Synergy

I just read the article by Mark Winston in the New York Times (July 15, 2014) in which he talks about the “thousand little cuts” suffered by honeybees which has led to the catastrophic decline of these insects. (The article is reproduced at the end of this blog.) I had been thinking about synergy and this seems to fit right in.

Synergy means the interaction of two (or more) things that produce an overall effect that’s greater than – or different from – the sum of the individual effects. In other words, we cannot predict the whole simply by looking at the parts.   Even so, we are challenged to understand and predict the impacts that contaminants have on communities – when understanding the effect of a single contaminant on a single organism is daunting. There are almost unlimited variables that impact any situation.

The EPA tests chemicals for adverse health effects, which they assume will occur individually. But in the real world, we’re exposed to a medley of chemicals every day – from car exhaust, to cosmetics, clothing, pesticide sprays for agriculture or mosquitos, even smog. The fact that these exposures can react with each other, and in effect, make each other more toxic, is a newly emerging science. In 1996, the EPA was required for the first time to consider cumulative pesticide exposure under the Food Quality Protection Act (FQPA). The FQPA recognizes that real-world pesticide exposure doesn’t occur as a single discrete exposure to a single pesticide, but rather as a combination of several pesticides at once. For example, USDA data shows that apples sold in the United States contained 22 different pesticide residues, and peaches contained 40.[1]

I just discovered the term “co-carcinogen”, which means the additive or synergistic effect of two or more agents which leads to cancer. These “co-carcinogens” may not themselves be a carcinogen. For example, a study by the University of Minnesota published a paper about the cancer-promoting effects of capsaicin – found in foods that contain hot chili peppers. It’s complicated – if you’re interested, please click here.

Here’s an interesting story:

In the summer of 1985, 30 year-old Thomas Latimer was leading a good life in the suburbs of Dallas, TX. He was a vigorous, athletic man with a promising engineering career. On one particular Saturday afternoon, Mr. Latimer spent the day mowing the lawn, picking up the clippings and edging the walkways. After about an hour, he began to feel dizziness, nausea, tightness in his chest and a pounding headache. Ten days later, he felt even worse and went to see his doctor.

Over the next six years, Mr. Latimer found himself unable to exercise. He suffered from brain seizures. He visited 20 different doctors and underwent numerous tests to determine the source of his medical problems. His symptoms were consistent with organophosphate poisoning, most likely from the insecticide diazinon that had been applied to his lawn. But because his symptoms were so severe and the amount of pesticide he was exposed to was so low, the doctors continued to look for a complicating factor. After further research, a toxicologist, three neurologists and two neuro-ophthalmologists all concluded independently that the popular ulcer drug Tagamet that Mr. Latimer was taking had suppressed his liver, making him more susceptible to pesticide poisoning.

Alfredo A Sudan, a professor of neurology and ophthalmology at the University of Southern California, who conducted extensive tests evaluating an eye disorder that Mr. Latimer developed, estimates that taking a medication like Tagamet “can make a person 100 to 1,000 times more sensitive to organophosphate poisoning.”[2]

In 2001, researchers at Duke University’s Department of Pharmacology and Cancer Biology published a series of papers looking at the synergistic effects of DEET (the active ingredient in most insect repellants) and permethrin (a pesticides commonly used in community mosquite programs, as well as many household bug killers.) The purpose of the studies was to determine a possible link between pesticides and other chemicals used during the Persian Gulf War and the “Gulf War Syndrome” – a neurological disease. When DEET, permethrin and pyridostigmine bromide (a drug taken by soldiers to counteract toxic gas warfare chemicals) were administered alone – even at doses three times the level soldiers received – no effects were observed. But when the three chemicals were used in combination, test animals suffered neurological symptoms similar to the Gulf War veterans.[3]

Neurology experts give three possible reasons for the synergistic effects seen in the above experiments. First, the stress endured by animals when exposed to a combination of chemicals undermines the protective role of the blood brain barrier, allowing the level of toxics to cross into the brain to be 100 times higher. Second, tissue that has been exposed becomes more sensitive and receptive to other toxic substances. Third, certain chemicals bind to enzymes that detoxify the body, making the enzymes unavailable to protect the body from other intruding chemicals. Dr. Goran Jamal, a neurologist at the West London Regional Neuro-Science Center of the Imperial College of Medicine, makes the following comparison, “It’s like releasing 200 criminals in London and taking away the police officers that are usually on duty. There is bound to be some damage.”[4]

The organization Beyond Pesticides suggests a variety of tests: testing for interactions between pesticides commonly used in agriculture, between pesticides used in agriculture and food contaminants, for pesticides commonly found in drinking water, for pesticides and pharmaceuticals, and for pesticides that are likely to drift. However, this testing is probably unrealistic so the best approach might be to limit exposure – by limiting exposure you also limit synergistic health effects.

Here is Mark Winston’s article, “Our Bees, Ourselves”:

New York Times, Katie Scott

AROUND the world, honeybee colonies are dying in huge numbers: About one-third of hives collapse each year, a pattern going back a decade. For bees and the plants they pollinate — as well as for beekeepers, farmers, honey lovers and everyone else who appreciates this marvelous social insect — this is a catastrophe.

But in the midst of crisis can come learning. Honeybee collapse has much to teach us about how humans can avoid a similar fate, brought on by the increasingly severe environmental perturbations that challenge modern society.

Honeybee collapse has been particularly vexing because there is no one cause, but rather a thousand little cuts. The main elements include the compounding impact of pesticides applied to fields, as well as pesticides applied directly into hives to control mites; fungal, bacterial and viral pests and diseases; nutritional deficiencies caused by vast acreages of single-crop fields that lack diverse flowering plants; and, in the United States, commercial beekeeping itself, which disrupts colonies by moving most bees around the country multiple times each year to pollinate crops.

The real issue, though, is not the volume of problems, but the interactions among them. Here we find a core lesson from the bees that we ignore at our peril: the concept of synergy, where one plus one equals three, or four, or more. A typical honeybee colony contains residue from more than 120 pesticides. Alone, each represents a benign dose. But together they form a toxic soup of chemicals whose interplay can substantially reduce the effectiveness of bees’ immune systems, making them more susceptible to diseases.

These findings provide the most sophisticated data set available for any species about synergies among pesticides, and between pesticides and disease. The only human equivalent is research into pharmaceutical interactions, with many prescription drugs showing harmful or fatal side effects when used together, particularly in patients who already are disease-compromised. Pesticides have medical impacts as potent as pharmaceuticals do, yet we know virtually nothing about their synergistic impacts on our health, or their interplay with human diseases.

Observing the tumultuous demise of honeybees should alert us that our own well-being might be similarly threatened. The honeybee is a remarkably resilient species that has thrived for 40 million years, and the widespread collapse of so many colonies presents a clear message: We must demand that our regulatory authorities require studies on how exposure to low dosages of combined chemicals may affect human health before approving compounds.

Bees also provide some clues to how we may build a more collaborative relationship with the services that ecosystems can provide. Beyond honeybees, there are thousands of wild bee species that could offer some of the pollination service needed for agriculture. Yet feral bees — that is, bees not kept by beekeepers — also are threatened by factors similar to those afflicting honeybees: heavy pesticide use, destruction of nesting sites by overly intensive agriculture and a lack of diverse nectar and pollen sources thanks to highly effective weed killers, which decimate the unmanaged plants that bees depend on for nutrition.

Recently, my laboratory at Simon Fraser University conducted a study on farms that produce canola oil that illustrated the profound value of wild bees. We discovered that crop yields, and thus profits, are maximized if considerable acreages of cropland are left uncultivated to support wild pollinators.

means a healthier, more diverse bee population, which will then move to the planted fields next door in larger and more active numbers. Indeed, farmers who planted their entire field would earn about $27,000 in profit per farm, whereas those who left a third unplanted for bees to nest and forage in would earn $65,000 on a farm of similar size.

Such logic goes against conventional wisdom that fields and bees alike can be uniformly micromanaged. The current challenges faced by managed honeybees and wild bees remind us that we can manage too much. Excessive cultivation, chemical use and habitat destruction eventually destroy the very organisms that could be our partners.

And this insight goes beyond mere agricultural economics. There is a lesson in the decline of bees about how to respond to the most fundamental challenges facing contemporary human societies. We can best meet our own needs if we maintain a balance with nature — a balance that is as important to our health and prosperity as it is to the bees.[5]

[1] http://www.beyondpesticides.org/infoservices/pesticidesandyou/Winter%2003-04/Synergy.pdf

[2] Allen, Frank Edward. 1991. One Man’s Suffering Spurs Doctors to Probe Pesticide-Drug Link. The Wall Street Journal. October 14.

[3] Abou-Donia, M.B., et. al. 1996. Neurotoxicity resulting from coexposure to pyridostigmine bromide, DEET, and permethrin: Implications of Gulf War chemical exposures. J. Toxicol. Environ. Health 48:35-56.

[4] http://www.beyondpesticides.org/infoservices/pesticidesandyou/Winter%2003-04/Synergy.pdf

[5] Winston, Mark, “Our Bees, Ourselves”, New York Times, July 15, 2014, pg. A25