10 Scientific Papers That Can Transform Your Understanding of Health & Medicine

young-woman-readingIn 2015 I put up an article here on the site entitled 10 Scientific Papers That Can Transform Your Understanding of Health & Medicine. In that article I listed 10 scientific papers that I believe everyone who’s interested in health and medicine should take the time to read. I thought I’d do the same thing this year. I’ve selected 10 new scientific articles for today’s post; all of which I like a lot and think are highly informative.

(R)evolutionary science

There’s a lot of bad science floating around. To an untrained eye, it can be very difficult to separate the bad stuff from the good stuff and locate high-quality research studies and papers. That’s one of the reasons why I frequently share links to scientific papers here on the site. I don’t claim that all of the papers listed in this post are perfect in every shape and form; however, I would argue that they represent some of the best modern science has to offer.

In the post I put up at the end of 2015 I made the case that anyone who reads and understands the 10 scientific papers I listed would likely know more about the true causes of chronic illness than most medical doctors, as well as have a better understanding of what it takes to solve many of the public health problems of our time. This holds true for today’s post as well.

Most students enrolled in health-related study programs, including students who study nutrition or medicine, learn little to nothing about Darwinian theory, hunter-gatherers, evolutionary health, or Paleolithic nutrition; hence, they aren’t equipped with all of the knowledge they need make sense of why disease exists and what it takes to build a robust, healthy human. Personally, I learned nothing about those things in school. I had to read up on those subjects on my own time.

Just like last time, all of the articles I’ve chosen are review papers that look into what I consider to be very important medical-related topics. I’ve steered away from articles that are very technical, so as to give the average Joe a fighting chance at understanding what all this science stuff is all about. Despite this effort, I realise that some people may find it difficult to grasp their heads around some of the articles in the list. What I would like to say to those people is that the most important thing isn’t that one understands all the details, but rather that one is able to make sense of the main ideas and concepts the authors of the papers are trying to present.

With that said, let’s get onto the articles… I hope you find them enjoyable.

1. Medicine in the 21st century: towards a Darwinian medical epistemology.

Abstract: In this review we reflect upon the new science of Darwinian medicine. It is a tenet of modern biology that evolutionary theory as proposed by Charles Darwin and further refined via the new synthesis is the common thread that ties all of biological inquiry into a coherent whole. This review aims at making clear how evolution by natural selection is relevant to medicine. A set of pertinent examples linking Homo sapiens sapiens‘ present disease conditions to its evolution during the Late Pleistocene and Holocene epochs are discussed. The review concludes with observations as to the epistemological value of evolutionary theory as a heuristic tool for articulating a medical paradigm in accord with modern biology.

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My comment: Over the past couple of decades, many scientific papers specifically dedicated to Darwinian/evolutionary medicine have been published. I’ve seen/come across most, if not all, of these papers, and I’ve read many of them. Among all of the papers I’ve read or scanned through, the above one is my favorite. I think it’s truly great. In the article, the author, Ángel A. Román-Franco, takes a close look at many of the theories, principles, and concepts that make up the field of Darwinian medicine and elegantly explains why evolution is integral to medicine. He makes the case that it’s long past time that medical schools open their doors to Darwin. I concur.

2. Evolution of Inflammatory Diseases

Abstract: The association of inflammation with modern human diseases (e.g. obesity, cardiovascular disease, type 2 diabetes mellitus, cancer) remains an unsolved mystery of current biology and medicine. Inflammation is a protective response to noxious stimuli that unavoidably occurs at a cost to normal tissue function. This fundamental tradeoff between the cost and benefit of the inflammatory response has been optimized over evolutionary time for specific environmental conditions. Rapid change of the human environment due to niche construction outpaces genetic adaptation through natural selection, leading increasingly to a mismatch between the modern environment and selected traits. Consequently, multiple tradeoffs that affect human physiology are not optimized to the modern environment, leading to increased disease susceptibility. Here we examine the inflammatory response from an evolutionary perspective. We discuss unique aspects of the inflammatory response and its evolutionary history that can help explain the association between inflammation and modern human diseases.

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My comment: Why is the human immune system designed the way it is? Why and how does inflammation cause disease? Why do so many contemporary humans develop chronic inflammatory diseases? The above article, which I came across very recently, answers all of these questions and more. It’s a really great paper. It’s definitely one of the best papers on inflammation I’ve ever read, and that’s saying something, seeing as I’ve read a lot of articles covering inflammation-related topics. Unlike many other papers on immunity and inflammation, the above one has evolutionary wisdom integrated into it. Moreover, the authors not only describe what causes inflammation, but also look into the mechanisms linking inflammation with disease.

3. Chronic inflammatory diseases are stimulated by current lifestyle: how diet, stress levels and medication prevent our body from recovering

Abstract: Serhan and colleagues introduced the term “Resoleomics” in 1996 as the process of inflammation resolution. The major discovery of Serhan’s work is that onset to conclusion of an inflammation is a controlled process of the immune system (IS) and not simply the consequence of an extinguished or “exhausted” immune reaction. Resoleomics can be considered as the evolutionary mechanism of restoring homeostatic balances after injury, inflammation and infection. Under normal circumstances, Resoleomics should be able to conclude inflammatory responses. Considering the modern pandemic increase of chronic medical and psychiatric illnesses involving chronic inflammation, it has become apparent that Resoleomics is not fulfilling its potential resolving capacity. We suggest that recent drastic changes in lifestyle, including diet and psycho-emotional stress, are responsible for inflammation and for disturbances in Resoleomics. In addition, current interventions, like chronic use of anti-inflammatory medication, suppress Resoleomics. These new lifestyle factors, including the use of medication, should be considered health hazards, as they are capable of long-term or chronic activation of the central stress axes. The IS is designed to produce solutions for fast, intensive hazards, not to cope with long-term, chronic stimulation. The never-ending stress factors of recent lifestyle changes have pushed the IS and the central stress system into a constant state of activity, leading to chronically unresolved inflammation and increased vulnerability for chronic disease. Our hypothesis is that modern diet, increased psycho-emotional stress and chronic use of anti-inflammatory medication disrupt the natural process of inflammation resolution ie Resoleomics.

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My comment: This is another great paper on inflammation and inflammation-associated diseases. Leo Pruimboom, one of the authors, always brings evolutionary thoughts into his work and has co-authored several great papers on evolutionary health. In this one, he, together with two other researchers, look into the true causes of modern disease and explain how contemporary environments interact with human genes in such a way that inflammation-related health problems arise.

4. 99th Dahlem Conference on Infection, Inflammation and Chronic Inflammatory Disorders: Darwinian medicine and the ‘hygiene’ or ‘old friends’ hypothesis

Abstract: The current synthesis of the ‘hygiene hypothesis’ suggests that the recent increase in chronic inflammatory disorders is at least partly attributable to immunodysregulation resulting from lack of exposure to microorganisms that have evolved an essential role in the establishment of the immune system. This document provides a background for discussion of the following propositions.

1. The essential role of these organisms is an example of ‘evolved dependence’.
2. The most relevant organisms are those that co-evolved with mammals, and already accompanied early hominids in the Paleolithic.
3. More recently evolved ‘childhood infections’ are not likely to have evolved this role, and recent epidemiology supports this contention.
4. This mechanism is interacting with other modern environmental changes that also lead to enhanced inflammatory responses [inappropriate diet, obesity, psychological stress, vitamin D deficiency, pollution (dioxins), etc.].
5. The range of chronic inflammatory disorders that is affected is potentially larger than usually assumed [allergies, autoimmunity, inflammatory bowel disease, but also vascular disease, some cancers, depression/anxiety (when accompanied by raised inflammatory cytokines), and perhaps neurodegenerative disorders and type 2 diabetes].

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My comment: Graham Rook is one of the world’s leading microbiome researchers. In many of his papers he talks about the old friends hypothesis, the link between the human microbiome and the human immune system, and the evolution of the microbial milieu in which we humans find ourselves. I suspect that no other person knows more about how the relationship between man and microbes has changed throughout evolutionary time than Graham Rook. Many of his papers, including the one above, contain a detailed overview of how our microbial milieu has changed over the past millennia and how these changes have affected our health. One of the things I really like about Dr. Rook is that his work is built on a solid foundation of evolutionary theory. I don’t agree with everything he says; however, there’s no doubt that he is a very skilled and knowledgeable scientist.

5. Cardiovascular disease resulting from a diet and lifestyle at odds with our Paleolithic genome: how to become a 21st-century hunter-gatherer.

Abstract: Our genetic make-up, shaped through millions of years of evolution, determines our nutritional and activity needs. Although the human genome has remained primarily unchanged since the agricultural revolution 10,000 years ago, our diet and lifestyle have become progressively more divergent from those of our ancient ancestors. Accumulating evidence suggests that this mismatch between our modern diet and lifestyle and our Paleolithic genome is playing a substantial role in the ongoing epidemics of obesity, hypertension, diabetes, and atherosclerotic cardiovascular disease. Until 500 generations ago, all humans consumed only wild and unprocessed food foraged and hunted from their environment. These circumstances provided a diet high in lean protein, polyunsaturated fats (especially omega-3 [omega-3] fatty acids), monounsaturated fats, fiber, vitamins, minerals, antioxidants, and other beneficial phytochemicals. Historical and anthropological studies show hunter-gatherers generally to be healthy, fit, and largely free of the degenerative cardiovascular diseases common in modern societies. This review outlines the essence of our hunter-gatherer genetic legacy and suggests practical steps to re-align our modern milieu with our ancient genome in an effort to improve cardiovascular health.

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My comment: This paper is written by Loren Cordain and James H. O’Keefe Jr. It’s fairly old – it was published in 2004 – however, the information contained within it is not obsolete. Far from it. The human genome obviously hasn’t changed much over the past decade; hence, it could be argued that the things Cordain and O’Keefe talk about in the article are as relevant today as they were in 2004. In the time that has passed since this paper was published, the evolutionary health movement has grown tremendously and many new theories and concepts that differ from those that evolutionary scientists such as Cordain, Lindeberg, and O’Keefe put forth in their scientific papers have gained foothold within the ancestral health community. In my opinion, most of these new concepts are inferior to the original evolutionary health concepts that were established via science. I think we would all be wise to take a step back and reconnect with the real science.

6. Paleolithic nutrition. A consideration of its nature and current implications.

The first 100 words of the article: HUMANITY has existed as a genus for about 2 million years, and our prehuman hominid ancestors, the australopithecines, appeared at least 4 million years ago (Table 1). This phase of evolutionary history made definitive contributions to our current genetic composition, partly in response to dietary influences at that time. The foods available to evolving hominids varied widely according to the paleontological period, geographical location, and seasonal conditions, so that our ancestral line maintained the versatility of the omnivore that typifies most primates. Natural selection has provided us with nutritional adaptability; however, human beings today are confronted with diet-related health problems…

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My comment: This paper by Boyd Eaton and Melvin Konner is by many considered to be “the scientific mother” of the Paleo diet movement. Much of the scientific research on Paleo and evolutionary health that has been carried out over the past couple of decades is a part of a scientific lineage that Eaton’s paper gave rise to. If you haven’t already read it, then you should strongly consider doing so now. Perhaps needless to say, not all of the information that Boyd Eaton and Melvin Konner presented in their seminal paper has stood the test of time; however, the fundamental theories and concepts have. Boyd Eaton has always reminded me a little of Yoda. His demeanor is somewhat similar to Yoda’s; moreover, he has a somewhat similar position in the evolutionary health movement as Yoda has in the Jedi order 😛 I doubt he’s as skilled with a lightsaber as Yoda is though.

7. Evolutionary science as a method to facilitate higher level thinking and reasoning in medical training

Abstract: Evolutionary science is indispensable for understanding biological processes. Effective medical treatment must be anchored in sound biology. However, currently the insights available from evolutionary science are not adequately incorporated in either pre-medical or medical school curricula. To illuminate how evolution may be helpful in these areas, examples in which the insights of evolutionary science are already improving medical treatment and ways in which evolutionary reasoning can be practiced in the context of medicine are provided. To facilitate the learning of evolutionary principles, concepts derived from evolutionary science that medical students and professionals should understand are outlined. These concepts are designed to be authoritative and at the same time easily accessible for anyone with the general biological knowledge of a first-year medical student. Thus, we conclude that medical practice informed by evolutionary principles will be more effective and lead to better patient outcomes. Furthermore, it is argued that evolutionary medicine complements general medical training because it provides an additional means by which medical students can practice the critical thinking skills that will be important in their future practice. We argue that core concepts from evolutionary science have the potential to improve critical thinking and facilitate more effective learning in medical training.

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My comment: I’ve made the case many times here on the site that it’s long past time that evolutionary science is incorporated into medical curricula. At present, medical students learn little to nothing about evolutionary theory or Darwinian medicine, which I find extremely worrying. It’s baffling that educational institutions leave Darwin to stand out in the cold, considering that they have so much to gain by letting him inside.

8. How holobionts get sick—toward a unifying scheme of disease

Abstract: All humans, animals, and plants are holobionts. Holobionts comprise the host and a myriad of interacting microorganisms—the microbiota. The hologenome encompasses the genome of the host plus the composite of all microbial genomes (the microbiome). In health, there is a fine-tuned and resilient equilibrium within the members of the microbiota and between them and the host. This relative stability is maintained by a high level of microbial diversity, a delicate bio-geographic distribution of microorganisms, and a sophisticated and intricate molecular crosstalk among the multiple components of the holobiont. Pathobionts are temporarily benign microbes with the potential, under modified ecosystem conditions, to become key players in disease. Pathobionts may be endogenous, living for prolonged periods of time inside or on the host, or exogenous, invading the host during opportunistic situations. In both cases, the end result is the transformation of the beneficial microbiome into a health-perturbing pathobiome. We hypothesize that probably all diseases of holobionts, acute or chronic, infectious or non-infectious, and regional or systemic, are characterized by a perturbation of the healthy microbiome into a diseased pathobiome.

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My comment: Over the most recent decades, numerous scientific articles connecting various diseases and health problems with microbiota disturbances have been published. At this point, virtually every disease under the sun has been scientifically linked with dysbiosis and/or loss of microbiota diversity. It’s become clear that it’s not just some diseases that are associated with microbiome disruption – virtually all diseases are. The authors of the above paper have recognized this fact and are not afraid to speak their minds. In my opinion, they hit the nail on the head when they say that disease goes hand in hand with microbiome disruption. This newfound understanding of the role microbes play in human disease has the potential to completely revolutionize the field of medicine. Historically, mainstream medicine has paid very little attention to the trillions of microorganisms that colonize human bodies. It’s long past time that this changes.

9. Epigenomic programing: a future way to health?

Abstract: It is now generally accepted that the ‘central genome dogma’ (i.e. a causal chain going from DNA to RNA to proteins and downstream to biological functions) should be replaced by the ‘fluid genome dogma’, that is, complex feed-forward and feed-back cycles that interconnect organism and environment by epigenomic programing – and reprograming – throughout life and at all levels, sometimes also down the generations. The epigenomic programing is the net sum of interactions derived from own metabolism and microbiota as well as external factors such as diet, pharmaceuticals, environmental compounds, and so on. It is a growing body of results indicating that many chronic metabolic and degenerative disorders and diseases – often called ‘civilization diseases’ – are initiated and/or influenced upon by non-optimal epigenomic programing, often taking place early in life. In this context, the first 1,000 days of life – from conception into early infancy – is often called the most important period of life. The following sections present some major mechanisms for epigenomic programing as well as some factors assumed to be of importance. The need for more information about own genome and metagenome, as well as a substantial lack of adequate information regarding dietary and environmental databases are also commented upon. However, the mere fact that we can influence epigenomic health programing opens up the way for prophylactic and therapeutic interventions. The authors underline the importance of creating a ‘Human Gut Microbiota and Epigenomic Platform’ in order to facilitate interdisciplinary collaborations among scientists and clinicians engaged in host microbial ecology, nutrition, metagenomics, epigenomics and metabolomics as well as in disease epidemiology, prevention and treatment.

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My comment: Your health and body are shaped by the interactions that take place between your genes and your environment. Over the most recent decades it has become increasingly clear that the human genome is not a “static machinery”, but rather a highly dynamic system that adjusts epigenetically in response to environmental inputs. The authors of the above paper look into the mechanisms by which environmental factors such as diet and gut microbiota affect our health, with a particular emphasis on epigenetic programming occurring early in life. The article is somewhat technical. Don’t be despaired if you don’t understand everything the authors are talking about. The most important thing is that you’re able to grasp your head around the major points they are trying to get across.

10. Timescales of human adaptation: the role of epigenetic processes.

Abstract: Human biology includes multiple adaptive mechanisms that allow adjustment to varying timescales of environmental change. Sensitive or critical periods in early development allow for the transfer of environmental information between generations, which helps an organism track gradual environmental change. There is growing evidence that offspring biology is responsive to experiences encoded in maternal biology and her epigenome as signaled through the transfer of nutrients and hormones across the placenta and via breast milk. Principles of evolutionary and comparative biology lead to the expectation that transient fluctuations in early experience should have greater long-term impacts in small, short-lived species compared with large, long-lived species such as humans. This implies greater buffering of the negative effects of early-life stress in humans, but also a reduced sensitivity to short-term interventions that aim to improve long-term health outcomes. Taking the timescales of adaptation seriously will allow the design of interventions that emulate long-term environmental change and thereby coax the developing human body into committing to a changed long-term strategy, yielding lasting improvements in human health and wellbeing.

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My comment: Biological researchers have historically devoted a lot of attention to how organisms adapt over time to their environments in response to natural selection sculpting their genetic make-up. Much attention has also been devoted to how organisms adjust the workings of their biological systems in response to acute stimuli induced by diet, exercise, etc. Less focus has historically been placed on the epigenetic processes that sculpt organisms during their developmental phase, in large part because it’s only quite recently that we started to elucidate the workings of those processes. Just like the paper entitled Epigenomic programming. A future way to health?, this one sheds light on the epigenetic processes that shape how organisms develop and function. One of the authors is Christopher Kurzawa, a great researcher who’s written several papers on evolution-related topics.

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Comments

  1. Lots of good information, Eirik. Thanks.

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