Muller Anthonie W J
Synthetic Systems Biology and Nuclear Organization, Swammerdam Institute for Life Sciences, University of Amsterdam, Kruislaan 904, 1098 XH Amsterdam, The Netherlands.
Med Hypotheses. 2017 Jul;104:104-115. doi: 10.1016/j.mehy.2017.05.030. Epub 2017 May 30.
As cancer usually follows reproduction, it is generally assumed that cancer does not select. Graham has however argued that juvenile cancer, which precedes reproduction, could during evolution have implemented a "cancer selection" that resulted in novel traits that suppress this juvenile cancer; an example is protection against UV sunlight-induced cancer, required for the emergence of terrestrial animals from the sea. We modify the cancer selection mechanism to the posited "cancer adaptation" mechanism, in which juvenile mortality is enhanced through the diminished care received by juveniles from their (grand) parents when these suffer from cancer in old age. Moreover, it is posited that the cancer adaptation selects against germline "dissipative genes", genes that result in enhanced free energy dissipation. Cancer's progression is interpreted as a cascade at increasing scale of repeated amplification of energy dissipation, a cascade involving heat shock, the Warburg effect, the cytokine IL-6, tumours, and hypermetabolism. Disturbance of any physiological process must enhance energy dissipation if the animal remains functioning normally, what explains multicausality, why "everything gives you cancer". The hypothesis thus comprises two newly invoked partial processes-diminished (grand) parental care and dissipation amplification-and results in a "selection against enhanced energy dissipation" which gives during evolution the benefit of energy conservation. Due to this benefit, cancer would essentially be an adaptation, and not a genetic disease, as assumed in the "somatic mutation theory". Cancer by somatic mutations is only a side process. The cancer adaptation hypothesis is substantiated by (1) cancer's extancy, (2) the failure of the somatic mutation theory, (3) cancer's initiation by a high temperature, (4) the interpretation of cancer's progression as a thermal process, and (5) the interpretation of tumours as organs that implement thermogenesis. The hypothesis could in principle be verified by monitoring in a population over several generations (1) the presence of dissipative genes, (2) the incidence of cancer, and (3) the beneficial effect of dissipative gene removal by cancer on starvation/famine survival.
由于癌症通常在繁殖之后出现,所以一般认为癌症不具有选择性。然而,格雷厄姆认为,在繁殖之前出现的幼年癌症,在进化过程中可能实施了一种“癌症选择”,从而产生了抑制这种幼年癌症的新性状;一个例子是陆地动物从海洋中出现时所需的对紫外线诱导癌症的防护。我们将癌症选择机制修改为假定的“癌症适应”机制,即在(外)祖父母年老患癌时,幼崽从他们那里得到的照料减少,从而增加了幼崽的死亡率。此外,假定癌症适应会淘汰种系中的“耗散基因”,即那些导致自由能耗散增加的基因。癌症的进展被解释为能量耗散重复放大的规模不断增加的级联反应,这个级联反应涉及热休克、瓦伯格效应、细胞因子白细胞介素 -6、肿瘤和高代谢。如果动物仍能正常运作,任何生理过程的紊乱都必然会增加能量耗散,这就解释了多因果关系,即为什么“一切都会导致癌症”。因此,该假说包含两个新提出的部分过程——减少的(外)祖父母照料和耗散放大——并导致一种“对增加能量耗散的选择淘汰”,这在进化过程中带来了能量守恒的益处。由于这种益处,癌症本质上是一种适应,而不是像“体细胞突变理论”所假定的那样是一种基因疾病。体细胞突变导致的癌症只是一个附带过程。癌症适应假说得到了以下几点的证实:(1)癌症的存在;(2)体细胞突变理论的失败;(3)高温引发癌症;(4)将癌症进展解释为一个热过程;(5)将肿瘤解释为实施产热的器官。原则上,可以通过在几代人的群体中监测以下几点来验证该假说:(1)耗散基因的存在;(2)癌症的发病率;(3)癌症去除耗散基因对饥饿/饥荒生存的有益影响。