How American Gray Wolves and Integrated Pest Management Explain a New Way To Treat Prostate Cancer
Author: Patrick Heizer
Patrick Heizer is a biomedical scientist who owns and operates Blue Glade Farm, a 12-acre permaculture farm in Frederick County, Maryland. In his spare time, he is a board member on the Frederick County Soil Conservation District and also writes The Counterpoint newsletter, where his goal is that you find it ‘worth reading’ rather than necessarily ‘being right.’
In December 1973, President Richard Nixon signed the Endangered Species Act was signed into law.
Through a series of steps, this eventually lead to the American Gray wolf being re-introduced to Yellowstone National Park in 1995, where they had been eradicated during the 1920s.
This re-introduction lead to profound ecological changes in the park. Wolves are obviously predators who hunt and kill other animals, so you might think that these changes only ‘subtracted’ from the local environment. But what occurred was a rapid and profound recovery of the ecosystems within Yellowstone.
What happened?
After the wolves were eradicated in the 1920s, the deer and elk population increased. Over the decades, these large and indiscriminate grazers had eaten the grasses down, disturbed many of the shrubs and underbrush, and killed many trees through antler rubbing, creating large open spaces.
Of course, the wolves killed some of the deer and elk, but more importantly, they changed the animal’s behavior. Because of pressure from the wolves, they could no longer roam and eat wherever and whenever they wanted and tended to avoid both wide-open spaces, where they could be easily spotted, and tight spaces (such as deep valleys and gorges), where they could be trapped.
These areas saw a rapid regrowth of shrubs, underbrush, and trees. With more habitat and food, this lead to a rapid increase in the number of birds, which compounded the effects, since birds spread seeds and their waste is a nutritious fertilizer. The number of beavers increased, since they need trees for their dams. These dams slow rivers, creating ponds and wetlands, which again compounded the effects by creating more habitat for ducks, muskrats, fish, amphibians, and water-loving insects, and through water retention, increased the growth of the shrubs, underbrush, and trees.
The wolves also competed against and killed coyotes. With fewer coyotes and the regrowth of habitat, there were increased numbers of small mammals, such as rabbit, mice, and voles. This brought more hawks, badgers, weasels, and other small predators to the park. As they hunted, the carcasses brought increased numbers of carrion birds and animals.
The increasing number of plants and animals also increased the number of bears, who as omnivores, enjoyed hunting the increased numbers of wildlife, foraging the increased number of berries, fishing in the increased numbers of ponds and wetlands, and of course, finding honey from the increased numbers of bees who helped pollinate all the new regrowth.
And the wolves didn’t just affect the wildlife and plants, but also the abiotic parts of the environment. The regrowth of the trees and understory meant more roots that stabilized the banks of the streams, rivers, and ponds, which decreased the erosion and meandering of the waterways. The increased animal ‘waste’ spread nutrients, improving the quality of the soil, which allowed the plants to grow faster. As the plants grew faster, they collaborated with fungi to release minerals from deep bedrock, propelling the nutrient cycle forward, as their dropped leaves decomposed each fall.
The re-introduction of wolves into Yellowstone is the quintessential example of a tropic cascade: powerful, indirect interactions and knock-on effects that alter and control entire ecosystems.
In February 1972, President Nixon directed federal agencies to advance the application of Integrated Pest Management to all relevant areas.
As synthetic chemical pesticides were developed and brought to market in the early 20th century, they were seen as a miracle development. Finally, the pests and diseases that had plagued farmers and decreased crop yields could be controlled. There use nearly tripled between the 1930s and the 1970s.
During the 1950s, there was increasing awareness that these chemicals can have profound negative effects on the environment and other species. This culminated in the publication of Silent Spring by Rachel Carson in 1962, which eventually lead to the banning of the persistent pesticide DDT and the creation of the Environmental Protection Agency (also by Richard Nixon).
But parallel to the research that looked at the negative effects of pesticides, were diverse lines of research that were discovering that pesticides weren’t the miracle technology they promised to be.
There are tens of millions of acres of corn in the United States (corn is just an example). Certain pests and diseases like to eat and destroy corn, so when synthetic chemicals were developed against those, certain pioneering farmers started spraying those chemicals and their yields (and profits) went up. This forced all the other corn farmers to start spraying. But even in the absolute best circumstances, pesticides are only 99.999% effective. Across all those acres of corn, there are many billions of pests, meaning a huge pool of genetic diversity. While you will kill the vast majority of them in the first, second, and even third years with a new pesticide, over time, you are slowly selecting for resistance in that genetically-diverse pest population.
Integrated Pest Management (IPM) was developed to better control pest populations with fewer synthetic chemicals. IPM is a diverse set of ecosystems-based strategies that focus on the long-term prevention of pests by using a combination practices, that vary from the biological and chemical to the common-sense and practical. Together, these practices minimize damage people, property, and the ecosystem.
While many IPM practices don’t include synthetic chemicals, it doesn’t write them off completely. In fact, “responsible use” of such chemicals is a critical part of IPM if other non-chemical methods have failed. One responsible use method is only spraying during peak efficacy of the chemical (i.e. if a synthetic pesticide inhibits the larval stage of an insect, only spray when the larval stage is most common). Another aspect of responsible use is not spraying the entirety of your acreage. While this might result in more pests this year, spraying less means fewer pests down the road.
While some individual pests in the population will have genes that provide pesticide resistance, that doesn’t come without cost. It takes energy to produce and operate whatever enzymes and proteins that confer resistance. This is absolutely worth it if the population gets sprayed, but it is an ever-so-slight disadvantage if not sprayed. If farms are responsible and don’t spray all of their acreage, the non-resistant pests will be more likely to reproduce in the non-sprayed areas, and thus re-populate the previously-sprayed areas. While not spraying means more pests now, it prevents resistance from being selected for, meaning fewer total pests in the future as the pesticides will continue to work.
IPM is just one example of ecological, non-zero sum thinking allowing all parts of the system to benefit.
In 1971, President Richard Nixon signed the Nation Cancer Act, beginning the “War on Cancer.
Cancer has been the second leading cause of death every single year in living memory (heart disease is always number one).
And below is both sexes on the same graph along with total incidence rates.
The drop in total cancer mortality from ~200 per 100,000 in 1975 to ~160 per 100,000 in 2024 is impressive and should be celebrated. But most people’s instincts about the causes of that drop aren’t quite right. Much of the decrease is due to better public health (reductions in smoking, the HPV vaccine, etc.), better screening regimens and detection methods (regular mammography, colonoscopies, and prostate exams, the invention of the MRI, etc.) and better surgical techniques, not because we’re that much better at “treating” cancer.
Now that is not to say that we’ve made zero improvements in cancer treatments over the past fifty years. We have. There have even been large, step-change improvements in a few cancers, such as CAR-T cell therapies for several lymphomas and myelomas and immunotherapies, such IL-2 therapy for melanoma, which have been gamechangers. But for many cancers, the improvement in actual treatments amounts to only months of additional survival.
Shown above are the changes in five-year survival rates for various cancers in the USA from the 1970s to the 2010s. This overall rate factors in all of better detection methods, screen regimens, surgical techniques, and treatment improvements. Even still, the majority of people with many types of cancer do not survive five years. And this is after nearly six decades of spending tens of billions of dollars per year on the “War on Cancer.”
Again, this is not to undercut the work and improvements that have been done. Cancer is a very hard, complex, and multifaceted disease.
Because of its difficulty, the main paradigm that we currently approach cancer treatment with is the “continuous, maximum tolerated dose until progression” method. Since cancer is very bad, we attempt to treat it with a knockout blow: the maximum dose that a patient can tolerate in order to ‘overwhelm’ the cancer. To quote a 2015 Lancet paper, “historically, the maximum tolerated dose has been thought of as the optimum biological dose.”
But what if there was another way of approaching cancer?
By the time a tumor is diagnosed, it is made up of billions of cells. Cancer cells by definition are highly mutated and growing rapidly. These facts together mean that a tumor is a genetically diverse population.
The critical insight is that if overuse of synthetic pesticides selects for resistance in a genetically diverse population of pests, then the maximum tolerated dose of pharmaceuticals probably selects for resistance in the genetically diverse population of tumor cells. Just like IPM was a new paradigm for managing pest populations, adaptive therapy is a new paradigm for managing cancer cell populations.
Now this isn’t saying the we should expect adaptive therapy to work for every possible cancer, but so far a small number of early trials have been promising.
For now, the most extensively adaptive therapy has been for prostate cancer. In a pilot trial, researchers enrolled patients with prostate cancer to begin taking abiraterone (a hormone therapy for prostate cancer) and prednisone. Once their PSA (a protein produced by the prostate) had declined by 50% of their baseline levels, the therapy was suspended. Abiraterone plus prednisone were reinitiated only when a patient’s PSA increased to or above the pre-abiraterone PSA baseline. This cycling off/on therapy went on as many times as a patient’s PSA cycled between a 50% decrease and return to baseline. This cohort was then compared to a contemporaneous cohort receiving the traditional therapy.
Despite the adaptive cohort (top) spending only ~50% of time on the therapy (red bars), only 1 out of 11 patients has a progression in their cancer compared to 14 out of 16 in the conventional cohort. (And since they spend ~50% of the time off the therapies, this generates huge cost savings.)
Now, this is far from a perfect study (small, not randomized, etc.) but it was promising enough to begin real clinical trials, and results of a Phase 1b trail were reported in 2022, with similar promising findings.
Researchers have also began the process of expanding adaptive therapy beyond prostate cancer, for example in breast and ovarian cancer.
I’ll reiterate that adaptive therapy remains extremely new and needs additional study. Moreover, it might not work for every cancer type or subtype. Yet it’s early-but-promising results, along with the success of the Yellowstone wolf re-introduction and Integrated Pest Management, are all examples of ecological thinking triumphing over pure reductionist practice.
The synthesis works because all three examples turn on the same hinge, even though you let the reader find it: suppression only holds when whatever escapes it pays a cost.
Elk pay in vigilance and lost foraging, resistant pests pay the enzymatic tax you describe, resistant tumor cells pay a metabolic one. That's the load-bearing assumption under adaptive therapy, and it's exactly why your caution about generalizing it is right. Where a resistant clone is close to cost-free, the sensitive cells can't hold it back, and the ecology stops rescuing you.
The cost is the whole game !
Great article, thank you.