Quick Guide to Evolutionary Medicine in Neuroimmunomodulation: Why “Evolved for the Benefit of the Species” Is Not a Valid Argument

Background: Evolutionary medicine builds on evolutionary biology and explains why natural selection has left us vulnerable to disease. Unfortunately, several misunderstandings exist in the medical literature about the levels and mechanisms of evolution. Reasons for these problems start from the lack of teaching evolutionary biology in medical schools. A common mistake is to assume that “traits must benefit the species, as otherwise the species would have gone extinct in the past” confusing evolutionary history (phylogeny) with evolutionary function (fitness). Summary: Here we summarise some basic aspects of evolutionary medicine by pointing out: (1) Evolution has no aim. (2) For adaptive evolution to occur, a trait does not have to be beneficial to its carrier throughout its entire life. (3) Not every single individual carrying an adaptive trait needs to have higher than average fitness. (4) Traits do not evolve for the benefit of the species. Using examples from the field of neuroimmunomodulation like sickness behaviour (nervous system), testosterone (hormones), and cytokines (immunity), we show how misconceptions arise from not differentiating between the explanatory categories of phylogeny (evolutionary history) and evolutionary function (fitness). Key Messages: Evolution has no aim but is an automatism that does not function for the benefit of the species. In evolution, successful individuals are those that maximise the transmission of their genes, and health and survival are just strategies to have the opportunity to do so. Thus, a trait enabling survival of the individual until reproductive age will spread even if at later age the same trait leads to disease and death. Natural and sexual selection do not select for traits that benefit the health or happiness of the individual, but for traits that increase inclusive fitness even if this increases human suffering. In contrast, our humane aim is to increase individual well-being. Evolutionary medicine can help us achieve this aim against evolutionary constraints.

Journal Section:

Review Article

Keywords:

Phylogeny, Fitness, Trade-off, Cytokine, Inflammation, Sickness, Disease

Introduction

Why does the psychoneuro-endocrine-immune network, which evolved to protect the individual against disease, sometimes cause disease and even death [1‒6]? This is a classical question for the emerging field of evolutionary medicine: Why has natural selection left us vulnerable to disease and ageing instead of favouring mechanisms that keep us young and healthy [7‒12]?

Evolutionary mechanisms of increasing fitness are not always in agreement with the aim to increase individual health. Understanding why evolution left us vulnerable for disease can help us better understand disease to improve research and medical treatment [7‒12]. Nevertheless, numerous publications by medical researchers, international experts in their bio-medical fields, still use flawed lines of evolutionary arguments to explain disease, including very recent publications [13]. In evolutionary biology, it was realised decades ago that traits cannot evolve for the benefit of the species but for individual benefits [14, 15]. This insight has been ignored by part of the medical sciences. There are many publications in which medical researchers still argue wrongly that traits evolved for the benefit of the species instead of trying to understand how they can increase individual fitness even though causing disease in some individuals ([16]; melatonin production [17]; memory-induced anxiety [18]; obesity [19]; hormonal imprinting [20]). The stress response has been interpreted to have evolved for the benefit of the species [21] with the adrenal medulla controlling catecholamine secretion to ensure species survival under environmental change [22]. It has also been argued that the immune response evolved for the survival of the species [23] and even that an overreaction of the immune system, leading to death of infected individuals evolved to protect the species [5]. The thymus was said to have evolved to regulate immunological self-tolerance as a necessity for the survival of the species [24]. All these reviews are of very high quality with regards to the proximate mechanisms, and if the correct evolutionary arguments about benefits for individual fitness had been employed, they would have achieved a better understanding of why disease occurs.

Here we (1) provide a quick guide to evolutionary biology and levels of selection for medical researchers, and (2) discuss how confusing phylogeny with function can lead to misunderstandings such as assuming that traits that were maintained during evolutionary history (phylogeny) must function to save the species from extinction, a function that does not exist in evolution, which is instead based on individual fitness benefits, before (3) giving examples of how to apply these concepts to topics important in the field of psychoneuroimmunology.

Evolutionary Medicine: Concepts and Misunderstandings

Clinical medicine focuses on understanding pathophysiological mechanisms that cause disease. Evolutionary medicine adds two additional questions: (1) what is the evolutionary history (=phylogeny) and (2) what are the fitness consequences (=function) of these mechanisms?

Proximate and Ultimate Approaches to Disease

Biological research has traditionally been divided into the study of proximate (including physiological and pathophysiological) mechanisms on the one hand and ultimate (evolutionary) causes on the other hand (Mayr 1961). Tinbergen (1963) formulated four questions which are the basis for an integrative approach to understand biological traits [25‒27].

Two questions are about the proximate causes of a trait, asking (i) how did the trait develop in individuals over their lifetime (Ontogeny)? (ii) What physiological machinery causes the observable trait (Causation)? Questions 3 and 4 are about the ultimate or evolutionary understanding of a trait, asking (iii) what is the Function, which means the fitness value of the trait? (iv) What is the Phylogeny, which means the evolutionary history of the trait? It is important to note that these four questions complement each other. Figure 1 shows how understanding the ultimate factors can allow us to better understand the proximate factors.

Fig. 1.

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An integrative approach to understanding immunology. (1) We measure the immunological response of individuals, which (2) influences an individual’s survival and reproduction (function, fitness) and as such (3) the gene pool of the population of future generations. Looking back at evolutionary history from today describes the phylogeny of a species and how the trait of interest evolved in its environmental context (3). Function and phylogeny are ultimate factors and studied in evolutionary biology and evolutionary medicine (box to the right). Classical medicine/psychology investigate how the system is influenced during individual ontogeny (4), which depends on the genotype of the individual (coming from the gene pool of the population) and the influencing environmental factors. The possible genotypes are determined by phylogeny; thus, historical fitness consequences, which determined what genotypes, were passed on over the generations. When exposed to a pathogen, the immune system responds (5. causation), and this response can be measured, for example, as cytokine concentration in the blood stream (1). While the pathway in the right box is unidirectional from function to phylogeny (see arrow), it can be reciprocal in the left box (the genotype influences causative factors, and causative factors can influence the epigenome). Figure modified from [12].

Psychoneuroimmune research is typically proximate (left box in Fig. 1), focusing on the (patho)physiological mechanisms and individual ontogenetic factors underlying, for example, behavioural changes, neuroinflammation, psychiatric conditions, allergies, or chronic inflammatory diseases [3]. Evolutionary medicine instead focuses on the ultimate explanation of disease [8, 12]. For this, evolutionary medicine in psychoneuroimmunology must separate between the function of a trait, i.e., its impact on individual fitness, and the evolutionary history (phylogeny) of the trait (right box in Fig. 1).

Misunderstandings in How to Apply Evolutionary Medicine in Psychoneuroimmunology

Wrong conclusions can arise when the two approaches in evolutionary medicine – function and phylogeny (right box in Fig. 1) – are not considered separately. Seeing a long evolutionary history of a trait that was already present hundreds of millions of years ago is sometimes used to argue that it evolved for the benefit of the species, explaining why the species survived until today instead of going extinct [5, 16‒24]. Below, we review in detail why this argument is wrong and explain why we should not use the argument of the “benefit for the species.” We also identify why this argument is so attractive that it is maintained, even though evolutionary biologists explained more than 5 decades ago why it is inappropriate [8, 14, 15, 28].