Leonardo Trasande is an expert on the environmental origins of certain diseases and their economic impact. For example, in a recent study he quantified that the cost of exposure to endocrine disruptors in the EU amounts to at least 163 billion euros a year, which represents 1.2 percent of Europe’s GDP. We had the opportunity to talk to him about his research during his recent visit to Barcelona, where he was invited to participate in a lecture organized by “La Caixa” Fellows Association.

Let’s start at the beginning. What kind of toxins can we find in the environment that may cause health issues?

Regarding children, for instance, and going back 50 or even 100 years, lead was the first chemical whose effects were understood. With time, we found that lower and lower levels of childhood lead exposure were associated not just with increases in blood pressure, but also with subtle effects on the developing brain. At first, we thought that there were no chemicals as problematic as lead was for the developing brain. But as we continued to study, we realized that a broader array of chemicals can also affect it.

How?

One of the major pathways is through disruption of the function of a key hormone called thyroid hormone. When I trained in pediatrics, I was taught to always check a newborn baby’s blood spot test to make sure they weren’t positive for congenital hypothyroidism, but now we realize that it’s not just gross effects on the thyroid hormone that are important. We now know that there are subtle decreases in the thyroid hormone that you might not even detect in a pregnant woman through routine blood screening. And babies born with this thyroid hormone decrease are more likely to suffer from subtle effects on their cognitive function, and they’re also more likely to be affected by attention deficit hyperactivity disorder (ADHD) and autism.

What is the basic definition of an endocrine-disrupting chemical or EDC?

EDCs are synthetic chemicals that interfere with hormone function and thereby contribute to disease. And they do this in a variety of ways: mostly they mimic the structure of, let’s say, testosterone, or estrogens, or some other key signaling molecule, but there are many ways in which chemicals can also disrupt the hormones in our body and thereby contribute to disease. It might be the case that they disrupt the function of hormones but don’t contribute to a disease; then you don’t have a definitive endocrine disruptor. However, many hormonal functions exist for the sole purpose of maintaining a healthy body, so by disrupting a hormonal function you’re likely to induce some disability or disease.

And reproductive systems can be especially affected by chemical disruptors, correct?

Most recently, we found evidence that chemicals can also affect male reproductive functions, and also potentially contribute to the development of certain cancers or adverse birth outcomes. Particularly, there is an entire syndrome that is now understood to arise when the testosterone function is disrupted during a boy’s development. This leads to a misplacement of the opening of the urethra — called hypospadias — that requires surgery. In addition, the story of Lance Armstrong successfully fighting off testicular cancer shows that we’ve come a long way in treating this disease, but now we know that there’s actually been a 30 to 40 percent increase in the incidence of testicular cancer, when it’s a highly preventable disease as much as it is a treatable one.

What about women?

We’ve found that some effects can also show up in the female reproductive tract. They don’t have to manifest directly as clinically observable disorders, but they can show up as subtle hormonal dysfunctions. The increase in polycystic ovarian syndrome, for example, may be a by-product of synthetic chemical exposures interacting with genetic susceptibility. We also know that endometriosis and fibroids are all too common. Studies in humans and laboratory studies have suggested that certain chemical exposures, in particular to plasticizing chemicals and certain pesticides, can induce and be associated with these conditions. They are painful problems and sometimes require surgery, in both young and older women.

Your research is also focused on two modern epidemics: obesity and diabetes.

Yes. Research now is suggesting that the obesity and diabetes epidemic is not simply a by-product of an unhealthy diet and poor physical activity: chemicals may represent a preventable third factor in this epidemic. Although perhaps they only explain a modest proportion, they may be a preventable factor. The key difference is that, whereas diet and physical activity can be exceedingly hard to change — or at least, the change can only be done one person at a time — chemicals can be regulated. So the resources that have to be invested in preventing obesity and diabetes might actually be more efficient if they are focused on preventing chemical exposures that may contribute to these diseases.

Where do EDCs come from?

EDCs are a diverse array of chemicals. One of the first times they were identified was in 1971, when a research study conducted at the Massachusetts General Hospital linked prenatal intake of diethylstilbestrol (DES) — a synthetic form of estrogen — to a rare vaginal cancer in girls. DES had been prescribed to pregnant women since the 1940s to prevent miscarriage and premature births, but as a consequence of this finding, the US Food and Drug Administration asked physicians to stop prescribing it. But it’s not just about pharmaceuticals that may not have had full safety screening. There are all sorts of synthetic chemicals that can act as EDCs used as pesticides, to prevent fires in electronics and furniture, to make plastic soft and bendable, to make certain types of plastic cards, or to prevent corrosion in the lining of aluminum cans.

So how do you gain knowledge about their relationship with disease?

The best way is to conduct studies in humans that associate an exposure with an outcome. But it can take decades to really study diseases that take that long to develop. Endometriosis, for instance, does not occur in infancy but it can develop in older women. The same is true for fibroids and breast cancer. Those studies can be extremely hard to design, because you often need biospecimens — blood, urine, etc. — ideally at multiple time points, and then you have to observe and wait to see who develops disease and who doesn’t.

That means it takes a long time to get scientific evidence.

And with that problem comes a challenge: many people assume that absence of evidence means absence of harm. And unfortunately, what we know from the laboratory, and from the limited human studies that have been done, is that diseases of chemical origin that involve hormone disruption do not just have a substantial impact on human health, they also have a substantial impact on our economy.

Let’s talk about that.

Toxic chemical exposure has an economic impact because it has a human health impact. Often, when policymakers are trying to decide whether or not to limit a particular chemical exposure, they compare the cost of safer alternatives with the benefits of prevention. And if you have limited human studies, the fact is that there are very few data on which to base credible estimates of disease or disability in order to help guide prevention. Fortunately, that evidence is increasingly available and growing at a faster pace.

In fact, you conducted a study on the costs associated with EDCs in Europe.

Yes, we looked at 15 conditions that had the greatest evidence of a cause-and-effect relationship, and we used a number of conservative assumptions which included reducing cost estimates for these diseases based upon the uncertainty of scientific evidence. And even after placing those limits, we found that the cost of EDCs in Europe was around 163 billion euros per year.

That’s rather a lot of money!

It’s actually 1.2 percent of Europe’s GDP. But this estimate is also extremely low, for three reasons: we looked at less than 5% of EDCs; we looked only at a subset of diseases that can be traced to these chemicals; and then we only looked at a subset of economic costs that were published in peer-reviewed journals that provided us with reliable data on which to base cost estimates. So this figure is an underestimate of an underestimate of an underestimate. But it says a lot about the considerable economic benefits of preventing the chemicals of greatest concern, recognizing that there still may even be greater economic benefits as we increase our understanding of the effects of many more chemicals on human health.

What was the reaction of European authorities to that figure?

The studies clearly attracted a lot of attention. I suspect we changed the dialog in a way that means that the best endocrine science will from now on inform regulatory policy, but our work is clearly not done. Europe is finalizing its criteria regarding EDCs and one of the concepts that we succeeded in pushing aside was this whole notion of potency. There is this 500-year-old concept stemming from the Dutch philosopher Paracelsus which states that the dose makes the poison, in the sense that a toxin is harmless in small doses. But chemicals don’t follow straight lines. The more we look, the more we realize that the effects of chemicals can actually be greater at the lowest levels of exposure. Yet, time and again, we see European policymakers debating this old notion.

And I imagine they’re asking for human data on exposure risk.

Yes, and that’s one of the concerns I have about the European policy as it has been drafted, since as I said, it could take decades before we prove that a chemical is having an effect on human health. We are needlessly and dangerously delaying protection when we know that, for example, some chemicals can disrupt thyroid function, and this can be very problematic for children’s brain development. By not taking action, we may inadvertently condemn the next generation of children to develop preventable diseases and disabilities that are costly to society.

What do you propose then?

I firmly believe we should look at all available evidence on the probability of cause and effect. And we should act when there’s evidence that a chemical is a probable cause of harm to human health. If the harm is significant, we should proactively act, even though the evidence might not be certain. We can always change our policy framework to accommodate a chemical exposure if it is ultimately found to be safe in current use. The whole concept underlying our economic work was to show policymakers that the cost of inaction, even under the less extreme scenarios, is likely to be large.

Some action has been taken though, and we as consumers can also play our part. For instance, now we can get plastic free of bisphenol A, which is known to act as an EDC.

The power of the purse or the wallet can be quite substantial. One of the reasons behind the shift to bisphenol A-free materials is that consumers demanded that companies change their ways. Now my concern is that we often replace one chemical with another untested alternative that may be as problematic. For example, bisphenol A has been increasingly replaced with bisphenol S, bisphenol F and bisphenol P, all chemicals that are structurally similar to the initial bisphenol A compound. And studies have already identified bisphenol S to be just as estrogenic and just as persistent in the environment, so it may have a similar profile of toxicity for human health.

But getting back to the example of lead toxicity you mentioned before, we are now driving cars with unleaded gasoline.

Globally, we got lead out of gasoline just a couple of years ago in low- and middle-income countries. The economic benefit of doing that is 2.4 trillion dollars a year. That’s a 4 percent economic stimulus to GDP alone, and that is a gift that keeps on giving. As long as we continue to use unleaded gasoline, children will have much lower lead levels and therefore be more able to contribute productively to society, and that is a huge economic benefit, not to mention other health effects that could be prevented. We still have a long way to go, but yes, we’ve taken away the biggest cost of childhood lead exposure, and that is giving a huge economic reward.

As a pediatrician you usually refer to children. Are they more vulnerable?

Yes, they are uniquely vulnerable. Pound for pound, they breathe more air; they drink more water and eat more food, and their organs are exquisitely vulnerable to injury. When a child has an exposure to a chemical that is toxic to the developing brain, critical connections between nerve cells are not made, and then that child is less likely to perform at school. Also, when children inhale air pollutants, their lung development is sometimes affected. They don’t develop as many air sacs that are used to exchange oxygen, and so they have a reduced ability to run and play and do vigorous activity.

And it’s a bigger problem when their hormones are affected.

When children's hormones are disrupted, in particular for metabolic functions, there might be some misalignments. For a certain caloric intake, for instance, instead of adapting appropriately and storing calories as protein, they shift their calorie storage to fat, which may lead to obesity in later life. They might also have a disruption of the insulin function, and they might become insulin resistant, and potentially they can develop diabetes later on. So children are exquisitely vulnerable to the effects of synthetic chemicals, so much so that they can develop chronic diseases earlier and with more intensity than adults.

For instance, you are carrying out analysis on children exposed to the World Trade Center collapse in New York City.

The WTC disaster is known to have produced a very large cloud of smoke that many children inhaled simply because they lived or played or attended school near the site. Not to mention the psychological trauma associated with the exposure. My greatest concerns are the more chronic exposures that occurred because children continued to live, work and play near the site despite the fires burning for many months after the disaster. And there were many chemical residues, especially persistent organic pollutants from the furniture, electronics and other materials that were burnt or collapsed in the disaster.

And what are you looking at?

I’m looking at the effects of those early-life chemical exposures together with psycho-social trauma to see if children are suffering from metabolic disorders, or if there has been any damage to their developing blood vessel systems and hearts. Adolescence is typically the time when these conditions emerge, and the children exposed to the accident 15 years ago are now aged between 15 and 22 years old. So they’re more likely to show these diseases. If we don’t find any effects from those exposures, I’ll be very relieved. That may actually suggest a better outcome for children who are already known to have a higher rate of asthma than others who were not exposed to the disaster.

It seems there was little people could do to avoid the exposure, but is it possible to prevent health effects after such a disaster?

Well, insofar as doctors can potentially work with these children to modify their diets and perhaps do more physical activity, there are ways to prevent the diseases from becoming more prominent. However, you can’t undo that exposure. The other reason to study disaster-related exposures is so that for future disasters we can figure out what program or follow-up or prevention, if any, we need to implement. Because, unfortunately, we live in a society where I hope there’s never a disaster of quite that magnitude again but, preventable or not, there might be.

Interview by Bru Papell

References:

Herbst, A.L., Ulfelder, H., Poskanzer, D.C. (1971), Adenocarcinoma of the vagina — Association of maternal stilbestrol therapy with tumor appearance in young women. N Engl J Med. Apr 15; 284(15): 878-81. doi: 10.1056/NEJM197104222841604

Trasande, L. (2016), Stand firm on hormone disruptors. Nature. 2016: 539(7630): 469-469. doi: 10.1038/539469a

Trasande, L., Vandenberg, L.N., Bourguignon, J-P., et al (2016), Peer-reviewed and unbiased research, rather than 'sound science', should be used to evaluate endocrine-disrupting chemicals. J Epidemiol Community Health, 70: 1051-1056. doi:10.1136/jech-2016-207841

Trasande, L., Zoeller, R. T., Hass, U., et al (2016), Burden of disease and costs of exposure to endocrine disrupting chemicals in the European Union: an updated analysis. Andrology, 4: 565–572. doi: 10.1111/andr.12178.