Ron Mittler, a plant scientist at the University of Missouri, wants researchers to change how they study stress in living organisms. His main question is simple: what happens when an organism faces multiple stressors at the same time?
For decades, scientists have tested one stressor at a time. For example, they might deprive a plant of water while keeping all other variables constant. While this method has taught us a lot about how living things react to a single challenge in a laboratory setting, real life is much messier.
Consider a plant in a Missouri field. It may have to cope with dry soil, intense heat, and strong sunlight all at once. Later, it might face flooding, salty soil, or pollution. These problems can range from mild to severe, can be short-lived or prolonged, and can occur in countless different combinations.
Earlier this year, Mittler tested this concept. His team exposed a common laboratory plant to heat, intense light, and high soil salinity simultaneously. They discovered that the plant’s survival depended on a protein called bHLH35. Plants lacking this protein died, while those with elevated levels of it remained healthy.
Remarkably, this protein did not save the plant when it faced only one of these stressors; it only became vital when all three conditions hit together. This demonstrates that a combination of stressors can trigger a unique biological response that none of the individual stresses would cause on their own.
Because of these findings, Mittler and his team published a commentary in Nature Reviews Molecular Cell Biology, urging scientists to design experiments that better reflect the real world.
Mittler explains the phenomenon this way: Imagine one protein reacts to heat and another reacts to strong sunlight. You might expect both to activate when heat and sun arrive together, but that is not always the case. Two concurrent stressors can initiate an entirely new response that differs completely from the individual responses to each stressor alone.
This concept extends well beyond agriculture. Animals and entire ecosystems face combined threats, such as pollution, pesticides, microplastics, and shifting weather patterns. Understanding how these threats interact could help protect wildlife and mitigate habitat loss.
Medicine stands to benefit as well. Doctors already combine medications to treat certain infections and cancers. If scientists can understand how these combinations interact inside cells, they may design more effective treatments with fewer harmful side effects.
In fact, Mittler’s lab found that an organism’s health drops sharply once four or five stressors strike simultaneously. He believes this tipping point could be medically useful. If a combination of two or three drugs fails, a mixture of four or five drugs administered in very small doses might prove more effective while sparing healthy cells.
Granted, this type of research is highly complex, time-consuming, and expensive. Each additional variable introduces exponentially more conditions to test—especially when factoring in different intensities, durations, and sequences of events. Nevertheless, Mittler believes the effort is vital because the results reflect real-world conditions.
He hopes that artificial intelligence and other modern computational tools will help researchers sort through these massive datasets faster than humanly possible. To champion this cause, he has spent years advocating for the methodology through scientific papers, conference presentations, and social media. Fortunately, his efforts are paying off, as more researchers globally are beginning to take notice.
Collaborating with peers at Missouri has heavily shaped Mittler’s perspective. He especially values his teamwork with field scientists at the Bond Life Sciences Center. Thanks to them, he can study crops in their natural environments. Mittler notes that this outdoor perspective revealed insights he could never observe in a laboratory, ultimately helping him unlock how living things truly cope with the multi-layered challenges of nature.
