Northern BioStrategies
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'Heat Vaccination' As A Biopharmaceutical Opportunity

Dieu Anh Nguyen •
#Global Health#biopharma#strategy

Biopharmaceutical solutions for heat tolerance

Imagine taking a pill or an injection that would protect you from heat-related illnesses, allowing you to continue with normal activities during heatwaves without using conventional cooling methods. The idea sounds appealing and somewhat fictitious. How viable is “heat vaccination” as a possibility?

Heat adaptation by biopharmaceutical means has received little academic and commercial interest, even in recent years, when global temperatures have reached the highest ever recorded 1. There is almost no publicly known direct research on a biopharmaceutical intervention for improving heat tolerance. This lack of enthusiasm likely comes from the abundance of cheap and effective conventional heat management methods. As the world gets hotter, however, such biopharmaceutical solutions might become increasingly appealing. They would reduce our reliance on mechanical cooling (e.g., air conditioning), which is energy-intensive, unsustainable, and could be unreliable when demand surges 2. They would also be particularly useful in outdoor settings, where cooling methods are either cumbersome (e.g., cooling suits) or not available.

Scientific feasibility

Despite the lack of direct research, existing studies may provide some insights into potential biopharmaceutical strategies for enhancing heat tolerance (note that these are just two potential routes):

Route 1: Reduce metabolic rates.Route 2: Genetic engineering.
How?Metabolic reactions often generate heat as a byproduct. Reducing metabolic rate = reducing the rate of heat generation 3.Delivering additional copies or an improved variant of a heat response gene, thereby improving the clearance of heat-induced toxicities 10.
Supportive evidence.> Various species in nature reduce their metabolism to cope with high temperatures 4, 5.

> The drug combination chlorpromazine + promethazine (C+P) induces hypothermia by reducing metabolic rate - currently being investigated to limit brain damage from stroke 6, 7.

> The drug propylthiouracil has been shown to help maintain low body temperatures in healthy rats when exposed to heat stress. This drug is an antithyroid, used to treat a condition associated with abnormally high metabolism (hyperthyroid) 8.		> Higher basal levels of heat-response proteins, HSPs, have been detected in desert species compared to their ambient-climate counterparts, contributing to their greater heat tolerance 11.

> The introduction of constitutively expressed HSP genes into cultured heart cells and intact animal hearts has been shown to be protective against heat stress 12.
Some concerns.> Unknown consequences of chronic manipulation of natural metabolism and overdosing. Many metabolism-altering drugs for weight loss have been discontinued due to concerns of toxicities, even death 9.

> Association with weight gain might repel consumers.		> High cost 13.

> Safety concerns (e.g., immune response against the gene delivery vector) 13.

Overall, initial research suggests some scientific feasibility of a biopharmaceutical solution to heat resilience, but further and more direct research is required.

Financial feasibility

A major challenge these biopharmaceutical interventions will face is being competitive against conventional cooling methods. This means having superior value-for-money, which will be a particular challenge for a genetic engineering solution. Gene therapies are notorious for their high price tags. The gene therapy Zolgensma for spinal muscular atrophy, for instance, could cost upward of nearly £5m 13. This is mostly attributed to the value-based pricing model these therapies are based on. Even when using cost-based pricing (which should bring the price tags down), these therapies could still cost above £300,000 per treatment 14. However, given the larger potential market for heat adaptation compared to existing gene therapy conditions, the cost per patient could be lower than this. Nonetheless, the final cost will also depend on the R&D expenditure and manufacturing cost. Safety is another concern with gene therapies 13. Thus, financial success will depend on the development of a highly effective and relatively safe therapy, available at a reasonable price. Without much direct research, it is difficult to tell the likelihood of this scenario, making heat resilience a high-risk biopharmaceutical venture with uncertain financial return.

Should there be more attention?

Although it may now seem financially unattractive, strategists, investors, and researchers have good reasons to pay more attention to heat resilience as a potential biopharmaceutical market.

A 2025 report by Climate Change Tracker showed that we have made no measurable progress in reducing the rate of warming since the Paris Agreement 15. With the US pulling back on climate change initiatives, reversing the trend will become even harder. Even if we cease all CO2 emissions now, it would still take decades before the planet starts to cool down 16, 17. Thus, along with reducing greenhouse gas emissions, adaptation is a central part of the climate change action plan 18, 19. The development of a biopharmaceutical solution for heat resilience could help make sustainable cooling, which mostly involves infrastructural changes and reducing the usage of energy-intensive cooling, easier 2. A successfully developed solution would not only bring financial, but also substantial societal value.

To have noticeable societal value, this solution should be affordable to the public majority, not just the wealthy. Scientific and technological advancements might one day make this possible. Consider the recombinant DNA technology that resulted in the founding of Genentech in 1976 20. The technology was a seemingly implausible idea at the time: the transfer and expression of genes from one species to another. This was developed from a culmination of various scientific discoveries, such as restriction enzymes and bacterial transformation. Or consider the revolutionary development of tyrosine kinase inhibitors for chronic myeloid leukaemia (CML), which was driven by the pivotal discovery of the causative protein, BCR-ABL. Previously a devastating disease with a 10-year survival rate of <20%, most people with CML now can expect to live a normal lifespan 21, 22. Similarly, the pivotal development for heat adaptation could come from the discovery of a single heat-stress response protein or a combination of scientific advances to produce a highly safe and low-cost gene therapy.

Given the overall lack of industry enthusiasm, investors might want to take the initiative to spot early scientific developments with potential for enhancing heat resilience. Genentech was founded after venture capitalist Robert A. Swanson read an academic paper about recombinant DNA technology and was convinced of its commercial potential. He reached out to Dr Herbert W. Boyer, one of its developers 20. After a three-hour meeting, Genentech was born 23. The company produced various blockbusters using the technology and was acquired by pharmaceutical giant Roche in 1990 24. Today, Genentech remains one of the key players in the industry.

The elephant in the room

While a biopharmaceutical solution for heat resilience could help reduce greenhouse gas emissions by reducing our reliance on energy-intensive mechanical cooling, the total environmental footprint from its lifecycle might still outweigh this benefit. The biopharmaceutical industry has a larger carbon footprint than many other major industries, including semiconductor and car 25. Its environmental impacts came from the high level of toxic waste generated during R&D/manufacturing, heavy reliance on petrochemical-derived raw materials and reagents, and energy-intensive manufacturing, among others 25, 26. Although many companies have taken bold steps toward sustainable changes and seen some progress, the industry is still far from achieving net zero 27. Again, technological advances offer hope in minimising environmental impacts 26. Any biopharmaceutical solutions for heat resilience must incorporate greener processes into their lifecycle to achieve a net positive impact.

Key takeaway

Heat adaptation is a market receiving little attention from the biopharmaceutical sector due to the high financial risk. However, existing scientific evidence and the current global trend suggest that this potential market deserves more attention. To achieve a net positive impact, any successful solution should also be produced and sold using processes that minimise its environmental footprint. Given these substantial challenges, such biopharmaceutical solutions are unlikely to come soon. Nonetheless, it is an idea worth having at the back of the mind. Investors and strategists should keep an eye out for promising scientific and technological advancements.

References
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