Health

Stay younger, longer. Great idea. But direct-to-consumer test kits that promise to gauge a person’s biological age by analyzing a drop of blood are not worth the $100 or so investment, says oncologist Mary Armanios. The tests measure the length of telomeres, the bits of DNA that cap and protect the ends of chromosomes. But the consumer tests are unreliable and can be misinterpreted, Armanios says.

“These kinds of tests can do harm, suggesting there is something wrong when there isn’t,” says the Johns Hopkins School of Medicine researcher, who uses a clinical test of telomere length to diagnose and treat people with certain rare disorders.
Armanios gets calls from people who panic when they get their results from consumer tests. One man in his 40s was told his telomeres were those of an 80-year-old. He sold his house and quit work to make the most of the short time he was convinced he had left. Worse, she says, because he was under the misguided impression that surgeries shorten telomeres, he had decided to delay removal of a precancerous skin spot.

Armanios trained in the lab of Carol Greider, who shared the 2009 Nobel Prize in physiology or medicine for discovering telomerase, the enzyme that controls telomere lengthening (SN: 10/24/09, p. 14). Today Armanios is clinical director of the telomere center at Johns Hopkins.

There is a wide range of “normal” when it comes to telomere length. Work by her team and others has shown that cells don’t stop dividing or die because of telomere shortening unless the ends get very short, far from the median.

Yet, commercial testing companies will label clients as older than their birthday suggests if their telomeres are anywhere shorter than the median. Longer means younger. But excessively long telomeres are not a guarantee of a long life and may be associated with higher cancer risk.

The test many consumer companies use, quantitative polymerase chain reaction, or qPCR, has a 20 percent variability rate — tests on different days can yield different answers, studies by Armanios and others have shown. The clinical test Armanios’ group uses is flow cytometry and fluorescent in situ hybridization, or flow-FISH, which has a lower, 5 percent, variability rate.
The researchers use the more precise test to study a small group of disorders united by telomere defects. For two of the illnesses, treatment decisions can change based on clinical telomere testing. A hereditary form of aplastic anemia, a failure of the bone marrow to make blood cells, can be treated with a stem cell transplant with immune suppression. People whose telomeres are short need less immune suppression with the transplant. In a study by Armanios and colleagues in the March 6 Proceedings of the National Academy of Sciences, telomere testing flagged nine of 38 patients who required a gentler approach.
Likewise, patients with short telomeres who are receiving lung transplants for idiopathic pulmonary fibrosis should get low immune suppression. In fact, traditional levels can be lethal. With this knowledge, the transplant can be done more safely.

“The telomere belongs in the clinic,” Armanios says, “and should not be used as a form of molecular palm reading.”

Air pollution caused 3.2 million new cases of diabetes worldwide in 2016, according to a new estimate.

Fine particulate matter, belched out by cars and factories and generated through chemical reactions in the atmosphere, hang around as haze and make air hard to breathe. Air pollution has been linked to chronic conditions such as heart disease and diabetes (SN: 9/30/17, p. 18), but this study is one of the first attempts to quantify the connection for diabetes. Researchers tracked 1.7 million U.S. veterans for almost a decade to assess their risk of developing diabetes. They also used data from global studies on diabetes risk, as well as air quality data from the U.S. Environmental Protection Agency and NASA, to create equations that analyzed the connection between air pollution exposure and diabetes globally.

The new estimate, reported in July in The Lancet Planetary Health, holds air pollution responsible for about 14 percent of new cases of diabetes worldwide. Factors such as genetics, weight, activity level and diet also influence the risk of the disease, which is on the rise globally. (The World Health Organization estimates that 422 million people now live with type 2 diabetes — up from 108 million in 1980.)

The burden isn’t the same around the globe: Unsurprisingly, countries with high pollution levels, such as Pakistan, India and China, also have especially high rates of air pollution-linked diabetes. The United States, which now has comparatively clean air, is also high on the list.

Forget all the ridicule heaped on treadmill-running shrimp.

About 80 percent of U.S. adults think that government spending on medical research, engineering and technology, and basic science usually leads to meaningful advances, a new survey from the Pew Research Center shows. The nonprofit, nonpartisan research organization queried 2,537 people from April 23 to May 6.

No matter where they fell on the political spectrum, a majority of Republicans and Democrats shared that view. Of liberal Democrats surveyed, 92 percent said government investments in basic scientific research “usually pay off in the long run.” Of conservative Republicans, 61 percent agreed.
That general agreement broke down when it came to private versus government spending. Two-thirds of conservative Republicans said that private investment alone would be enough to see that scientific progress is made, compared with 22 percent of liberal Democrats.

Surveys in 2017, 2014 and 2009 by Pew also found similar support among Americans for spending taxpayer dollars on science.

Some seemingly silly government-funded experiments, such as the exercising shrimp, have been singled out by politicians and others in the past as examples of wasteful spending. But appearances can be misleading. Putting the crustaceans through their paces, for example, was part of a larger project studying infection in farmed shrimp in hopes of finding treatments.

Today’s young women are more likely to experience depression and anxiety during pregnancy than their mothers were, a generation-spanning survey finds.

From 1990 to 1992, about 17 percent of young pregnant women in southwest England who participated in the study had signs of depressed mood. But the generation that followed, including these women’s daughters and sons’ partners, fared worse. Twenty-five percent of these young women, pregnant in 2012 to 2016, showed signs of depression, researchers report July 13 in JAMA Network Open.
“We are talking about a lot of women,” says study coauthor Rebecca Pearson, a psychiatric epidemiologist at Bristol University in England.

Earlier studies also had suggested that depression during and after pregnancy is relatively common (SN: 3/17/18, p. 16). But those studies are dated, Pearson says. “We know very little about the levels of depression and anxiety in new mums today,” she says.

To measure symptoms of depression and anxiety, researchers used the Edinburgh Postnatal Depression Scale — 10 questions, each with a score of 0 to 3, written to reveal risk of depression during and after pregnancy. A combined score of 13 and above signals high levels of symptoms.

From 1990 to 1992, 2,390 women between the ages of 19 and 24 took the survey while pregnant. Of these women, 408 — or 17 percent — scored 13 or higher, indicating worrisome levels of depression or anxiety.
When researchers surveyed the second-generation women, including both daughters of the original participants and sons’ partners ages 19 to 24, the numbers were higher. Of 180 women pregnant in 2012 to 2016, 45 of them — or 25 percent — scored 13 or more. It’s not clear whether the findings would be similar for pregnant women who are older than 24 or younger than 19.
That generational increase in young women scoring high for symptoms of depression comes in large part from higher scores on questions that indicate anxiety and stress, Pearson says. Today’s pregnant women reported frequent feelings of “unnecessary panic or fear” and “things getting too much,” for instance.

Those findings fit with observations by psychiatrist Anna Glezer of the University of California, San Francisco. “A very significant portion of my patients present with their primary problem as anxiety, as opposed to a low mood,” says Glezer, who has a practice in Burlingame, Calif.

The study’s cutoff score for indicating high depression risk was 13, but Pearson points out that a lower score can signal mild depression. Women who score an 8 or 9 “still aren’t feeling great,” she says. It’s likely that even more pregnant women might have less severe, but still unpleasant symptoms, she says.

The researchers also found that depression moves through families. Daughters of women who were depressed during pregnancy were about three times as likely to be depressed during their own pregnancy than women whose mothers weren’t depressed. That elevated risk “was news to me,” says obstetrician and gynecologist John Keats, who chaired a group of the American College of Obstetricians and Gynecologists that studied maternal mental health. Asking about whether a patient’s mother experienced depression or anxiety while pregnant might help identify women at risk, he says.

Negative effects of stress can be transmitted during pregnancy in ways that scientists are just beginning to understand, and stopping this cycle is important (SN Online: 7/9/18). “You’re not only talking about the effects on a patient and her family, but potential effects on her growing fetus and newborn,” says Keats, of the David Geffen School of Medicine at UCLA.

Although researchers don’t yet know what’s behind the increase, they have some guesses. More mothers work today than in the 1990s, and tougher financial straits push women to work inflexible jobs. More stress, less sleep and more time sitting may contribute to the difference.

Time on social media may also increase feelings of isolation and anxiety, Glezer says. Social media can help new moms get information, but that often comes with “a whole lot of comparisons, judgments and expectations.”

The first global maps of Pluto and its moon Charon are now available, putting a bookend on NASA’s New Horizons mission.

“From a completionist’s point of view, they are all the good data we have, stitched together into a coherent, complete mosaic,” says planetary scientist Ross Beyer of NASA’s Ames Research Center in Moffett Field, Calif.

The charts focus on the 42 percent of Pluto and 45 percent of Charon where New Horizons snapped images from at least two angles during its 2015 flyby, revealing the landscapes’ height and depth (SN: 6/27/15, p. 16).
These measurements add topographic detail to already familiar features. For instance, the smooth plains of Pluto’s distinctive, heart-shaped ice sheet, known as Sputnik Planitia, lie two to three kilometers below the region’s rim.

The biggest surprise on Pluto is a 3,200-kilometer-long system of ridges and troughs that traces a single, long line across the dwarf planet. That streak may stretch all the way around the globe, Beyer and colleagues report online June 11 in Icarus. This feature was only visible with all the data put together, Beyer says. The team doesn’t have a good explanation for its formation yet.
Charon’s map confirmed that the moon is made up of two large zones: smooth plains in the southern hemisphere and fractured blocks and canyons in the north, Beyer and colleagues report online July 3 in another paper in Icarus (SN: 4/2/16, p. 20). Initially, scientists thought both terrains were at the same elevation, but the new map shows that the plains are situated a kilometer or two lower than the northern terrain.
“We don’t know quite why that is yet, but it sure is interesting,” Beyer says.

Other planetary scientists will use these charts to continue unearthing Pluto and Charon’s secrets. “These maps really form the basis, the cartographic foundation, for anything any other scientist will do,” Beyer says.

Antibiotic resistance in leeches really sucks.

A bacterium found in leeches’ guts needs exposure to only 0.01 micrograms per milliliter of ciprofloxacin to become resistant to that drug, scientists report July 24 in mBio. That’s about 400 times less than the amount of antibiotics thought to trigger drug resistance in this species of bacteria, says study coauthor Joerg Graf, a biologist at the University of Connecticut in Storrs.

Certain leeches are approved for medical use by the U.S. Food and Drug Administration to help patients heal from reconstructive surgery (SN: 10/23/04, p. 266). The slimy creatures suck up blood and secrete anticoagulants, aiding tissue growth.
In the early 2000s, researchers noticed an uptick in antibiotic-resistant infections in these patients that were caused by the Aeromonas bacteria found in Hirudo verbana, one of several medicinal leech species. Scientists analyzed the contents of leeches’ stomachs using mass spectrometry, and found drug-resistant bacteria as well as low levels of both ciprofloxacin and enrofloxacin, a veterinary antibiotic used on poultry farms. The researchers say the leeches may have been exposed to these antibiotics through poultry blood used for food on leech farms.

Graf suggests that leech farmers eliminate ciprofloxacin and other antibiotics from their operations. But Aeromonas is also found in freshwater environments. “It is concerning because similarly low amounts [of antibiotics] have been detected in the environment,” he says.

It’s unclear if Aeromonas alone has this lower drug resistance threshold, or if other bacteria can also become resistant at a lower threshold. If so, that could complicate global efforts to prevent drug-resistant infections.

At 11:47 p.m. on July 25, 1978, a baby girl was born by cesarean section at the Royal Oldham Hospital in England. This part of her arrival was much like many other babies’ births: 10 fingers and 10 toes, 5 pounds, 12 ounces of screaming, perfect newborn. Her parents named her Louise. But this isn’t the most interesting part about Louise’s origins. For that, you have to go back to November 12, 1977, also near midnight. That’s when Louise Joy Brown was conceived in a petri dish.

Louise was the first baby born as a result of in vitro fertilization, or IVF, a procedure that unites sperm and egg outside of the body. Her birth was heralded around the world, with headlines declaring that the first test-tube baby had been born. The announcement was met with excitement from some, fear and hostility from others. But one thing was certain: This was truly the beginning of a new era in how babies are created.

To celebrate Louise’s 40th birthday, I took at look at IVF’s origins, its present form and its future. IVF’s story starts around 1890, when scientist Walter Heape transferred a fertilized egg from an Angora rabbit into a different breed, and saw that Angora bunnies resulted.
Scientists soon began to work on other animals before turning eventually to humans. A fascinating account of the early days, written by IVF pioneer Simon Fishel in the July issue of Fertility and Sterility, recounts some of the more lively — and shocking — aspects of the nascent field. For example, IVF researcher Robert Edwards, who won a 2010 Nobel Prize for his work, used to carry eggs between labs in Oldham and Cambridge in a container strapped to his body. And some of the early experiments involved inseminating the eggs with the researchers’ own sperm. There was a steep learning curve that led to many failures: More than 300 women had oocytes, or egg cells, removed without success before Louise was conceived.

Bu then things turned around. On November 9, Lesley Brown began to ovulate (naturally, since the researchers hadn’t had success using hormones to stimulate ovulation in many women). The next day, researchers saw that her left ovary contained a single follicle, the structure that holds an oocyte. Along with the surrounding fluid, that follicle was aspirated and carried by a nurse to another researcher and then finally to Edwards, who was waiting at a microscope. The egg was fertilized with sperm and allowed to mature into an 8-cell embryo. At midnight on the 12th, it was ready for the fateful transfer back to Lesley.

From there, the research took off, often with dicey funding and public outcry. Along with colleague Patrick Steptoe, Edwards and other pioneers opened the first private IVF clinic in 1980. Today, clinics exist worldwide. That brings us to more modern numbers. In 2016 in the United States, an estimated 76,930 babies were born via assisted reproductive technologies. The vast majority of those babies were born via IVF. Over the past decade, assisted reproductive technology birth rates have doubled over the past decade, the CDC estimates. Today, about 1.7 percent of all babies born in the United States each year are conceived via the technology. Worldwide, millions of babies have been born with IVF.

The method has been hugely successful in helping families who otherwise wouldn’t be able to have children. And overall, the procedure has a good safety record. A study of Israeli teenagers born via IVF, for instance, didn’t turn up any problems when the teens were compared with those conceived the old-fashioned way. The teenagers all had comparable mental health, physical health and brainpower, researchers reported in 2017 in Fertility and Sterility.
But that doesn’t mean the technology will stay in its current form forever. Evolving biological capabilities might one day lead to better genetic screenings of embryos before they are implanted. And genetic tweaks might one day be possible, given the rapid rise of gene editing technology. Already, scientists have repaired a gene related to a heart defect in human embryos.

Other improvements might come too, such as making it easier on women to produce eggs for extraction. Less extreme hormone regimens might one day become more standard. With advances in stem cell technology, eggs may no longer be needed at all. Scientists may one day be able to coax skin cells into gametes. Scientists have already turned mouse skin cells into eggs and combined them with sperm to produce pups.

As I mull over the past and present of IVF, I’m amazed at how much progress has been made, both in labs and in clinics, and I suspect that the most exciting advances are yet to come. I also think about all of these well-loved babies, born to families destined to treasure them for the masterpieces of biology that they are.

Meet the ionocyte. This newly discovered cell may be the star of future cystic fibrosis therapies. Researchers have found that the gene tied to the disease is very active in the cells, which line the air passages of the lungs.

While the cells are rare, making up only 1 to 2 percent of cells that line the airways, they seem to play an outsized role in keeping lungs clear. The identification of the ionocyte “provides key information for targeting treatments,” says medical geneticist Garry Cutting of Johns Hopkins School of Medicine in Baltimore, who was not involved in the research. Two teams, working independently, each describe the new cell online August 1 in Nature.
The ionocyte shares its name with similar cells found in fish gills and frog skin. This type of cell regulates fluid movement at surfaces — skin, gills, airways — where air and water meet. In people, special proteins that tunnel across cell membranes lining the airways allow chloride ions (half of what makes salt) to move into the airway. This causes water to move into the airway through a different channel to moisten mucus along the lining, which helps it remove bacteria and inhaled particles from the body.

The tunnel protein that allows chloride ions through is made by a gene called CFTR. In cystic fibrosis patients, that gene is flawed. Airways can’t regulate water movement properly and get clogged with thick mucus that traps bacteria and leads to persistent infections and lung damage. The genetic disease affects at least 70,000 people worldwide, according to the Cystic Fibrosis Foundation in Bethesda, Md.

Researchers had suspected CFTR was most active in ciliated cells — cells with brushlike projections that work along with the mucus in airways to move invaders out. But the new work found very little gene activity in those cells, compared with the ionocytes.

In experiments with laboratory samples of mouse cells from the airway lining, cell biologist Jayaraj Rajagopal of Massachusetts General Hospital in Boston and his colleagues found that the gene was very active in ionocytes: out of all the instructions for building the tunnels detected in the cells, 54 percent came from ionocytes. Aron Jaffe, a respiratory disease researcher at Novartis Institutes for Biomedical Research in Cambridge, Mass., and his colleagues reported that, in laboratory samples of human airways cells, ionocytes were the source of 60 percent of the activity of the tunnels.
The discovery of the new cells raises a lot of questions. Jaffe wonders where ionocytes are positioned in the lining of the airways, and how that placement supports the coordination of water movement and mucus secretion by other cells. “You can imagine the distribution [of ionocytes] is really important,” he says.

A question Rajagopal has: “How does a rare cell type do all of this work?” In fish and frogs, ionocytes are loaded with mitochondria, the so-called cellular energy factories, he notes. Maybe that will be true for human ionocytes, too, giving them lots of energy to do the lion’s share of regulating the movement of water.

Both researchers say the ionocyte’s discovery should lead to a better understanding of cystic fibrosis. “It will let us think about creative new ways to approach the disease,” Rajagopal says.

Google Glass may have failed as a high-tech fashion trend, but it’s showing promise as a tool to help children with autism better navigate social situations.

A new smartphone app that pairs with a Google Glass headset uses facial recognition software to give the wearer real-time updates on which emotions people are expressing. In a pilot trial, described online August 2 in npj Digital Medicine, 14 children with autism spectrum disorder used this program at home for an average of just over 10 weeks. After treatment, the kids showed improved social skills, including increased eye contact and ability to decode facial expressions.
After her son Alex, now 9, participated in the study, Donji Cullenbine described the Google Glass therapy as “remarkable.” She noticed within a few weeks that Alex, who was 7 years old at the time, was meeting her eyes more often — a behavior change that’s stuck since treatment ended, she says. And Alex enjoyed using the Google Glass app. Cullenbine recalls her son telling her excitedly, “Mommy, I can read minds.”
Unlike most children, who naturally learn to read facial expressions by interacting with family and friends, children with autism often have to hone these skills through behavioral therapy. That typically involves a therapist leading the child through structured activities, like exercises with flash cards that depict faces wearing different expressions. But therapists are so few and far between that a child diagnosed with autism can spend 18 months on a waiting list before starting treatment.
Dennis Wall, a biomedical data scientist specializing in pediatrics at Stanford University, and colleagues built the new Google Glass program to offer children with autism at-home, on-demand behavioral therapy. The headset’s camera records the faces of people in the child’s field of view and feeds that information to a smartphone app. The app, trained on hundreds of thousands of face photos, is designed to recognize eight core expressions: happiness, sadness, anger, disgust, surprise, fear, contempt and calm. When the app recognizes an expression of one of these feelings, it sends the information to the Google Glass wearer — either by naming the emotion through the headset speaker or by displaying an emoticon on a small screen in the corner of the right spectacle frame.

In the pilot trial, children ages 3 to 17 with autism used this Google Glass program around their families for at least three 20-minute sessions per week. Before and after treatment, parents completed questionnaires that rated their children’s social skills. On this Social Responsiveness Scale, scores below 60 fall within the “normal” range, whereas scores 60 to 65, 65 to 75, and above 75 indicate mild, moderate and severe autism, respectively. Over the course of treatment, the children’s average score dropped from 80.07 to 72.93.

Eleven of the 14 children also completed an emotion recognition exam at the start and end of treatment. In this test, an examiner acted out each of the eight core emotions five times, and the child guessed which emotion the examiner was expressing. Before therapy, kids got an average 28.45 out of 40 questions right; afterward, they averaged 38 correct responses.

While these results are encouraging, the study did not include a control group of children who didn’t receive the treatment. So it’s not entirely clear whether the Google Glass program was the only reason that children showed improved social skills over the course of treatment, says Ned Sahin, a neuroscientist at Brain Power, a company that develops wearable technology to help people with autism, in Boston. A randomized controlled trial, where children are randomly assigned to receive treatment or not, could provide further insight into the therapy’s effects, Sahin says.

Wall and his team are currently working on one such experiment with 74 children ages 6 to 12. If the Google Glass therapy performs well in future clinical trials and is cleared for widespread use, it could be a powerful learning aid for many children with autism — which affects an estimated 1 in 59 children in the United States, according to the U.S. Centers for Disease Control and Prevention.

Already, Cullenbine expects that Alex will have better relationships with people, “and that’s life changing.”

When researchers announced last year that they had edited human embryos to repair a damaged gene that can lead to heart failure, critics called the report into question.

Now new evidence confirms that the gene editing was successful, reproductive and developmental biologist Shoukhrat Mitalipov and colleagues report August 8 in Nature. “All of our conclusions were basically right,” Mitalipov, of Oregon Health & Science University in Portland, said during a news conference on August 6.
But authors of two critiques published in the same issue of Nature say they still aren’t convinced.

At issue is the way that the gene was repaired. Mitalipov and colleagues used the molecular scissors CRISPR/Cas9 to cut a faulty version of a gene called MYBPC3 in sperm (SN: 9/2/17, p. 6). People who inherit this version of the gene often develop heart failure. Cutting the gene allows cells to fix the problem by replacing erroneous instructions in the gene with correct information.

Researchers supplied the correct information in the form of small foreign pieces of DNA, but the embryos ignored that repair template. Instead, Mitalipov and colleagues say, embryos used a healthy version of the gene on the mother’s chromosome to fix the error. That action is called gene conversion.

Gene conversion typically happens when reproductive, or germline, cells swap DNA before making eggs and sperm. So it was completely unexpected to find that type of repair happening in embryos, says geneticist Paul Thomas of the South Australian Health & Medical Research Institute in Acton.
If human embryos do ignore foreign bits of DNA that could be a problem for fixing genetic diseases that result when both parents pass on damaged versions of a gene. In that scenario, there would be no healthy version of the gene to copy and paste.

But Thomas and colleagues propose that Mitalipov’s group may not have detected gene conversion at all. Instead, large chunks may have been cut out of the chromosome containing the faulty version of the gene and not replaced. That wouldn’t fix the defective gene, but could make it look like gene conversion had happened, fooling researchers into thinking they’d made a repair.

Mitalipov’s group used a technique called polymerase chain reaction, or PCR, to confirm that they had repaired the faulty copy of the gene. PCR essentially photocopied stretches of the repaired gene for analysis. The team found that only the mother’s version of the gene was in the edited embryos. That result led the researchers to conclude that gene conversion had copied the maternal version of the gene onto the father’s chromosome.

But because the researchers weren’t able to take a closer look at the gene, they can’t be sure it was gene conversion, Thomas says. Cutting out a portion of the father’s gene would leave only the mother’s version to be copied during PCR. That might give the impression that the father’s gene was converted to the maternal form, when that piece of DNA is missing from the father’s gene.

Such large DNA deletions were common in experiments with mice, Thomas and colleagues say in one critique. About 45 to 57 percent of mouse embryos tested were missing big chunks of genetic material. But Mitalipov and colleagues didn’t report finding any evidence that portions of DNA were deleted from the human embryos.

“I find that surprising,” Thomas says. He is skeptical that the data presented in the new report completely settle the problem.

Rock solid evidence of gene correction was missing from Mitalipov’s original report, agrees Maria Jasin, a developmental biologist at Memorial Sloan Kettering Cancer Center in New York City. The new report presents more convincing data, “but I’m still left with this doubt,” says Jasin, a coauthor on the other critique. “I wouldn’t rule out that gene conversion can happen” in such cases, she says. But in mouse experiments, that type of repair happens infrequently, she says, and there’s no reason to suppose that human embryos do it more frequently.

While there is optimism that scientists will be able to repair broken genes in human embryos, researchers aren’t there yet, Jasin and Thomas say.

Given all the things that might go wrong with gene editing, such as accidentally making mutations, there’s no room for uncertainty about whether the technique works. “You have to be 100 percent confident,” Thomas says, “and we’re a long, long way from being in that position.”