Human Sciences – Bring Researcher in the Center

Posted on July 4, 2014 by Leave a comment |

The Brave New World of Three-Parent I.V.F.

In August 1996, at St. Barnabas Medical Center in Livingston, N.J., a 39-year-old mechanical engineer from Pittsburgh named Maureen Ott became pregnant. Ott had been trying for almost seven years to conceive a child through in vitro fertilization. Unwilling to give up, she submitted to an experimental procedure in which doctors extracted her eggs, slid a needle through their shiny coat and injected not only her husband’s sperm but also a small amount of cytoplasm from another woman’s egg. When the embryo was implanted in Ott’s womb, she became the first woman on record to be successfully impregnated using this procedure, which some say is the root of an exciting medical advance and others say is the beginning of the end of the human species.

The fresh cytoplasm that entered Ott’s eggs (researchers thought it might help promote proper fertilization and development) contained mitochondria: bean-shaped organelles that power our cells like batteries. But mitochondria also contain their own DNA, which meant that her child could possess the genetic material of three people. In fact, the 37 genes in mitochondrial DNA pass directly from a woman’s egg into every cell of her offspring, including his or her germ cells, the sperm or eggs that eventually produce the next generation — so if Ott had a girl and the donor mitochondria injected into Ott’s egg made it into the eggs of her daughter, they could be passed along to her children. This is known as crossing the germ line, something that scientists generally agree is a risky proposition.

Ott, who is Catholic, remembers weighing whether altering the makeup of her descendants in this way was O.K. “Being a person who’s been involved in science my whole life, the way I looked at it is: God gives us doctors to help us, and they help us with things like infertility,” she told me recently. As far as anyone knows, mitochondrial DNA (mtDNA) governs only basic cellular functions; Ott understood that her and her husband’s nuclear DNA would determine their child’s characteristics — height, eye color, intelligence and so on. “If I was doing something like, say, I only wanted a blond-haired girl, I would feel that was unethical,” she said. “But what I was trying to do was use whatever medical procedures were available to me to get pregnant, and I didn’t think that was unethical.” In May 1997, she gave birth to a healthy baby girl.

Two months later, her doctors published her case in the journal Lancet; soon, at least seven other U.S. clinics were doing the injection. Because the amount of donor mitochondria added to Ott’s egg was small, it was unclear how much third-party DNA would be present in the cells of her daughter. Ott says her doctors ran tests and did not find any, but it has been found in two other children born from the procedure. Although I.V.F. drugs and devices are regulated by the Food and Drug Administration, I.V.F. procedures (like all medical procedures) are generally not. But what media outlets came to call “three-parent babies” compelled the agency to take action. In 2001, the F.D.A. informed I.V.F. clinics that using a third person’s cytoplasm — and the mtDNA therein — would require an Investigational New Drug application.

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Posted on July 2, 2014 by Leave a comment |

How to Teach Old Ears New Tricks

“Hi! I’m Gabe. What’s your name?”

“Seung-heon. Nice to meet you, Gabe.”

“Seung-heon.”This is bad.

“Sung-hon?”

“Seung-heon. It’s okay—just call me Jerry. Everyone does.”

I hate it when this happens. I have every intention of learning this person’s name, and my brain is simply not cooperating. I can’t seem to hear what he’s saying, I can’t pronounce it correctly, and there’s no way I’m going to remember it for more than five seconds. Thankfully, these Seung-heonexperiences do not occur frequently; in most parts of the English-speaking world, we encounter far more Johns, Susans and Franks than Seung-heons. Generally, we can go about our usual social interactions without much trouble.

When we decide to do something rash like learn a foreign language, however, we run into difficulties. Nearly every new word is another Seung-heon. Our brain struggles to categorize the new sounds in each word—was it Seung, Seong or Sung? —and without the ability to do so accurately, the words do not stick in memory. That aural roadblock is one of the reasons that learning a language as an adult can be so challenging. Fortunately, researchers are starting to find ways to overcome this hurdle. If we train our ears for a few hours before diving into vocabulary and phrases, learning a language can become easier than we ever imagined.

Why We Can’t Learn Like Kids
Most of us English speakers can’t tell the difference between Seung, Seong and Sungnow, but back when we were babies we could. A large body of work shows that babies possess a remarkable ability to distinguish all sounds in all languages. But between six and 12 months of age, they begin homing in on their native language’s sounds. They become experts in their own language, and as a consequence they lose their facility with the unfamiliar sounds of foreign languages. As it turns out, it’s challenging to regain that ability.

Some of the best data on this phenomenon come from studies of Japanese adults learning to hear the difference between r and l. Why the Japanese? For one, because the r-versus-l problem is notorious; Japanese speakers tend to do little better than chance when attempting to tell their rocks from their locks. Second, they know they have this difficulty, and many will happily volunteer to come into a research laboratory—whereas English speakers do not care much about learning the difference between Hindi’s four nearly identical-sounding d’s.

When you were a baby, you learned to tell rocks from locks by listening to lots of auditory input. You heard about rakes and lakes, fires and files, and your little brain began figuring out that certain sounds fit into the r-like group and that other sounds fit into the l-like group. Unfortunately, adults do not learn in the same way. In one robust study from 2002, researchers led by psychologist James L. McClelland, then at Carnegie Mellon University, sat Japanese adults down in front of a computer with headphones, played a recording of rock or lock at random, and asked them to press the R or L key on their keyboards accordingly. As expected, they performed terribly, only slightly better than chance. After continuing the test for an hour, straining to hear any hint of the difference between r and l, they still did not improve. Auditory input might work for babies, but it simply does not for adults.

The researchers then tried something new. Same study, same dismal test scores, different Japanese adults. This time, in the training phase of the experiment, researchers gave their test subjects immediate feedback. Every time a subject pressed the R or L button on their keyboard, they got a green check mark or a red X on their screen, indicating whether they were right or wrong. Suddenly, everyone began to learn. Within an hour of testing, subjects were reaching 80 percent accuracy at identifying r and l, even in unfamiliar words. In a similar study in 1999, subjects even began spontaneously pronouncing the two sounds substantially better.

Many studies have subsequently confirmed that feedback is an essential ingredient in training our brain to hear new sounds, and when we can hear new sounds, we naturally start to produce them more accurately. Granted, some sounds may still cause difficulties—just because you can discern a Czech word such as zmrzl doesn’t mean that your mouth will cooperate without practice—but overall, a few hours of this type of ear training is a tremendously effective tool for improving listening comprehension, memorization and pronunciation. Yet most language-learning programs dive right into conversation or vocabulary, expecting students to pick up these tough foreign sounds on the fly.

Pushing beyond the Plateau
The disconnect between research and real-world language training does not end there. Studies that train their students with a small amount of input—just a few words uttered by a single speaker, as you often find in a classroom or a language-study book on tape—fail to produce comparable results in real-world tests where subjects encounter many different words, speakers and dialects. It turns out that the more voices and the more words tested in the lab, the better the results outside of the lab. In a study published in 2013, for example, linguist Melissa M. Baese-Berk, then at Michigan State University, and her colleagues showed that an hour of training over two days on five different varieties of accented English improved understanding of all types of accented English, even totally novel accents. These findings gel with the research about learning foreign sounds—in general, listening to a broad array of speakers will train your brain faster and let you more reliably transfer that knowledge to the real world.

Study after study—including Spanish, Greek and German speakers learning English, Greek speakers learning Hindi, and English speakers learning Mandarin—all confirm that this type of training produces significant changes in the brain’s ability to process foreign sounds. And as scientists learn more, they are discovering ways to produce better results. In a 2011 study at Carnegie Mellon, researchers found that people who trained through video games—where they are not explicitly aware of what they are learning—improved more in much less time than when they tried explicit training. Some people might even hone their speech perception skills by training other cognitive brain functions first. In a pilot study not yet published, researchers led by psychologist Erin M. Ingvalson of NorthwesternUniversity found that giving elderly adults exercises to boost working memory and attention span helped them better understand speech sounds in noisy environments. Ingvalson believes that with more research, the same technique may also help foreign-language learners.

As science reveals how the adult brain adapts to foreign sounds, you can start to re-create the successful research results at home. Many language textbooks begin with a list of hard-to-hear words—the rocks and locks you can expect to encounter along the way to fluency. With a handful of recordings of those words (freely accessible through Web sites such as Rhinospike.com and Forvo.com) and with testing software such as Anki (ankisrs.net), you can build powerful ear-training tools for yourself. These are tools that, after just a few hours of use, will make foreign words easier to hear and easier to remember, and they may give you the edge you need to finally learn the languages you’ve always wanted to learn.

Posted on June 30, 2014 by Leave a comment |

Noninvasive brain control: New light-sensitive protein enables simpler, more powerful optogenetics

Optogenetics, a technology that allows scientists to control brain activity by shining light on neurons, relies on light-sensitive proteins that can suppress or stimulate electrical signals within cells. This technique requires a light source to be implanted in the brain, where it can reach the cells to be controlled.

MIT engineers have now developed the first light-sensitive molecule that enables neurons to be silenced noninvasively, using a light source outside the skull. This makes it possible to do long-term studies without an implanted light source. The protein, known as Jaws, also allows a larger volume of tissue to be influenced at once.

This noninvasive approach could pave the way to using optogenetics in human patients to treat epilepsy and other neurological disorders, the researchers say, although much more testing and development is needed. Led by Ed Boyden, an associate professor of biological engineering and brain and cognitive sciences at MIT, the researchers described the protein in the June 29 issue of Nature Neuroscience.

Optogenetics, a technique developed over the past 15 years, has become a common laboratory tool for shutting off or stimulating specific types of neurons in the brain, allowing neuroscientists to learn much more about their functions.

The neurons to be studied must be genetically engineered to produce light-sensitive proteins known as opsins, which are channels or pumps that influence electrical activity by controlling the flow of ions in or out of cells. Researchers then insert a light source, such as an optical fiber, into the brain to control the selected neurons.

Such implants can be difficult to insert, however, and can be incompatible with many kinds of experiments, such as studies of development, during which the brain changes size, or of neurodegenerative disorders, during which the implant can interact with brain physiology. In addition, it is difficult to perform long-term studies of chronic diseases with these implants.

Mining nature’s diversity

To find a better alternative, Boyden, graduate student Amy Chuong, and colleagues turned to the natural world. Many microbes and other organisms use opsins to detect light and react to their environment. Most of the natural opsins now used for optogenetics respond best to blue or green light.

Boyden’s team had previously identified two light-sensitive chloride ion pumps that respond to red light, which can penetrate deeper into living tissue. However, these molecules, found in the bacteria Haloarcula marismortui and Haloarcula vallismortis, did not induce a strong enough photocurrent — an electric current in response to light — to be useful in controlling neuron activity.

Chuong set out to improve the photocurrent by looking for relatives of these proteins and testing their electrical activity. She then engineered one of these relatives by making many different mutants. The result of this screen, Jaws, retained its red-light sensitivity but had a much stronger photocurrent — enough to shut down neural activity.

“This exemplifies how the genomic diversity of the natural world can yield powerful reagents that can be of use in biology and neuroscience,” says Boyden, who is a member of MIT’s Media Lab and the McGovern Institute for Brain Research.

Using this opsin, the researchers were able to shut down neuronal activity in the mouse brain with a light source outside the animal’s head. The suppression occurred as deep as 3 millimeters in the brain, and was just as effective as that of existing silencers that rely on other colors of light delivered via conventional invasive illumination.

A key advantage to this opsin is that it could enable optogenetic studies of animals with larger brains, says Garret Stuber, an assistant professor of psychiatry and cell biology and physiology at the University of North Carolina at Chapel Hill.

“In animals with larger brains, people have had difficulty getting behavior effects with optogenetics, and one possible reason is that not enough of the tissue is being inhibited,” he says. “This could potentially alleviate that.”

Restoring vision

Working with researchers at the Friedrich Miescher Institute for Biomedical Research in Switzerland, the MIT team also tested Jaws’s ability to restore the light sensitivity of retinal cells called cones. In people with a disease called retinitis pigmentosa, cones slowly atrophy, eventually causing blindness.

Friedrich Miescher Institute scientists Botond Roska and Volker Busskamp have previously shown that some vision can be restored in mice by engineering those cone cells to express light-sensitive proteins. In the new paper, Roska and Busskamp tested the Jaws protein in the mouse retina and found that it more closely resembled the eye’s natural opsins and offered a greater range of light sensitivity, making it potentially more useful for treating retinitis pigmentosa.

This type of noninvasive approach to optogenetics could also represent a step toward developing optogenetic treatments for diseases such as epilepsy, which could be controlled by shutting off misfiring neurons that cause seizures, Boyden says. “Since these molecules come from species other than humans, many studies must be done to evaluate their safety and efficacy in the context of treatment,” he says.

Boyden’s lab is working with many other research groups to further test the Jaws opsin for other applications. The team is also seeking new light-sensitive proteins and is working on high-throughput screening approaches that could speed up the development of such proteins.

The research at MIT was funded by Jerry and Marge Burnett, the Defense Advanced Research Projects Agency, the Human Frontiers Science Program, the IET A. F. Harvey Prize, the Janet and Sheldon Razin ’59 Fellowship of the MIT McGovern Institute, the New York Stem Cell Foundation-Robertson Investigator Award, the National Institutes of Health, the National Science Foundation, and the Wallace H. Coulter Foundation.