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History Connections: The Epigenetics Revolution, Part 1


April 29, 2011
By Steve Zoltai

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It seemed like a case of Bertlmann’s socks for biologists. Reinhold
Bertlmann was an Austrian theoretical physicist noted for – among other
things – his fondness for never wearing matching socks.

It seemed like a case of Bertlmann’s socks for biologists. Reinhold Bertlmann was an Austrian theoretical physicist noted for – among other things – his fondness for never wearing matching socks. An allegory based on Bertlmann’s peculiar wardrobe choices illustrates the quirkiness of quantum mechanics. It runs like this: Suppose that Bertlmann’s socks were rigorously colour co-ordinated as well as mismatched. If he wore a red sock, the other was always green, and a blue sock was always matched with orange. We could be absolutely certain that if we only saw one of Bertlmann’s socks, and it was orange, the other should be blue and definitely could not be red or green. Assuming that we could persuade Bertlmann to exchange a red sock for a blue one while we were watching, common sense tells us that the other sock is not going to somehow turn orange. Yet, in the natural world, on a subatomic level, this kind of counterintuitive sleight of hand seemed to be happening – and is now actually known to occur.

Darwin-1  
Charles Darwin’s On the Origin of Species celebrated its 150th anniversary in 2009.

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Many organisms were displaying a remarkable ability to radically alter their bodies – their phenotypes – in response to specific environmental cues. In a piece of leger de main reminiscent of Bertlmann’s socks, for example, the blue-headed wrasse has shown itself capable of changing its sex on demand. It is one of several species of fish whose sex is determined by others of the same species it meets. If an immature wrasse encounters an area with many females defended by a single male, the young fish will develop into a female. On the other hand, had the immature newcomer encountered an area undefended by a male, it would become male itself. More surprisingly, the wrasse is capable of changing sex again, if necessary, later in its life. “If the territorial male dies, one of the females (usually the largest) becomes a male; within a day, its ovaries shrink and testes grow.”1

And human beings. While our species is capable of creating billions of different types of immune cells from our genetic repertoire, the actual types of antibody-producing cells our bodies create are not determined by our chromosomes, but by the bacteria and viruses we encounter. It is a personalized response to environmental conditions. We can also regulate our muscular phenotype. Continued physical stress on muscles will cause them to grow. Anyone who has seen before-and-after pictures of a bodybuilder knows how dramatic this change can be. Likewise, experience alters human brain development making learning possible.2

Examples of this type of environmentally influenced phenotypic plasticity have been well known since the late 19th century. Factors such as temperature, nutrition, light, the presence of predators and other agents can all have a profound effect on an organism’s phenotype. But how is all this variation, this phenotypic plasticity possible? And what is the mechanism that permits this amazingly flexible response to environmental conditions? Clearly, not everything that determines the physical expression of our bodies is predetermined in the packaged DNA of a fertilized egg.

MEANWHILE, IN SWEDEN
Lars Bygren was in for a shock. Lying in the registries of births and deaths of Sweden’s isolated northernmost county was a secret that turned traditional scientific thinking on its head.

Registry-1  
A secret lay hidden in the registries of births and deaths of Sweden’s northernmost county. Photo by Jason Romero, CMCC


 

Bygren, a preventive-health specialist, knew that the inhabitants of Norrbotten had experienced recurring cycles of feast and famine during the early to mid-19th century. While some years were marked by complete crop failure, others produced an extravagance of abundance. Villagers, who starved in the lean years, gorged themselves in seasons of plenty. In the 1980s, Bygren became interested in the potential long-term health effects of these cycles of feast and famine on Norrbotten’s children and wondered what effect it would have on the health of future generations. By analyzing detailed harvest records and comparing them with a random sample of individuals born in 1905, Bygren was able to trace their parents and grandparents and find out how much food had been available to them in their youth. When Bygren analyzed the data, it seemed to suggest that boys who overate during winters of plenty produced sons and grandsons who lived shorter lives, dying an average of six years earlier than the grandsons of boys who had suffered near starvation. The difference in longevity ballooned to an incredible 32 years when controlled for socioeconomic variations. Further research confirmed the reduction in life spans and revealed a similar relationship along the female line. In short, “the data suggested that a single winter of overeating as a youngster could initiate a biological chain of events that would lead one’s grandchildren to die decades earlier than their peers.”3 How is this possible?

Scientific orthodoxy maintains “that DNA carries all our heritable information and that nothing an individual does in their lifetime will be biologically passed to their children.”4 Bygren’s research implied that an environmental effect can be inherited in humans and seemed to suggest that genes have a “memory” – that the lives of your immediate ancestors can directly affect you despite never having experienced health-impacting events yourself. Conversely, what you do in your lifetime could, in turn, affect your grandchildren.

According to Charles Darwin, who marked a double anniversary in 2009 – the bicentennial of his birth and the 150th anniversary of the publication of On the Origin of Species – changes in species came about at the genetic level. When environmental conditions change, forces of natural selection increase the survival of individuals with genes that are more adaptive to changing conditions or through the creation of mutations that turn out to be more adaptive than those of other individuals within the species. Natural selection, through death, removes less adaptive genes and gives an edge to favourable genetic material and the population as a whole evolves. But this interplay between selection and mutation was supposed to bring about changes to the species as a whole, not just to individuals – the unit that natural selection acts on.5 Furthermore, “any such effects of nurture (environment) on a species’ nature (genes), was [sic] not supposed to happen so fast . . . evolutionary changes take place over many generations and through millions of years of natural selection.”6 The immediacy of these changes even appeared to invoke the shade of a long banished ghost – the Lamarckian notion that evolution was driven in part by the inheritance of acquired traits. Bygren’s research threatened to reopen the old nature versus nurture debate and overthrow the Darwinian apple cart.

ENTER THE EPIGENOME
At the heart of these seeming contradictions is epigenetics. The new science of epigenetics proposes the notion that changes in gene expression may take place in an organism during its lifetime. These changes do not involve alterations to the fundamental genetic code but can still cause heritable effects, effects that get passed down to at least one successive generation. “These patterns of gene expression are governed by the cellular material – the epigenome – that sits on top of the genome. It is these epigenetic “marks” that tell your genes to switch on or off, to speak loudly or whisper. It is through epigenetic marks that environmental factors like diet, stress and prenatal nutrition can make an imprint on genes that is passed from one generation to the next.”7

Epigenetics adds a whole new perspective to understanding genes beyond the DNA and incorporates consideration of genomic and environmental inputs that generate the instructions for phenotype change.8 Its proposed system of control switches governing gene expression may be compared to the relationship between a music score– (the DNA) and how the music is played (the epigenome). Like DNA, the score is a fixed arrangement of notes, but how a musician plays the notes can differ dramatically depending on who is playing it or which interpretation they choose to put on the melody. Some notes may be played fast, others slow, some loud, some softly. Anyone who has heard Glenn Gould’s unorthodox interpretation of Brahms’s First Piano Concert in D minor knows how radically different renditions of the same score can be. Epigenetics provides the framework for the interpretation of our hard-wired genetic material –interpretations which are influenced by environmental factors – and these interpretations, for good or ill, may be passed on to future generations.

The concept that genes and the environment are not mutually exclusive but inextricably intertwined is at the vanguard of a paradigm shift in our understanding of how evolution can act that rewrites the rules of disease, heredity, and identity.9 “It will change the way the causes of disease are viewed, as well as the importance of lifestyles and family relationships. What people do no longer just affects themselves, but also can determine the health of their children and grandchildren in decades to come.”10 Paradigm shifts of this magnitude, however, often come with far-reaching and sometimes unanticipated societal consequences. Advances in our understanding of epigenetic mechanisms may, on the one hand, lead to powerful new therapies, but also could present the ethically laden potential to engineer human health into future generations.11

AND WHAT does this have to do with CHIROPRACTIC?
Quite a lot, as it turns out.

According to Dr. Marion McGregor, Director of Year II Education at the Canadian Memorial Chiropractic College (CMCC), “It is really challenging to recognize there is so much of relevance in epigenetics, tying so many different fields together. It actually touches all of the sciences, including the clinical sciences, and ties them all together. It is truly the ultimate in integration. Everybody has had their separate piece, their separate area. Epigenetics is what assimilates all of them.”

Epigenetics has implications for three core areas of chiropractic practice: mechanobiology, pain and wellness. But it is in the area of mechanobiology that, for chiropractors, the rubber really hits the road.

“When you start to look at the relationships between mechanobiology, the individual and epigenetics,” Dr. McGregor observes, “they are expansive and incredibly complex. You’ve got the environmental system interacting in a number of different ways. We are just beginning to tease out the variety of events that happen in a single cell if we do different things to it. In chiropractic, we possess an anecdotal history of all kinds of clinical behaviours that are difficult to understand or explain and that may only occur once in a single subject, and never again. Mechanobiology and epigenetics provide us with the opportunity to observe these phenomena through new theoretical perspectives. This has opened up an entirely new science that allows us to look towards putting together a future that makes some real sense.”

In Part 2 of The Epigenetics Revolution, we will take a deeper look at the implications of epigenetics for mechanobiology, and also explore how epigenetics opens doors for the pain model and wellness. It will appear In the June 2011 issue of Canadian Chiropractor magazine.

REFERENCES

  1. Gilbert SF, Epel D. Ecological Developmental Biology: Integrating Epigenetics, Medicine and Evolution. Sunderland, MA: Sinauer Associates; 2009; p. 5.
  2.  Ibid.
  3. Cloud J. Why Your DNA Isn’t Your Destiny, http://www.time.com/time/printout/0,8816,1951968,00.html
  4. The Ghost in Your Genes, BBC Science and Nature, http://www.bbc.co.uk/sn/tvradio/programmes/horizon/ghostgenes.shtml
  5. Gilbert SF, Epel D. Ecological Developmental Biology: Integrating Epigenetics, Medicine and Evolution. Sunderland, MA: Sinauer Associates; 2009; p. 307.
  6. Cloud J. Why Your DNA Isn’t Your Destiny, http://www.time.com/time/printout/0,8816,1951968,00.html
  7.  Ibid.
  8. Gilbert SF, Epel D. Ecological Developmental Biology: Integrating Epigenetics, Medicine and Evolution. Sunderland, MA: Sinauer Associates; 2009; p. 12-13.
  9. Watters, E. DNA Is Not Destiny. Discover Magazine, November, 2006. http://discovermagazine.com/2006/nov/cover
  10.  The Ghost in Your Genes, BBC Science and Nature,http://www.bbc.co.uk/sn/tvradio/programmes/horizon/ghostgenes.shtml
  11. Ellington, AD. Epigenetics and Society. The Scientist. March, 2011: p. 14.

Steve Zoltai is the collections development librarian and archivist for CMCC and is a member of the Canadian Chiropractic Historical Association. He was previously the assistant executive director of the Health Sciences Information Consortium of Toronto. He has worked for several public and private libraries and with the University of Toronto Archives. Steve comes by his interest in things historical honestly – he worked as a field archeologist for the Province of Manitoba. He can be contacted at szoltai@cmcc.ca.


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