The History of Epigenetics and the Science of Social Progress


by Shea Robison (@EpigeneticsGuy)

The importance of Jean-Baptiste Lamarck and of Lamarckism in the contemporary debates about epigenetics and genetics is difficult to overstate, primarily because one of the most common epithets used against contemporary epigenetics is that it is ‘Lamarckian’, which distinction is deemed sufficient to dismiss any subsequent discussion. As discussed here, such references demonstrate fundamental misunderstandings of both Lamarckism and epigenetics. The contemporary indictment of epigenetics qua Lamarckism, though, is quite helpful in revealing the underlying political and ethical commitments of genetics.

As I discuss here, the scientific flaws of Lamarckism—which, although numerous, are also understandable in its historical context—are actually of little relevance for contemporary epigenetics. What is relevant is that Lamarckism is invoked so often as a conversation-stopper [1] about contemporary epigenetics. The guiding model of my project helps to explain why these unsubstantiated epithets are being used against epigenetics, as a means to protect the often unrecognized underlying political and ethical commitments of genetics. This post will use the experiments of August Weismann to demonstrate how this has worked in the past.

Weismann v. Lamarck?

The scientific rationale for the rejection of Lamarckian inheritance—and, by extension, much of contemporary epigenetics—is largely provided by August Weismann’s experiments on whether mutilations of parents (i.e., cutting off the tails of 22 generations of rats) could be passed on to their offspring. (Similarly, the repeated need for circumcision in Jewish populations is still often offered as anecdotal proof for the rejection of the inheritance of acquired characteristics [2].)

From his experiments Weismann postulated a tissue barrier that protects those cells involved in sexual reproduction (germline cells) from environmental influences registered in the cells which constitute the body of an organism (somatic cells). This barrier is what prevents Lamarckian inheritance. With the support of experiments by Castle and Phillips in 1911 of the transplantation of albino guinea pig ovaries into non-albino guinea pigs which appeared to verify empirically that adaptations of such characteristics were not heritable [3], Weismann’s Barrier soon gained widespread acceptance and still constitutes a central assumption of the conventional orthodoxy of genetics as an inviolate barrier against the transmission of acquired traits [4]. Notably, there have been significant modifications of this concept since Weismann, but the contemporary articulation of this barrier is still that there must necessarily be some kind of barrier which prevents the transfer of genes from the somatic cells to germline cells [5].

However, there are a couple of substantial issues with both the history and the science of this concept. First, according to E.J. Steele, these experimental protocols did not accurately reflect the mechanisms of inheritance as theorized by Lamarck and thus were not actually a valid test of Lamarckism [6]. Second, the results of these experiments were obviously only deductively valid (i.e., while these experiments showed that the specific mechanisms of tail generation may not be subject to transgenerational inheritance, it is logically invalid to infer that these results definitively disprove the possibility of the inheritance of acquired characteristics in general). Yet the results of these experiments were promulgated as definitive disproof of the inheritance of acquired characteristics.

Even Weismann himself admitted that his justification for this barrier was based on almost pure speculation only tenuously informed and supported by empirical evidence [7]. To be fair, Weismann also declared that his intent was to speculate so as to spur further research in this area, and acknowledged that his ideas were likely woefully incomplete and would require much experimental work to verify or disprove. Regardless, this concept was quickly accepted as being presumptively true without much of the empirical work Weismann recommended be done.

While subsequent research has largely supported the assumption of Weismann’s Barrier, the actual physical grounding of this barrier has not been established until quite recent [8]. Notably, as the actual make-up of this barrier is just now being verified, this same work is also establishing that there is no such inviolable barrier per se, but rather a collection of mechanisms which prevent the transmission of acquired traits [9]. At the same time, work in this area is also providing evidence that genetic material does cross this supposedly inviolable soma-germline ‘barrier’ [10], that genes may be transferred both vertically (between parents and offspring) and horizontally (i.e., between unrelated organisms) [11], and that there are epigenetic mechanisms which do allow the inheritance of environmentally induced characteristics [12].

The look before the leap

So why did Weismann, one of the most respected experimental scientists of his time, see fit to engage in such speculative theorizing to derive his crowning achievement? And why did a concept with so little initial empirical support so quickly attain the status of a presumptively true assumption to become a cornerstone of contemporary genetics that only now is being questioned?

The conventional view of science and of the history of genetics is that Weismann ‘merely’ took a creative leap which contributed to subsequent advances in our scientific understanding of biology. This may be true, but a reasonable hypothesis—per the guiding model of this project—is that there were also political and ethical impetuses which influenced the direction and the trajectory of this leap.

This hypothesis finds significant support in the context of Weismann’s bitter—and well cataloged—dispute with Herbert Spencer [13]. This dispute between Spencer and Weismann, according to Stephen Jay Gould, was the “focal point and most widely cited set of documents in the great debate between ‘neo-Darwinism’ and ‘neo-Lamarckism,’ perhaps the hottest subject in evolutionary theory of the 19th century” [14].

In this ‘debate’ Weismann disagreed vociferously with Spencer—and, by extension, with Freidrich Engels and Karl Marx and other neo-Lamarckians of this time—who used Lamarckism as scientific support for their theories of social improvement. Many of these neo-Lamarckians preferred Lamarckism for the emancipatory possibilities it offered as in contrast to the practical immutability of biological essences promoted first by conventional religion, and continued by Darwin and neo-Darwinists. Instead of organisms (and humans in particular) being fixed in their basic endowments, or subject to the grace of God or random forces for change, dramatic changes were deemed possible for these social reformers through the guidance and instruction of their environments [15].

For example, in 1891 the prominent American geologist and president of the American Natural History Museum Henry Fairfield Osborn described the social implications of these differences in biological science, writing that:

If the Weismann idea triumphs, it will be in a sense a triumph of fatalism; for, according to it…each new generation must start de novo, receiving no increment of the moral and intellectual advance made during the lifetime of its predecessors. It would follow that one deep, almost instinctive motive for a higher life would be removed if the race were only superficially benefited by its nurture, and the only possible channel of actual improvement were in the selection of the fittest chains of race plasma[16].

For these reasons, as described by Lenoir and Ross in their brief history of natural museums in England, Lamarckism was a fundamental aspect of many of the rationalist (i.e., secular), progressive reform movements of the 1800s in which “a belief in the perfectability of humankind and the self-organizing power of matter according to natural laws [was] joined to a faith in the environment as a determinant of form and character” [17]. This combination of scientific and philosophical beliefs supported the expectation that “through the appropriate social and material environment, humanity’s spiritual qualities could be molded as a prelude to political change” [18].

It was against such politically and ethically loaded ideas that Weismann and other Darwinists and neo-Darwinists set themselves. Although much of this debate was couched in scientific language about ostensibly scientific subjects, underneath much of it were competing worldviews as to the proper place of humanity on the earth and in the universe. In other posts, I have likewise written about the significant though largely ignored roles of competing political ideologies in the scientific history of genetics and epigenetics, as well as about the ideological implications of epigenetics.

In hindsight we are able to see how this dynamic has played out in the early and mid 20th century, with conventional genetics being declared the winner (i.e., the one true science) while the other combatants have been relegated as quaint relics of a bygone era (i.e., unscientific). However, the recent (re)emergence of contemporary epigenetics strongly suggests that neither the motives nor the outcomes of these ‘scientific’ debates were as pristine as they are now assumed to be.

Likewise, that these ideological influences on science in the past are as obvious as they are now also suggests that ideological influences are similarly present in science today. That most scientists working today would be offended at this suggestion that ideology has any influence in their work is understandable, but this umbrage does not mean that such influences are not operative today as well (how aware were Weismann or any of the other scientists of his time of the now obvious ideological influences on their work?).

Per the guiding model of this project, these political and ethical influences on science—and scientific influences on politics and ethics—are always present. My project is to identify the effects of these political and ethical influences on the emergence of the science of epigenetics.

I am curious to hear what you think so far. Leave your comments below and I will respond.

Also, if you find these thoughts I’ve shared interesting and worthwhile, Like this post, Reblog it, or Tweet about it using the buttons on this page.

[1] Rorty, Richard. 1994. “Religion as a Conversation-Stopper,” Common Knowledge 3(1): 1-6.

[2] Levin, Harold. 2009. The Earth Through Time. 8th ed. Hoboken, NJ: Wiley. 133.

[3] Chiras, D. D. (2013). Human biology. Jones & Bartlett Publishers.

[4] Alexander, Richard. 1979. Darwinism and Human Affairs. Seattle: University of Washington Press.

[5] Steele, E.J. 1999. Lamarck’s Signature: How Retrogenes Are Changing Darwin’s Natural Selection Paradigm. Basic Books.

[6] Steele, E.J. 1999. Lamarck’s Signature: How Retrogenes Are Changing Darwin’s Natural Selection Paradigm. Basic Books.

[7] Weismann, August. 1892. Essays Upon Heredity and Kindred Biological Problems. Clarendon Press, 81-82.

[8] Sabour, D., & Schöler, H. R. (2012). Reprogramming and the mammalian germline: the Weismann barrier revisited. Current opinion in cell biology24(6), 716-723.

[9] Solana, J. (2013). Closing the circle of germline and stem cells: the Primordial Stem Cell hypothesis. EvoDevo4(1), 1-17

[10] Boyce, N. (2001). Trial halted after gene shows up in semen. Nature,414(6865), 677-677.

[11] Riley, D. R., Sieber, K. B., Robinson, K. M., White, J. R., Ganesan, A., Nourbakhsh, S., & Hotopp, J. C. D. (2013). Bacteria-human somatic cell lateral gene transfer is enriched in cancer samples. PLoS computational biology9(6), e1003107.

[12] Sharma A, Singh P. Detection of transgenerational spermatogenic inheritance of adult male acquired CNS gene expression characteristics using a Drosophila systems modelPLoS One 4, e5763 (2009); Sharma, A. (2013). Transgenerational epigenetic inheritance: focus on soma to germline information transfer. Progress in biophysics and molecular biology, 113(3), 439-446; Sharma A. Novel transcriptome data analysis implicates circulating microRNAs in epigenetic inheritance in mammalsGene 538:366-372 (2014); Sharma A. Bioinformatic analysis revealing association of exosomal mRNAs and proteins in epigenetic inheritanceJ. Theor. Biol. 357:143-149 (2014).

[13] Bowler, P. J. (1992). The eclipse of Darwinism: Anti-Darwinian evolution theories in the decades around 1900. JHU Press.

[14] Gould, S. J. (2002). The structure of evolutionary theory. Harvard University Press.

[15] Morange, M. (2010). What history tells us XXII. The French neo-Lamarckians. Journal of biosciences35(4), 515.

[16] Osborn, Henry Fairfield. 1891. The Present Problem of Heredity. The Atlantic Monthly 57, 363.

[17] Lenoir, Tim and Cheri Ross. 1996. The Naturalized History Museum. In Peter Galison and David Stump, eds., The Disunity of Science: Boundaries, Contexts, and Power. Stanford; Stanford University Press: pp. 370-397.

[18] Lenoir, Tim and Cheri Ross. 1996. The Naturalized History Museum. In Peter Galison and David Stump, eds., The Disunity of Science: Boundaries, Contexts, and Power. Stanford; Stanford University Press: pp. 370-397.

Epigenetics: The Next Frontier for Cancer Research

(This article was originally published in the March 2015 issue of Frontline Genomics magazine–A downloadable .pdf of that article is also available here)


by Shea Robison (@EpigeneticsGuy)

(See also Mosaic Epigenetic Dysregulation of Ectodermal Cells in Autism Spectrum DisorderAutism, Ethics and Epigenetics, and Epigenetics Minority Report Part I: Epigenetics, blame, precrime and politics)

Epigenetics deals with the biochemical processes ‘above’ or ‘before’ the genes which regulate the expression of genes in the genome, usually in response to influences in the immediate environment. What is particularly intriguing about epigenetics is how much it blurs the traditional boundaries we have erected between our genes and our environments. The novel complications introduced by epigenetics suggest—if not require—commensurately novel ways of conceptualizing our relationships with ourselves and with our environments that transcend this conventional dichotomization.

The unique nexus of genetics and the environment presented by epigenetics is of considerable practical relevance for diseases such as cancer which have as yet defied understanding via existing approaches that dichotomize genetics versus the environment (or vice versa). In this context, one major purpose of this article is to provide a brief survey of how the conventional emphasis on genetics in cancer research is being extended and empowered by epigenetics to perhaps finally realize the much-anticipated promise of cancer genomics[1].

Cancer, genes and “bad luck”

The unique perspective from epigenetics in cancer as compared to the more conventional dichotomy of genes versus the environment are particularly noticeable in the discussions of a recent paper by Cristian Tomasetti and Bert Vogelstein[2] on the causes of cancer which has already generated a significant amount of controversy[3].

In this paper the main question the authors attempt to answer is why there is such a disparity in the incidence of cancer between different kinds of tissues—e.g., as the authors note, “the lifetime risk of being diagnosed with cancer is 6.9% for lung, 1.08% for thyroid, 0.6% for brain and the rest of the nervous system, 0.003% for pelvic bone and 0.00072% for laryngeal cartilage,” just as “cancer risk in tissues within the alimentary tract can differ by as much as a factor of 24 [esophagus (0.51%), large intestine (4.82%), small intestine (0.20%), and stomach (0.86%)].” These disparities in risk of cancer between tissue types has been recognized for more than a century, but have not yet been reducible to either hereditary or environmental factors, which until now have been the only ways to parse the causes of cancer.

Building on Vogelstein’s previous pioneering work in somatic mutation, or mutational changes in cells’ DNA that are not passed along via the germ line but which occur during a person’s life[4], Tomasetti and Vogelstein hypothesized that the relative incidences of cancer in different kinds of tissues could be caused by random mistakes when DNA is copied during cell division. In other words, the more times cells in a particular tissue type divide, the more opportunities for such copying errors to occur, the greater the risk of cancer.

However, to test this idea Tomasetti and Vogelstein needed a way to assess the rates of cell division of different kinds of tissues. Because only stem cells (versus differentiated cells) live long enough to initiate a tumor, Tomasetti and Vogelstein plotted the rates of stem cell divisions of the 31 tissue types for which the rates of stem cell divisions are known against the lifetime risk for cancer for each type of tissue on a log-log axis, predicting that “there should be a strong, quantitative correlation between the lifetime number of divisions among a particular class of cells within each organ (stem cells) and the lifetime risk of cancer arising in that organ”[5].

Data from Tomasetti and Vogelstein (2015), chart from Jennifer Couzin-Frankel at without permission
Data from Tomasetti and Vogelstein (2015), chart from Jennifer Couzin-Frankel at without permission

As shown in the figure above, there is a clearly noticeable relationship between these two very different measures. Tomasetti and Vogelstein report a strong positive correlation (0.80) between the lifetime risk of cancer and the number of stem cell divisions for a particular tissue type. From this correlation, the authors thereby conclude that around two-thirds of the variation in cancer risk between tissue types can be explained by the total number of stem cell divisions unique to that tissue.

To distinguish this stochastic cell division from external environmental and heredity causes, Tomasetti and Vogelstein construct an “extra risk score” (ERS) as a function of lifetime risk and the total number of cell divisions (log10 values). Utilizing machine learning methods and unsupervised classification, the 31 cancers clustered into two groups, high ERS (9) and low ERS (22): the higher the ERS (basically, the higher the risk of cancer relative to the number of stem cell divisions), the more likely are external environment factors to play a role. The authors found that the high ERS cancers were those with known links to specific environmental or hereditary risk factors, with the low ERS cancers being more likely to be caused by these stochastic errors during DNA replication.

These findings are particularly noteworthy for a couple of reasons. First, because before now the term “environmental” in cancer epidemiology has been used to denote anything not hereditary, such that these kinds of developmental processes had been “grouped with external environmental influences in an uninformative way.” Now these stochastic errors in DNA replication can be distinguished from external environmental factors. Second, because these non-hereditary genetic causes were found to contribute more to cancer risk than either hereditary or external environmental factors. This is important because, as reiterated by Tomasetti in a follow-up interview with Science, “if you go to the American Cancer Society website and you check what are the causes of cancer, you will find a list of either inherited or environmental things. We are saying two-thirds is neither of them”[6].

So what?

What are the implications of this identification of a third way by Tomasetti and Vogelstein, and how is it related to epigenetics?

To the first point, as explained by one of the reviewers of the Tomasetti and Vogelstein paper[7], it is—or should be—common knowledge that even though the somatic mutations identified by Tomasetti and Vogelstein are legitimately genetic phenomena, they “are not in the germ line…are not transmitted from parents to offspring…don’t generate family risk correlations [and therefore] can’t be found by GWAS or other studies based on sequencing inherited genomes.” This reviewer also describes how it is—or should be— common knowledge that “environmental or life-history risk factors, like diet or reproductive history and so on,” can affect the risk of mutations identified by Tomasetti and Vogelstein, but that because this exposure “has to affect a cell in a given tissue and in a particular relevant gene being used by that tissue,” the net effect of these mutagens, and hence their predictability, is usually very small. In the end, for this reviewer the Tomasetti and Vogelstein paper uses new data but doesn’t show much that wasn’t already understood; perhaps the most salient point of this paper is how it demonstrates that “the love affair with inherited genotypes, enabled, encouraged, and funded by a variety of enthusiasms, opportunities, and vested interests, has distracted attention from working from what we knew.”

However, this point about the effects of age on the rate of somatic mutation is what opens the door for an epigenetic explanation of Tomasetti and Vogelstein’s results. Although Tomasetti and Vogelstein do not explicitly identify the epigenetic components of their findings as such, the copying errors which are such an important component of their model likely have epigenetic causes. This oversight is more than a little curious as Vogelstein has been a central figure in cancer epigenetics from its very beginning.[8]

To explain how this might work, the reviewer from before goes on to identify a very clear environmental factor related to cancer risk not addressed by Tomasetti and Vogelstein in their model: “If mutations arising by chance during cell division ultimately lead to transforming genotypes in some cells, the longer one lives the more likely such changes are likely to arise in at least one such cell in the person. This is generally why most cancer rates rise with age in ways correlated with rates of cell division…That is environmental causation, even if indirect!”[9] This oversight about the causal influence of age, “though it won’t change the empirical fact that neither inherited genotypes nor most environmental exposures do not have highly predictive effects,”[10] suggests that Tomasetti and Vogelstein missed something important.

There are a number of recent papers published on the connections between DNA methylation and aging which have relevance for this proposed connection between somatic mutations and cancer. In particular, a 2013 paper by Steve Horvath describes his discovery of a highly accurate epigenetic clock based on DNA methylation age as a measure of the cumulative effect of an epigenetic maintenance system which predicts not the age of the cells but of the person the cells inhabit[11]. The median error of this clock is 3.6 years, which means it can predict the age of half the donors to within 43 months for a broad selection of tissues. Horvath also analyzed 6,000 cancer samples of 20 cancer types, all of which showed significant age acceleration, except for “a significant negative relationship between age acceleration and the number of somatic mutations.” Subsequent studies have also found an advanced methylation aging rate in tumor tissue, and that DNA methylation-derived measures of accelerated ageing predict mortality independently of health status, lifestyle factors, and known genetic factors[12].

That epigenetics could be playing such a significant role in this longstanding puzzle about the disparity between the cancer risks of different tissue types, is intriguing. These results are preliminary at best, but quite suggestive of the profound role of epigenetics in cancer. Tomasetti and Vogelstein provided one important piece by identifying the role of stem cell divisions in risk of cancer. The next step is suggested by the connection between DNA methylation, somatic mutation, aging and cancer. The next step remains to be seen, but with the recent release of the first full mappings of the human epigenome, new developments are likely to come even more frequently.

[1] Lima, S. C., Hernandez-Vargasl, H., & Hercegl, Z. (2010). Epigenetic signatures in cancer: Implications for the control of cancer. Current Opinion in Molecular Therapeutics, 12(3), 316-324; Verma, M. (Ed.). (2015). Cancer Epigenetics: Risk Assessment, Diagnosis, Treatment, and Prognosis. Humana Press; Ling, H., Vincent, K., Pichler, M., Fodde, R., Berindan-Neagoe, I., Slack, F. J., & Calin, G. A. (2015). Junk DNA and the long non-coding RNA twist in cancer genetics. Oncogene 34(8). Vad-Nielsen, J., & Nielsen, A. L. (2015). Beyond the Histone Tale: HP1α Deregulation in Breast Cancer Epigenetics. Cancer biology & therapy, (Just accepted for publication).

[2] Tomasetti, C. and B. Vogelstein (2015). Variation in cancer risk among tissues can be explained by the number of stem cell divisions. Science 347(217), 78-81.

[3] Divide and Cancer? Stem Cell Divisions Impact Tissue’s Cancer Risk. (2015, January 11). Retrieved February 26, 2015, from; Couzin-Frankel, J. (2015, January 1). The simple math that explains why you may (or may not) get cancer. Retrieved February 26, 2015, from; Knoepfler, P. (2015, January 2). Review of Vogelstein “Bad Luck” Cancer & Stem Cell Paper in Science. Retrieved February 26, 2015, from; Meyer, A. (2015, January 2). The Bad Luck of Improper Data Interpretation · Retrieved February 26, 2015, from; O’Hara, B., & GrrrlScientist. (2015, January 2). Bad luck, bad journalism and cancer rates. Retrieved February 26, 2015, from; Weiss, K. (2015, January 5). Is cancer just bad luck? Part I. Known risk factors are poor predictors. Retrieved February 20, 2015, from; Weiss, K. (2015, January 6). Is cancer just bad luck? Part II. It’s a genetic, but usually unpredictable, disease. Retrieved February 20, 2015, from; Couzin-Frankel, J. (2015, January 13). Bad luck and cancer: A science reporter’s reflections on a controversial story. Retrieved February 26, 2015, from

[4] Powell, S. M., Zilz, N., Beazer-Barclay, Y., Bryan, T. M., Hamilton, S. R., Thibodeau, S. N., Vogelstein, B., and Kinzler, K. W. (1992). APC mutations occur early during colorectal tumorigenesis. Nature 359, 235-237; Su, L. K., Vogelstein, B., and Kinzler, K. W. (1993). Association of the APC tumor suppressor protein with catenins. Science 262, 1734-1737.

[5] Tomasetti, C. and B. Vogelstein (2015). Variation in cancer risk among tissues can be explained by the number of stem cell divisions. Science 347(217), 78-81.

[6] Couzin-Frankel, J. (2015, January 13). Bad luck and cancer: A science reporter’s reflections on a controversial story. Retrieved February 23, 2015, from

[7] Weiss, K. (2015, January 5). Is cancer just bad luck? Part II. It’s a genetic, but usually unpredictable, disease. Retrieved February 20, 2015, from

[8] Feinberg, A. P., & Vogelstein, B. (1983). Hypomethylation distinguishes genes of some human cancers from their normal counterparts. Nature, 301(5895), 89-92.

[9] Weiss, K. (2015, January 5). Is cancer just bad luck? Part II. It’s a genetic, but usually unpredictable, disease. Retrieved February 20, 2015, from

[10] Weiss, K. (2015, January 5). Is cancer just bad luck? Part II. It’s a genetic, but usually unpredictable, disease. Retrieved February 20, 2015, from

[11] Horvath, S. (2013). DNA methylation age of human tissues and cell types. Genome biology, 14(10), R115.

[12] Marioni, R. E., Shah, S., McRae, A. F., Chen, B. H., Colicino, E., Harris, S. E., … & Deary, I. J. (2015). DNA methylation age of blood predicts all-cause mortality in later life. Genome Biol, 16(1), 25.