Policy shifts for evolutionary medicine

Evolutionary medicine, which blends principles from evolutionary biology and medicine, is poised to offer fresh solutions to several of today’s major public health issues. In their Frontiers in Science article, Natterson-Horowitz et al. shed new light on current health challenges—ranging from the COVID-19 pandemic to obesity and its associated comorbidities—through the lens of evolutionary principles (1). Despite its potential, evolutionary medicine is still in its infancy, and, with a few notable exceptions (2, 3, 4), its tenets have yet to find their way into mainstream medical practice and health policy.

Why has it been so hard for evolutionary medicine to move from “bench to bedside”? Crespi and Hochberg, in their Viewpoint articles, argue that clinicians, policymakers, and the broader public remain relatively unfamiliar with evolutionary biology (5, 6). Evolutionary principles are not, for example, traditionally included in medical school curricula. Yet, repairing this knowledge deficit by providing education in evolutionary principles will be insufficient if those learnings are not put into practice—and practice is where the major obstacles lie. As I see it, there are three main challenges to overcome before treatments based on the precepts of evolutionary medicine can be successfully integrated into standard healthcare practices and policy development.

Two cultures

CP Snow famously derided the lack of mutual understanding between scientists and what he called “literary intellectuals” and artists of the mid-twentieth century West (7). The result, he feared, was missed opportunities for progress and real-world impact generated through collaboration. The same might be said of the intellectual gulf between evolutionary biology and medicine. Evolutionary biologists and medical practitioners, including health policymakers, speak very different languages, making real progress at their intersection difficult.

The essence of the problem involves what constitutes a useful scientific explanation. Evolutionary biology seeks to answer the question “why?”, while medicine focuses on “what?”. The evolutionary mismatch theory described by Natterson-Horowitz et al. is a good example. Ill-health, the theory goes, results from living in environments to which we are not well adapted. As an explanation for why post–World War II high-income societies experience rampant noncommunicable diseases such as obesity and type 2 diabetes, the theory does its job. But, on its own, the theory says little about what might be done to reduce rates of these ailments. Until evolutionary biologists and clinical scientists spend more time together, deliberately focused on using evolutionary principles to design effective medical interventions, progress will be limited.

The problem of prediction

For much of its history, evolutionary biology has been a retrospective rather than a prospective science. It has looked to the past—to the fossil record or to the signatures of evolutionary processes in our genomes—to provide explanations for why humans are who we are and why we succumb to diseases. Evolutionary medicine is arguably leading the shift towards a more forward-looking approach. Natterson-Horowitz et al. highlight two examples of using general evolutionary principles to design effective therapeutic interventions—phage therapy for treating bacterial infections and evolutionary-informed cancer treatments such as adaptive therapy and extinction therapy.

Yet, moving beyond general principles to understanding evolution-in-action for any individual patient remains extremely challenging. For both cancer and infection, genetic changes that improve replication rates of certain lineages relative to others can be a main driver of disease progression. Genetic changes are rare, stochastic events and thus it is difficult to predict which ones will arise and contribute to the future success (or demise) of a lineage. Like the weather, which is difficult to forecast days or weeks into the future, forecasting the genetic routes a cancerous cell line or pathogen will take is challenging. Evolutionary processes are arguably even harder to forecast than the weather owing to the immense complexity of living systems and the virtually unimaginable number of potential combinatorial factors influencing a species’ evolution.

The ongoing COVID-19 pandemic illustrates this difficulty. In the early stage of the pandemic, evolutionary models did a fairly good job predicting that SARS-CoV-2 would become more transmissible rather than immune evasive. It proved far harder to predict which genetic mutations were responsible in advance of their occurrence. The evolutionary process is constantly experimenting with new mutations and their combinations; the SARS-CoV-2 virus replicates so quickly and infects so many individuals that the number of potential viral variants is enormous. Even several years into the pandemic, with an unprecedented volume of viral genome sequence data, we struggle to predict the next variant of concern. The best we can do is survey currently circulating viruses, monitor changes in their prevalence, and look for instances in which mutations seen across lineages start to spread. But when it comes to making stronger, evidence-based claims about what is coming next—be it the next SARS-CoV-2 variant or the next pandemic—the evolutionary process itself is working against us.

Short-term thinking

One interpretation of Natterson-Horowitz et al.’s discussion of human life history is that changing reproductive norms, for example having fewer children or reducing the duration of breastfeeding, can change our physiologies in ways that increase the risk of disease and illness. Quick fixes such as drugs or therapies that allow us to return to “normal”—if normal even exists in such a highly variable group as humans—may not be possible.

Managing susceptibility to disease in the long term—over the entire human life-course and that of our children and grandchildren—is not something the policymaking process is always well designed to handle. Policymaking—especially when driven by political forces—is often short-term in its approach. Meanwhile, longer-term stewardship and management-based approaches do not generally garner as much attention and support at the policy level, although they may be more in line with evolutionary principles and may ultimately offer effective solutions.

Antimicrobial resistance (AMR), which already represents a major public health and economic burden on healthcare systems around the world, provides a compelling example. AMR is only expected to worsen over time, with projected cumulative economic impacts as high as $100 trillion globally by 2050 (8). Reducing the burden of resistance is thus a major global health priority. But, how best to do this?

The usual policy response is to incentivize research and development initiatives, effectively doubling down on the discovery of novel antibiotics as a “silver bullet” solution to AMR (e.g., NICE.org.uk). While we absolutely need new drug options, this solution alone is insufficient. The widespread therapeutic and prophylactic use of antimicrobials in healthcare and agriculture constitutes a strong, persistent selective pressure that practically guarantees the evolution and spread of resistance. There is an urgent need to manage our remaining existing arsenal of antimicrobials to ensure they remain effective for as long as possible, if only to give us the extra time we need to develop new drugs (9).

Moving forward

The promise of evolutionary medicine remains high, but acceptance by medical practitioners and policymakers is stubbornly low. What can be done?

On the most practical level, some dimensions of evolutionary medicine suggest policy interventions that deserve more attention. The evolutionary mismatch theory, for example, posits that reducing our intake of sugar-rich, highly refined foods could help reduce rates of obesity and its comorbidities. Policies such as marketing restrictions and food taxes, as Natterson-Horowitz et al. mention, could shift the burden of management from the individual (e.g., exercise more and eat less) to society as a whole. Reducing the burden of AMR could involve more deliberate efforts to manage our existing arsenal of antibiotics using evolutionary principles, buying time for novel drug discovery. The use of “drug sanctuaries” in hospitals—wards where the use of certain drugs is restricted – is one idea that my group has begun exploring, for example (10). We must also ensure that data, like the genome sequences of emerging pathogens, are shared widely, so we can catch spillover events from animals into humans and the genomic changes driving pathogen evolution as early as possible. 

It will also be important to facilitate collaboration between evolutionary scientists, clinicians, and policymakers, with the aim of fostering opportunities for wide stakeholder engagement and cross-fertilization of ideas. As noted by both Crespi (5) and Hochberg (6), international societies and journals can help, although arguably more could be done. We must look for additional ways to overcome the inherently conservative nature of the research ecosystem. For starters, we could support more clinical evaluations of interventions stemming from evolutionary medicine. Evolutionary ideas and principles are well-established; what is missing are the data required to evaluate their clinical effectiveness. Data generated from such work are valuable because they could support new or more comprehensive policy decisions, in an iterative process.    

More broadly, we must remain mindful of the cultural divides that separate scientists, clinicians, and policymakers. Each is a distinct cultural group with its own priorities, pressures, and methods that do not always align well with each other. All scientific knowledge is provisional; what science does best is to reduce uncertainty. Policymakers should strive to understand that science cannot always deliver the level of certainty they desire. Scientists, for their part, must appreciate that they are just one of many stakeholders informing the policy-making process. In essence, experts are an interest group like any other, a sentiment captured in the expression often attributed to Winston Churchill: “Science should be on tap, not on top.” The most effective policies are those in which the interests of all stakeholders are aligned. Evolutionary medicine holds much promise for helping ensure that public health outcomes align with broader societal goals.

https://doi.org/10.25453/plabs.22189354.v1

References

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4.  Pontali E, Raviglione MC, Migliori GB, Akkerman OW, Alffenaar JW, Blanc FX, et al. Regimens to treat multidrug-resistant tuberculosis: past, present and future perspectives. Eur Respir Rev (2019) 28: 190035. doi: 10.1183/16000617.0035-2019

5. Hochberg ME. Addressing challenges in evolutionary medicine: three priorities. Front Sci (2023) 1:1123806. doi: 10.3389/fsci.2023.1123806

6. Crespi BJ  The possible futures of evolutionary medicine. Front Sci (2023) 1:1124128. doi: 10.3389/fsci.2023.1124128

7. Snow CP. The two cultures and the scientific revolution. New York: Cambridge University Press (1959). Available at: https://sciencepolicy.colorado.edu/students/envs_5110/snow_1959.pdf

8. O’Neill J. The Review on Antimicrobial Resistance. (2015). Available at: https://amr-review.org/

9. Palumbi SR. Humans as the world’s greatest evolutionary force. Science (2001) 293:1786–1790. doi: 10.1126/science.293.5536.1786

10. Kassen R. ‘Drug sanctuaries’ offer hope for a post-antibiotic world. The Conversation website (2018). Available at :https://theconversation.com/drug-sanctuaries-offer-hope-for-a-post-antibiotic-world-94473