Emergentism as a default: Cancer as a problem of tissue organization
Emergentism as a default: Cancer as a problem of tissue organization
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DOI：
10.1007/bf02705155
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发表时间：
2005-02-01
影响因子：
2.9
通讯作者：
Sonnenschein, C
中科院分区：
文献类型：
--
作者：
Soto, AM;Sonnenschein, C
在过去的50年里，实验生物学的主导立场一直是还原论。在大多数情况下，研究计划是基于这样的概念，即基因在“驾驶座”控制发育程序，并决定正常和疾病（遗传还原论和遗传决定论）。哲学家们首先意识到孟德尔基因被简化为DNA分子的信念是值得怀疑的。在这些声明发表后不久，实验数据证实了他们的担忧。分子生物学家的乐观主义，早期成功地解决了相对简单的问题，现在已经被试图理解复杂的生物学问题时发现的困难所冲淡。在这里，我们分析了实验数据，说明了这种简化论的缺点。我们还研究了癌症研究中的流行范式，体细胞突变理论（SMT），其前提是：（i）癌症来自于积累了多个DNA突变的单个体细胞;（ii）后生动物细胞增殖的默认状态是静止;（iii）癌症是由控制增殖和细胞周期的基因突变引起的细胞增殖疾病。我们挑战的概念，癌症是一个细胞问题引起的突变基因通过评估数据收集从还原论范式内，并从另一种观点，认为致癌作用是一个发展过程出错。这种以组织组织场理论（TOFT）为名的替代观点，是基于将癌症置于与SMT所提出的复杂性不同的层次结构中的前提，即：（i）癌发生代表了一个与器官发生相当的组织组织问题，（ii）增殖是所有细胞的默认状态。我们提出，有机主义者的观点，其中TOFT是基于，是探索涌现现象的一个很好的起点然而，需要新的理论概念，以解决发展和致癌过程中复杂生物现象的明显循环因果关系。
During the last fifty years the dominant stance in experimental biology has been reductionism. For the most part, research programs were based on the notion that genes were in 'the driver's seat' controlling the developmental program and determining normalcy and disease (genetic reductionism and genetic determinism). Philosophers were the first to realize that the belief that the Mendelian genes were reduced to DNA molecules was questionable. Soon after these pronouncements, experimental data confirmed their misgivings. The optimism of molecular biologists, fueled by early success in tackling relatively simple problems, has now been tempered by the difficulties found when attempting to understand complex biological problems.Here, we analyse experimental data that illustrate the shortcomings of this sort of reductionism. We also examine the prevailing paradigm in cancer research, the somatic mutation theory (SMT), the premises of which are: (i) cancer is derived from a single somatic cell that has accumulated multiple DNA mutations; (ii) the default state of cell proliferation in metazoa is quiescence; and (iii) cancer is a disease of cell proliferation caused by mutations in genes that control proliferation and the cell cycle. We challenge the notion that cancer is a cellular problem caused by mutated genes by assessing data gathered both from within the reductionist paradigm and from an alternative view that regards carcinogenesis as a developmental process gone awry. This alternative view, explored under the name of the tissue organization field theory (TOFT), is based on premises that place cancer in a different hierarchical level of complexity from that proposed by the SMT, namely: (i) carcinogenesis represents a problem of tissue organization comparable to organogenesis, and (ii) proliferation is the default state of all cells.We propose that the organicist view, in which the TOFT is based, is a good starting point from which to explore emergent phenomena. However, new theoretical concepts are needed in order to grapple with the apparent circular causality of complex biological phenomena in development and carcinogenesis.