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Epigenetics: Origins and Implications for Cancer Epidemiology Medical Hypotheses 74 (2010) 377–382 Contents lists available at ScienceDirect Medical Hypotheses journal homepage: www.elsevier.com/locate/mehy Epigenetics: Origins and implications for cancer epidemiology Melissa S. Nise, Puran Falaturi, Thomas C. Erren * Institute and Policlinic for Occupational and Social Medicine, University of Cologne, Kerpener Strasse 62, 50937 Cologne-Lindenthal, Germany article info summary Article history: This paper provides information on the evolution of the ‘epigenetics’ concept since Aristotle and draws Received 24 August 2009 attention to the importance of epigenetic implications for cancer epidemiology in the years to come. Accepted 6 September 2009 Clearly, to understand origins of the concept of epigenetics, it is worthwhile to consider historical argu- ments associated with evolution. Equally clearly, in the last half of the 20th century, great advances in the understanding of epigenetics and, more specifically, great advances in the understanding of epigenetics in cancer have been made. However, reaping the full benefits of epigenetics lies beyond the predominant experimental studies of today. In general, epigenetics opens many doors in the field of cancer, but it also adds another level of complex, inter-related, and multi-dimensional information to research, and to its interpretation. Overall, future cancer studies should consider, or at least be sensitive to, epigenetic effects and mechanisms. Moving the focus beyond ‘pristine’ inheritance via DNA alone, cancer epidemiology investigating epigenetic exposures such as environmental factors (exposure to heavy metals, air pollu- tion, arsenic and other toxins), dietary patterns (starvation, famine, contamination), and lifestyle habits (smoking, level of physical activity, and BMI) in populations has the prospect to significantly benefit future cancer prevention and treatment schemes. Ó 2009 Elsevier Ltd. All rights reserved. Introduction associated with evolution. The theory of evolution has in and of itself ‘evolved’. The mechanisms through which life develops Studies and observations concerning the biological develop- have occupied the minds of many well-known and respected ment of living organisms are long-standing and still ongoing. Aris- philosophers, theologians, and natural scientists, alike. Although totle pulled together existing theories and sparked new the more abstract questions pertaining to the meaning of life conversations regarding early development in his book De generati- have been juggled around without much, or any, progress, inqui- one animalium (On the Generation of Animals), where he alludes to ries about the developmental process have drastically changed the role of epigenetics in human development without citing spe- and advanced throughout the course of the last several hundred cific causes or explanations [1–3]. Thousands of years later, years. thousands of questions remain, particularly relating to the devel- Intriguingly, centuries before Darwin, the topic of evolution opment of abnormal cells, such as those found in cancer. was heating among scholars. Discussions favoring so-called Although many complicated scientific subjects are now well- preformation were eventually matched with those supporting understood and some are considered elementary (and almost triv- epigenesis. Preformation argues that a being (human or other- ial), numerous scientific answers, in particular, those related to the wise) is completely developed within the egg/germ and grows development of cancer, are still undiscovered. Understanding (and to adult form through nutrition. Whereas, epigenesis contends integrating) the roles of genes, genetics, and epigenetics seems to that the growth from egg/germ to adulthood is a develop- be a promising approach. As the intellectual capacity of genetics mental process, in which many factors play a role throughout and epigenetics in cancer continues to grow, so will the knowledge the lifetime of the organism. Epigenesis has proven to be a base for future studies (be they of epidemiological or experimental more accurate description of development, with a stronger nature), databases/catalogs, prevention measures, and treatments. evidence base, compared to the arguments favoring preforma- tion alone. A history of epigenetics A literary dissection of the word ‘‘epigenesis” into its two main components (‘epi’ and ‘genesis’) reveals the basic concept epigene- In order to better understand and appreciate the concept of sis employs. The prefix ‘‘epi-” stands for propositions such as, ‘epigenetics’, one must also consider the historical arguments ‘‘upon, besides, attached to, over, outer, after” [4]. ‘‘Genesis” is the ‘‘origin or coming to being of something” [5]. If one considers substituting ‘attached to’ for ‘epi-‘, a simplified definition of epi- * Corresponding author. Tel.: +49 221 4784450; fax: +49 221 4785119. E-mail address: [email protected] (T.C. Erren). genesis emerges, such that ‘epigenesis’ is something which is 0306-9877/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved. doi:10.1016/j.mehy.2009.09.008 378 M.S. Nise et al. / Medical Hypotheses 74 (2010) 377–382 attached to / ‘‘in conjunction with” an organism’s materialization. 2. Wolff emphasizes the need for good science to have a balance Considering the actual definition of epigenesis, ‘‘the development between observation, theory, and experimentation. of a plant or animal from an egg or spore through a series of pro- 3. Wolff infuses the field of embryology with the doctrine of epi- cesses in which unorganized cell masses differentiate into organs genesis, strongly advocating that organisms develop over the and organ systems” [6], the two-part construction of ‘epi-’ and duration of their lifetimes [3]. ‘genesis’ offers a minimalist version, in this case ‘‘something”isa ‘‘series of processes”. Wolff’s experimentation influenced the embryologists Wilhelm As mentioned above, references to some of the chief principles of Roux, and compelled epigenesist Oscar Hertwig to argue that the epigenesis are described by academics as early as Aristotle; however, era in which Wolff made his exclamations had worked against the terminology and wording used today was not established until him. Hertwig writes, much later. According to Preus, ‘‘[Aristotle] knew that something ‘‘It was very different in earlier days; the acutest biologists and had to carry the dynamic structure from parent to child. His version philosophers were evolutionist, and an epigenetic* conception of the theory was a considerable advance on the theories of his pre- of the process of development could find no foothold alongside decessors...Not until the 19th century did epigenesis, the theory the apparent logical consistency of the theory of preformation. suggested by Aristotle, win general scientific approval,” [2]. Wolff’s Theoria Generationis (1759) failed to convince his con- The long delay in new information and the advancement of the temporaries, because he could bring against the closed system theory of epigenesis was largely due to the religious beliefs and of the evolutionists only isolated observations, and these doubt- available technology at that time, Roe explains; ‘‘it was much more ful of interpretation; and because, in his time, on account of the difficult to explain the development of the embryo epigenetically, rudimentary state of the methods of research in biology, men that is, through gradual formation of parts from unorganized mat- attached more importance to abstract reasoning than to obser- ter,” [7]. She continues to point out specific questions that hindered vation,” [11]. the advancement of embryological theory, even in a post-enlight- enment era, such as, ‘‘If the embryo develops through successive Therefore, the greatness of Wolff’s work was not able to be formation of structures, then where is the source of its eventual appreciated in the time period in which it was composed; hence, organization? What guides this process?” [7]. These questions, in the dormant century in the development of epigenetic theory. some respects, are still relevant today. Epigenesists are currently It appears that Hertwig’s publication which was translated into trying to pin-point the different driving forces that guide develop- English is one of the oldest articles to have used the word ‘‘epige- ment through epigenetics within specific areas of medicine. netic” (*). In his untranslated work, Präformation oder Epigenese? Despite the challenge of gaining followers within the scientific [12], Hertwig used the German word ‘‘epigenetische” as an adjec- community of the 16th century through innovative concepts, Caspar tive to describe the noun ‘‘Auffassung” (concept) (together meaning Friedrich Wolff attempted to answer these questions in their most ‘‘epigenetic concept”). However, the use of the word ‘‘epigenetic” fundamental sense. In an effort to surface the deep-seated flaws of in Hertwig’s case is not a one-to-one correlation with the ‘‘epige- preformationism, according to Roe, Wolff argued, ‘‘One can always netic” Conrad Waddington used when he wrote of the ‘‘epigenetic see the tiny particles, or globules, that are the basic components of landscape”. In Hertwig’s time, the concept of genetics was not all parts of the organism. But if the structure itself were preexistent, widely considered and the term ‘‘genetics” was not even coined only needing to become large enough to be visible, one should not be until 1905 [13]. Therefore, the first use of the word ‘‘epigenetic”, able to decipher
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