TIME medicine

Genetic Screening Saved This Baby’s Life

Researchers say sequencing genomes can lead to quicker diagnoses and effective treatments for more than half of children affected by brain disorders

Mya Burkhart was only six months old when she went into cardiac arrest. Fortunately, she was in the hospital when it happened, brought there by her parents because she had trouble breathing. It was her eighth or ninth visit to the emergency room for her respiratory problems, but each time the doctors had sent the Burkharts home with more questions than answers.

Mya wasn’t developing at the normal rate. She couldn’t lift her head and wasn’t responding to people and things around her. Doctors thought she might have a muscle disorder, but her other symptoms did not fit with that diagnosis.

After her heart scare, Mya spent three weeks, including her first Christmas, in the ICU on a ventilator. “I couldn’t pick her up or anything,” says her mother Holly. Still unable to solve the mystery of what was ailing her, the doctors finally suggested she have her genome tested. Maybe, they hoped, her DNA would offer some clues about why she wasn’t growing normally.

MORE: The DNA Dilemma: A Test That Could Change Your Life

Holly knew the test was still in the research stages, and that there was a chance that even it might not yield any more answers about her daughter’s condition. “At that point, I just wanted to try anything to find out what was wrong with her,” she says. It boiled down to balancing a chance that their baby would live or die.

Genetic screening, especially whole-genome screening in which people can learn about their possible risk for certain diseases, remains controversial, since the information is neither definitive nor always accurate. In most cases, genes can only predict, with a limited amount of certainty, whether a disease such as breast cancer or Alzheimer’s looms in a person’s future. As the Food and Drug Administration (FDA) contemplates the merits and efficacy of such screening, some doctors and researchers are using it with great success, according to a new study published in the journal Science Translational Medicine.

Researchers at Children’s Mercy Hospital in Kansas City, where Mya was treated, say that for 100 families, including the Burkharts, with children affected by either unknown disorders or brain abnormalities, genome screening helped 45% receive a new diagnosis, and guided 55% to a different treatment for their child’s disorder. Of the 100 families, 85 had been going from doctor to doctor in search of a diagnosis for an average of six and a half years.

“I was surprised by how many cases we found where a specific intervention can make a difference,” says Sarah Soden from the Center for Pediatric Genomic Medicine at Children’s Mercy and the study’s lead author. “For me it’s compelling enough to push the envelope and get younger kids diagnosed.”

MORE: Faster DNA Testing Helps Diagnose Disease in NICU Babies

In Mya’s case, her genome revealed a mutation in a gene responsible for transporting citrate; without it, her cells could not get the energy they needed. So far, only 13 babies have been confirmed with the condition, and all died before their first birthday after having seizures and respiratory infections. Once the genetic analysis revealed the deficiency, however, Mya was started on citrate supplements. She’s now 18 months old, having already lived nearly twice as long as the other confirmed cases. She has some developmental delays but she has not had any seizures and managed to avoid getting any serious respiratory infections.

Their success at Children’s Mercy are encouraging Soden and the study’s senior author, Dr. Stephen Kingsmore, to push ahead and determine how such screening can benefit more babies. About 5% of the 4 million babies born in the U.S. each year are admitted to the neonatal intensive care unit (NICU), and between those who are born with a genetic disorder and those who may have adverse drug interactions, he and his team anticipate that about 30%, or 60,000, may benefit from the personalized screening they offer.

For now, he and his team are targeting babies like Mya who are sick almost from the minute they enter the world, with symptoms and abnormalities that doctors simply cannot explain. For them, the screening can save families from uncertainty as well as the financial burden of having many different experts perform many different tests looking for a diagnosis. The average genetic sequencing for newborns costs around $5,000, but the average cost of a night’s stay in the Neonatal Intensive Care Unit (NICU) hovers around $8,000, and most babies spend days, if not weeks, in the units awaiting a diagnosis.

Kingsmore received a $1.5 million grant from the NIH to expand the screening program to other institutes, and he has reached out to hospitals in Florida, at the University of Maryland and in Oklahoma City to test the strategy in more babies. “If we can decrease the length of stay in the NICU it could certainly lead to huge potential cost savings,” says Dr. Alan Shuldiner, associate dean of personalized medicine at the University of Maryland.

In the latest study, Soden says that on average, families spent more than $30,000 on genetic testing alone to figure out what was ailing their babies; those who had their genomes screened paid about $3,000 for an answer.

The key to Kingsmore’s success is a system that starts with a doctor punching in a newborn’s baffling symptoms and ends with a genetic readout. The “magic juice,” as he calls it, is a database of 10,000 symptoms that typically affect infants, from simple coughs and fevers and enlarged hearts to all manner of abnormal lab readings. The baby’s unique combination of these symptoms is mapped onto the 3,000 genes that experts have so far connected to about 4,000 diseases. “No physician on the planet earth could carry that database around in his head,” says Kingsmore. But that’s what desperate parents, whose babies’ lives are at stake, expect them to do. So Kingsmore’s program accomplishes the feat, spitting out, in rank order, a list of potential genetic diagnoses. That targeted tally of diseases then directs doctors to focus on a much more manageable list of 10 or, at the most, 50 genes (from a possible 20,000 or so) that could be mutated and responsible for the baby’s condition.

While there is no argument that such testing can save lives, the more challenging question is who should be tested, and when. There is also still debate among those in the genetics and medical communities about how to interpret genomic data. “Some people would argue that he is still reporting his experimental findings, and moving too soon from the research arena into the clinical arena,” says Dr. Edward McCabe, chief medical officer of the March of Dimes.

Ethicists are concerned about the coerciveness inherent in any hand extended to parents whose babies would otherwise die; no matter how carefully and comprehensively doctors word their request, parents in that situation may not fully process the risks and benefits and be unable to provide a truly informed consent. What if the baby falls into the minority for whom the testing doesn’t yield a diagnosis or treatment? When faced with inevitable death on the one hand, and a chance, however, small, of avoiding that death on the other, can there ever really be a choice?

The stakes are especially high since in some cases, the disorders won’t lead to established and approved treatments, but experimental ones without known risks and benefits. But as the value of such testing becomes more obvious, more centers may consider sequencing more newborns’ genes. “These babies, because they are brand new, are salvageable,” says Kingsmore. “Many patients we see with genetic illnesses already have ravaged organs. In contrast, with newborn babies we have the opportunity to halt a disease early in its progression,” he says.

“I think this testing is definitely something that everybody should consider,” Holly Burkhart says. “Without it, we probably never would have figured out what was wrong with Mya. We probably would be in the same place we were a few months ago.” Instead, Mya is now smiling at her mom and making progress. “The testing helped us find answers, and tell us where we need to go from here,” she says.

TIME animals

You Always Knew Your Cat Was Half Wild But Now There’s Genetic Proof

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Paula Daniëlse—Getty Images/Flickr RM

That kitty curled up on your lap is only one genetic step away from jungle killer

A new study on house cats has found that our feline companions are actually only semi-domesticated.

People began domesticating cats around 9,000 years ago but DNA researchers from Washington University in St. Louis found that house cats still have many of the same traits as their wild cousins. The fact that cats have retained the ability to hunt and survive effortlessly in the wild just underscores how little impact we humans have had on them.

Wes Warren, an associate professor of genomics at the university, told the Los Angeles Times, “We believe we have created the first preliminary evidence that depicts domestic cats as not that far removed from wildcat populations.”

That’s not to say humans haven’t had any influence on cats. We originally took them into our homes to hunt rodents and rewarded that behavior with food. According to researchers, this lead to eventual changes in a group of stem cells that resulted in more docile (but not fully domesticated) felines and produced colors and fur patterns that humans liked.

“Our results suggest that selection for docility, as a result of becoming accustomed to humans for food rewards, was most likely the major force that altered the first domesticated cat genomes,” researchers wrote.

Read more at the Los Angeles Times.

Read next: Celebrate National Cat Day With the Most Ridiculous Cover in TIME History

TIME Science

Looking to Science for Answers About Race

Theodosius Dobzhansky
Theodosius Dobzhansky, circa 1960s Pictorial Parade / Getty Images

How a forgotten scientist changed the way we talk about race

History News Network

This post is in partnership with the History News Network, the website that puts the news into historical perspective. The article below was originally published at HNN.

Americans are constantly reminded of the contradictions concerning the meaning and impact of race.

We can as a nation claim progress as it pertains to race. After all, a majority of American voters have twice elected President Barack Obama to the most powerful office in the world.

Yet, for as much progress as we have made there is as much work to be done. The recent killings by police of unarmed black men in Ferguson, Missouri and Staten Island, New York remind us how race shapes the often hostile relationship between law enforcement and some communities. Racist comments by several NBA owners remind us that some remain polluted by the foolish belief in the fundamental superiority and inferiority of different groups. Skin color still limits economic and other opportunities. Take home loans: over the past few years the U.S. Justice Department settled cases with several banks for having steered non-whites into expensive subprime loans despite having qualified for standard mortgages.

Race matters, of course, and so too does the meaning we give it. We have often turned to science for that meaning—to justify beliefs and to provide a vocabulary for explaining human differences. But science too struggles with understanding race.

When we talk about the scientific meaning of race today we do so largely because of the work of the distinguished evolutionary biologist Theodosious Dobzhansky, who spent most of his career at Columbia University. Though today forgotten outside of scientific circles, Dobzhansky was almost single-handedly responsible for reshaping the race concept in the 20th century through his classic book, Genetics and the Origin of Species (1937).

Until Dobzhansky’s work appeared, race was defined largely in typological terms, meaning that one member of a race was thought to share the same traits with other members of that race. This kind of thinking helped perpetuate racist actions and stereotypes. For example, from 1932-1972 the infamous Tuskegee Study followed the natural course of syphilis in African American men because it was mistakenly believed that syphilis was a different disease in blacks than it was in whites.

Although Dobzhansky was unaware of the Tuskegee Study at that time, he did understand that such classifications were bad science. Dobzhansky, through new techniques in population genetics and evolutionary biology, came to understand first in the non-human animals he studied like fruit flies and ladybug beetles, and later in humans, that genetic diversity at the racial or population level was far greater than most people knew. Racial groups were much more genetically complex than a typological race concept would allow.

So how did Dobzhansky redefine race? To Dobzhansky, race was simply a methodological tool to facilitate the scientific study of human and other populations. Race was not a fixed entity, it was a way to organize individuals within a species based on the frequency with which a gene or genes appeared in that population. Depending on the genes being investigated, there could be just a few or many races. What made his definition so important and so radical was that he understood that the way we choose to organize differences in gene frequencies within species were about data and methodology, not about an underlying racial hierarchy or about the fixity of certain traits within specific groups. Dobzhansky thus sought to extract racism from the race concept.

By the 1960s, Dobzhansky grew disillusioned with the race concept, and came to believe that the scientific study of race was not only inseparable from its broader social meanings, but that it could also be put in the service of reinforcing those social meanings. The rise of the Civil Rights Movement and his own battles with other scientists over the imprecise and often inappropriate use of the term ‘race’ led him to issue a challenge to the field: devise better and more meaningful methods to investigate genetic diversity.

More than fifty years later biology still struggles with Dobzhansky’s challenge and still operates within a paradox that he himself struggled with. On the one hand, race can be an important tool to help scientists organize genetic diversity. On the other, race is an imprecise marker of genetic diversity and not a great proxy for elucidating the relationship between our ancestry and our genes.

This paradox remains central to the use of race in our genomic age. For example, it is currently too expensive to sequence everyone’s genomes, so the rapidly growing field of personalized medicine relies on race as a proxy to make best guesses about an individual’s disease risk and how one’s genes influence the response (positively or negatively) to drug treatments. Because genetic variants can cluster in populations, the belief is that this can help clinicians and drug companies make medical decisions based on one’s race. The potential danger here is that we inadvertently reinforce a crude understanding of race, forgetting that it is a highly flawed concept that cannot be used as a proxy for an individual’s own genome.

It turns out that muddled thinking about race is as deeply ingrained in scientific as non-scientific thought, and that scientists are as conflicted about race as the rest of society. It is neither cynical nor misguided to acknowledge this. It is only a reflection of a society that continues to struggle with the meaning and impact of racial difference.

Michael Yudell, Interim Chair and Associate Professor at the Drexel University School of Public Health, is author of “Race Unmasked: Biology and Race in the 20th Century,” which was recently published by Columbia University Press.

TIME ebola

This Might Be Why Some Survive Ebola

A new mice study may help explain Ebola's varying impacts

Scientists in a biosafety level 4 lab have discovered that genetics are likely involved in how susceptible someone is to Ebola, finds a new mice study published in the journal Science.

Why some people survive Ebola and others do not, even when they’re treated in the same conditions, is a question that’s long intrigued researchers. The current outbreak has also revealed that humans show symptoms of the disease differently; a significant number do not present hemorrhagic fever symptoms like heavy diarrhea, vomiting and bleeding before death.

So far, researchers have primarily used monkeys to study the Ebola virus, but in the new study, the researchers discovered that a genetically diverse population of mice had wide variations in their responses and symptoms to the Ebola virus—similar to how humans have reacted. It’s notable because mice very rarely have similar immune responses to humans, which is why discoveries made in mouse models are evaluated skeptically.

When the researchers infected the mice with Ebola, they found that some of the mice survived with mild disease symptoms, some died, and some died with severe hemorrhagic fever symptoms similar to those observed in humans. Researchers Michael G. Katze and Angela L. Rasmussen of the University of Washington also identified a few potential genetic pathways that might differ in mice who survive the disease versus those who die from it. The hope is that these pathways could help researchers develop drugs for the disease.

“We now have a model that represents the human Ebola disease that we could test vaccines in, we could test novel therapeutics in, and we also could start getting information about the genes that are responsible for the resistance to Ebola and the susceptibility to Ebola,” said Katze in a video about the study. Before the researchers can make the leap to developing drugs for humans, they will have to confirm that the pathways also exist in humans and work in the same way. But the new research is a starting point.

The team started studying the progression of the Ebola virus in mice a few years ago, before the current outbreak of Ebola started in West Africa. Only a handful of of scientists work in the few high-security containment labs in the United States. The training, Katze told TIME, is intense and requires psychological testing. “We’ve been studying Ebola for almost a decade. We’ve always been interested in Ebola because it’s a very interesting virus. It’s like the rockstar of viruses,” Katze told TIME in early October.

Read on for more about the scientists’ emerging Ebola research.

TIME Autism

Major Autism Studies Identify Dozens of Contributing Genes

Researchers collaborate on two large studies identifying the genetic basis of autism

Two new studies exploring the genetic basis of autism tie mutations in hundreds of genes to the disease.

Several teams of researchers collaborated on the studies, both published in the journal Nature, and found that about 60 of the genes are considered “high confidence,” meaning there’s a 90% chance that mutations within those genes contribute to risk for autism. Both studies show through genomic sequencing that many of these mutations are de novo, meaning that parents do not have the gene mutation, but they present spontaneously just before a child is conceived in either the sperm or egg.

It’s long been believed that autism is genetic, but a lack of large studies and advanced genomic sequencing has precluded any sort of consensus about what genes might be at play. But in the last couple years, scientists have been able to look at the genetic mutations in hundreds of people with autism and identify genes that likely factor into a child’s development of the disorder. In the two new studies, scientists were able to expand their work and look at thousands of people.

In one of the studies, several institutions used data from the Simons Simplex Collection (SSC), which is a collection of DNA samples from 3,000 families. In each of the families, one individual had autism. The researchers compared the gene sequences of the individual with autism to their unaffected family members. After analysis, they estimated that de novo mutations contribute to autism in at least 27% of families, where only one member has the disorder.

The other study, by researchers at 37 different institutions as part of the Autism Sequencing Consortium, looked at 14,000 DNA samples of parents with affected children. It found 33 genes the researchers say definitely increase risk for autism, should there be a mutation.

Even though there may be hundreds or even thousands of genes that contribute to a child’s risk of developing autism, the researchers on both studies found that the mutations appear to converge on a much smaller number of biological functions, like nerve-cell communication or proteins known to cause inherited disability. “In my view, the real importance of these studies is not diagnosis, and it’s not figuring out exactly what percentage of people have de novo mutations, it’s about laying the foundation to transform the understanding of the biological mechanisms of autism,” says Dr. Matthew State, chair of the psychiatry department at University of California, San Francisco and a co-leader of the SSC study, as well as a senior participant on the other study.

State doesn’t believe that the findings will mean that families will one day get their genomes sequenced to spot hundreds of possible mutations. Instead, they could lay the groundwork for discovering how autism develops, and what potential treatments, or even drugs, could help fight it.

TIME Innovation

Five Best Ideas of the Day: October 14

The Aspen Institute is an educational and policy studies organization based in Washington, D.C.

1. Fix the system, don’t fight individual diseases: Why Ebola may change how aid dollars are spent on healthcare in Africa.

By Lesley Wroughton at Reuters

2. Plan for a global body to regulate the great promise of genetics — balancing unfettered innovation with sensible rules to prevent abuse.

By Jamie F. Metzl in Foreign Affairs

3. Because it increases disease and exacerbates resource scarcity, the Pentagon sees climate change as a threat multiplier.

By Laura Barron-Lopez in the Hill

4. The U.S. should call out Egypt’s rising authoritarian leadership and the plight of repressed people there.

By the Editorial Board of the Washington Post

5. Successful community collaborations build civic confidence for increasingly audacious projects that can improve lives.

By Monique Miles in the Collective Impact Forum blog

The Aspen Institute is an educational and policy studies organization based in Washington, D.C.

TIME Ideas hosts the world's leading voices, providing commentary and expertise on the most compelling events in news, society, and culture. We welcome outside contributions. To submit a piece, email ideas@time.com.

TIME Genetics

Gene-Therapy Trial Shows Promise Fighting ‘Bubble Boy’ Syndrome

The immune system-related disease affects about 1 in 100,000 babies each year

A new gene-therapy treatment is showing promise in treating a rare and severe congenital condition that involves extreme immune-system deficiencies.

“Bubble boy” syndrome, an X-linked condition, takes its name from a famous case in which an affected boy, vulnerable to infection, lived inside a plastic bubble that protected him from the world’s germs. Outside of such sterile environments, babies with the syndrome seldom live longer than a year, the Wall Street Journal reports.

The condition has for decades bested medical researchers, despite occasional bouts of optimism — hope for one previous gene-therapy treatment was felled when some recipients developed leukemia.

Gene-therapy treatment works, essentially, by replacing unperforming genes with functional ones. Dysfunctional cells are removed from the child’s immune system and exposed to a genetically engineered virus that can reprogram the cells to function properly, explains Reuters. Those cells are then reinserted back into the patient.

In the earlier treatment, the virus to which the cells were exposed apparently activated a part of their genetic code that leads to leukemia, Reuters says.

But initial results reported in the New England Journal of Medicine show that none of the nine babies from the U.S. and Europe who received the latest treatment are exhibiting any signs of cancer.

Of the nine infant participants in the research — who were between 4 and 10½ months old when they began receiving the therapy — eight were still alive 16 to 43 months later, without living in a protective “bubble.” (The ninth child died four months after treatment began from an earlier infection he had been fighting.)

Out of the eight boys still living, the treatment upped blood T-cell levels, rebuilding the immune system, of seven. In the case of the eighth child, the treatment did not rebuild his immune system, but a successful stem-cell transplant has kept him in improved health, Reuters reports.

TIME Addiction

Addicted to Coffee? It’s Probably in Your Genes

coffee crema
Getty Images

A new genetic explanation for your caffeine cravings

If you feel like you literally could not survive a day without coffee, you might have your genes to thank (or blame).

A new genome-wide study published in Molecular Psychiatry has identified genetic variants that may have a lot to do with your coffee obsession. Researchers from Harvard School of Public Health and Brigham and Women’s Hospital looked at more than 120,000 coffee drinkers and found six markers linked to responsiveness to caffeine—some of which had been previously identified as being related to smoking initiation and other types of potentially addictive behaviors, but had never before been linked to coffee consumption, says Marilyn Cornelis, research associate in the Department of Nutrition at Harvard School of Public Health and lead author of the study.

MORE: You Asked: Is Coffee Bad For You?

Caffeine is a drug—a fact many of us forget until we madly crave a double shot. “There is controversy as to whether it can be addictive, and some of the genes that come up in the study suggest that’s quite possible,” Cornelis says. “The stimulating effects caffeine has would suggest that caffeine is a major driving in habitual coffee consumption at the genetic level.”

MORE: How Coffee Might Lower the Risk of Heart Failure

The results might help add nuance to coffee research, she says, which generally treats everyone as the same. It could also help pinpoint people who’d most benefit from coffee consumption, and who should stick to decaf. “We assume that any health effects from one cup of coffee will be the same for everyone, but this data suggests that’s not true,” Cornelis says.

Scientists have known for a long time that genetics play a role in coffee consumption and caffeine response, Cornelis says. “But it’s only until just recently that we’ve actually been able to pinpoint these exact genetics. That’s an important step forward in the research.”

TIME medicine

New Genes Found that Determine Your Height

The latest analysis doubles the number of genes connected to height

How tall you are is strongly related to the genes you inherit, and previous studies suggested that as much as 80% of the variance in height among people is due to their DNA.

And in the largest genetic study of height-related genes to date, scientists involved in the appropriately titled GIANT consortium (Genetic Investigation of Anthropometric Traits) identified 423 genetic regions connected to height — which could explain as much as 60% of that genetic component.

Dr. Joel Hirschhorn, leader of the GIANT consortium at Boston Children’s Hospital, Harvard Medical School and the Broad Institute of MIT says that for a trait like height, which isn’t determined by a single gene but likely the combined effects of multiple genes involved in multiple different processes from bone growth to cell growth, the new findings are like finding biggest nuggets of gold in a riverbed. The latest analysis, published in the journal Nature Genetics, describes the gene variants most commonly shared among people (not the rare mutations) that likely contribute to height.

They emerged from a sweep of the genomes of more than 250,000 people of various heights, and from correlating their stature with their genetics. Many of the known and familiar factors related to height, including those dealing with skeletal growth and collagen that are mutated in people with medically short stature, for example, appeared in the study, confirming their role in determining how tall people get.

But there were also some surprises — genetic regions that previous had never been thought to be related to height, including a gene known to be involved in cell growth but not in skeletal functions. “It’s a mix ranging from completely known things, to those that make sense to things that are completely surprising and things we don’t even know what to think about them,” says Hirschhorn.

What the group has identified are gene regions of interest, and a new round of studies will have to delve deeper into those areas to isolate specific genes — and the proteins they make, such as growth factors, enzymes, or other agents — that are actually responsible for determining height. But it’s a critical first step, and could lead to potential new ways of treating medical conditions of short stature or gigantism that can have health negative health effects on the heart and joints.

TIME Genetics

New Study Makes Great Strides in Understanding Human Height

Nearly 700 gene variants linked to height have been identified

What makes tall people tall and short people short is becoming less of a mystery to scientists. An international team of researchers has identified nearly 700 gene variants in more than 400 gene regions that are connected to height — an estimated 20 percent of all the gene variants that play a role in determining one’s size.

The findings of the study were published in the journal Nature Genetics, Reuters reports. It is believed to be the biggest study of its kind to date.

Scientists believe that about 80 percent of a person’s height is hereditarily determined, with environmental factors such as nutrition determining the rest. The average height of humans around the world has risen throughout the last few generations as world nutrition generally improves.

Researchers studied the genomes of 253,288 people from Europe, North America and Australia, all with European ancestry and found 424 gene regions with 697 gene variants that are linked to height. Many of the genes identified were not previously known to have an effect on skeletal growth.

“For over 100 years, [height has] been a great model for studying the genetics of diseases like obesity, diabetes, asthma that are also caused by the combined influence of many genes acting together,” Dr. Joel Hirschhorn, a pediatric endocrinologist and geneticist at Boston Children’s Hospital and the Broad Institute. “So by understanding how the genetics of height works, we can understand how the genetics of human disease works.”

[Reuters]

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