Clarkesworld Magazine Issue 166

by Neil Clarke

  This brings us back to the diversity problem in science: most GWAS findings have identified disease-causing variants in individuals of European ancestry. These findings are important in that we now understand how the genes in which these SNPs reside function to cause disease, but our interpretation of how these diseases may develop is lensed only through one population. It is a problem that must be addressed.

  Many SNPs can actually be protective against diseases, including cancer, Alzheimer’s, heart disease, and even infectious disease. For example, a recent study compared the ability of white blood cells to clear out and destroy the bacterial pathogens that cause listeria and salmonella. Cells were isolated from individuals with either European or African ancestry for this comparison and those cells with African genomic variation were able to clear out the bacteria faster and had stronger inflammatory responses. This response was genetically controlled as nearly 10 percent of all genes involved in bacterial clearance had ancestral-associated differences related to their level and duration of expression.

  These findings highlight the importance of inclusivity in studies examining the genetic role of our immune system, as we can further understand how our genetic variation influences disease susceptibility and progression. This may also partially explain why some inflammatory diseases are more aggressive in individuals with African ancestry and help us eliminate health disparities rooted in environmental stress and other social determinants of health.

  In this time of the COVID-19 pandemic, this information could also assist in understanding how the coronavirus infects our bodies, giving us insight into new vaccine options and helping clinicians better understand how there can be a myriad of symptoms that occur upon infection.

  The GWAS Diversity Monitor calculates that over half of all GWAS discovery studies in 2019 were conducted in individuals with European ancestry, with the next highest at 17 percent for studies including individuals of Asian ancestry. African ancestry was represented in only 5 percent of studies in 2019 and accounted for less than 1 percent of all participants of any ancestry in 2019 studies. Yet, it is known that genomes of those with African ancestry have the most variation of any ancestral group and have the most to contribute to our understanding of human variation. It is a sobering statistic and highlights that much more work needs to be done.

  Variation in our genome also records our prior historical exposures, as well as influencing our assumptions. The abovementioned SNPs responsible for sickle cell disease are classic examples of natural selection in the human population. Those harboring variants in the HBB gene have an innate protection against malaria, a very deadly infectious disease. While many people associate sickle cell disease and malaria resistance to those of sub-Saharan African ancestry, HBB variants are also prevalent in the Middle East, parts of India, and even Greece. Malaria resistance can also be found in populations in Asia and elsewhere that is linked to SNPs in other genes related to red blood cell function.

  Immunity to infectious disease is not the only benefit of exploring and understanding our genomic diversity. It has been well understood that our extinct hominin relatives the Neanderthals and the Denisovans bred with our ancestors tens of thousands of years ago and that has resulted in gene flow between our species. Nearly all individuals with non-African ancestry have a small percentage of genetic variation introduced by Neanderthals and Denisovans, which have contributed genetic information to the genomes of those with Oceania ancestry.

  A February 2020 study turned much-needed attention toward the African genome and discovered that additional hominin relatives contributed to West African genomic diversity well before Neanderthals even separated from our distant human ancestors. These findings establish a more comprehensive understanding of the origin of humanity. Published in March 2020, an analysis of over nine hundred individual genomes spread across fifty-four geographically—and linguistically—diverse communities identified tens of millions of SNPs and other types of genomic variation that are common in specific populations.

  Exploring these differences and similarities will broaden our understanding of ourselves and finally bring the biomedical field into a more equitable place. Genetics has a tainted history of prejudice that still impacts lives today. It is time these issues are always at the front and center of every research discussion so study recruitment and focus ensure that history is not repeated and we can move forward, together.

  About the Author

  Douglas Dluzen, PhD, is an Assistant Professor of Biology at Morgan State University in Baltimore, MD. He is a geneticist and has studied the genetic contributors to aging, cancer, hypertension, and other age-related diseases. Currently, he studies the biology of health disparities and the microbiome in Baltimore City. He teaches evolution, genetics, and scientific thinking and you can find more about him on Twitter @ripplesintime24. He loves to write science and science fiction while sitting on the couch with his wife Julia, their dog, cat, and newborn son Parker.

  Coffee Prince, Avatar, and Robot Rebellions:

  A Conversation with Madeline Ashby

  Arley Sorg

  If you search the Tor.com site for Madeline Ashby, you will find this entry: “Hi. My name is Madeline Ashby, and I write the Cowboy Bebop rewatch posts.” Dig deeper and you’ll find an individual who is passionate about a great many things: anime, novels, film, and the future among them.

  Born in Panorama City, CA, Ashby grew up in Washington state, in a household of science fiction fans, then moved to Canada. She graduated from Seattle University (after having written a departmental thesis on science fiction) and later earned an MA from York University in Interdisciplinary Studies with a focus on Japanese animation, cyborg theory, and fan cultures. She went to the Ontario College of Art and Design University and earned an MDes in Strategic Foresight and Innovation with a focus on the future of border security.

  Ashby has been writing science fiction since around age thirteen, but in 2005, she met Ursula K. Le Guin in the basement of The Elliott Bay Book Company, after which she decided to write science fiction in earnest. While immigrating to Canada from the United States in 2006, she joined the Cecil Street Irregulars, a genre writers’ workshop founded by Judith Merril. Her first published story was in the 2007 anthology Tesseracts Eleven, edited by Cory Doctorow and Holly Phillips: “In Which Joe and Laurie Save Rock n’ Roll.” Her first SFWA-qualifying professional sale was “The Chair” in Nature in 2009. Slate published short story “Domestic Violence” in 2018, which was a Sunburst Award finalist. “Work Shadow/Shadow Work” in the 2018 Saga anthology Robots vs. Fairies placed her on the 2019 Locus Recommended Reading list.

  Ashby’s debut novel vN came out in 2012 and was a finalist for both the Kitschies’ Golden Tentacle Award and the First Novel category Locus Award. The Machine Dynasties series continued with 2013’s iD, and forthcoming ReV, due in July. Stand-alone Company Town, published in 2016, was a finalist for the Aurora Award, the Best SF Novel category Locus Award, and the 2017 CBC Books Canada Reads competition; it won a Copper Cylinder Award, and it’s currently in development for television. She has another stand-alone near-future novel on the way.

  Ashby coedited Aurora Award finalist Licence Expired: The Unauthorized James Bond anthology with horror writer and husband David Nickle, she was a contributor to tie-in serial Orphan Black: The Next Chapter for Serial Box, and she cowrote nonfiction book How to Future with Changeist cofounder Scott Smith. As if all this weren’t impressive enough: she works as a futurist, with clients such as the World Health Organization, Intel Labs, and the Institute for the Future. Her essays have appeared at Boing Boing, io9, WorldChanging, The Atlantic, MISC Magazine, and FutureNow.

  Come for the anime, the great fiction, or the visions of the future. Madeline Ashby is a multifaceted powerhouse.

  You grew up reading books and have always been an avid reader. What is important to you in a story or book? What do you look for; what keeps you interested?

  I usually know within a few para
graphs if a book is for me. What the first kiss is for sex, the opening chapter is for a novel. If I’m not sure, then I flip to the middle and check out the prose there. The true test of any book is the middle. Can it hold you through the laggy parts? What is that book doing, during the seventh inning stretch? When I was younger, I guess I was more shallow about it: I had this whole phase as a teenager where I could pick books out just by touch, because certain imprints like Vintage International and others were doing brushed covers. Brushed cover books were my whole entire jam for this really intense two-year period. So, I would go through used bookstores with my eyes closed and my fingers drifting over the covers until I found the right one for me.

  In your 2016 essay on cyberpunk at Tor.com you talked about the daunting nature of writing in genre and “participating in a conversation that’s been going on for just about as long as you’ve been alive.” To that point, is it important for science fiction writers to read the classics of science fiction? Is having that foundation necessary to participating in the literary conversation?

  This is tough, in that I went to a Jesuit university, and I was part of a classics-oriented program, and I derived a lot of value from that and I think it helped get me where I am today. So, for example, we had to read Joseph Andrews, by Henry Fielding, in our Origin of the Novel class. We had to write a diary about each chapter, and my every entry was just about how this book made me pine for the sweet release of death. And that’s how I feel reading a lot of Asimov and Heinlein. Having written a series of robot novels, I used to get asked all the time if Asimov inspired me. No. He didn’t. His ideas inspired me, but his robot stories read like frustrated Agatha Christie imitations. And if you read parts of the Foundation novels in a quiet room, and you listen carefully, you can hear his ghost jerking off.

  The thing about the literary conversation is that yes, you should do your homework. But there are a lot of ways to go about that: there are people who swear up and down that you need to read a classic writer’s entire backlist, but they’ve never picked up a book of peer reviewed essays critiquing that author’s work. Reading those books doesn’t mean you’ve delved into them. How can you have a “literary conversation” about a book or a writer if you aren’t aware of their position in a larger critical discourse, or the broader implications of their ideas? Am I fake geek girl if I tell a hardcore Vinge fan that I found A Fire Upon the Deep almost impenetrable, but I’m fascinated by the Tines from the perspective of Husserl’s phenomenology of consciousness and Nagel’s critique of materialism? No. I’m just a slightly different order of geek.

  Life is too short. Read stuff that speaks to you and then read the authors that inspired those people. And then, look at the gaps in your reading. Who aren’t you reading? Who got left out? Why is that? That’s the homework.

  What are a few of the books or stories (old or new) that have been most important to you, and why?

  I became a history major in university because I read The English Patient the summer before ninth grade, by Michael Ondaatje. (It’s probably also on some level why I came to Toronto.) That was the book I wanted to write when I was a teenager. When I was that age, I really wanted to be literary. Like I was reading a lot of Millhauser, and Murakami later on in university. One of my short stories, “Domestic Violence,” is patterned after one of his, called “Barn Burning,” which is named for a Faulkner story and was later made into a really stunning Korean film called Burning. “Barn Burning” is one of those stories where you read it once and then you read it again after you’ve done some living, and then it chills you to the core. Another of his stories, “Ice Man” is like that for me too. The second time I read it I just burst into tears. When I read it at twenty, I didn’t get it. At twenty-seven, it knocked me out.

  I return to films more often than books, because although I’m a fast reader, films are still faster. When I was little, I wanted to direct. Part of me still wants to. I’ve directed a short film and written two. If I could have instant investment capital in another career, it would be filmmaking. I have films I watch over and over again. Aside from the usual franchise subjects, I watch Jaws and The Godfather and Rosemary’s Baby and The Exorcist and The Wicker Man at least once a year. I’m a big fan of Branagh’s uncut Hamlet. I’ve probably seen The Silence of the Lambs over ten times. I watch it to feel better. Ditto some Fincher films: like everyone, I watched Fight Club a lot in high school, although I watched the commentary track most often. I’ve seen Gone Girl and Zodiac at least five times each. Probably more. Drive, too.

  There was a month during the process of writing one of my books when I would put on Manhunter every night before I went to bed. I watched Once Upon A Time . . . in Hollywood three times in a forty-eight hour period, but I think critics will eventually recognize The Hateful Eight as the truer statement on America. I watch Inception every time I’m on a plane. As a kid I watched Rear Window and Vertigo and North by Northwest multiple times a day on Betamax tape. (I’m sure you’re sensing a theme, here, and the theme is that I’m your dad.) I’ve probably seen Midsommar and Hereditary each at least three times now. Aster does catharsis in the Aristotelian style: a purification, a draining of emotion that brings those emotions into balance. (“Catharsis,” you’ll recall, was originally a medical term.)

  I really appreciate the generation of horror cinema that Ari Aster is part of, with Ti West, Adam Wingard, Jeremy Saulnier, Jim Mickle, that whole movement made possible by Leigh Whannell and James Wan. Karyn Kusama’s part of that, generation, too. The Invitation turned out to be so prophetic; I can’t wait for her Dracula. I know people call it “elevated horror” or whatever, but I bristle at that term. Horror should be beautiful, because beauty requires vulnerability to appreciate. That’s why dictators always have bad taste. I think people fail to understand the difference between terror and horror. Terror is knowing that you might die. Horror is knowing you absolutely will die, and so will everyone you love, and that the only reward for living long enough is getting to watch it happen. The heart is the organ through which we apprehend the void. Aristotle knew this, that we cannot feel fear without empathy.

  Otherwise, I probably reread Jane Eyre once a year, because it’s a favorite of my mother’s, and then I often end up rereading The Hound of the Baskervilles in the autumn. My mother used to tell me stories about Scout and Jem from To Kill A Mockingbird when I was very little, and so finally in the second grade I just read the thing. In the third grade I went through a really intense Bradbury phase. Then the requisite Michael Crichton, Thomas Harris, and Stephen King phases in elementary school. A Margaret Mahy phase. The Changeover still slays me. There’s not a wrong note in it. A Dickens phase after that. Dickens and King have so much in common.

  There’s sort of a blank after that, because a lot of people in my family were dying and all I remember are funerals. Then a big Sébastien Japrisot phase in junior high. I once chased my teacher around the classroom for his copy of Trap for Cinderella. He gave me a first edition copy of A Very Long Engagement as a graduation present. My husband is a horror writer, but I’m the one who got him to read du Maurier. I guess the theme here is a Gothic one: secrets, monstrousness, unspoken yearning. It’s part of how I see the world. I assume there’s some secret pain making people act the way they do. I assume everyone is wounded.

  You have the Machine Dynasty series, Company Town, and the book you’re working on now for Tor. Which of your characters do you relate to most; or, which are closer to you, and why?

  There’s a lot of me in Hwa. Not the self-discipline part, or the physical prowess part, obviously. Obviously, she’s a lot tougher than I am, a lot more able to inflict pain. She was based on the protagonist of Coffee Prince because I had done a graduate major in East Asian Studies with my first master’s and one of my instructors got me hooked on K-dramas. I wanted that combination of learned toughness protecting the last shred of innocence at someone’s core. What’s funny is when I did promotion for the book in Newfoundland, women wh
o lived there told me that they thought of Hwa as a Newfoundlander first, because she was so tough, and particularly as a Newfoundland woman, because of how she used that toughness to care for the people around her.

  And I had always thought of those qualities as being inspired from elsewhere. Shows how much I know, right? But our sense of humor is the same. When I read the screenplay for the Company Town pilot, what made me happiest was that they’d preserved the sense of humor. Well, that and the fact that she was still Korean, and they’d kept the sex workers’ union, and Daniel was Black. That’s not canonical to the novel, but I think it’s a great choice and a really subtle, layered role for a Black actor when those roles are still in such short supply. If you told me tomorrow that Daniel was being played by Lakeith Stanfield I would be thrilled. A workshop friend of mine always envisioned his character as Black, oddly enough. She’s dead, now. So, I like to think she was hanging over the writers’ room.

  In your 2016 interview with PSTD, you briefly mention Shirley Jackson, saying “I think there’s this well of anger at the core of her work,” as well as James Tiptree Jr. Does your work often come from a similar well of anger? Is there personal catharsis or is it more of an intellectual engagement? Or do some stories tap into anger/emotion/the personal more than others?

  Yes.

  I’m most articulate when I’m angry. People have a lot of different manifestations of anger, but mine is that I tell you exactly what I’m thinking. It’s surprisingly intimate. It requires a lot of vulnerability. I would argue that writing (or creating in general) requires that same vulnerability. It’s similarly intimate. I have a friend who won’t read my work, he says, because it would be too intimate. And I think this is what he’s getting at. (That, or he knows he’ll hate it, and also that he’ll be incapable of hiding it from me. In all likelihood it’s the latter.) But I can count on the fingers of one hand how many people have seen me truly angry. So, I suppose my work is a way of dealing with the things that make me angry, in a way I can share with other people.