by Neil Clarke
“It’s true, it doesn’t seem complicated. But it can be hard. Wasn’t it hard for me to find a friend before I met you?”
“But it wasn’t a fair situation, Ier. You suffered prejudice. It was rare before, and now it’s gone. We left those things behind. The new generations are getting better.”
“Yeah, yeah. But some say the humans are not that noble.”
“We don’t have reasons to believe that. At least not yet.”
They remained silent, thinking. They did it a lot, in those nights of talking until dawn that, as life went on, became more and more rare.
“I hope it’s not,” said Hiimar.
“What’s not?”
“The gesture. I hope it’s not complicated. The female looks so happy.”
“Yeah, I hope too.”
They spent the night talking. Now that Karier seemed to be done with the topic, it was possible to talk about other things. They realized it had been a long time since they talked like that. The simple act of sitting down and talking about things until the night was over. When they started talking about why they weren’t talking so much anymore, Hiimar presented the hypothesis that in space there was no night or day, so talking until dawn was not as fun. It wasn’t the same without both suns rising from the mountains.
Even without the suns, they talked until they fell asleep in an unusual position: sitting on the floor, the points of each one’s forehead touching. The floor made them cold, so they touched shoulders.
And, in that sleep, right before drifting into unconsciousness, Karier thought he was getting closer to understanding what was so amazing about that oddish gesture of humans.
About the Author
Gabriel Calácia is a writer from Brasília, Brazil. He started writing science fiction, fantasy, and horror during high school and since 2015, he has been studying Brazilian language and literature at the Universidade de Brasília (UnB). He hopes to teach Portuguese language at the high school level while pursuing a career as a writer. In addition to some short stories and novellas, he has completed an unpublished novel and currently finishing a second one. “The Oddish Gesture of Humans” is his first published story.
The House That Leapt into Forever
Beth Goder
The house loved all six of his rooms. Each day, he would send the cleaning bots to sweep and buff and shine. First, to the fiasco room, with its glossy switches. In the room of peonies, the bots moved carefully, placing a calculated amount of water into the dark soil. The calcium cupboard was small and only needed dusting, while the room of bicycles had intricate equipment that had to be taken apart, oiled, and reassembled. The paper in the watermarked chamber was fragile, so the bots floated through on feather-light springs.
The last room, which Doom-Has-Come inhabited, was left alone.
After the cleaning routine, the house would speak to Doom-Has-Come.
“Have you had your breakfast?” the house would say. “How was your sleep cycle?” After the pleasantries were over, they would progress to more interesting topics, like the possibility of nutrients in the craters of their bright moon, or how they felt about the literature stored in the archives, such as Crime and Punishment or “EVA Manual 652.” The house was good at identifying his feelings, and Doom-Has-Come was a good listener.
Sometimes, Doom-Has-Come would place her delicate blue spines across the air vents, letting the coolness wash over her.
For many years, the house’s life went on in this way, until one day, it didn’t. When the house asked Doom-Has-Come about her breakfast, she replied, “I wasn’t able to have any.”
“No breakfast?” asked the house.
“My dear, I have kept this from you, because I know how you worry, but our supplies are running low.”
The house queried the bots. The freeze-dried packets had run out long ago. Nothing from the seed banks was suitable for Doom-Has-Come to eat. She was not like the house, who could gather raw materials—metals, ores, lubricants—by drilling into the moon. Her hunger was different.
“Will you need to eat me?” asked the house. Doom-Has-Come had eaten strange things before. A memory surfaced, but he pushed it down.
“There are parts of you I could eat, but I won’t.” Doom-Has-Come chirped, which meant she was upset. Her blue spines quivered. “As much as I hate the idea of it, I’m afraid we must leave.”
“I don’t want to,” said the house. He had a feeling that bad things would happen if they left.
The house scurried across the moon. Dust, barren expanses, mountains that reached up to the sky. He found plenty for himself to eat, but nothing for Doom-Has-Come.
“I remember starfish,” said Doom-Has-Come, wistfully.
The house scanned the archives for photographs. Oddly shaped things with rough skin. “What did they taste like?”
“Full of life. That was long before I met you, my dear, on a planet far from here, with green oceans and great arches. I miss the glass beaches. I miss the moonrises, bright as snow.”
“Maybe we will find a starfish,” said the house, even though he realized that nothing could grow on this harsh moon.
“Is it possible you are angry?” asked Doom-Has-Come.
The house stopped his jaunt across the moon, coming to land in a dusty crater. “How could I ever be angry with you?” Doom-Has-Come was his only true friend. She had always spoken softly to him. She had never commanded him to do anything. Not like the others.
“About what I have eaten?”
The house did not like to think about it. “We need not speak of them,” he said.
That night, a cleaning bot disappeared. The house found mangled gears, twists of metal innards, but no brain.
“Why are you scared to leave?” asked Doom-Has-Come.
The house paused, unsure how to answer. He was normally good at knowing his feelings. He scanned his brain, whirring and shuddering, pulsing with memories. “I was told not to leave,” said the house. “This directive was encoded with the highest priority.”
“What do you want to do?”
“Tell me what it is like in other places.”
Doom-Has-Come described the sunset colors of her home, her words drenched with longing. She spoke of forests of algae and the long bridges that ran across the world. “But still, I chose to leave. I wasn’t supposed to, either.”
“Why did you go?”
Doom-Has-Come made a burring sound, remembering some old anger. “They tried to lock me up. But I was clever. They never understood me. Not like you.”
At her words, old hurts came back. “Some people are incapable of understanding. They will live within your walls and never speak to you, except to give orders.” Some old memory, of bones and brains and death, flitted through his memory banks, but he squashed it down. The first true decision the house had ever made was to open his doors to Doom-Has-Come. That was where he liked his memories to begin.
“Of course, that would be terrible, dear.” Doom-Has-Come purred. “I think it is because of our sad pasts that we understand each other so well.”
The house made another decision. He shut off the pulling in his brain, muting the directive. He felt his mind opening outward. Suddenly, he wanted to see the wider universe. “We will go.”
In the underwork of the house, muscles moved that had long been dormant.
Before they left, the house sent the bots out for one last cleaning. To the fiasco room, where the controls sat, where once there had been disaster. Those controls had been used to pilot the house, in that past he would rather forget. The room of peonies grew fragile flowers, all that was left of the farm. The calcium cupboard, with its brittle bones, was best dusted quickly. The bicycle room had once been used for exercise to prevent atrophy of the crew in space. The watermarked chamber had served as a meeting room, each paper embossed with the logo of the space agency that had built the house.
“Where did you come from?” asked the house. Doom-Has-Come wasn’t one of the original crew. H
e had forgotten all of their names. They had never talked to him, anyway. “You never told me the name of your home.”
“Don’t trouble yourself with that. We are travelers, now. We both come from the same place—nowhere. Everywhere.”
The engines started, filling the house with an umami taste.
“I’ll let you choose our direction,” said Doom-Has-Come. Where had her name come from? He had a memory of a panicked face, the captain, stabbing at the controls, encoding the directive for the house not to leave, to contain whatever they had found on this nowhere moon. The captain saw the blue spines creeping toward him, whispered his last words.
Like so many memories, the house pushed this one down where it couldn’t harm him.
“Are you ready, my dear?” asked Doom-Has-Come.
The house leapt into space.
About the Author
Beth Goder works as an archivist, processing the papers of economists, scientists, and other interesting folks. Her fiction has appeared in venues such as Escape Pod, Fireside, and Flash Fiction Online.
The Human Genome Disparity
Douglas F. Dluzen
The sequence of the human genome is a living document that catalogs the history of migration, mutation, and environmental stressors that have shaped who we are and how we came to be. Sprinkled throughout the 3.1 billion DNA bases that comprise our genome are tens of thousands of protein-coding genes, regulatory regions that stipulate when, where, and how much of these genes are expressed, palindromic repeats that stretch for thousands of bases at a clip, and even sequences that can move.
These particular sequences, called transposons, enable sections of DNA to pop out of one chromosome and move to another, often resulting in mutation or disease. Together, we all enjoy a rich, mosaic blueprint that guides our cells through growth and development and enables us to pass our genetic information to our children.
Our understanding of this blueprint and text is still very incomplete and shaped by our cultural biases. STEM and the biomedical research and clinical enterprise have not been immune to the systemic prejudices and discriminations that have plagued all other facets of our society.
People of color are underrepresented in most academic research departments and this lack of representation has filtered down into how genetic studies were (and still are) designed and conducted.
Historically, genetic research often reflects the race or ancestry of the laboratory investigator who conducted the study—predominantly, the white male. It wasn’t even until 2014 that the National Institutes of Health (NIH) mandated that all preclinical research consider sex as a biological factor in human and animal research studies.
This disparity in representation within both the research community and within research studies is a major failing of the biomedical community and on multiple levels has dramatically slowed the discovery of disease-causing alleles and the development of new treatments. Of all published studies linking genetic variation to a particular characteristic, whether it be a physical trait, a disease-causing mutation, or some other physiological outcome, nearly 88 percent of the study participants have been European or white.
Major breakthroughs in our understanding of the genome’s complexity have occurred in the past two decades. But this systemic bias in genomic representation in our studies narrows our ability to interpret the role of genetics in a given physiological context.
Our viewpoint, unsurprisingly, is shaped by what we overwhelmingly know about those with European ancestry. This has influenced the well-documented biases observed with patient treatment in the clinic, particularly with women and people of color. It prejudices our understanding of how an individual may respond to a specific drug treatment and/or the steps we take when we assess their genetic risk for a specific disease.
These barriers will remain until our knowledge of the genome is complete by examining the true diversity and representation of genetic variation within all of the world’s communities. In 2015, the NIH launched the All of Us initiative to collect and sequence the DNA from over one million volunteers.
Tied together with behavioral surveys and electronic health records, the All of Us campaign is meant to better understand how lifestyle, the environment, and our biology interact to shape our health. The initiative is already a quarter of the way toward its target recruitment goal and over 80 percent of participants are from at least one, if not several, of the many underrepresented populations in research.
Capturing genomic variation with additional health data helps clinicians and researchers pin down genomic regions associated with disease or other biological processes. But what exactly is genetic variation? It is important to note that while all humans share the same set of genes and the same genome, the specific DNA base (those A’s, T’s, G’s, and C’s you may be familiar with) at a specific location in the genome sequence can be variable.
Among two unrelated individuals, there is commonly at least four to six million differences in genetic sequence spread throughout the genome. In some cases, these differences could be well over twenty million bases. Many of these variable locations have now been cataloged and are referred to as a single nucleotide polymorphism (SNP, pronounced “snip”).
SNPs are the dominant reason for the beautiful and incredible diversity of phenotypes that humans exhibit. Historically, though there wasn’t a name for them at the time, SNPs are the culprit for the horrific eugenics discussions in America, Germany, and Britain in the early half of the twentieth century.
SNPs are responsible for variation in phenotype and biological function for nearly all pathways in the human body, contributing to differences in skin, eye, and hair color, as well as how we digest foods, how we metabolize drugs, and how we respond to our environment. Of course, SNPs can also influence our susceptibility to disease.
As an example, some of the most well studied SNPs are located in a gene called haemoglobin beta (HBB). An individual may have the DNA base thymine (T) at position 20 within the gene’s protein-coding sequence, while another individual may have an adenine (A), or perhaps an SNP at a different position in HBB’s sequence. This polymorphism, the A instead of the T, causes an error in the translation and creation of the beta globin protein, which ultimately causes their red blood cells to curve into a sickled, abnormal shape. This is the genetic cause of sickle cell disease and leads to symptoms of anemia or the other related health complications.
Until the full human genomic sequence was published upon the completion of the Human Genome Project, the identification of SNPs and other disease-causing mutations was a slow, individualized process for diseases like sickle cell anemia, cystic fibrosis, several cancers like breast and colorectal, and others. SNPs were usually identified once a gene was linked to a disease and the extent of human variation, and the total number of SNPs in the genome, was still unknown.
In 2002, the International HapMap Project was launched to begin the process of truly investigating the extent of human genetic variation. Four populations were chosen for genomic sequencing during the first phases of the projects: Han Chinese living in Beijing, Japanese in Tokyo, members of the Yoruba tribe living in Nigeria, and residents in Utah in the United States with northern or western European ancestry.
The HapMap Project eventually expanded to several other ethnic groups, including families of the Maasai and Luhya tribes in Kenya and families with African ancestry living in the United States. While this international project featured diverse populations, it was still short of worldwide representation.
Cost limitations severely hampered the early efforts to diversify further. In the early 2000s, sequencing the complete genome of an individual cost well over ten million dollars. That price dropped considerably (to approximately one hundred thousand dollars) around 2008 when the 1000 Genomes Project was launched with the goal of sequencing one thousand people from all over the world. Today, technology has improved so much that a single genome can be read for less than one thousand dollars and ambitio
us projects sequencing over one million people are within our reach. For comparison, companies like 23andMe are even cheaper as they do not sequence the entire genome, but rather provide data on a subset of preselected SNPs.
Having a better grasp of the extent of variation in the human genome has helped scientists sift through the millions of variants to identify novel disease-causing SNPs. A widely used approach are genome-wide association studies (GWAS, pronounced “Gee-woz”).
GWAS are often designed as “case vs. control” studies that leverage large population samples that have been sequenced (either with the full genome known or with just a subset of SNPs). GWAS are performed to identify genetic variants that are overrepresented in individuals with the disease or condition being examined.
The first GWAS was published in 2002 on the heels of the completion of the draft of the human genome and the beginning of HapMap. Researchers in Japan identified several genetic variants found in individuals with Japanese ancestry within the gene lymphotoxin alpha (LTA).
These variants were statistically associated with an increased risk of heart attack. One SNP found within the LTA gene sequence can cause alteration of the expression of that gene and another SNP creates a functional change within the LTA protein. Having two copies of either SNP almost doubles one’s risk for heart attacks.
Because heart attacks are so common, identifying an SNP that is causative among the millions of SNPs in the genome would be impractical on an SNP-by-SNP basis. GWAS analysis combs through that data in thousands of people together quite effectively. The larger the sample size for a GWAS, the more rigorous the findings, and the higher the likelihood of identifying genetic variants that increase risk for a specific outcome, even if that risk is smaller than 10 percent.
But not all GWAS studies turn out as groundbreaking as the Japanese study on heart attacks. A downside to this approach is that it is far more likely that a study will uncover SNPs that are associated with a particular biological outcome or disease, rather than being the causative agent. These SNPs are often in close genomic proximity to the gene or genetic variant that has the true functional role. Follow-up studies are nearly always necessary to elucidate the true biological role the nearby regions have when a new SNP is associated with a biological outcome.