Exposome Perspectives Blog by Robert O. Wright, MD, MPH
“Have you reckon’d a thousand acres much? have you reckon’d the earth much?
Have you practis’d so long to learn to read?
Have you felt so proud to get at the meaning of poems?
Stop this day and night with me and you shall possess the origin of all poems,
You shall possess the good of the earth and sun, (there are millions of suns left,)
You shall no longer take things at second or third hand, nor look through the eyes of the dead, nor feed on the spectres in books,
You shall not look through my eyes either, nor take things from me,
You shall listen to all sides and filter them from your self.”
From “Song of Myself” by Walt Whitman
Pop music, muddled lyrics, and misinterpretations
The Monkees are an underrated band. While they were a slick prefabricated collection of 1960s actor-musicians created to appeal to preteens—since the world’s biggest “real” band, i.e. the Beatles, had become too counter-cultural, too hippie, and too musically ambitious—they made some genuinely good music (my favorite being the hidden gem “The Girl I Knew Somewhere”). Their songs were catchy, overtly commercial, and after their break-up, became kitschy, which gave them staying power. Their most famous song, “I’m a Believer,” features a gospel-like chorus: “Then I saw her face, now I’m a believer,” led by Micky Dolenz, who lamented:
“What’s the use in trying?
All you get is pain
When I needed sunshine on my brain.”
Now that last line is what my 9-year-old self heard when the song played on the radio, and I sang it that way for years. My sister pointed out that the line was “when I needed sunshine, I got rain,” but I argued that it was actually about psychedelics. Eventually, I had to concede I was wrong, since I didn’t actually know anything about psychedelics at age 9.
The transdisciplinary nature of grunge
When I got to high school, I discovered punk rock, and about a decade later its successor: grunge. I still remember seeing Nirvana’s Nevermind album plastered all over Tower Records, with its iconic cover photo of a swimming, naked baby chasing a dollar bill—perhaps the greatest album cover ever made. Their song “Smells Like Teen Spirit” was on a near constant loop on MTV, and I loved it. Even on my first listen I could tell it was mocking the corporate slickness of MTV itself, which Nirvana also parodied in their music video via a pseudo-high school pep rally.
The lyric “Here we are now, entertain us!” is both demanding and obsequious, capturing the pressures youth feel as they are bombarded with commercial messages to buy “cool” products. These products are presented as rebellious, but ultimately just enrich uncool, wealthy old men. My keen observations were especially evident in the line leading into the refrain, which Kurt Cobain shouted as if he were screaming up to his parents from a dark, dank, humid basement bedroom- that he was done with manufactured teenage angst.
“A MULATTO, AN ALBINO, A MOSQUITO, NOT A BEATLE”
I immediately recognized this line as an oblique, clever reference to the 1965 Gilligan’s Island episode where a “mop-top” rock band called The Mosquitos was temporarily stranded on a deserted island with the SS Minnow’s crew.
What a perfect metaphor for intergenerational betrayal! The Mosquitos abandoned Gilligan and friends rather than rescuing them— because they feared competition from Ginger, Marianne and Mrs. Howell’s girl band, the Honey Bees. This reference brilliantly encapsulates both the ongoing struggle between generations and the slow decline of modern music, as it succumbed to the vices of corporate America. No doubt inspiring Nirvana to put one over on the record company by describing the corrupting influence of the industry’s faux rebellious, money-grubbing coolness in ways out of touch executives couldn’t possibly see.
Then I learned the line is actually “A Mulatto, an Albino, a Mosquito, my Libido.” Oh, I guess it wasn’t about the Beatles; it was about teenage hormones. If I had been ten years younger, I might have actually understood Cobain’s lyrics. Despite my knowledge of pop music and 1970s punk rock, I misinterpreted a key part of this new grunge song because, by 1991, I no longer had any expertise in being a teenager. At that time, I was too busy as a pediatric resident to give a lot of thought to what made grunge so great.
Looking back, I now recognize that grunge bears a resemblance to two different musical genres: punk rock and heavy metal. Punk rock was fast, irreverent, and rebellious—a declaration that you wouldn’t play by society’s rules. Heavy metal, on the other hand, was slow, laborious and loud, like a horror movie where you’re being chased by a relentless killer. Nirvana integrated both of these styles, with songs that alternated between slow and fast, soft and loud—sometimes rebellious, sometimes foreboding. Kurt Cobain, the lead singer and guitarist, perfectly mixed them into a “transdisciplinary” new genre. The genius of his approach was that the punk rock fans saw Nirvana as punk, while metalheads claimed him as one of their own.
What can Kurt Cobain teach us about team science?
Great artists often blend the strengths of different genres to create entirely new ones. Doris Lessing, a heralded writer of serious literature on the human condition, unexpectedly turned to Science Fiction in the 1970s, a time when literary critics dismissed such work as frivolous “space opera.” Lessing recognized that science fiction allowed her to explore social issues in ways that traditional realism could not. For example, in the Sirian Experiments, Earth’s governments and economies are manipulated by an unseen extraterrestrial society—an allegory for the influence of oligarchs in the modern world.
Science can learn valuable lessons from Kurt Cobain and Doris Lessing, integrating knowledge from different disciplines can lead to new insights and a deeper understanding of biology. Exposomic scientists are now beginning to study autism—a field long dominated by genetics. One would think that studies combining the skills and approaches of these two vastly different fields would abound, since they are studying the same disorder. But surprisingly, such interdisciplinary studies are extremely rare. Why?
Unfortunately, science may be even more siloed than art or music. Although we often study the exact same diseases, we do so in isolation never seeking input from other scientific disciplines to incorporate what they have learned into our research. In fact, fields often claim existing knowledge as a new finding because they never read studies outside their own field. Genetics famously “discovered” population substructure” after the Human Genome Project, which is just the age-old concept of “confounding by ethnicity” repackaged with a new name.
Science’s “Song of Myself”
There is a path forward though—a scientific “Song of Myself.” Transdisciplinary Team Science is an attempt to break out of these silos. Like Lessing and Cobain, it’s about blending and mixing together different expertise, knowledge bases, and skill sets to create something new. Yes, there is value in crossovers through cover songs. Lauryn Hill did a great rap/reggae version of Frankie Valli’s “Can’t Take My Eyes Off of You,” and the Rolling Stones performed the occasional country song, like “Dead Flowers.” But these examples were “one-offs” that didn’t create new genres. These examples are better seen as multidisciplinary, rather than transdisciplinary. They combine elements from different genres, but the fusion ends with the song.
That’s the difference. In multidisciplinary research, scientists from different fields collaborate but largely maintain their individual expert perspectives. A multidisciplinary study on autism might add blood lead measurements to a genetic study of 10-year-olds. Adding blood lead levels to an existing genetics study may be convenient, but it doesn’t consider the best way to blend environmental research with genetics. The problem with that approach is that 10-year-olds rarely have lead poisoning, unlike 2-year-olds. Lead poisoning peaks at age 2 years, and that peak will be missed if it is measured in 10-year-olds. This means that many of them will be mischaracterized as unexposed to lead, because the lead exposure at age 2 years is now gone. So the fact that they had been exposed 8 years earlier is missed. Merging Environmental Health measures with Genetics in this case is a failure- and we might not realize why.
Environmental Genomics: A transdisciplinary approach
In contrast, a transdisciplinary study would integrate genetics with the role of life stage in a manner consistent with the knowledge already culled from environmental health. We know that lead exposure is most common at age 2 years- and then it becomes uncommon as a child ages. Age 2 is a “window” at which lead exposure occurs at high rates due to normal crawling and mouthing behaviors that go away as a child ages. Furthermore, lead is most toxic to the brain during the window of age 2, as brain development is rapid fire at this age. Age 2 is also a window of biological vulnerability to lead exposure. So transdisciplinary research would factor all these behavior and biological issues in. Instead of measuring lead exposure at age 10 in the earlier example, a transdisciplinary study would not use blood lead from age 10 years which was simply done for convenience in the multi-disciplinary example. The study would be “redone” on a new set of children and lead measured at age 2 years. On the genetic side, certain genes that regulate brain development are linked to an increased risk of autism, but they haven’t been studied in connection with lead exposure. These genes have limited predictive value for autism when studied in isolation- i.e. in the absence of data on lead exposure. It’s possible that autism develops when lead exposure occurs at age 2, but only in children carrying these genetic variants. It’s the combination of the genetics and lead exposure that matters. You have to measure both and at the right life stage. In this scenario, autism won’t occur even if these genetic variants are present unless there is also lead exposure at age 2. Autism also won’t occur when lead exposure occurs at age 2 in children without these genetic variants. It’s the combination of genetics and environmental exposure at critical life stage that drives autism, rather than genes or environment factors alone. But if we only measure environment or only measure genetics, we never see this. At present, our research rarely attempts this level of integration. The preceding is just an example of how gene-environment interactions likely work. To my knowledge there are no studies that have attempted to do what I just described. So the question is still unknown as to whether lead exposure at ~age 2 years interacts with genetic variants for autism.
Conducting this kind of research is more challenging than simply adding blood lead measurements to an existing autism study of 10 year olds. It requires avoiding the convenience of working with what exists and instead working toward getting resources that are needed to optimize the science. It is simpler and convenient to tag blood lead levels on to an existing study of 10 year old but it is also ignoring the known biology of lead poisoning. We need to address the principles of both fields to be transdisciplinary. This type of study could even lead to a new field – Environmental Genomics.
Why transdisciplinary research is more challenging than multi-disciplinary research
Obviously, scientists are like all other human beings. We don’t like to leave the comfort zones of our expertise. There are even language barriers when we collaborate. Different fields don’t always use the same terms for exact same biological concepts, leading to miscommunication.
In our example, a transdisciplinary study might require starting from scratch with a brand new study. The existing study of autism genetics in our example didn’t have blood samples from the optimal life stages for environmental lead measurement- so we have to start over. This is actually a common scenario because a person’s genetics remain the same from infancy through age 10. Geneticists often don’t have to consider age when sampling for their studies, and blood collection is much easier at age 10 than in infancy. If you don’t have to think about what is the important age to collect blood lead in children, you will likely not collect it at the optimal age. Too often, convenience wins in research, and science promotes collaboration poorly. If we could overcome these barriers, learn from each other and form truly transdisciplinary teams, we could gain a much deeper understanding of health. Taking this lesson to heart, if science can finally “listen to all sides and filter them from yourself,” it can begin to write a new and better “song” of discovery.