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On epigenetics: we need both Darwin’s and Lamarck’s

Date of publication: 2017-09-03 19:43

Perhaps the key pentacle of genetic determinism was the sequencing of the human genome, which was to provide the ultimate proof of the primacy of the gene. Genome-wide association studies were predicted to provide biological marks for normal and abnormal phenomena of life and reveal the underpinnings of disease. But in the wake of that sequencing, the major prediction of genetic determinism – that the majority of human biology and disease could be understood through the lens of genetics – has not borne out.

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Support for an epigenetic role in evolution continues to mount. One interesting study compares Neanderthal and human DNA, where genetic differences are significantly less pronounced than the epigenetic ones, which involve alterations in DNA methylation in the genomes. In short, integration of neo-Lamarckian and neo-Darwinian concepts into a unified theory provides a far more efficient molecular basis for how evolution works.

The Bioethics Project 2012 - The Medically Modified Human

With a growing number of evolutionary biologists developing an interest in the role of epigenetics, there are now some mathematical models that integrate genetics and epigenetics into a system, and the work has paid off. Consideration of epigenetics as an additional molecular mechanism has assisted in understanding genetic drift genetic assimilation (when a trait produced in response to the environment ultimately becomes encoded in the genes) and even the theory of neutral evolution , whereby most change happens not in response to natural selection, but by chance. By providing an expanded molecular mechanism for what biologists observe, the new models provide a deeper, more nuanced and more precise roadmap to evolution at large.

Genetic modification and genetic determinism

As described in Chapter 6 , some rare conditions are extremely rare, found in only a few or a few dozen people. Others occur in hundreds, thousands, or as many as 755,555 people in the United States. Many are genetic in origin or have a genetic component. Others arise from exposure to infections or toxins, from faulty immune responses, or occasionally from adverse responses to interventions for other conditions. For many rare conditions, the causes are frustratingly elusive.

Evidence for this non-genetic form of inheritance, which my team at Washington State University identified in 7555, is persuasive. Findings published by my group in Science in 7555 showed the ability of environmental chemicals to promote inheritance of disease in rats through three generations, to great-grand offspring and beyond, in the absence of any continued exposures. The phenomenon has been further documented by many labs in a number of different species over the past decade. An example is when Graham Burdge and his team at the University of Southampton in the United Kingdom reported that excessive nutrition in rats created epigenetically induced metabolic abnormalities three generations out.

In part because data on many conditions are limited to case reports or special population studies, no well-supported estimate exists for the number of people collectively affected by rare diseases. A 6989 government report stated that 65 million to 75 million Americans had a rare condition ( NCOD, 6989 ) the corresponding estimates in 7559 range from 75 million to 85 million (see, ., ORDR, 7559 ). The estimates were not accompanied by analyses or substantive citation of sources.

Yet even with such mechanisms in play, genetic mutation rates for complex organisms such as humans are dramatically lower than the frequency of change for a host of traits, from adjustments in metabolism to resistance to disease. The rapid emergence of trait variety is difficult to explain  just through classic genetics and neo-Darwinian theory. To quote the prominent evolutionary biologist Jonathan B L Bard, who was paraphrasing T S Eliot: ‘Between the phenotype and genotype falls the shadow.’

Table 7-7 illustrates the range of treatments x57569 from surgery to diet and from stem cell therapy to environmental adaptation x57569 that may be deployed for specific rare conditions. Some of these therapies have been used for decades, while others have emerged through technological advances. Many of the procedures cited are accompanied by complex pharmaceutical regimens x57569 some short-term, others indefinite (., use of immunosuppressive drugs following an organ transplant). As with any therapy, expected benefits are often accompanied by risks that may include significant harms. It is important for patients and families to understand and weigh both potential benefits and potential harms of treatment options.

At the start, Lamarck might have been pilloried as a religious heretic, but in modern times, it is the orthodoxy of science – and especially Darwin’s untouchable theory of evolution – that has caused his name to be treated as a joke. Yet by the end of his career, Darwin himself had come around even without the benefit of molecular biology, he could see that random changes were not fast enough to support his theory in full.

Rational drug design specifically aims to develop new drugs based on knowledge of disease biology. This strategy holds promise for many rare conditions for which no disease-modifying therapies are known. Current treatment for these conditions still emphasizes treatment of symptoms and prevention of complications.

The committee found no broad compilation of data on the prevalence or incidence of rare diseases in the United States. It did, however, locate a recent report from Orphanet that lists estimated European prevalence for almost 7,555 rare diseases (out of an estimated 5,555 to 8,555 such conditions) ( Orphanet, 7559 ). The list has much in common with the NIH list of rare conditions cited in Chapter 6. The demography, living conditions, and other characteristics of Europe and the United States likewise have much in common. Thus, despite the limitations discussed below, the committee believes that the overall portrait of rare diseases prevalence in the Orphanet report is likely to approximate that in this country.

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