Publications

2018
Adams, C.D., Blacksher, E.B. & Burke, W. The precautionary principle for shift-work research and decision-making. Public Health Ethics 12, 1, 44-53 (2018). Publisher's VersionAbstract
Shift work (working outside of 6:00 AM to 6:00 PM) is a fixture of our 24-hour economy, with approximately 18 per cent of workers in the USA engaging in shift work, many overnight. Since shift work has been linked to an increased risk for an array of serious maladies, including cardiometabolic disorders and cancer, and is done disproportionately by the poor and by minorities, shift work is a highly prevalent economic and occupational health disparity. Here we draw primarily on the state of science around shift work and breast cancer to argue that shift work represents a public health threat serious enough to warrant a precautionary stance. We use the precautionary principle to advance our case and view it as a moral compass for shift work research, empowering public health to cast shift work within the domain of health disparities deserving action despite scientific uncertainty. With the precautionary principle, we call for a deliberative decision-making process and formation of a broad shift work research collaboration to protect the health of many millions who work at night.
precautionary_principle_for_shift-work_research.pdf
2017
Adams, C.D., et al. Nightshift work, chronotype, and genome-wide DNA methylation in blood. Epigenetics 12, 10, 833-840 (2017). Publisher's VersionAbstract
Molecular mechanisms underlying the negative health effects of shift work are poorly understood, which remains a barrier to developing intervention strategies to protect the long-term health of shift workers. We evaluated genome-wide differences in DNA methylation (measured in blood) between 111 actively employed female nightshift and 86 actively employed female dayshift workers from the Seattle metropolitan area. We also explored the effect of chronotype (i.e., measure of preference for activity earlier or later in the day) on DNA methylation among 110 of the female nightshift workers and an additional group of 131 male nightshift workers. Methylation data were generated using the Illumina Infinium HumanMethylation450 BeadChip (450K) Array. After applying the latest methylation data processing methods, we compared methylation levels at 361,210 CpG loci between the groups using linear regression models adjusted for potential confounders and applied the false-discovery rate (FDR) ≤ 0.05 to account for multiple comparisons. No statistically significant associations at the genome-wide level were observed with shift work or chronotype, though based on raw P values and absolute effect sizes, there were suggestive associations in genes that have been previously linked with cancer (e.g., BACH2, JRK, RPS6KA2) and type-2 diabetes (e.g., KCNQ1). Given that our study was underpowered to detect moderate effects, examining these suggestive results in well-powered independent studies or in pooled data sets may improve our understanding of the pathways underlying the negative health effects of shift work and the influence of personal factors such as chronotype. Such an approach may help identify potential interventions that can be used to protect the long-term health of shift workers.
nightshift_chronotype_and_methylation.pdf
Adams, C.D. Genetics, Fear, and the Slippery Slope of Moral Authoritarianism. Quillette (2017). Publisher's VersionAbstract

I write this essay as a newly minted geneticist, trained especially in the societal implications and ethics of genetics. As the Google memo saga unfolded last month, I was reminded of social pressures I was subject to in my own training at the University of Washington. I was also reminded of the lines of this song, by Malvina Reynolds:

And the people in the houses
All went to the university,
Where they were put in boxes
And they came out all the same,
And there’s doctors and lawyers,
And business executives,
And they’re all made out of ticky tacky
And they all look just the same1

I graduated from the University of Washington’s public health genetics doctoral program in December 2016, for which, in addition to my dissertation, I took two years of courses in genetics, ethics, law, and various social sciences, woven together to appreciate how genetics is construed by scientists and the public.

As one might expect, eugenics was well-covered ground in the public health genetics program. Many warnings were offered up to us about how well-meaning scientists and policy makers could slip into using genetic information maleficently. The warnings included the history of early 20th century statisticians advancing eugenics in the United States; compulsory sterilization laws permitting the maiming of “imbeciles” in mental hospitals; and narratives like GATTACA’s dystopian future—where the government uses DNA information to limit  citizens’ employment prospects. An otherwise rational society might again use genetic technology in the wrong ways, such that large swathes of the population are harmed. Perhaps they would be harmed with gene-editing tools such as CRISPR. Or perhaps these tools could be used on insects or microorganisms, inadvertently introducing chaos into ecosystems, avalanching downstream effects on food supplies and possibly increasing vector-borne diseases in densely crowded municipalities.

Standard cautionary tales in my training also included the potential misuse of forensic genetics in criminal investigations. This includes either the purposeful or accidental swapping of blood samples to tie someone to a crime scene and incriminate them or the use of genetics to advance stereotypes. But this last cautionary tale—that of using genetics to advance stereotypes—ultimately led to what appeared to me to be censorship and moral indoctrination. My program was shrouded in this fear like a cloud. Like Google’s motto, “Don’t be evil”, what was evil was assumed and any utterances out of step with certain assumptions were silenced—their holders punished. With this backdrop, three memories come readily to mind.

Memory one
I was in a small group of maybe four other students and one faculty member from the law school. We were discussing a lawsuit wherein a white, same-sex couple had sued a fertility clinic for giving them sperm from a black donor, resulting in the birth of a non-white child. When I referred to the donor as “black”, as had the author of the popular press piece I’d read, the faculty member corrected my speech: “You mean African-American”—we don’t say “black””. With the implication that I’d committed an egregious microaggression, it was clear to all in the room that I harbored latent racism. I sat there stunned. The lawsuit was brought because the child was black, the argument being that the child’s darker skin would induce prejudice that the parents hadn’t anticipated when they paid for the artificial insemination service. But instead of concentrating on the merits of the wrongful birth case, whether a judge was likely to dismiss it and why—it was more important to call out my “bias”.

Memory two
Shortly after Mr. Trump was elected as president, I penned a few words of a budding memoir, starting with growing up in Trump country (poor, mostly white and Hispanic, rural Arizona) and the political polarization that keeps academics from talking meaningfully with those who voted for Trump. I sent a draft of the blurb to a professor, who wrote back with reflections about checking white privilege and wondering whether it is racist for white people (I’m white) to talk about their own poverty.

Memory three
One Seattle day, a classmate asked me if I “believed in The Bell Curve”. I was a bit confused by her wording, as I had just come from a biostatistics class. Not wanting to sound like an idiot, I nodded and said something along the lines of “Of course, I believe in bell curves. How can you be in science and not use population distributions to aid decisions?” Her face wrinkled like a prune, and I didn’t know why. How could a very basic acceptance of statistics evoke disgust? A few days later, a friend of hers and fellow classmate remarked to me, “How did you get into our program?” While I can’t pin down a causal link between the two interactions, I later realized that the first classmate was referring to the book by Richard Hernstein and Charles Murray, which I had not yet encountered.

In addition to being unaware of Hernstein and Murray’s book, I was also unaware of authoritarian threads within the Left, until the final year of my program, when I heard the term “Regressive Left”, probably from the evolutionary biologist, Jerry Coyne. Slowly, the cold, shaming signals I received within the genetics community began to make sense. Genetics, I began to see, has a tribal culture, interlaced with post-modern thinking about race, gender, and intelligence. The mark of the post-modern tinge being the taboo nature of these otherwise academic topics. If you touch these topics, the gods (your peers) may punish you, even if you strive by your occupation to reduce inequalities, are an equal opportunity feminist, and think differences in intelligence matter socially but don’t constrain a person’s innate worth as a human being.

James Damore’s Breaking of Taboo

Within the purview of academia, Silicon Valley, and to a large degree polite society, James Damore’s infamous memo touched the untouchable—an authoritarian-protected category that marks someone as in or out of the postmodern tribe. He voiced arguments, over which a sense of moral certitude reigns in many academic fields including human genetics, which holds itself culpable for the misuse of its technologies, its role in the eugenics movement and other past crimes. The past is seared into its collective memory, and reparations for these past blemishes, include both educating its members but also by signalling its newly found virtue. Its virtue-signalling is an attempt to establish trust in a era in which many people will be, or already have been, genetically tested, either in the clinic or research settings or through direct-to-consumer organizations, such as 23andMe.

Human geneticists want the population not to fear what will be done with their genetic information. Damore’s memo, in some ways, threatened this goal. He committed the sin of referencing research in genetics to support, at least some biological differences between groups. His doing so conjured seemingly instinctive but, nonetheless ideologically-patterned, indignation and scorn among those who want to spread the belief that human genetics is noble and will not ever be used to promote bigotry or stereotypes, (under the assumption that Damore’s referencing research on differences was a form of bigotry). As such, he was punished, setting an example that powerful corporations take authoritarian norms seriously and this punishment was held out for all on the Internet to see.

While in 2017 the academy and corporate extensions of it, for example Google, don’t sever heads and parade them along roads to strike fear into the hearts of enemies, we do call for the shaming and economic dislocation of those who verbally stray away from tribal norms—which Damore did and which I had been taught not to do in my training at the University of Washington.

What neither those deciding to fire Damore nor the more well-meaning but censorious geneticists seem to grasp is that one can be for diversity and social justice and also critical of authoritarian moral missions. In fact, it may be our duty to do so, as shticks, even moral ones, can cloud judgment even, and perhaps especially, when masked in the language of justice. As such, genetics, public health, and Google need people who are willing to express ideas that are outside of our “little boxes” of norms clutched so tightly dear. Otherwise, we all come out with the same ticky-tackied call to think and act like each other. And there’s not much diversity in that. Moreover, being all the same is dangerous.

The aim of protecting from the slippery slope that human geneticists fear, that we will be stridden unconsciously into an endorsement of eugenics and stereotype, is trammeled by a culture of ideologically uniform members. Who will catch such a gradual slip? The majority won’t, as intuitions about harm and “right” and “wrong” are subject to the majority’s sensibilities and needs and, hence, undercurrents that move groups towards adopting unconscionable practices are likely to go unnoticed or unchallenged by those enjoying the warm rays of the majority’s safe sun. No, the majority is selectively blind to covert biases that make it vulnerable to evil. Not even diversity training, with its promise to root out bias, can rid us of the spell that in-group solidarity casts, a spell that is ancestral, chimp-like—part our social nature: our tribal solidarity unites but also divides; sneaked intimately into our familial sense of normal and purpose, can Pied Piper us even murderously; and is not going away. We are beset with it. Therefore, a tolerance of the ideologically errant (those not entranced by the moral Piper), safeguarding against the horrors of the past and the horrors of the future, is necessary. Society needs the voices of its prophets, the soul-rumbling words of those with perceptions that rattle value-laden holds and thwart cerebral creep into unforeseen but majority-vetted peril.

The Slippery Slope of Moral Authoritarianism

Recently, after the neo-Nazi march in Charlottesville, photos of Auschwitz staff laughing in between the slaughter of millions have been circulating online. The photos—one of which is below—show normal people, not psychopaths—happy and drunk with an ideology wrapped in moral justification for their actions, blinkered from their own evil.

 

The timing of these photos circulating after Charlottesville, not long after the Damore affair, is uncanny. We can and should condemn Nazis and eugenicists. But the small band of poorly educated neo-Nazis getting too much attention is not the sort of ideological wasteland our majority needs to fear. We can handle—stymie, frustrate, and ridicule—self-professed racists into corners of meaninglessness, where they can sit until eaten by their own delusions of grandeur. In fact, our majority has already decried them, despite the failure to do so by the dangerous buffoon in the White House. However, what our majority needs to protect against is the horror that we can’t see so clearly—normal people, sanctioned by the majority, committing atrocities not yet recognized by the majority as harms. This is why we must tolerate the voices of dissent and, in particular, dissent against core values, the values that make groups take up moral crusades.

For this reason, Google should end its shunning and offer back to Damore his job. Far from Damore’s words being a threat to diversity, they protected diversity in Silicon Valley from the creeping boxed thinking that sets communities up for moral malaise. Likewise, the genetics and public health communities, while their majorities must continue to perennially warn about eugenics and potential unintended consequences of technology, they must also receive and engage, not browbeat and remove, their ideologically daring members, those sometimes risible taboo-wranglers who dispute sacredly held principles.

Not unlike the instinct to rapidly dismiss a reviewer whose critique of an excruciatingly sweated-over manuscript is felt to be stupid but whose thoughts, in the end, make the manuscript better, moving through the initial impulse to blast away the different is virtuous. The intellectually crippling fear of catching taboo’s stain and actions to purify a group, ridding it of morally suspect members, aren’t, however, virtuous and don’t protect against the mayhem that the un-tainted, in-group majority—be that Google, genetics, public health, or the wider academy—can create. Excepting those rare occasions where literally running, dashing away, would wisely save one’s hide—a scenario far more likely to occur in a bar after a pint too many than at the Googleplex or wet lab—ideas are best addressed by facing them, not by ousting members with ideas deemed contentious. Engaging on the battlefield of ideas is how we balance and protect each other.

 

Endnote

1. Reynolds, M (1967). Malvina Reynolds Sings the Truth. Columbia Records. CS-9414.

 

Adams, C.D., Blacksher, E. & Burke, W. Night shifts: Circadian biology for public health. Nature 551(7678, 33, (2017). Publisher's VersionAbstract
The award of the 2017 Nobel Prize in Physiology or Medicine has piqued public and scientific interest in circadian research (see Nature 550, 18; 2017). The time has come to translate our understanding of the circadian molecular clock into publichealth benefits. Circadian biology is the archetypal gene–environment interaction. We know that certain transcription factors interact with each other in a loop to produce the biological outputs that make up 24-hour patterns. And we know that light and time-zone travel affect the timing of this system to the detriment of human health. But even after 30 years of circadian biology, we still don’t know how best to use this information to protect the public’s health. Some activities that disrupt circadian clocks are voluntary. Others can be the result of limited opportunity — as in the case of night-shift workers. Scientists and the public need to engage in dialogue to develop precautionary and mitigation strategies that are feasible and acceptable to all. 
circadian_biology_for_public_health.pdf
2016
Kalejaiye, A., et al. Otologic manifestations of Fanconi anemia and other inherited bone marrow failure syndromes. Pediatric Blood & Cancer 62, 12, 2139-2145 (2016). Publisher's VersionAbstract

Background

The inherited bone marrow failure syndromes (IBMFSs) are diverse disorders with syndrome-specific features; their otologic and audiologic manifestations have not been well described. Our objective was to characterize these in patients with Fanconi anemia (FA), dyskeratosis congenita (DC), Diamond–Blackfan anemia (DBA), and Shwachman–Diamond syndrome (SDS), and to determine the association between physical findings and hearing loss.

Methods

Patients with an IBMFS underwent comprehensive clinical and laboratory evaluations and testing for syndrome-specific gene mutations. Hearing loss was measured by pure tone audiometry and otologic abnormalities by otomicroscopy.

Results

Patients included 33 with FA, 37 with DC, 32 with DBA, and nine with SDS. Hearing loss was most frequent in patients with FA (45%) and DBA (14%). The most common type of hearing loss in FA was conductive (65%). Absent or hypoplastic radius, noted in 21% of the patients with FA, was associated with hearing loss in all cases. Otomicroscopy was abnormal in 66% of patients with FA. Characteristic ear abnormalities included small tympanic membrane (66%), malformed malleus (57%), aberrant tympanic bony island (48%), narrow external auditory canal (EAC) (32%), and abnormal course of chorda tympani (34%). Ear malformations were almost always associated with hearing loss. Hearing loss was rare in patients with DC and SDS.

Conclusions

FA is the major IBMFS with associated hearing loss, which is most commonly conductive. Radial hypoplasia or aplasia and characteristic congenital ear malformations are associated with hearing loss in patients with FA. Recognition of these syndrome-specific abnormalities should lead to earlier management of hearing loss.

2015
Bhatti, P., et al. Response to Civil time≠biological time: Recent options for empirically testing possible effects of chronodisruption. Chronobiology International 32, 5, 699-700 (2015). Publisher's Version
Pathak, A., et al. Prospectively identified incident testicular cancer risk in a familial testicular cancer cohort. Cancer Epidemiology Biomarkers and Prevention 24, 10, 1614–1621 (2015). Publisher's VersionAbstract
Background—Human testicular germ cell tumors (TGCT) have a strong genetic component and a high familial relative risk. However, linkage analyses have not identified a rare, highly-penetrant familial TGCT (FTGCT) susceptibility locus. Currently, multiple low-penetrance genes are hypothesized to underlie the familial multiple-case phenotype. The observation that two is the most common number of affected individuals per family presents an impediment to FTGCT gene discovery. Clinically, the prospective TGCT risk in the multiple-case family context is unknown. Methods—We performed a prospective analysis of TGCT incidence in a cohort of multipleaffected-person families and sporadic-bilateral-case families; 1,260 men from 140 families (10,207 person-years of follow-up) met our inclusion criteria. Age-, gender-, and calendar timespecific standardized incidence ratios (SIR) for TGCT relative to the general population were calculated using SEER*Stat. Results—Eight incident TGCTs occurred during prospective FTGCT cohort follow-up (versus 0.67 expected; SIR=11.9; 95% confidence interval [CI]=5.1–23.4; excess absolute risk=7.2/10,000). We demonstrate that the incidence rate of TGCT is greater among bloodline male relatives from multiple-case testicular cancer families than that expected in the general population, a pattern characteristic of adult-onset Mendelian cancer susceptibility disorders. Two of these incident TGCTs occurred in relatives of sporadic-bilateral cases (0.15 expected; SIR=13.4; 95%CI=1.6–48.6). Conclusions—Our data are the first indicating that despite relatively low numbers of affected individuals per family, members of both multiple-affected-person FTGCT families and sporadicbilateral TGCT families comprise high-risk groups for incident testicular cancer. Impact—Men at high TGCT risk might benefit from tailored risk stratification and surveillance strategies.
familial_testicular_cancer_incidence.pdf

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