Genomic Data Has a Diversity Problem, But Global Efforts Are Underway to Fix It
Genomics has begun its golden age. Just 20 years ago, sequencing a single genome cost nearly $3 billion and took over a decade. Today, the same feat can be achieved for a few hundred dollars and the better part of a day . Suddenly, the prospect of sequencing not just individuals, but whole populations, has become feasible.
The genetic differences between humans may seem meager, only around 0.1 percent of the genome on average, but this variation can have profound effects on an individual's risk of disease, responsiveness to medication, and even the dosage level that would work best.
Already, initiatives like the U.K.'s 100,000 Genomes Project - now expanding to 1 million genomes - and other similarly massive sequencing projects in Iceland and the U.S., have begun collecting population-scale data in order to capture and study this variation.
The resulting data sets are immensely valuable to researchers and drug developers working to design new 'precision' medicines and diagnostics, and to gain insights that may benefit patients. Yet, because the majority of this data comes from developed countries with well-established scientific and medical infrastructure, the data collected so far is heavily biased towards Western populations with largely European ancestry.
This presents a startling and fast-emerging problem: groups that are under-represented in these datasets are likely to benefit less from the new wave of therapeutics, diagnostics, and insights, simply because they were tailored for the genetic profiles of people with European ancestry.
We may indeed be approaching a golden age of genomics-enabled precision medicine. But if the data bias persists then there is a risk, as with most golden ages throughout history, that the benefits will not be equally accessible to all, and existing inequalities will only be exacerbated.
To remedy the situation, a number of initiatives have sprung up to sequence genomes of under-represented groups, adding them to the datasets and ensuring that they too will benefit from the rapidly unfolding genomic revolution.
Global Gene Corp
The idea behind Global Gene Corp was born eight years ago in Harvard when Sumit Jamuar, co-founder and CEO, met up with his two other co-founders, both experienced geneticists, for a coffee.
"They were discussing the limitless applications of understanding your genetic code," said Jamuar, a business executive from New Delhi.
"And so, being a technology enthusiast type, I was excited and I turned to them and said hey, this is incredible! Could you sequence me and give me some insights? And they actually just turned around and said no, because it's not going to be useful for you - there's not enough reference for what a good Sumit looks like."
What started as a curiosity-driven conversation on the power of genomics ended with a commitment to tackle one of the field's biggest roadblocks - its lack of global representation.
Jamuar set out to begin with India, which has about 20 percent of the world's population, including over 4000 different ethnicities, but contributes less than 2 percent of genomic data, he told Leaps.org.
Eight years later, Global Gene Corp's sequencing initiative is well underway, and is the largest in the history of the Indian subcontinent. The program is being carried out in collaboration with biotech giant Regeneron, with support from the Indian government, local communities, and the Indian healthcare ecosystem. In August 2020, Global Gene Corp's work was recognized through the $1 million 2020 Roddenberry award for organizations that advance the vision of 'Star Trek' creator Gene Roddenberry to better humanity.
This problem has already begun to manifest itself in, for example, much higher levels of genetic misdiagnosis among non-Europeans tested for their risk of certain diseases, such as hypertrophic cardiomyopathy - an inherited disease of the heart muscle.
Global Gene Corp also focuses on developing and implementing AI and machine learning tools to make sense of the deluge of genomic data. These tools are increasingly used by both industry and academia to guide future research by identifying particularly promising or clinically interesting genetic variants. But if the underlying data is skewed European, then the effectiveness of the computational analysis - along with the future advances and avenues of research that emerge from it - will be skewed towards Europeans too.
This problem has already begun to manifest itself in, for example, much higher levels of genetic misdiagnosis among non-Europeans tested for their risk of certain diseases, such as hypertrophic cardiomyopathy - an inherited disease of the heart muscle. Most of the genetic variants used in these tests were identified as being causal for the disease from studies of European genomes. However, many of these variants differ both in their distribution and clinical significance across populations, leading to many patients of non-European ancestry receiving false-positive test results - as their benign genetic variants were misclassified as pathogenic. Had even a small number of genomes from other ethnicities been included in the initial studies, these misdiagnoses could have been avoided.
"Unless we have a data set which is unbiased and representative, we're never going to achieve the success that we want," Jamuar says.
"When Siri was first launched, she could hardly recognize an accent which was not of a certain type, so if I was trying to speak to Siri, I would have to repeat myself multiple times and try to mimic an accent which wasn't my accent so that she could understand it.
"But over time the voice recognition technology improved tremendously because the training data was expanded to include people of very diverse backgrounds and their accents, so the algorithms were trained to be able to pick that up and it dramatically improved the technology. That's the way we have to think about it - without that good-quality diverse data, we will never be able to achieve the full potential of the computational tools."
While mapping India's rich genetic diversity has been the organization's primary focus so far, they plan, in time, to expand their work to other under-represented groups in Asia, the Middle East, Africa, and Latin America.
"As other like-minded people and partners join the mission, it just accelerates the achievement of what we have set out to do, which is to map out and organize the world's genomic diversity so that we can enable high-quality life and longevity benefits for everyone, everywhere," Jamuar says.
Empowering African Genomics
Africa is the birthplace of our species, and today still retains an inordinate amount of total human genetic diversity. Groups that left Africa and went on to populate the rest of the world, some 50 to 100,000 years ago, were likely small in number and only took a fraction of the total genetic diversity with them. This ancient bottleneck means that no other group in the world can match the level of genetic diversity seen in modern African populations.
Despite Africa's central importance in understanding the history and extent of human genetic diversity, the genomics of African populations remains wildly understudied. Addressing this disparity has become a central focus of the H3Africa Consortium, an initiative formally launched in 2012 with support from the African Academy of Sciences, the U.S. National Institutes of Health, and the UK's Wellcome Trust. Today, H3Africa supports over 50 projects across the continent, on an array of different research areas in genetics relevant to the health and heredity of Africans.
"Africa is the cradle of Humankind. So what that really means is that the populations that are currently living in Africa are among some of the oldest populations on the globe, and we know that the longer populations have had to go through evolutionary phases, the more variation there is in the genomes of people who live presently," says Zane Lombard, a principal investigator at H3Africa and Associate Professor of Human Genetics at the University of the Witwatersrand in Johannesburg, South Africa.
"So for that reason, African populations carry a huge amount of genetic variation and diversity, which is pretty much uncaptured. There's still a lot to learn as far as novel variation is concerned by looking at and studying African genomes."
A recent landmark H3Africa study, led by Lombard and published in Nature in October, sequenced the genomes of over 400 African individuals from 50 ethno-linguistic groups - many of which had never been sampled before.
Despite the relatively modest number of individuals sequenced in the study, over three million previously undescribed genetic variants were found, and complex patterns of ancestral migration were uncovered.
"In some of these ethno-linguistic groups they don't have a word for DNA, so we've had to really think about how to make sure that we communicate the purposes of different studies to participants so that you have true informed consent," says Lombard.
"The objective," she explained, "was to try and fill some of the gaps for many of these populations for which we didn't have any whole genome sequences or any genetic variation data...because if we're thinking about the future of precision medicine, if the patient is a member of a specific group where we don't know a lot about the genomic variation that exists in that group, it makes it really difficult to start thinking about clinical interpretation of their data."
From H3Africa's conception, the consortium's goal has not only been to better represent Africa's staggering genetic diversity in genomic data sets, but also to build Africa's domestic genomics capabilities and empower a new generation of African researchers. By doing so, the hope is that Africans will be able to set their own genomics agenda, and leapfrog to new and better ways of doing the work.
"The training that has happened on the continent and the number of new scientists, new students, and fellows that have come through the process and are now enabled to start their own research groups, to grow their own research in their countries, to be a spokesperson for genomics research in their countries, and to build that political will to do these larger types of sequencing initiatives - that is really a significant outcome from H3Africa as well. Over and above all the science that's coming out," Lombard says.
"What has been created through H3Africa is just this locus of researchers and scientists and bioethicists who have the same goal at heart - to work towards adjusting the data bias and making sure that all global populations are represented in genomics."
Is there a robot nanny in your child's future?
From ROBOTS AND THE PEOPLE WHO LOVE THEM: Holding on to Our Humanity in an Age of Social Robots by Eve Herold. Copyright © 2024 by the author and reprinted by permission of St. Martin’s Publishing Group.
Could the use of robots take some of the workload off teachers, add engagement among students, and ultimately invigorate learning by taking it to a new level that is more consonant with the everyday experiences of young people? Do robots have the potential to become full-fledged educators and further push human teachers out of the profession? The preponderance of opinion on this subject is that, just as AI and medical technology are not going to eliminate doctors, robot teachers will never replace human teachers. Rather, they will change the job of teaching.
A 2017 study led by Google executive James Manyika suggested that skills like creativity, emotional intelligence, and communication will always be needed in the classroom and that robots aren’t likely to provide them at the same level that humans naturally do. But robot teachers do bring advantages, such as a depth of subject knowledge that teachers can’t match, and they’re great for student engagement.
The teacher and robot can complement each other in new ways, with the teacher facilitating interactions between robots and students. So far, this is the case with teaching “assistants” being adopted now in China, Japan, the U.S., and Europe. In this scenario, the robot (usually the SoftBank child-size robot NAO) is a tool for teaching mainly science, technology, engineering, and math (the STEM subjects), but the teacher is very involved in planning, overseeing, and evaluating progress. The students get an entertaining and enriched learning experience, and some of the teaching load is taken off the teacher. At least, that’s what researchers have been able to observe so far.
To be sure, there are some powerful arguments for having robots in the classroom. A not-to-be-underestimated one is that robots “speak the language” of today’s children, who have been steeped in technology since birth. These children are adept at navigating a media-rich environment that is highly visual and interactive. They are plugged into the Internet 24-7. They consume music, games, and huge numbers of videos on a weekly basis. They expect to be dazzled because they are used to being dazzled by more and more spectacular displays of digital artistry. Education has to compete with social media and the entertainment vehicles of students’ everyday lives.
Another compelling argument for teaching robots is that they help prepare students for the technological realities they will encounter in the real world when robots will be ubiquitous. From childhood on, they will be interacting and collaborating with robots in every sphere of their lives from the jobs they do to dealing with retail robots and helper robots in the home. Including robots in the classroom is one way of making sure that children of all socioeconomic backgrounds will be better prepared for a highly automated age, when successfully using robots will be as essential as reading and writing. We’ve already crossed this threshold with computers and smartphones.
Students need multimedia entertainment with their teaching. This is something robots can provide through their ability to connect to the Internet and act as a centralized host to videos, music, and games. Children also need interaction, something robots can deliver up to a point, but which humans can surpass. The education of a child is not just intended to make them technologically functional in a wired world, it’s to help them grow in intellectual, creative, social, and emotional ways. When considered through this perspective, it opens the door to questions concerning just how far robots should go. Robots don’t just teach and engage children; they’re designed to tug at their heartstrings.
It’s no coincidence that many toy makers and manufacturers are designing cute robots that look and behave like real children or animals, says Turkle. “When they make eye contact and gesture toward us, they predispose us to view them as thinking and caring,” she has written in The Washington Post. “They are designed to be cute, to provide a nurturing response” from the child. As mentioned previously, this nurturing experience is a powerful vehicle for drawing children in and promoting strong attachment. But should children really love their robots?
ROBOTS AND THE PEOPLE WHO LOVE THEM: Holding on to Our Humanity in an Age of Social Robots by Eve Herold (January 9, 2024).
St. Martin’s Publishing Group
The problem, once again, is that a child can be lulled into thinking that she’s in an actual relationship, when a robot can’t possibly love her back. If adults have these vulnerabilities, what might such asymmetrical relationships do to the emotional development of a small child? Turkle notes that while we tend to ascribe a mind and emotions to a socially interactive robot, “simulated thinking may be thinking, but simulated feeling is never feeling, and simulated love is never love.”
Always a consideration is the fact that in the first few years of life, a child’s brain is undergoing rapid growth and development that will form the foundation of their lifelong emotional health. These formative experiences are literally shaping the child’s brain, their expectations, and their view of the world and their place in it. In Alone Together, Turkle asks: What are we saying to children about their importance to us when we’re willing to outsource their care to a robot? A child might be superficially entertained by the robot while his self-esteem is systematically undermined.
Research has emerged showing that there are clear downsides to child-robot relationships.
Still, in the case of robot nannies in the home, is active, playful engagement with a robot for a few hours a day any more harmful than several hours in front of a TV or with an iPad? Some, like Xiong, regard interacting with a robot as better than mere passive entertainment. iPal’s manufacturers say that their robot can’t replace parents or teachers and is best used by three- to eight-year-olds after school, while they wait for their parents to get off work. But as robots become ever-more sophisticated, they’re expected to perform more of the tasks of day-to-day care and to be much more emotionally advanced. There is no question children will form deep attachments to some of them. And research has emerged showing that there are clear downsides to child-robot relationships.
Some studies, performed by Turkle and fellow MIT colleague Cynthia Breazeal, have revealed a darker side to the child-robot bond. Turkle has reported extensively on these studies in The Washington Post and in her book Alone Together. Most children love robots, but some act out their inner bully on the hapless machines, hitting and kicking them and otherwise trying to hurt them. The trouble is that the robot can’t fight back, teaching children that they can bully and abuse without consequences. As in any other robot relationship, such harmful behavior could carry over into the child’s human relationships.
And, ironically, it turns out that communicative machines don’t actually teach kids good communication skills. It’s well known that parent-child communication in the first three years of life sets the stage for a very young child’s intellectual and academic success. Verbal back-and-forth with parents and care-givers is like fuel for a child’s growing brain. One article that examined several types of play and their effect on children’s communication skills, published in JAMA Pediatrics in 2015, showed that babies who played with electronic toys—like the popular robot dog Aibo—show a decrease in both the quantity and quality of their language skills.
Anna V. Sosa of the Child Speech and Language Lab at Northern Arizona University studied twenty-six ten- to sixteen- month-old infants to compare the growth of their language skills after they played with three types of toys: electronic toys like a baby laptop and talking farm; traditional toys like wooden puzzles and building blocks; and books read aloud by their parents. The play that produced the most growth in verbal ability was having books read to them by a caregiver, followed by play with traditional toys. Language gains after playing with electronic toys came dead last. This form of play involved the least use of adult words, the least conversational turntaking, and the least verbalizations from the children. While the study sample was small, it’s not hard to extrapolate that no electronic toy or even more abled robot could supply the intimate responsiveness of a parent reading stories to a child, explaining new words, answering the child’s questions, and modeling the kind of back- and-forth interaction that promotes empathy and reciprocity in relationships.
***
Most experts acknowledge that robots can be valuable educational tools. But they can’t make a child feel truly loved, validated, and valued. That’s the job of parents, and when parents abdicate this responsibility, it’s not only the child who misses out on one of life’s most profound experiences.
We really don’t know how the tech-savvy children of today will ultimately process their attachments to robots and whether they will be excessively predisposed to choosing robot companionship over that of humans. It’s possible their techno literacy will draw for them a bold line between real life and a quasi-imaginary history with a robot. But it will be decades before we see long-term studies culminating in sufficient data to help scientists, and the rest of us, to parse out the effects of a lifetime spent with robots.
This is an excerpt from ROBOTS AND THE PEOPLE WHO LOVE THEM: Holding on to Our Humanity in an Age of Social Robots by Eve Herold. The book will be published on January 9, 2024.
Story by Big Think
In rare cases, a woman’s heart can start to fail in the months before or after giving birth. The all-important muscle weakens as its chambers enlarge, reducing the amount of blood pumped with each beat. Peripartum cardiomyopathy can threaten the lives of both mother and child. Viral illness, nutritional deficiency, the bodily stress of pregnancy, or an abnormal immune response could all play a role, but the causes aren’t concretely known.
If there is a silver lining to peripartum cardiomyopathy, it’s that it is perhaps the most survivable form of heart failure. A remarkable 50% of women recover spontaneously. And there’s an even more remarkable explanation for that glowing statistic: The fetus‘ stem cells migrate to the heart and regenerate the beleaguered muscle. In essence, the developing or recently born child saves its mother’s life.
Saving mama
While this process has not been observed directly in humans, it has been witnessed in mice. In a 2015 study, researchers tracked stem cells from fetal mice as they traveled to mothers’ damaged cardiac cells and integrated themselves into hearts.
Evolutionarily, this function makes sense: It is in the fetus’ best interest that its mother remains healthy.
Scientists also have spotted cells from the fetus within the hearts of human mothers, as well as countless other places inside the body, including the skin, spleen, liver, brain, lung, kidney, thyroid, lymph nodes, salivary glands, gallbladder, and intestine. These cells essentially get everywhere. While most are eliminated by the immune system during pregnancy, some can persist for an incredibly long time — up to three decades after childbirth.
This integration of the fetus’ cells into the mother’s body has been given a name: fetal microchimerism. The process appears to start between the fourth and sixth week of gestation in humans. Scientists are actively trying to suss out its purpose. Fetal stem cells, which can differentiate into all sorts of specialized cells, appear to target areas of injury. So their role in healing seems apparent. Evolutionarily, this function makes sense: It is in the fetus’ best interest that its mother remains healthy.
Sending cells into the mother’s body may also prime her immune system to grow more tolerant of the developing fetus. Successful pregnancy requires that the immune system not see the fetus as an interloper and thus dispatch cells to attack it.
Fetal microchimerism
But fetal microchimerism might not be entirely beneficial. Greater concentrations of the cells have been associated with various autoimmune diseases such as lupus, Sjogren’s syndrome, and even multiple sclerosis. After all, they are foreign cells living in the mother’s body, so it’s possible that they might trigger subtle, yet constant inflammation. Fetal cells also have been linked to cancer, although it isn’t clear whether they abet or hinder the disease.
A team of Spanish scientists summarized the apparent give and take of fetal microchimerism in a 2022 review article. “On the one hand, fetal microchimerism could be a source of progenitor cells with a beneficial effect on the mother’s health by intervening in tissue repair, angiogenesis, or neurogenesis. On the other hand, fetal microchimerism might have a detrimental function by activating the immune response and contributing to autoimmune diseases,” they wrote.
Regardless of a fetus’ cells net effect, their existence alone is intriguing. In a paper published earlier this year, University of London biologist Francisco Úbeda and University of Western Ontario mathematical biologist Geoff Wild noted that these cells might very well persist within mothers for life.
“Therefore, throughout their reproductive lives, mothers accumulate fetal cells from each of their past pregnancies including those resulting in miscarriages. Furthermore, mothers inherit, from their own mothers, a pool of cells contributed by all fetuses carried by their mothers, often referred to as grandmaternal microchimerism.”
So every mother may carry within her literal pieces of her ancestors.