UGS (Universal Genome Sequencing) in the Mid-21st Century

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?Hi.?

?Hi.?

?This is awkward.?

?Yeah. I thought it might be.?

?But you?re what I asked for, from what I can tell.?

They slowly looked each other over, absently sloshing their drinks, and then Liam smiled. ?You too.?

?Blond hair and green eyes,? they blurted, Sierra giggling. ?I?m glad we still have a few choices.?

?Right. So, tell me about yourself. Something that?s not in the GenHealth Profile.?

Photo: Josh Simons

?Ugh, the GHP. That doesn?t leave very much. Let?s see. I hate sprinting, love mountain climbing, but had no choice given my ACTN3 genotype and mitochondrial gene variants. I love broccoli, despite my ?bitter taste? genotype. And I?m a big fan of dystopian novels. You??

Liam was quiet for a few moments. ?I?ve never thought much about what I like. Everything?s what I expect.?

Sierra and Liam had been born during a flicker of technological flux, when universal newborn genome sequencing had become law, yet gamete (for those still religious) and conception sequencing/selection were in pilot studies. A quick swish of a cheek swab gathered their DNA as they howled their first cries.

They?d all known newborn profiling was coming, an outgrowth of the heel prick screening started nearly a century earlier. Francis Collins, winner of the 2016 Nobel Peace Prize, had said back in 2009, ?Whether you like it or not, a complete sequencing of newborns is not far away.? The Collins prophecy had come true within 3 years.

Thankfully, exome sequencing vanished once bioinformaticians developed algorithms to mine the 98+% of the genome that doesn?t encode protein, but holds the controls. The algorithms even forecast the effects of environmental exposures deemed likely from the social workers? reports. Epigenetic profiling had proven a useful adjunct to sequencing, for it predicted such things as which smokers would develop which cancers, and who might snap under stress.

Photo: U.S. Department of Energy Genomic Science program

The universal genome sequencing ? UGS ? of neonates provided a life-plan, taking the mystery out of health care, dictating diet to maintain optimal body mass index, and, basically, steering each individual to be the best he or she could be. UGS had guided Sierra and Liam?s childhoods. They hadn?t even known what they?d inherited until seeing their profiles at age 18, when the institution they were assigned ? Faber College ? consulted their neuromes to select academic majors and career paths.

?You should think about what you like and don?t like, what you?re good at and not,? Sierra said, not allowing Liam rely on his profile alone.

?So far the predictions have been pretty accurate. I don?t know if I?d have been bad at languages, since I never took any, based on the brain MRIs. But I?ve always loved science. I wonder about things, especially how all this testing actually describes us.?

?What were you treated for??

?Gene therapy to stop hemophilia. Cell therapy to tweak dopamine activity, shot into my nucleus accumbens using nanocatheters to halt any addictions before I had a chance to toddle towards temptation,? Liam laughed.

?I had my blindness corrected. Took just minutes, I?m told, using the very first approved gene therapy. I also had gene therapy to correct a nasty p53 mutation, so no cancer. And I had an RNAi topical to fade the port-wine stain on the back of my neck. My dad says it looked like a map of Martha?s Vineyard. My mom wanted me to keep it. Wanna feel where it was?? Sierra lifted her ponytail.

?No thanks, I?ll pass. If you couldn?t see it, why?d they remove it??

?Let a genetic imperfection persist? Never! If it was congenital we might have had an argument, but my profile identified ?congenital capillary malformation.? It would?ve faded naturally, but the government ordered the treatment.? Sierra paused. ?I sometimes think I would have liked it. Just to be different. To be me.?

?At least we didn?t have to put up with ear infections, flu, colds. I learned all about that in health history. Did you take that??

?Sure. I?m glad we had those 110 vaccines. And that all those ?A? conditions are gone.?

?Yeah. Autism. Asthma. AIDS. Allergies. Asperger?s. Hey, even Alzheimer?s. But that?ll take awhile. Two of my great-great grandparents have it,? Liam said.

?I guess that?s why it seems we have so many accidents ? another A. The Darwin awards were ahead of their time.?

Liam thought a moment. ?I broke my arm falling out of a tree, age 12. Broke my nose when I tripped on a cat, age 3. Broke a finger playing basketball. Good thing the UGS ruled out osteogenesis imperfecta. I?m just a klutz.?

Photo: U.S. Department of Energy Genomic Science program

Sierra smiled. ?My 110-year-old grandmother, in perfect health, died when she slipped on a wet floor and whacked her head against the toilet. Shit happens, even with genome sequencing.?

By the time Liam and Sierra had turned 6, the GAGVIP ? Global Analysis of Gene Variant Interactions Project ? had indicated other problems and protections. It enabled Liam to stop the special diet to counter his Cliff?s Wasting Disease, a very rare inborn error of metabolism that would otherwise have disabled his intellect. GAGVIP found a mutation in a second gene that dampened the effect of the first.

Of course Sierra and Liam?s UGS-dictated treatments were somatic, and would therefore protect only them. When they were infants the germline was still off-limits, keeping the bioethicists in business. But once gamete and conception genome sequencing became law, informed selection became possible, and popular. Suboptimal fertilized ova were simply discarded. The term ?eugenics? was only used in health history class.

* * *

?I have to tell you about my sister, Luddy,? Sierra said.

Liam?s eyebrows shot up as he sipped his tall skinny chocolate chip no whip orange latte, a few weeks after they?d met.

?She was born 5 years before us.?

?So? ?

?2020. You know, when genome sequencing of newborns was still opt-out.?

Liam looked puzzled. Then astonished. ?You don?t mean ??

Sierra squirmed, pushing her iced lavender moonberry tea away.

?My mom insisted. No vaccines. No genome sequencing. No gene or cell therapies. No microbiome engineering.?

?So your sister .. Cuddy? ? what happened to her? Did she die? Of something that could?ve been prevented, or corrected??

?Luddy. And not exactly.?

Liam finished his drink and stuffed his napkin into it, still confused. ?So what happened to her??

Sierra?s eyes began to fill, as she spoke softly.

?I barely remember her. She had beautiful reddish-blond curls. She used to tickle me with them. Luddy was sick a lot. Sneezing, fevers, like old people get today. She got angry really easily, had fits, not like us. And she had the weirdest thing, a second little finger on her right hand.? She grimaced. ?A new mutation, they said. My mom wanted her to keep it, but the pediatrician reported Luddy and the government enforced amputation.?

?Why would your mother want a mutant daughter? I don?t get it.?

?Well, you ?d have to know my mom. When everyone else saw a hideous deviant, my mother saw ?an interesting variant.??

Both were silent for a few moments.

?Luddy played with me a lot, which was great when my mom was still in prison. ?

?What??

?I thought you knew. It?s in the psychosocial report on my family. You got it when we were matched.?

?Oh, I didn?t pay much attention to that stuff. Just scanned the recessives.?

Sierra took a deep breath. ?My mom was one of the founders of PAGS. She was arrested for blowing up that old biotech company, Total Genomics.?

?Holy shit! People Against Genome Sequencing! And your mom ? was Hillary Dorn??

Sierra shrugged, then nodded. ?I didn?t know her well. There wasn?t time.?

?What do you mean??

?Well, once the law went into effect, the Gene Police went after kids like Luddy, the unsequenced. Her GHP was tagged. And the school kicked her out.?

?Why? They can?t do that, what about those old hate crime laws??

?They don?t apply to the unsequenced. And it was more than that. It was fear.?

?Of what? A snotty kid with an extra finger??

?Nope. An ancient fear, actually. Infection.?

?But that can?t happen anymore.?

?It can to the unsequenced. Luddy hadn?t had her microbiome regulated, nor her cytokines optimized. And even though most microbial pathogens have been disarmed for years, there?s still that crazy Venter Institute dredging up new bugs from all over. An errant bacterium taking up residence in the body of an unsequenced could mutate. Then she might spew on one of us normal kids whose immune systems are so regimented that we can?t respond to new challenges.?

?Whoa, that?s a lot to digest. My family?s so boring,? Liam said.

Sierra took a deep, shuddering breath and then the story continued to pour out. ?So my mom took Luddy to one of the PAGS communes. My dad had them traced to Dubuque, then Altoona, then Santa Barbara. Like all the anti-DNA activists, they moved around a lot. We lost track.?

?But didn?t I read that ??

?Yes, she died. She was dropped off at a wellness center near Tucson. The docs didn?t know what to do because it?d been years since they?d seen someone with widespread cancer. The monthly somatic mutation screens catch cancer so early nowadays.?

?So what happened to Luddy??

Sierra just shrugged.

* * *

Sequencing a fetus will be obsolete by the time of my scenario. Photo: Shendure lab

Liam quickly got over his disgust at Sierra?s mutant sister and militant mom, and he and Sierra succumbed to something even the most powerful genome sequencers couldn?t predict ? they fell in love. After marrying, they did graduate work in cancer genomics at the Mendel Institute in Washington, DC, then moved to San Francisco to take positions at the historic Genentech.

It was time to start a family.

Having children was very different than it was just a generation ago. Nothing was left to chance. The matching eliminated the possibility of recessive conditions and complex disorders stemming from the 1 in 17 base sites in the genome where people varied. To think the old genetics textbooks considered ?genetic load? a mere 7 faulty genes! Now gamete and zygote scans spot spontaneous mutations, and couples can choose the traits of their offspring anytime, as the 1997 film GATTACA had so accurately predicted.

?I wonder what it must?ve been like, in the days before UGS, to just have a kid,? Sierra said one day while she and Liam were hiking, watching a family with young children up ahead.

?Just have a kid? Aren?t we trying to do that??

?No, I mean to have a child who?s a blank slate, like Luddy. With only family history to go on. That?s scary!? she paused, slapping at a two-headed mosquito descended from the escapees from the 2036 Global Malaria Initiative. ?But also exciting.?

?I don?t think I could stand the stress of not knowing what could happen. And wouldn?t diseases come back?? Liam said, twisting a thin branch bearing fragrant hairy honeysuckle. ?Just think about what we could?ve had. I?d still be taking clotting factor every day and be addicted to caffeine. Or worse.?

?Yeah, and I?d be blind and have cancer. But still. What didn?t my parents let me do because of ?genomic limitations???

?I wonder, with our kids, if we could do both. Follow the GenHealth protocols, but try to look beyond that.?

?Now you sound like my mother. As if we could,? Sierra sighed.

They wanted to have children before they turned 30 so they could live to see 5 generations, the norm since human life expectancy hit triple digits. Society had turned against the reproductive technologies enabling women in their sixties to conceive and bear children, once the novelty had worn off and the reality of exhaustion had set in. Maybe average age at first parenthood would creep up once the non-sequenced elders died off and people no longer suffered the decrepitude of advancing age, like the current cohort of healthy 30-year-olds.

But Liam and Sierra weren?t completely healthy. They couldn?t conceive.

?I don?t get it,? Sierra said at yet another disappointing visit to the fertility center. ?I knew exactly when I ovulated, and we synched your maximal sperm count. Then we did it. Just once, so as not to thin the troops. What?s wrong??

They didn?t tell anyone when they went the IVF route, scanning genomes and jettisoning unappealing zygotes. None took. Even more embarrassing, when the technician applied donor sperm to Sierra?s eggs, and Liam?s sperm to donor eggs, zygotes formed and started cleaving. They?d be good stem cell sources.

?We just don?t work,? Sierra cried, clutching at Liam as the doctor gave them the sad news. Infertility struck only one in ten million couples.

UGS had made matching so powerful that assisted reproductive technologies, once used for convenience by the wealthy, had become a stigma, a sign of failure. People had become so focused on perpetuating their own DNA that any technology that introduced DNA from a third party ? surrogate mothers, intrauterine insemination ? was doomed.

Adoption wasn?t really an option anymore either. In most countries, parentless children were raised in wonderful facilities run by social scientists.

And so the years passed. Sierra and Liam became well-regarded researchers, each leading a group at Genentech. They?d sometimes become depressed watching their friends? growing families, but they were so happy with each other, their careers, and their many cats, that life was good.

And then, suddenly, it got better. Much better.

One Saturday morning, very early, the doorbell rang. Liam was in the shower after his morning run, and Sierra was making coffee. She padded through the hallway, opened the door, and saw no one. But she heard a whimper. Looking down, she saw a basket holding a newborn, swaddled in pink.

With a gasp, Sierra looked about, then brought the baby inside. Liam, coming down the stairs, rushed over.

?Omigod! A baby! Whose is it??

?I have no idea!? Sierra said as she lifted the infant out and cradled her.

?Is this a joke? Because it isn?t very funny,? Liam said, striding over to the open door and checking around the outside of the house before coming back in.

?Hi little girl! Oh my, you?re just a few days old, aren?t you?? Sierra cooed to the baby. She stroked the tiny infant?s shimmery reddish-blond tufts, until she stopped suddenly, her eyes narrowing.

?What?s the matter?? Liam asked.

?I don?t know. The skin here doesn?t feel right.?

Sierra gently parted the silken strands covering the back of the baby?s head, peered closely, then looked up, tears forming. ?Liam, c?mere. Now!? she shouted and the baby started to wail.

They stared, stunned, at the dark purple birthmark on the back of the child?s neck, in the shape of Martha?s Vineyard. And when Sierra pulled the blankets away and placed her finger in the tiny hand, all six fingers wrapped tightly around it.

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