in Nature two decades ago to offer sizeable prizes for practical approaches to either eliminate a problem in medicine or reduce the cost of its solution. Examples from the 20th and 21st centuries illustrate that prizes--small and big--have generated sustained and successful attacks on defined problems in biology, physics and, lately, mathematics. Provided that glittering prizes are offered and awarded with care, they can lead to effective problem-solving in medicine and related biomedical sciences as well.
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I believe that people will not feel comfortable and positive about the contemporary world until we can endorse and believe an evolutionary cosmology which is appropriate to modern conditions. A cosmology is a mythical account of the universe as it presents itself to the human mind; it needs to be poetic, symbolic, inspiring of a sense of awe and mystery. Furthermore, a complete cosmology should include the three levels of macro-, meso- and micro-cosm, in order to understand the nature of the universe, human society, and the individual's relation to them. ⋯ The same dynamic, neophiliac and open-ended process of 'creative destruction' can be seen at work in science, economics, and modern spirituality. But a modern cosmology will only be experienced as both deep and spontaneous when it takes the form of a mythic account that is first encountered and assimilated during childhood. Since myths arise as a consequence of human creativity; there is a vital future mythogenic role for artists in the realm of ideas, images and stories: people such as mystics, poets and philosophers--including, I hope and expect, creatively inspired scientists.
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People often suggest that scientists should have a specific personality type, usually conscientious and self-critical. But this is a mistake. Science as a social system needs to be conscientious and self-critical, but scientists as people do not necessarily have to conform to that stereotype. ⋯ But the modern science superstar is more like the Nutty Professor's alter ego, nightclub singer 'Buddy Love': a sharp-suited, good-looking and charismatic charmer. While Nutty was dull but impartial, Buddy is compelling but self-seeking. Our attitude towards public scientific pronouncements should be adjusted accordingly.
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Vascular calcification is a common feature in advanced atherosclerosis and also a predictor of future cardiovascular events such as unstable angina and myocardial infarction, especially in diabetes. There is a growing body of evidence that advanced glycation end products (AGEs), senescent macroprotein derivatives formed at an accelerated rate in diabetes, exist within atherosclerotic lesions, thereby being implicated in the pathogenesis of accelerated atherosclerosis in diabetes. Indeed, we have previously shown that AGE - their receptor (RAGE) interaction could induce angiogenesis through autocrine production of vascular endothelial growth factor, suggesting its role for plaque formation and enlargement in diabetes. ⋯ Since we, along with others, have shown that nifedipine inhibits glycation of low-density lipoprotein in vitro and blocks the AGE-induced RAGE expression in endothelial cells through its anti-oxidative properties, nifedipine could inhibit vascular calcification by blocking the AGE formation or the downstream signaling in diabetes. In this paper, we would like to propose the possible ways of testing our hypothesis. Does nifedipine treatment slow down the progression of coronary calcification in diabetic patients? If the answer is yes, is this beneficial effect of nifedipine superior to that of other DHPs with equihypotensive properties? Does nifedipine treatment decrease expression levels of AGEs and RAGE in diabetic atherosclerosis? Is the unique effect of nifedipine on vascular calcification correlated with its AGE or RAGE-suppressing properties? These prospective studies will provide further valuable information whether nifedipine could prevent vascular calcification in diabetic atherosclerosis by blockade the AGE-RAGE signaling in vascular wall cells.
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A priori hypotheses are considered a cornerstone of the scientific method. A posteriori hypotheses, on the contrary, are judged by many as inappropriate and are hardly ever acknowledged as such. Such practice is inadequate. ⋯ And yet, their unambiguous formulation in the study publication can enable others to follow up on the findings and the modified conjectures fast and thus facilitate scientific progress. In this vein, a posteriori hypotheses should be encouraged as a thinker's prime tool rather than be discouraged. Indeed, it is suggested, that information on a posteriori hypotheses should be formally required when research is published.