The evolution of early life and of contemporary viruses has been driven in significant part by random genetic mutations, while modern unicellular and organismal evolution primarily leverages evolved, efficient and active cell biology processes for adaptive changes prior to selection. Random mutations are often buffered by cell homeostasis, or they have a negative role, e.g., by causing death or monogenic diseases, or by triggering real-time cancer evolution. Accordingly, the Modern Synthesis theory no longer adequately describes the efficient, often punctuated and at times directionally adaptive natural genetic engineering (NGE) processes deduced from the DNA record of evolution.

Similarly, the somatic mutation theory (SMT) of cancer describes driver mutations that can trigger oncogenesis, and passenger mutations characteristic of periods of genetic microevolution in cancer. At the precancerous stage, most somatic mutations are repaired or buffered in the cell, aberrant cells are removed, or organismal bioelectric tissue signals or other physiological functional networks maintain control of rogue, mutated cells. However, the SMT is not sufficient to describe the observed punctuated macroevolution of cancer-cell genes, chromosomes, karyotypes and epigenomes, nor of expressed cancer-cell transcriptomes, proteomes and epiproteomes, which include non-DNA-templated post-translational modifications, protein-protein interactions and metabolites. Moreover, punctuated cancer cell macroevolution often culminates in macro-effects, which include epithelial-mesenchymal transitions (EMT), cancer cell polyploidies and even giant multinucleated cancer cells that drive cancer progression, therapy resistance and metastasis. All of this cancer-cell evolution competes in a molecular and cellular arms race with host immune cells and antibodies, as well as with the host tumor microenvironment.

Empirically observed punctuated, multilevel and multiclonal cancer macroevolution, and the concomitant, rapid co-development of the host immune system and tumor microenvironment, can occur with the efficiency, speed and lethality of cancer that is enabled by evolved, active natural genetic engineering (NGE) mechanisms. NGE affects both vertical cancer-cell genomic inheritance and evolution towards therapy resistance and metastasis, as well as viral or cancer-cell exosome vector-driven horizontal gene transfers that contributes to cancer cell cooperation, or to transforming previously non-cancerous somatic cells into destabilized cancer cells during metastasis.

In addition, externally driven, irreversible and transferable (EDIT) adaptations are exemplified by mitotically heritable, non-templated cancer cell epigenetics, and by mitotically heritable cancer-cell surface protein and lipid glycosylation, as important examples of fast time-scale molecular evolution mechanisms in which genes are followers, similar to evo-devo processes in organismal evolution.

早期生命和当代病毒的进化在很大程度上是由随机基因突变驱动的，而现代单细胞和生物体进化主要利用进化的、有效的和活跃的细胞生物学过程在选择之前进行适应性变化。随机突变通常受到细胞稳态的缓冲，或者它们具有负面作用，例如导致死亡或单基因疾病，或触发实时癌症进化。因此，现代综合理论不再充分描述从进化的 DNA 记录中推导出的有效的、经常断断续续的、有时是定向适应性的自然基因工程(NGE) 过程。

同样，癌症的体细胞突变理论(SMT) 描述了可以触发肿瘤发生的驱动突变，以及癌症遗传微进化时期特征的乘客突变。在癌前阶段，大多数体细胞突变在细胞中得到修复或缓冲，异常细胞被去除，或者有机体生物电组织信号或其他生理功能网络保持对流氓、突变细胞的控制。然而，SMT 不足以描述观察到的癌细胞基因、染色体、核型和表观基因组的间断宏观进化，也不足以描述表达的癌细胞转录组、蛋白质组和表观蛋白质组，其中包括非 DNA 模板的翻译后修饰、蛋白质-蛋白质相互作用和代谢物。此外，间断的癌细胞宏观进化通常以宏观效应告终，其中包括上皮间质转化 (EMT)、癌细胞多倍体，甚至是驱动癌症进展、治疗抵抗和转移的巨大多核癌细胞。所有这些癌细胞进化都在分子和细胞军备竞赛中与宿主免疫细胞和抗体以及宿主肿瘤微环境竞争。

经验观察到的间断、多水平和多克隆癌症宏观进化，以及宿主免疫系统和肿瘤微环境的伴随、快速共同发展，可以随着进化的、活跃的自然基因工程(NGE ) 实现的癌症的效率、速度和致死率而发生) 机制。NGE 影响垂直癌细胞基因组遗传和向治疗抵抗和转移的进化，以及病毒或癌细胞外泌体载体驱动的水平基因转移，有助于癌细胞合作，或将以前的非癌性体细胞转化为不稳定的体细胞转移过程中的癌细胞。

此外，外部驱动的、不可逆的和可转移的(EDIT) 适应性以有丝分裂可遗传的非模板癌细胞表观遗传学和有丝分裂可遗传的癌细胞表面蛋白和脂质糖基化为例，作为快速时间尺度分子进化机制的重要例子其中基因是跟随者，类似于生物进化中的 evo-devo 过程。