July 11, 2011 | 8
Looking around the ever-more-crowded globe, you might conclude that human sperm counts are just fine, thank you very much. Hitting the 7 billion mark as a species can lead to such conclusions. Yet that inference would counter what some involved in the field of endocrine-disruption research have long asserted: that sperm counts have, in fact, been dropping, and a Children of Men scenario of creakingly empty playground swings and absent children’s voices menaces the future of our species.
We’ve got a lot of menaces, among them shifting climate and disease patterns, and what I’m just positive will turn into frontier-days water wars in South Texas in the coming decades. But what about that stolen future, that assault on the male that the first reports of falling sperm counts heralded two decades ago?
What about them? Sperm counts are not falling after all. That’s supposed to be the story.
Endocrine disruption, meet controversy. Again.
But as a scientist and a writer, I’m finding it hard to decide which is the bigger story here: Study data that appear to reverse decades-old findings that sperm counts are falling, or study data that weren’t released by the study initiator but instead wended their way from the lab to a Ministry of Health to a Web site and then into a commentary in the peer-reviewed journal Epidemiology. As someone who was involved for about 10 years in endocrine-disruption research, I’m not surprised to see a soupcon of controversy focused on a Big Story in the field. After all, this research subject does nothing if not engender controversy. Google “BPA,” and you’ll see what I mean.
In spite of my dithering over what the larger story is, I know, I know. The bigger story is the tiny one: the sperm. But let’s take a look at the thread of conflict and controversy and the littered battlefield of endocrine-disruptor research before we get back to those sperm.
Something in the state of Denmark
Left: A woman needs a man like a sperm needs a bicycle
The story of falling sperm counts, and indeed much of the modern-day endocrine-disruption saga, started in 1992, when Danish researchers led by Niels Skakkebaek of the University of Copenhagen published a paper in the British Journal of Medicine reporting declining sperm counts. Their findings were based on an analysis of dozens of published papers describing semen quality. According to their results, global sperm counts had dropped by 50% in the five decades before the report.
Among possible culprits in the case were compounds—at the time referred to as environmental estrogens—that might be fubarring sperm production. What had been called environmental estrogens morphed into a larger category known as endocrine-disrupting compounds, chemicals that could behave like hormones or interfere with native hormone behavior. They are considered especially potent during developmental periods—embryonic and fetal development, puberty—and may have epigenetic effects lasting into generations following exposure.
Decades of disruptors
The 1990s became The Decade of the Endocrine Disruptors, the compounds in the environment that act like hormones in you or amphibians or reptiles or rats. Data piled upon data. There were accidental discoveries, like the plasticizer in vials holding a hormone-sensitive breast cancer cell line that sent the cells into hyperdrive. There’s the compilation of the decade’s research into Theo Colborn’s Our Stolen Future. While the book was not an environmental grenade exploding complacency the way Rachel Carson’s Silent Spring did, it did offer a good compendium of what the highest-profile—and not so high-profile—researchers in the baby field of endocrine disruptors had found so far.
Right: Hmm. Only five sperm. Not a good sign.
Sure, there were bumps along the way. A zingy buzzword in the arena of endocrine-disrupting compounds became the word “synergy.” As in, the effects of compounds together exceeded the sum of their effects separately. This concept was a big deal because of the hundreds and hundreds of potentially disruptive compounds out there and the fact that no one, no organism would be exposed to a single compound at once. What happened in mixtures? was the burning question. The concept got a big boost from a 1996 Nature paper boasting relatively extravagant synergy in a yeast reporter assay using estrogen receptors. This paper also then became famously retracted once no one could find the basis for the data reported, especially from the notes of the first author. Full disclosure: That same author was supposed to serve on my PhD dissertation committee but suddenly vanished from the scene just before the retraction and other embarrassing sequelae.
Thanks to debacles like this and pushback from various interests with dollar signs in their collective eyes, endocrine disruption research was, in some ways, the Rodney Dangerfield of sciences. It sometimes seemed to get no respect. Part of the problem was that it could appear to lean more to the "applied” parts of science than the “basic.” In the social hierarchy of scientific investigation, basic and mechanistic research take precedence over applied research and receive a similar proportion of respect.
Endocrine-disruption research certainly addresses mechanisms but has an applied aspect, as a chimeric field that interweaves many disciplines and perhaps bemuses the unimaginative. Just as an example, though, thanks to people investigating disrupted reproduction in birds about 35 years ago, everyone now knows about that mystery of mysteries, the aryl hydrocarbon receptor. Yet a high-profile researcher at my postdoctoral institution once told me that he thought people turned to endocrine-disruption research because they’d just run out of things to do. At the time, I found that insulting, as I’d been involved in the field for about 10 years at that point, and not because I couldn’t find anything to do. Given the endless number of affected species, compounds, mixtures and exposure routes, we’ll be able to find things to do for decades, including mechanistic investigations.
Trust: You have to earn it
The list of compounds identified as having hormonal activity continued to grow through the 1990s. It included just about anything that qualified as a persistent organic pollutant. It seemed to encompass anything that ended in –cide, which did not make some manufacturers of said –cides very happy. I witnessed one particularly embittered and fascinating exchange at a Society for Environmental Toxicology and Chemistry conference, where Berkeley scientist Tyrone Hayes—who, the first time I ever saw him, was wearing large chandelier earrings—blasted Syngenta, the maker of the herbicide atrazine, producing emails and other evidentia to back up what he was saying. (Full disclosure: I am currently one of many authors on a review paper that Hayes has spearheaded.) Hayes, you see, had annoyed Syngenta by finding that frogs exposed during development to astonishingly low levels of atrazine turned up with way too many gonads (two’s enough, you know?), sometimes of the wrong kind for the presumed sex of the animal.
Right: Is the clock ticking for men’s reproductive capacities?
Syngenta scientists were in the conference room, as well, and when Hayes popped up the first email exchange between himself and Syngenta reps onto the screen, the oxygen level in the packed conference room—the most packed I’ve ever seen—dropped almost to zero. It was indeed a giant sucking sound. That contretemps has been covered extensively and continues, so I won’t say anything else about it here. What I will say is that what struck me most about Hayes’ comments in that forum was a recollection he passed on about his mother. To the best of my years’-old recollection, she trusted, he said, in what trained scientific types told her. It was that very trust in expertise, he explained, that drove him to make sure that scientific types earned that trust. These days, of course, that sort of trust has eroded almost into unrecognizability.
Um…does that penis look tiny to you?
Those comments stayed with me because, in spite of dismissals of endocrine-disruption research as negligible or peripheral or ephemeral, I had always found it quite important, not only for people and their sperm counts (which were peripheral to my area of the research) but also for animals at ground zero of exposure: the ones who lived, bred in, ate and drank the –cides we dump into their environments. It’s one thing to worry about falling sperm counts in a world of 7 billion people. But eggshells that crumple under the slight weight of a mother bird? Females pair-bonding because of an absence of males? Tiny alligator penises? Males making egg yolk? I found these manifestations disturbing. This is a world of effects and reverberations that requires careful mapping, even if some paths lead to dead ends, even if some controversies mask the important findings.
Left: Polar bears: full of persistent organic pollutants while living where no one uses persistent organic pollutants.
Even more disturbing to me was what I found with the turtles I worked on. One of my first studies involved applying extremely low-concentration mixtures of common organochlorine pesticides to eggshells of developing turtles. As I mixed the stock solutions and diluted them again and again and again to achieve the parts-per-trillion doses that reflect a relevant environmental exposure, I was completely and utterly skeptical of seeing any effect at all. But that one drop in a trillion overrode the temperature signal for my turtle species that said “develop as a boy” and caused a significant percentage of the turtles to develop as female. Those results hooked me. They convinced me. They kinda terrified me.
Turtles, frogs, other amphibians, alligators with tiny penises, the now infamous bisphenol A. No hormone system untouched. Passage from mother to child established. Breast milk chock full of PCBs… all over the world. Polar bears packed with POPs (persistent organic pollutants). There seemed to be no end to the contamination, or to ways of studying it. Much unmapped territory for species, contaminants and exposures remains to be explored —including examining what happens to sperm.
Oh, what a piece of work is sperm
Indeed, since that first study by Skaakeback et al. identifying falling sperm counts, sperm has often remained a research target, in humans and other species. Is there any other cell with seemingly so little going for it—some DNA, a mitochondrial motor, enzymes in the tip, almost insurmountable odds of success—that conjures so much interest? Certainly, there is no other cell that has inspired a Monty Python song. And as with most things endocrine-disruption-related, it also conjures some controversy and a tiny hint of conspiracy.
When Niels Skakkebaek published that first meta-analysis announcing falling sperm counts oh-so-long ago, some experts expressed concerns about the study design and analysis. Yet, as with so many “fright” findings in science, the publication set off a blizzard of interest in the news media and was cited in more than 1,000 scientific papers, according to the Epidemiology commentary authors. I can only imagine what would have happened today, almost 20 years later, in our viral internet world. Undoubtedly, it would have been an even bigger frightstorm. At the time, the blizzard ultimately took shape into a giant pile of a documentary called “The Estrogen Effect: Assault on the Male.”
Based on the latest report, males may be able to remove the body armor. If sperm counts aren’t really falling, linking falling sperm counts to, say, endocrine disruptors assaulting the sperm-production machinery may be the scientific version of premature release. Oddly enough, this revelation comes to us not by way of an original research paper, but as a peer-reviewed recent commentary in the journal Epidemiology.
Sperm counts aren’t falling but Children of Men still looms
The journal is the endpoint of the long, strange trip the most recent data took. Niels Skakkebaek, it seems, initiated the study but is awaiting its publication as a research paper before commenting. Niels Jorgenson, according to a Time.com health blog the current leader of the Danish study group, turned the data over to the Danish Ministry of Health, where it appeared on the ministry Web site. The authors of the Epidemiology commentary—the science version of an editorial—then based their piece on what they found on the site. That’s a more circuitous path to a target than a sperm has ever had to take. Why? It’s unclear.
In their commentary (available as a free PDF download), authors Jens Peter Bonde, Cecilia Host Ramlau-Hansen and Jorn Olsen evaluated the sperm-count results available on the Web site from about 5,000 young Danish men reporting for compulsory fitness exams for the military. Providing a sperm count was not compulsory, but it was “encouraged.” I can’t even begin to prophesy what the response of our tea-partying nation would be to that kind of national service. Would there be a Christian backlash against the onanism, a Catholic backlash against the sacredness of every sperm, or a libertarian backlash against Big Government trying to tell sperm how to live?
At any rate, in Denmark, apparently there are no such misgivings. And according to the authors, these data and more from a Swedish study—the Scandinavians really are committed to giving it up for science—show no recent drop whatsoever in sperm counts. Indeed, as I noted in a post I wrote for EarthSky, a graph in their commentary covering each year from 1996 to 2010 shows very little change in median counts over time. These data have the merit, according to the authors, of being “the best longitudinal semen data yet available.” Not very many researchers can make that claim to fame.
What is it about Scandinavian semen?
What has left me confused is that Bonde and co-authors describe a 1998 study of theirs that found a “surprisingly large” proportion of young men who turned up with low sperm counts. So even though sperm counts aren’t changing over the years, they were low in a lot of men 13 years ago. Add to that findings from a more recent Finnish study—see the devotion of the Scandinavians to reproductive research?—that some factors indicating semen health are on the decline. The authors blame “environmental factors,” and the picture of a healthy sperm, or sperm count, remains fuzzy. Even fuzzier is any cause-and-effect relationship between sperm degradation or decrease and exposure to a hormonally active contaminant, or to anything else…except possibly living in Scandinavia.
As with so much in the endocrine-disruption world, reports and research studies leave more gaps than they fill and open the way to more controversy and media frightstorms. If sperm are in trouble, are they in trouble everywhere, or only in Scandinavia? If they’re not in trouble, why does a commentary seeming to say as much then conclude with dire warnings and references to Children of Men? The controversies will continue, but this time, the discussion in the public arena will move faster and be more intense and inflammatory.
As the flagellum turns
Anyone involved in endocrine-disruption research must be prepared to gird some loins for battle on many fronts. Pitfalls such as data retractions are not specific to the field. But what about odd presentations of new data such as this Epidemiology commentary on unpublished original data taken from a Web site? It seems that nothing about endocrine-disruption investigations follows the path of “normal” scientific pursuit. Not least among its accoutrements is that the most minor studies may make big news, along with expansive overinterpretations. As the commentary authors themselves note, it’s not the science, it’s not the nuance, it’s not the new questions that get people’s notice. It’s the headlines. A sampling via a Google news search on “endocrine disruptor” the day I wrote this piece makes it clear:
- A personal favorite: Chemical-free Father’s Day gift ideas (how did they manage to find a gift that does not consist of matter?)
Fat, unborn babies, Dad, erections, autism! Buzzwords and frightstorms aplenty.
The Epidemiology commentary authors compared the two recent studies—the one from Sweden finding no changes over time and the Finnish study finding declines in semen quality—and drily commented parenthetically that, “Needless to say, it was the Finnish study that was featured in a BBC news report—’Sperm quality fall "due to chemicals",’ even though the study addressed no causation of any kind." Regardless of why any investigator engages in endocrine-disruption research—money, fame, fighting with big business interests, being misinterpreted in the popular press, risking their own reproductive effects—the controversy from all sides will come with the territory. Much of that territory remains uncharted, and I’ll continue to argue that it requires assiduous and careful mapping from battle-ready scientific explorers.
Yes, Dear Reader, endocrine-disruption research does matter, even if the sperm counts aren’t falling.
About the Author: Emily Willingham, author of The Complete Idiot’s Guide to College Biology, has a B.A. in English and a Ph.D. in biology, and she’s not afraid to use them, often together. She blogs for EarthSky and at The Biology Files and tweets her interests, random thoughts and cool stuff from other people as @ejwillingham. In a previous life, Emily was an assistant professor of biology and an actual practicing researcher.
The views expressed are those of the author and are not necessarily those of Scientific American.