Posts in category evolutionary medicine

Evolutionary Determinants of Cancer

Mel Greaves, The Institute of Cancer Research

July 20, 2015, doi: 10.1158/2159-8290.CD-15-0439 Full Text PDF

Abstract

Our understanding of cancer is being transformed by exploring clonal diversity, drug resistance, and causation within an evolutionary framework. The therapeutic resilience of advanced cancer is a consequence of its character as a complex, dynamic, and adaptive ecosystem engendering robustness, underpinned by genetic diversity and epigenetic plasticity. The risk of mutation-driven escape by self-renewing cells is intrinsic to multicellularity but is countered by multiple restraints, facilitating increasing complexity and longevity of species. But our own species has disrupted this historical narrative by rapidly escalating intrinsic risk. Evolutionary principles illuminate these challenges and provide new avenues to explore for more effective control.

Significance: Lifetime risk of cancer now approximates to 50% in Western societies. And, despite many advances, the outcome for patients with disseminated disease remains poor, with drug resistance the norm. An evolutionary perspective may provide a clearer understanding of how cancer clones develop robustness and why, for us as a species, risk is now off the scale. And, perhaps, of what we might best do to achieve more effective control. Cancer Discov; 5(8); 1–15. ©2015 AACR.

New articles in EMPH

Microbiology and Ecology Are Vitally Important to Premedical Curricula
Val H. Smith, Rebecca J. Rubinstein, Serry Park, Libusha Kelly, and Vanja
Klepac-Ceraj
Evol Med Public Health published 21 July 2015, 10.1093/emph/eov014
http://emph.oxfordjournals.org/content/early/2015/07/20/emph.eov014.abstract?papetoc

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Clinical Brief
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Horizontal Gene Transfer
Alita R. Burmeister
Evol Med Public Health published 29 July 2015, 10.1093/emph/eov018
http://emph.oxfordjournals.org/content/early/2015/07/28/emph.eov018.full.pdf?papetoc

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Original Research Article
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Why did children grow so well at hard times? The ultimate importance of
pathogen control during puberty
Peeter Hõrak and Markus Valge
Evol Med Public Health published 21 July 2015, 10.1093/emph/eov017
http://emph.oxfordjournals.org/content/early/2015/07/20/emph.eov017.abstract?papetoc
Europeans became larger and smarter throughout the 20^th century despite
the temporally worsening access to nutrients during and after WWII.
Measurements of Estonian adolescent girls born between 1938 -1953 suggest
that a reduction of disease burden during puberty drives secular trends,
overriding the adverse effects of resource shortage at birth.

The evolution of capture myopathy in hooved mammals: a model for human
stress cardiomyopathy?
Daniel T. Blumstein, Janet Buckner, Sajan Shah, Shane Patel, Michael E.
Alfaro, and Barbara Natterson-Horowitz
Evol Med Public Health published 21 July 2015, 10.1093/emph/eov015
http://emph.oxfordjournals.org/content/early/2015/07/20/emph.eov015.abstract?papetoc

Selection shaped us to be endurance athletes…AND couch potatoes!

“Is Exercise Really Medicine? An Evolutionary Perspective:”
By Daniel E. Lieberman
Current Sports Medicine Reports 14, no. 4 (2015): 313–19.
Click here for the open access pdf

This superb short evolutionary analysis of the role of exercise in human health should be required reading for everyone interested in exercise and health…that is, all health professionals, and most of the rest of us us.  Lieberman shows that we were shaped to be endurance athletes by the benefits of chasing big game animals until they could go no further. But our ancestors also faced intermittent calorie shortages that shaped mechanisms to minimize unnecessary exercise, and to shrink unneeded tissues. Extensive daily exercise was so intrinsic to human life that the health benefits of exercise were never a selection force.

Several quotes offer eloquent summaries: READ MORE »

New articles in Evolution, Medicine & Public Health

After a long history of applying the sterile insect technique to suppress populations of disease vectors and agricultural pests, there is growing interest in using genetic engineering both to improve old methods and to enable new methods. The two goals of interventions are to suppress populations, possibly eradicating a species altogether, or to abolish the vector’s competence to transmit a parasite. New methods enabled by genetic engineering include the use of selfish genes toward either goal as well as a variety of killer-rescue systems that could be used for vector competence reduction. This paper reviews old and new methods with an emphasis on the potential for evolution of resistance to these strategies. Established methods of population suppression did not obviously face a problem from resistance evolution, but newer technologies might. Resistance to these newer interventions will often be mechanism-specific, and while it is too early to know where resistance evolution will become a problem, it is at least possible to propose properties of interventions that will be more or less effective in blocking resistance evolution.

John H McCullough
Clinical Brief:  Iron Restriction 
Full Text (PDF)

Amber Gigi Hoi and   Luseadra McKerracher
Clinical Brief:  Breastfeeding and infant growth 
Full Text (PDF)

Progress on reconstituting the depleted biome to prevent immune disorders

A review and update of an important topic

By William Parker and Rajendra A. Morey
Departments of Surgery (WP) and Psychiatry (RAM)
Duke University Medical Center, Durham, NC 27707

Historical Developments

The story of resolving immune dysfunction in Western society is one of uncovering a profound evolutionary mismatch. The story began 39 years ago when a parasitologist, John Turton, intentionally colonized himself with the human hookworm and eliminated his own hayfever [1].  Sadly, the story is littered with long pauses, and Turton’s observations went unappreciated for decades. The story took a new turn in the late 1980s when David Strachan pointed an accusing finger at some aspects of modern sanitation as being responsible for the plague of chronic immune disease affecting Western society [2]. READ MORE »

Fighting HIV Evolution with an Evolved Therapeutic Agent: Phase I Dose Escalation Clinical Trial of a Potent Broadly Neutralizing Human Antibody

In previous commentaries (http://evmedreview.com/?p=1863; http://evmedreview.com/?p=837; http://evmedreview.com/?p=385), I have discussed the critical role of extensive B-cell and immunoglobulin gene evolution in generating broadly neutralizing antibodies for HIV-1.  Of course, the unprecedented magnitude of antibody evolution necessary to achieve potent neutralization of a high percentage of HIV strains reflects the unprecedented evolutionary plasticity of HIV that originates in both high mutation and recombination rates for the HIV genome (Korber et al., 2001).  A new study by Caskey et al. (Nature, 2015) from the Nussenzweig Laboratory reports results for a first-in-human dose escalation phase I clinical trial of a human monoclonal antibody (mAb) specific for the HIV envelope (env) protein. READ MORE »

Ashley Montague on Anthropology and Medicine

Thanks to Holly Smith who provided a copy of a lovely little 1947 article in The Interne, by Ashley  Montague titled, Anthropology in Medicine.
Some quotes offer crucial historical perspective, such as: “Any suggestion that another course should be added to the already overcrowded medical curriculum will justly be viewed with alarm” He goes on to suggest that an anthropological perspective is crucial for physicians to have a view of the whole person in context, and to recognize individual variation as intrinsic to science and medicine.  Click here for the full pdf.

Montague 1947
Montague 1947
Montague titled,

MICROBIOTA Mother’s littlest helpers

By Katie Hinde and  Zachery T. Lewis
Science 26 June 2015:
DOI: 10.1126/science.aac7436 (not open access)

Commensal bacteria underlie, in part, our nutritional status, immune function, and psychological well-being. The trillions of beneficial microbes within our intestinal tract convert dietary nutrients, inhibit pathogen colonization, regulate immune processes, and produce neural signals (1, 2). Advances in our understanding of the importance of microbes have motivated the commercial development of products intended to boost “good” commensals and confer health benefits. Probiotic dietary supplements contain live beneficial microbes hoped to subsequently colonize the gut. Prebiotic nutrients are thought to enhance good gastrointestinal microflora by preferentially nourishing beneficial microbes. Even “psychobiotics” are being explored to ameliorate symptoms of psychiatric illness. These live organisms influence the brain through metabolites and neuroactive compounds in rodent models and preliminary human studies (3). How to most effectively be the landscape architects of our microbial community, however, often remains unclear. An opportunity to gain insights into how natural selection has shaped the coevolution of hosts and microbes can be found in mammalian mother-infant dyads, as our microbiota are ecologically engineered by mothers and breastmilk. Such insights can be leveraged to improve clinical management and nutritional technologies, enhancing human health not just in infancy, but across the life course (4, 5).  Read more (not open access)

Extent of Tumor Evolution as Assessed by Numbers of Nonsynonymous Somatic Mutations Correlates with the Effectiveness of Anti-Checkpoint Therapy

It would be hard to identify an approach to cancer treatment that has received more attention recently than anti-checkpoint therapy (Pollack, 2015).  This strategy for eliminating tumor cells is based on interfering with one or another pathway that inhibits the initial activation or functions of T cells, such as CD8+ cytotoxic T cells (CTL).  Activated tumor-specific CTL can directly kill their targets.  However, if copies of the T-cell surface molecule, PD-1, are bound by their physiological ligands on tumor cells, either PD-L1 or PD-L2, or other cells the ability of the T cell to perform its functions is substantially reduced.  A report published in Science (2015) by Rizvi et al. last month addresses the question of whether tumor mutation burden correlates with response to anti-checkpoint therapy for non-small cell lung cancer (NSCLC).

READ MORE »

Causes and consequences of coagulation activation in sepsis: an evolutionary medicine perspective

By Maiara Marx Luz Fiusa, Marco Antonio Carvalho-Filho1, Joyce M Annichino-Bizzacchi and Erich V De Paula
Published in BMC Med. 2015 May 6;13(1):105. doi: 10.1186/s12916-015-0327-2. (open access)

Abstract

BACKGROUND: Coagulation and innate immunity have been linked together for at least 450 million years of evolution. Sepsis, one of the world’s leading causes of death, is probably the condition in which this evolutionary link is more evident. However, the biological and the clinical relevance of this association have only recently gained the attention of the scientific community.

DISCUSSION: During sepsis, READ MORE »

Stearns – Medzhitov textbook to be published in August

Evolutionary Medicine 
Stephen C. Stearns, the Edward P Bass Professor of Ecology and Evolutionary Biology at Yale University
Ruslan Medzhitov, the David W. Wallace Professor of Immunobiology at Yale University School of Medicine and an Investigator with the Howard Hughes Medical Institute

This textbook is intended for use in undergraduate, graduate, medical school, and continuing medical education (CME) courses, aimed at both students and professionals in medicine and public health.  It discusses the evolution of patients and diseases, defenses and pathogens, cancer as an evolutionary process, vulnerabilities created by the evolution of reproduction, mismatch to modern environments, the evolution of mental disorders, and conflicts between the good of the individual patient and the welfare of the population (see brief Table of Contents below and detailed Table of Contents via the following link). This book’s professional illustrations and summaries of chapters and sections make its messages readily accessible.

To view Chapter 5 and the detailed Table of Contents visit the ‘Sample Content’ link:
http://www.sinauer.com/evolutionary-medicine-704.html READ MORE »

A Functional Classification of Genomic Elements Informed by the Principles of Evolution

In an EMR commentary (http://evomed.org/?p=1644) from March two years ago, I discussed issues related to the functional classification of genomic DNA sequences that arose in the context of claims from the ENCODE (ENCyclopedia Of DNA Elements) consortium.  A particular focus of that piece was an article by Graur and colleagues (2013) that offered an often humorous but rather stinging critique of the definition of “function” applied by the ENCODE authors to genomic DNA sequences.  Graur and two of his associates have now published (2015) an interesting and valuable functional classification of genomic sequences that is critically informed by their understanding of evolution. READ MORE »

Zurich EvMed meeting: Travel support available, Abstracts due NOW

 

Travel support for this meeting is available from Tri-CEM, the new evolutionary medicine Center at Duke University directed by Charlie Nunn.

The abstract deadline is NOW!

Evolutionary Medicine Conference: Interdisciplinary Perspectives on Human Health and Disease

July 30 – August 1, 2015
Institute of Evolutionary Medicine (IEM)
University of Zurich, Switzerland

This international conference will bring together distinguished keynote speakers as well as experts from different research areas (including medicine, anthropology, molecular/evolutionary biology, paleopathology, archaeology, epidemiology, and other fields) to debate the evolutionary origins of diseases and on how the knowledge of the past informs the present and the future. Furthermore, the specific implications of interdisciplinary research in the understanding and management of human health issues will be addressed.

All abstracts for mini-symposia, oral and poster presentations will be reviewed by a scientific committee and – when accepted – published in the Journal of Evolutionary Medicine. The best student abstract will be awarded a prize by the scientific committee. Students can also apply for a competitive travel grant.

 

This is the sister meeting to the recent meeting of the International Society for Evolution, Medicine and Public Health at Arizona State University’s Center for Evolution and Medicine 

An evolutionary strategy for treating metastases

Divergent and convergent evolution in metastases suggest treatment strategies based on specific metastatic sites

By Jessica J. Cunningham, Joel S. Brown, Thomas L. Vincent, and Robert A. Gatenby

In Evol Med Public Health published 20 March 2015, 10.1093/emph/eov006   (open access)

Abstract: Cancer cells, although maximally fit at their primary site, typically have lower fitness on the adaptive landscapes offered by the metastatic sites due to organ-specific variations in mesenchymal properties and signaling pathways. Clinically evident metastases will exhibit time-dependent divergence from the phenotypic mean of the primary population as the tumor cells evolve and adapt to their new circumstances. In contrast, tumors from different primary sites evolving on identical metastatic adaptive landscapes exhibit phenotypic convergence so that, for example, metastases in the liver from different primary tumors will evolve toward similar adaptive phenotypes. The combination of evolutionary divergence from the primary cancer phenotype and convergence towards similar adaptive strategies in the same tissue cause significant variations in treatment responses particularly for highly targeted therapies. This suggest that optimal therapies for disseminated cancer must take into account the site(s) of metastatic growth as well as the primary organ.

Chromosomal Catastrophe (Chromothripsis) Causing Curative Clonal Conquest

Last month, Murphy and colleagues (Cell, 2015) published a fascinating report about a patient with an immunodeficiency syndrome that underwent spontaneous resolution.  The mechanism for this remarkable outcome points to the importance of somatic cell selection and evolution in the origins, pathogenesis, and most dramatically in this case, elimination of disease. READ MORE »

Gil Omenn Prizes awarded at the ISEMPH meeting

Gil Omenn, Matthew Barber, Ann Demogines, & Randolph Nesse

The winners of the Gil Omenn Prize for 2013 and 2014 received recognition and their $5000 prize money at the inaugural meeting of the International Society for Evolution, Medicine & Public Health. Gil Omenn has just announced a major donation to the Society that will sustain the prize for at least three more years.  The prize is awarded for the best article published each year on a topic related to evolution in the context of medicine and public health in any journal.

Matthew Barber was awarded the 2014 Prize for his paper  “Escape from bacterial iron piracy through rapid evolution of transferrin” by Matthew Barber and Nels Elde from the University of Utah. The article appeared in Science 346:1362-6, 2014.
See more at: http://evomed.org/?p=2504#sthash.SdjjYTYI.dpuf
Thanks to the prize committee: Sarah Tishkoff, Joe Alcock, Noah Rosenberg, and Alison Galvani

Ann Demogines was awarded the 2013 Prize for her paper  Dual Host-Virus Arms Races Shape an Essential Housekeeping Protein by Demogines A, Abraham J, Choe H, Farzan M, Sawyer SL (2013). PLoS Biol 11(5):e1001571. doi: 10.1371/journal.pbio.1001571
See more at: http://evomed.org/?p=2080#sthash.utCaEpAG.dpuf
Thanks to the Prize Committee, Allen Rodrigo (chair), Carl Bergstrom, and Sarah Tishkoff

Also, note that the Society now also sponsors the George C Williams Prize for the best article published in the Oxford Press journal, Evolution, Medicine, and Public Health

 

 

Live streaming of Thursday talks at ISEMPH meeting

The final program for the inaugural meeting of the International Society for Evolution, Medicine, & Public Health  is now online. 

All talks on Thursday March 19 will be live streamed at http://www.ustream.tv/asutv

The time zone is the same as California, so 3 hours earlier that EDT, and 7 hours earlier than London UK.

 

March 30 abstract deadline for Zurich EvMed meeting

The abstract deadline for the “Evolutionary Medicine Conference: Interdisciplinary Perspectives on Human Health and Disease” (Juli 30-August 1 2015 in Zurich, Switzerland) is approaching now:

– Abstract Deadline: March 30, 2015
– Early registration Deadline: May 31, 2015

Find all relevant information (abstract submission, registration, accommodation, etc.) on our official conference webpage:http://www.iem.uzh.ch/evolmedconf2015.html

Please get in contact with us if you have questions: evolmedconf@gmail.com

Thanks for sharing the event and the call for abstracts among your colleagues!

We would be happy to welcome you in Zurich soon…

Best wishes

Frank Rühli, Nicole Bender and Kaspar Staub (Conference Organisers)”

Omenn Prize for 2014 awarded for an article on iron piriacy by Barber and Elde

The Gilbert S. Omenn Prize is awarded by the International Society for Evolution, Medicine, and Public Health for best article published each year on a topic related to evolution in the context of medicine and public health.  The prize for 2014 goes to, “Escape from bacterial iron piracy through rapid evolution of transferrin” by Matthew Barber and Nels Elde from the University of Utah. The article appeared in Science 346:1362-6, 2014. First author Matthew Barber, a postdoctoral student, will receive the $5,000 prize and present a talk on March 21 at the 2015 ISEMPH meeting in Tempe Arizona.  The prize is made possible by a generous donation from Gilbert Omenn.

The Prize Committee—Sarah Tishkoff, Joe Alcock, Noah Rosenberg, and Alison Galvani—found the paper impressive in its scope, integrating phylogenetic, bioinformatic, and experimental approaches to show that primate hosts and bacterial pathogens causing diseases such as meningitis, gonorrhea, and influenza, have co-evolved in competition for a key growth-limiting nutrient: iron.  Barber & Elde show that natural selection during primate evolution produced specific functional adaptations in the iron-binding protein transferrin that prevent iron piracy by bacterial transferrin binding protein (TbpA). This result is a vivid illustration of the role that natural selection and “nutritional immunity” play in host-pathogen “arms races”, mediated by recurrent episodes of positive selection between hosts and pathogens.

Three papers were selected for honorable mention. They are listed below in alphabetical order.

Byars, Sean G., Stephen C. Stearns, and Jacobus J. Boomsma. “Opposite risk patterns for autism and schizophrenia are associated with normal variation in birth size: phenotypic support for hypothesized diametric gene-dosage effects.” Proceedings of the Royal Society B: Biological Sciences 281.1794 (2014): 20140604.

This article uses extensive health registry data from 1978 – 2009 in Denmark to demonstrate associations between birth weight and risk patterns for autism and schizophrenia.  They argue that their findings add support to the hypothesis that genomic conflict and imprinting may play a role in common diseases whose etiology has been difficult to unravel using standard approaches.

Pennings, Pleuni S., Sergey Kryazhimskiy, and John Wakeley. “Loss and recovery of genetic diversity in adapting populations of HIV.” PLoS genetics10.1 (2014): e1004000.

This article uses a population genetics approach to infer effective population size of HIV infections based on the prevalence of “hard and soft” selective sweeps. This study helps to explain actual patterns of drug resistance evolution in patients and suggests evolutionary principles for strategies to keep drug resistance to a minimum.

Warinner, Christina, et al. “Pathogens and host immunity in the ancient human oral cavity.” Nature genetics 46.4 (2014): 336-344.

This article characterizes the microbiota from dental calculus obtained from ~1000 year old human skeletons, observing pathogens associated with disease in modern populations and also antibiotic resistance genes prior to the use of antibiotics to treat disease.

Please join the Society in congratulating the authors of the winning and runner up articles. Nominations for next year’s prize will be received starting early in 2016.  The Society also sponsors the $5,000 George C. Williams Prize for the best paper published each year in the Society’s flagship journal, Evolution, Medicine and Public Health. All papers published in the journal in 2015 will have author’s fees waived and will be automatically entered into the Prize competition.

 

 

 

Human evolution and arsenic detoxification

Carina Schlebusch and colleagues just published an article in Molecular Biology and Evolution demonstrating human adaptation to the locally high arsenic levels in groundwater in the Argentine Andes. This work is the first to show a genetic adaptation that allows the detoxification of a environmental toxin (arsenic) in humans.

Title: Human adaptation to arsenic-rich environments

Abstract: “Adaptation drives genomic changes; however, evidence of specific adaptations in humans remains limited. We found that inhabitants of the northern Argentinean Andes, an arid region where elevated arsenic concentrations in available drinking water is common, have unique arsenic metabolism, with efficient methylation and excretion of the major metabolite dimethylated arsenic and a less excretion of the highly toxic monomethylated metabolite. We genotyped women from this population for 4,301,332 single nucleotide polymorphisms (SNPs) and found a strong association between the AS3MT (arsenic [+3 oxidation state] methyltransferase) gene and mono- and dimethylated arsenic in urine, suggesting that AS3MT functions as the major gene for arsenic metabolism in humans. READ MORE »

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