The new Op-Ed feature started last month with a piece by Joe Alcock, “Disabling the smoke detector in sepsis.” Our hope was that this feature would spark interest and contributions by more authors and so far we are off to a great start. Veterinary pathologist Edmund LeGrand has volunteered the following piece which examines, from an adaptationist viewpoint, the intriguing question as to why the human heart has such limited powers of post-infarction regeneration. We’d like to thank both Ed and Joe for their contributions and remind readers that we are open to contributions from anyone. We also want to encourage commentary on all of our Op-Ed pieces; please feel free to submit contributions and comments for approval to firstname.lastname@example.org.
Regeneration and the Heart of the Adaptationist Approach
Edmund K. LeGrand, DVM, PhD, DACVP
The ability to regrow an arm, a leg, or another large portion of the body that has been amputated is a more widespread trait than you might think. Invertebrates like sea stars and flatworms can replace most of their body parts after removal, but even some vertebrates have impressive regenerative abilities. Lizards regenerate their tails, newts can regrow limbs and repair parts of the eye, and zebrafish can regrow fins and repair other tissues like the heart. Mammals, however, are pretty limited in this realm of regrowth. Humans can regrow muscle and liver tissue, but regenerative repair of other organs, including the heart, is extremely limited. Why might this be? Two recent papers are notable in addressing the question (1, 2).
A few months ago, the editors of Evmedreview decided to open an Op-Ed feature and asked Joe Alcock if he would kick this new venture off by writing a series of op-ed articles, once a month. Thankfully, Joe agreed and this is the first article of the new Op-Ed feature. In a week or so this, and all future op-eds, will be moved to a dedicated Op-Ed page which can be easily accessed from the home page. We want to take this opportunity to thank Joe immensely for taking this on. The idea of the op-ed is that it should act as a target article for commentary – to spark a debate and exchange of thoughts and ideas. We want you all to volunteer comments! They can be constructively critical or complementary. Just email to email@example.com and we will review them and post them!
Disabling the smoke detector in sepsis
The pharmaceutical company was Eisai, a Japanese firm. The drug was eritoran, an investigational drug to treat sepsis, a condition that is the second leading cause of death among intensive care patients. By inhibiting inflammation in sepsis, eritoran was lauded as a potential blockbuster drug. It had shown great promise in reducing mortality in pre-clinical trials. In 2010 a phase II clinical trial of eritoran showed that it was apparently safe in humans, and the results also suggested lower mortality in those with severe sepsis. Eritoran was supposed to make the company millions, and the investors rich too.
It did not work out that way. In 2013, JAMA published the results of the final phase 3 clinical trial necessary for FDA approval of eritoran. This was the ACCESS trial, a randomized controlled trial involving 1961 patients with sepsis assigned to eritoran versus placebo. Unfortunately for Eisai and its investors, eritoran did not improve survival at 28 days and at 1 year. The drug never made it to market, and it joined an impressive and growing list of failed drugs for sepsis.
Was this just another failed pharmaceutical R&D venture? Or was this result predictable with a little knowledge of evolutionary medicine?
“… instigated 25 years ago as George Williams and I discussed and grappled with how evolution could be useful for medicine, and what to call the enterprise.”
In her chapter (Bentley, 2016) introducing the just published book, “Evolutionary Thinking in Medicine: from Research to Policy and Practice,” the author acknowledges activity that can be considered evolutionary medicine in the years prior to 1991 but confines it to before roughly 1940. Following the end of World War II, Professor Bentley finds little to no evidence of significant work in the field until the 1990s. Unfortunately, these claims disregard substantial numbers of evolution-related studies that either influenced fundamental understanding of human health and disease or affected medical practice. (more…)
There is a mature literature on evolution and aging intended to explain how, despite selection for the morphological, metabolic, physiological, and behavioral prerequisites for survival and procreation, with the passage of time bodies deteriorate ultimately resulting in death. The focus of such explanations is typically on concepts such as age-related variation in the potency of selection and the related notion of antagonistic pleiotropy (Fabian and Flatt, 2011), by which suggests that genes able to promote survival and reproductive success in youth may increase loss of function with age. These concepts address selection on intact organisms. In contrast, a recent article in Science (Goodell and Rando, 2015) contains an article addressing the role of selection directly on somatic cells and in particular tissue-specific stem cells. (more…)
The German philosopher, Friedrich Nietzsche, is known for a number of ideas among which a particularly oft-quoted one is, “That which does not kill us makes us stronger” (https://www.goodreads.com/quotes/30-that-which-does-not-kill-us-makes-us-stronger). A recent report in Cell (Fonseca et al., 2015) offers evidence that in the context of infection and immunity, the above aphorism may not be a reliable guide to reality. (more…)