This Special Music Helped Preemie Babies’ Brains Develop
Move over, Baby Einstein: New research from Switzerland shows that listening to soothing music in the first weeks of life helps encourage brain development in preterm babies.
For the study, the scientists recruited a harpist and a new-age musician to compose three pieces of music.
The Lowdown
Children who are born prematurely, between 24 and 32 weeks of pregnancy, are far more likely to survive today than they used to be—but because their brains are less developed at birth, they're still at high risk for learning difficulties and emotional disorders later in life.
Researchers in Geneva thought that the unfamiliar and stressful noises in neonatal intensive care units might be partially responsible. After all, a hospital ward filled with alarms, other infants crying, and adults bustling in and out is far more disruptive than the quiet in-utero environment the babies are used to. They decided to test whether listening to pleasant music could have a positive, counterbalancing effect on the babies' brain development.
Led by Dr. Petra Hüppi at the University of Geneva, the scientists recruited Swiss harpist and new-age musician Andreas Vollenweider (who has collaborated with the likes of Carly Simon, Bryan Adams, and Bobby McFerrin). Vollenweider developed three pieces of music specifically for the NICU babies, which were played for them five times per week. Each track was used for specific purposes: To help the baby wake up; to stimulate a baby who was already awake; and to help the baby fall back asleep.
When they reached an age equivalent to a full-term baby, the infants underwent an MRI. The researchers focused on connections within the salience network, which determines how relevant information is, and then processes and acts on it—crucial components of healthy social behavior and emotional regulation. The neural networks of preemies who had listened to Vollenweider's pieces were stronger than preterm babies who had not received the intervention, and were instead much more similar to full-term babies.
Next Up
The first infants in the study are now 6 years old—the age when cognitive problems usually become diagnosable. Researchers plan to follow up with more cognitive and socio-emotional assessments, to determine whether the effects of the music intervention have lasted.
The first infants in the study are now 6 years old—the age when cognitive problems usually become diagnosable.
The scientists note in their paper that, while they saw strong results in the babies' primary auditory cortex and thalamus connections—suggesting that they had developed an ability to recognize and respond to familiar music—there was less reaction in the regions responsible for socioemotional processing. They hypothesize that more time spent listening to music during a NICU stay could improve those connections as well; but another study would be needed to know for sure.
Open Questions
Because this initial study had a fairly small sample size (only 20 preterm infants underwent the musical intervention, with another 19 studied as a control group), and they all listened to the same music for the same amount of time, it's still undetermined whether variations in the type and frequency of music would make a difference. Are Vollenweider's harps, bells, and punji the runaway favorite, or would other styles of music help, too? (Would "Baby Shark" help … or hurt?) There's also a chance that other types of repetitive sounds, like parents speaking or singing to their children, might have similar effects.
But the biggest question is still the one that the scientists plan to tackle next: Whether the intervention lasts as the children grow up. If it does, that's great news for any family with a preemie — and for the baby-sized headphone industry.
"There's a Bacteria For That"
"There's an app for that." Get ready for a cutting-edge twist on this common phrase. In the life sciences, researchers in the field of synthetic biology are engineering microbes to execute specific tasks, like diagnosing gut inflammation, purifying dirty water, and cleaning up oil spills. Here are five academic and commercial projects underway now that will make you want to add the term "designer bacteria" to your vocab.
1) Bacteria that can sense, diagnose and treat disorders of the gut.
Dr. Pamela Silver at Harvard Medical School has engineered non-pathenogenic strains of E. Coli bacteria, which she calls "living diagnostics and therapeutics," to accurately sense whether an animal has been exposed to antibiotics and whether inflammation is present in its intestines.
Imagine a "living FitBit" that could report on your gut health in real time.
So how does it work? "The bacteria have a genetic switch like a light switch," she explains, "and when they are exposed to an antibiotic or an inflammatory response, the light switch flips to on and the bacteria turn color." In a study that Silver and her colleagues published earlier this year, the bacteria in mouse guts turned blue when exposed to the chemical tetrathionate, which is produced during inflammation. Then, when the animal excreted waste, its feces were also blue. For safety reasons, the excreted bacteria can additionally be programmed to self-destruct so as not to contaminate the environment.
The implications for human health go way beyond a non-invasive alternative to colonoscopies. Imagine "a living FitBit," Silver says with a laugh – a probiotic your doctor could prescribe that could colonize your gut to report on your intestinal health and your diet—and even treat pathogens at the same time. Another potential application is to deploy this new tool in the skin as a living sensor. "Your skin has a defined population of bacteria and those could be engineered to sense a lot," she says, such as pathological changes and toxic environmental exposures.
But one big social question in this emerging research remains how open the public and regulators will be to genetically modified organisms as drugs. Silver says that acceptance will require "patient advocacy, education, and showing these actually work. We have shown in an animal that it can work. So far, in humans, it's unclear."
"Live biotherapeutic products" is a whole new category of drug.
2) Bacteria that can treat a rare metabolic disease.
The startup company Synlogic, based in Cambridge, Mass., has designed an experimental pill containing a strain of E. Coli bacteria that can soak up excess ammonia in a person's stomach, treating those who suffer from toxic elevated blood ammonia levels. This condition, called hyperammonemia, can occur in those with chronic liver disease or genetic urea cycle disorders. The pill is genetically engineered to convert ammonia into a beneficial amino acid instead.
Just a few weeks ago, the company announced positive data from its Phase 1 trial, in which the pill was tested on a group of 52 healthy volunteers for the first time. The study was randomized, double-blind and placebo-controlled, which means that neither the researchers nor the subjects knew who was getting the active pill vs. a sham one. This design is the gold standard in clinical research because it overcomes bias and produces objective results. So far, the pill appears to be safe and well-tolerated, and the company plans to continue the next phase of testing in 2018. Synlogic's treatment stands to be the first of this category of therapy—called "live biotherapeutic products"—that will be scrutinized by the FDA when the time comes for possible market approval.
3) Bacteria that can be sprayed on land to clean up an oil spill.
"This is science fiction, but it's become a lot less science fiction in the last couple of years," says Floyd E. Romesberg, a professor of chemistry whose lab at the Scripps Research Institute in California is on the forefront of synthetic biology.
"We have literally increased the biology that cells can write stories with."
His lab has added two new letters to the code of life. At the most fundamental level, all life on Earth, including human, animal, and bacteria, relies on the four "letters" or chemical building blocks of A, T, C, and G to store biological information inside a cell and then retrieve it in the form of proteins that perform essential tasks. For the first time in history, Romesberg and his team have now developed an unnatural base pair—an X and a Y—capable of storing increased information.
"We have literally increased the biology that cells can write stories with," he says. "With new letters, you can write new words, new sentences, and you can tell new stories, as opposed to taking the limited vocabulary you have and trying to rearrange it."
The implications of his research are immense; applications range from developing therapeutic proteins as drugs, to bestowing cells with new properties, such as oxidizing oil after a spill. He imagines a future scenario in which, for example, specially engineered bacteria are sprayed on a beach, eat the oil for three generations of their life—less than a day—and then die off, since they will be unable to replicate their own DNA. Afterwards, the beach is clean.
"What we are struggling with now is the first steps toward doing that – the cell relying on unnatural information to survive, rather than doing something new yet," he says, "but that's where we are headed."
4) Bacteria that can deliver cancer-killing drugs inside tumors.
Researcher Jeff Hasty at UCSD has engineered a strain of Salmonella bacteria to penetrate cancer tumors and deliver drugs that stop their growth. His approach is especially clever because it solves a major problem in cancer drug delivery: chemotherapy relies on blood vessels for transit, but blood vessels don't exist deep inside tumors. Using this fact to his advantage, Hasty and his team designed bacteria that can sneak drugs all the way into a tumor and then self-destruct, taking the tumor down in the process.
So far, the treatment in mice has been successful; their tumors stopped growing after they were given the bacteria, and along with the use of chemotherapy, their life expectancy increased by half.
Many questions remain in terms of applicability to tumors in human beings, but the notion of a bacterial therapy remains a promising clinical approach for treating cancer in the future.
Craft beer experts couldn't tell the difference between beer brewed with regular vs. recycled water.
5) Bacteria that can convert wastewater into drinkable water.
Boston-based company Cambrian Innovation has a patented product called the EcoVolt MINI that uses microbes to generate energy through contact with electrodes. The company has collaborated with breweries across the country, taking their waste water and converting it to clean water and clean energy. Through the company's bioelectrochemical system, microbes eat the contaminants in the wastewater, and as a byproduct they produce methane, which can be converted to heat and power; in some cases, the process generates enough energy to send some back to the brewery.
"The main goal of the system is to produce cleaner water; the energy is an added product," explains Claire Aviles, Cambrian's marketing and communications manager.
The wastewater treatment is so effective that the water can be made suitable for reuse. One brewery client, for example, recently experimented with using the recycled water to brew a beer at a festival in California. They used the same recipe for two beers—one with typical city water and one with recycled water from Cambrian's system—and offered a side-by-side taste test to consumers and craft beer experts alike.
"Most people couldn't tell which was which," Aviles says.
In fact, most of the tasters preferred the beer brewed with the recycled water.
Turns out bacteria aren't always dirty after all.
Kira Peikoff was the editor-in-chief of Leaps.org from 2017 to 2021. As a journalist, her work has appeared in The New York Times, Newsweek, Nautilus, Popular Mechanics, The New York Academy of Sciences, and other outlets. She is also the author of four suspense novels that explore controversial issues arising from scientific innovation: Living Proof, No Time to Die, Die Again Tomorrow, and Mother Knows Best. Peikoff holds a B.A. in Journalism from New York University and an M.S. in Bioethics from Columbia University. She lives in New Jersey with her husband and two young sons. Follow her on Twitter @KiraPeikoff.
The New Prospective Parenthood: When Does More Info Become Too Much?
Peggy Clark was 12 weeks pregnant when she went in for a nuchal translucency (NT) scan to see whether her unborn son had Down syndrome. The sonographic scan measures how much fluid has accumulated at the back of the baby's neck: the more fluid, the higher the likelihood of an abnormality. The technician said the baby was in such an odd position, the test couldn't be done. Clark, whose name has been changed to protect her privacy, was told to come back in a week and a half to see if the baby had moved.
"With the growing sophistication of prenatal tests, it seems that the more questions are answered, the more new ones arise."
"It was like the baby was saying, 'I don't want you to know,'" she recently recalled.
When they went back, they found the baby had a thickened neck. It's just one factor in identifying Down's, but it's a strong indication. At that point, she was 13 weeks and four days pregnant. She went to the doctor the next day for a blood test. It took another two weeks for the results, which again came back positive, though there was still a .3% margin of error. Clark said she knew she wanted to terminate the pregnancy if the baby had Down's, but she didn't want the guilt of knowing there was a small chance the tests were wrong. At that point, she was too late to do a Chorionic villus sampling (CVS), when chorionic villi cells are removed from the placenta and sequenced. And she was too early to do an amniocentesis, which isn't done until between 14 and 20 weeks of the pregnancy. So she says she had to sit and wait, calling those few weeks "brutal."
By the time they did the amnio, she was already nearly 18 weeks pregnant and was getting really big. When that test also came back positive, she made the anguished decision to end the pregnancy.
Now, three years after Clark's painful experience, a newer form of prenatal testing routinely gives would-be parents more information much earlier on, especially for women who are over 35. As soon as nine weeks into their pregnancies, women can have a simple blood test to determine if there are abnormalities in the DNA of chromosomes 21, which indicates Down syndrome, as well as in chromosomes 13 and 18. Using next-generation sequencing technologies, the test separates out and examines circulating fetal cells in the mother's blood, which eliminates the risks of drawing fluid directly from the fetus or placenta.
"Finding out your baby has Down syndrome at 11 or 12 weeks is much easier for parents to make any decision they may want to make, as opposed to 16 or 17 weeks," said Dr. Leena Nathan, an obstetrician-gynecologist in UCLA's healthcare system. "People are much more willing or able to perhaps make a decision to terminate the pregnancy."
But with the growing sophistication of prenatal tests, it seems that the more questions are answered, the more new ones arise--questions that previous generations have never had to face. And as genomic sequencing improves in its predictive accuracy at the earliest stages of life, the challenges only stand to increase. Imagine, for example, learning your child's lifetime risk of breast cancer when you are ten weeks pregnant. Would you terminate if you knew she had a 70 percent risk? What about 40 percent? Lots of hard questions. Few easy answers. Once the cost of whole genome sequencing drops low enough, probably within the next five to ten years according to experts, such comprehensive testing may become the new standard of care. Welcome to the future of prospective parenthood.
"In one way, it's a blessing to have this information. On the other hand, it's very difficult to deal with."
How Did We Get Here?
Prenatal testing is not new. In 1979, amniocentesis was used to detect whether certain inherited diseases had been passed on to the fetus. Through the 1980s, parents could be tested to see if they carried disease like Tay-Sachs, Sickle cell anemia, Cystic fibrosis and Duchenne muscular dystrophy. By the early 1990s, doctors could test for even more genetic diseases and the CVS test was beginning to become available.
A few years later, a technique called preimplantation genetic diagnosis (PGD) emerged, in which embryos created in a lab with sperm and harvested eggs would be allowed to grow for several days and then cells would be removed and tested to see if any carried genetic diseases. Those that weren't affected could be transferred back to the mother. Once in vitro fertilization (IVF) took off, so did genetic testing. The labs test the embryonic cells and get them back to the IVF facilities within 24 hours so that embryo selection can occur. In the case of IVF, genetic tests are done so early, parents don't even have to decide whether to terminate a pregnancy. Embryos with issues often aren't even used.
"It was a very expensive endeavor but exciting to see our ability to avoid disorders, especially for families that don't want to terminate a pregnancy," said Sara Katsanis, an expert in genetic testing who teaches at Duke University. "In one way, it's a blessing to have this information (about genetic disorders). On the other hand, it's very difficult to deal with. To make that decision about whether to terminate a pregnancy is very hard."
Just Because We Can, Does It Mean We Should?
Parents in the future may not only find out whether their child has a genetic disease but will be able to potentially fix the problem through a highly controversial process called gene editing. But because we can, does it mean we should? So far, genes have been edited in other species, but to date, the procedure has not been used on an unborn child for reproductive purposes apart from research.
"There's a lot of bioethics debate and convening of groups to try to figure out where genetic manipulation is going to be useful and necessary, and where it is going to need some restrictions," said Katsanis. She notes that it's very useful in areas like cancer research, so one wouldn't want to over-regulate it.
There are already some criteria as to which genes can be manipulated and which should be left alone, said Evan Snyder, professor and director of the Center for Stem Cells and Regenerative Medicine at Sanford Children's Health Research Center in La Jolla, Calif. He noted that genes don't stand in isolation. That is, if you modify one that causes disease, will it disrupt others? There may be unintended consequences, he added.
"As the technical dilemmas get fixed, some of the ethical dilemmas get fixed. But others arise. It's kind of like ethical whack-a-mole."
But gene editing of embryos may take years to become an acceptable practice, if ever, so a more pressing issue concerns the rationale behind embryo selection during IVF. Prospective parents can end up with anywhere from zero to thirty embryos from the procedure and must choose only one (rarely two) to implant. Since embryos are routinely tested now for certain diseases, and selected or discarded based on that information, should it be ethical—and legal—to make selections based on particular traits, too? To date so far, parents can select for gender, but no other traits. Whether trait selection becomes routine is a matter of time and business opportunity, Katsanis said. So far, the old-fashioned way of making a baby combined with the luck of the draw seems to be the preferred method for the marketplace. But that could change.
"You can easily see a family deciding not to implant a lethal gene for Tay-Sachs or Duchene or Cystic fibrosis. It becomes more ethically challenging when you make a decision to implant girls and not any of the boys," said Snyder. "And then as we get better and better, we can start assigning genes to certain skills and this starts to become science fiction."
Once a pregnancy occurs, prospective parents of all stripes will face decisions about whether to keep the fetus based on the information that increasingly robust prenatal testing will provide. What influences their decision is the crux of another ethical knot, said Snyder. A clear-cut rationale would be if the baby is anencephalic, or it has no brain. A harder one might be, "It's a girl, and I wanted a boy," or "The child will only be 5' 2" tall in adulthood."
"Those are the extremes, but the ultimate question is: At what point is it a legitimate response to say, I don't want to keep this baby?'" he said. Of course, people's responses will vary, so the bigger conundrum for society is: Where should a line be drawn—if at all? Should a woman who is within the legal scope of termination (up to around 24 weeks, though it varies by state) be allowed to terminate her pregnancy for any reason whatsoever? Or must she have a so-called "legitimate" rationale?
"As the technical dilemmas get fixed, some of the ethical dilemmas get fixed. But others arise. It's kind of like ethical whack-a-mole," Snyder said.
One of the newer moles to emerge is, if one can fix a damaged gene, for how long should it be fixed? In one child? In the family's whole line, going forward? If the editing is done in the embryo right after the egg and sperm have united and before the cells begin dividing and becoming specialized, when, say, there are just two or four cells, it will likely affect that child's entire reproductive system and thus all of that child's progeny going forward.
"This notion of changing things forever is a major debate," Snyder said. "It literally gets into metaphysics. On the one hand, you could say, well, wouldn't it be great to get rid of Cystic fibrosis forever? What bad could come of getting rid of a mutant gene forever? But we're not smart enough to know what other things the gene might be doing, and how disrupting one thing could affect this network."
As with any tool, there are risks and benefits, said Michael Kalichman, Director of the Research Ethics Program at the University of California San Diego. While we can envision diverse benefits from a better understanding of human biology and medicine, it is clear that our species can also misuse those tools – from stigmatizing children with certain genetic traits as being "less than," aka dystopian sci-fi movies like Gattaca, to judging parents for making sure their child carries or doesn't carry a particular trait.
"The best chance to ensure that the benefits of this technology will outweigh the risks," Kalichman said, "is for all stakeholders to engage in thoughtful conversations, strive for understanding of diverse viewpoints, and then develop strategies and policies to protect against those uses that are considered to be problematic."