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Dying Organs Restored to Life in Novel Experiments

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When Georgia Bowen was born by emergency cesarean on May 18, she took a breath, threw her arms in the air, cried twice, and went into cardiac arrest.

The baby had had a heart attack, most likely while she was still in the womb. Her heart was profoundly damaged; a large portion of the muscle was dead, or nearly so, leading to the cardiac arrest.

Doctors kept her alive with a cumbersome machine that did the work of her heart and lungs. The physicians moved her from Massachusetts General Hospital, where she was born, to Boston Children’s Hospital and decided to try an experimental procedure that had never before been attempted in a human being following a heart attack.

They would take a billion mitochondria — the energy factories found in every cell in the body — from a small plug of Georgia’s healthy muscle and infuse them into the injured muscle of her heart.

Mitochondria are tiny organelles that fuel the operation of the cell, and they are among the first parts of the cell to die when it is deprived of oxygen-rich blood. Once they are lost, the cell itself dies.

But a series of experiments has found that fresh mitochondria can revive flagging cells and enable them to quickly recover.

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In animal studies at Boston Children’s Hospital and elsewhere, mitochondrial transplants revived heart muscle that was stunned from a heart attack but not yet dead, and revived injured lungs and kidneys.

Infusions of mitochondria also prolonged the time organs could be stored before they were used for transplants, and even ameliorated brain damage that occurred soon after a stroke.

In the only human tests, mitochondrial transplants appear to revive and restore heart muscle in infants that was injured in operations to repair congenital heart defects.

For Georgia, though, the transplant was a long shot — a heart attack is different from a temporary loss of blood during an operation, and the prognosis is stark. There is only a short time between the onset of a heart attack and the development of scar tissue where once there were living muscle cells.

The problem was that no one knew when the baby’s heart attack had occurred. Still, said Dr. Sitaram Emani, a pediatric heart surgeon who administered the transplant, there was little risk to the infant and a chance, though slim, that some cells affected by her heart attack might still be salvageable.

“They gave her a fighting chance,” said the infant’s mother, Kate Bowen, 36, of Duxbury, Mass.

The idea for mitochondrial transplants was born of serendipity, desperation and the lucky meeting of two researchers at two Harvard teaching hospitals — Dr. Emani at Boston Children’s and James McCully at Beth Israel Deaconess Medical Center.

Dr. Emani is a pediatric surgeon. Dr. McCully is a scientist who studies adult hearts. Both were wrestling with the same problem: how to fix hearts that had been deprived of oxygen during surgery or a heart attack.

“If you cut off oxygen for a long time, the heart barely beats,” Dr. McCully said. The cells may survive, but they may never fully recover.

While preparing to give a talk to surgeons, Dr. McCully created electron micrographs of damaged cells. The images turned out to be revelatory: The mitochondria in the damaged heart cells were abnormally small and translucent, instead of a healthy black.

The mitochondria were damaged — and nothing Dr. McCully tried revived them. One day, he decided simply to pull some mitochondria from healthy cells and inject them into the injured cells.

Working with pigs, he took a plug of abdominal muscle the size of a pencil eraser, whirled it in a blender to break the cells apart, added some enzymes to dissolve cell proteins, and spun the mix in a centrifuge to isolate the mitochondria.

He recovered between 10 billion and 30 billion mitochondria, and injected one billion directly into the injured heart cells. To his surprise, the mitochondria moved like magnets to the proper places in the cells and began supplying energy. The pig hearts recovered.

Meanwhile, Dr. Emani was struggling with the same heart injuries in his work with babies.

Many of his patients are newborns who need surgery to fix life-threatening heart defects. Sometimes during or after such an operation, a tiny blood vessel gets kinked or blocked.

The heart still functions, but the cells that were deprived of oxygen beat slowly and feebly.

He can hook the baby up to a machine like the one that kept Georgia Bowen alive, an extracorporeal membrane oxygenator, or Ecmo. But that is a stopgap measure that can work for only two weeks. Half of the babies with coronary artery problems who end up on an Ecmo machine die because their hearts cannot recover.

But one day Dr. Emani was told of Dr. McCully’s work, and the two researchers met. “It was almost an ‘aha’ moment,” Dr. Emani said.

Dr. McCully moved to Boston Children’s, and he and Dr. Emani prepared to see if the new technique might help tiny babies who were the sickest of the sick — those surviving on Ecmo.

It was not long before they had their first patient.

Early one Saturday morning in March 2015, the hospital got a call from a hospital in Maine. Doctors there wanted to transfer to Boston Children’s a newborn baby boy whose heart had been deprived of oxygen during surgery to fix a congenital defect.

The baby was on an Ecmo but his heart had not recovered.

“We turned the intensive care unit into an operating room,” Dr. Emani said.

He snipped a tiny piece of muscle from the baby’s abdomen. Dr. McCully grabbed it and raced down the hall.

Twenty minutes later, he was back with a test tube of the precious mitochondria. Dr. Emani used an echocardiogram to determine where to inject them.

“The spot that is weakest is where we want to go,” he said. “It is important to give as much of a boost as you can.”

He injected a billion mitochondria, in about a quarter of a teaspoon of fluid.

Within two days, the baby had a normal heart, strong and beating quickly. “It was amazing,” Dr. Emani said.

The scientists have now treated 11 babies with mitochondria, and all but one were able to come off Ecmo, Dr. Emani said. Still, three of them ultimately died, which Dr. Emani attributes to a delay in treatment and other causes.

Two died because their hearts were still so damaged, and one died of an infection. All of the more recent patients survived and are doing well.

In comparison, the death rate among a similar group of babies that did not get mitochondrial transplants was 65 percent. And none of the untreated babies recovered any of their heart function — more than a third of the survivors ended up on heart transplant lists.

More recently, Dr. Emani and his colleagues have discovered that they can infuse mitochondria into a blood vessel feeding the heart, instead of directly into the damaged muscle. Somehow the organelles will gravitate almost magically to the injured cells that need them and take up residence.

He and his colleagues are persuaded that these transplants work, but acknowledge that it would take a randomized trial to prove it.

The main problem is a scarcity of patients. Even if every pediatric center in the United States participated, along with every infant with injured heart muscle, it still would be hard to enroll enough participants in the trial.

But what about adult heart patients? Researchers are hoping that mitochondrial transplants also can repair heart muscle damaged during heart attacks in adults. And finding enough of those patients should not be an issue, said Dr. Peter Smith, chief of cardiothoracic surgery at Duke University.

Already researchers are planning such a trial. The plan is to infuse mitochondria or a placebo solution into the coronary arteries of people having bypass surgery or — an even more dire situation for the heart — having both bypass and valve surgery.

The patients would be those whose hearts are so damaged that it would be difficult to wean them from heart-lung machines after surgery. For these desperate patients, mitochondrial transplants “are a really intriguing option,” Dr. Smith said.

“The likelihood is very high” that the study will begin next year, said Annetine Gelijns, a biostatistician at Mount Sinai Medical Center in New York.

For Georgia Bowen, the procedure came too late: The portion of her heart muscle affected by the heart attack had died. Her doctors implanted a device that takes over the heart’s pumping, and hope her heart will recover enough for them to remove the device.

But, to be safe, they put her on a list for a heart transplant. She seems to be improving, though — she is breathing on her own and can drink breast milk through a tube. Her heart is showing signs of healing.

“Georgia is a miracle who continues to fight daily and persevere through the obstacles she is dealt,” Ms. Bowen said.

“In our hearts, we know she will pull through this and come home.”

Correction:

Because of an editing error, a previous version of this article referred incorrectly to the source of the mitochondria infused into Georgia Bowen. They were taken from neck muscle, not abdominal muscle.

Gina Kolata writes about science and medicine. She has twice been a Pulitzer Prize finalist and is the author of six books, including “Mercies in Disguise: A Story of Hope, a Family's Genetic Destiny, and The Science That Saved Them.” @ginakolata Facebook

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kazriko
8 hours ago
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I believe there was some sci-fi stories about this that I read at one point. In that one, they replaced mitochondria of dead cells with a nuclear powered alternative organelle... Of course, they created glowy-eyed zombies that didn't need to breathe or eat that way.
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satadru
18 hours ago
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Wait, what?
New York, NY
mareino
12 hours ago
midichlorians
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Making Amazon Alexa respond to sign language using AI

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Using a JavaScript machine learning package called TensorFlow.js, Abhishek Singh built a program that learned how to translate sign language into verbal speech that an Amazon Alexa can understand. “If voice is the future of computing,” he signs, “what about those who cannot [hear and speak]?”

See also how AirPods + the new Live Listen feature “could revolutionize what it means to be hard of hearing”.

Tags: Abhishek Singh   Alexa   American Sign Language   artificial intelligence   audio   video
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kazriko
2 days ago
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Useful, both for my son who is deaf and for me, who knows a little sign language. But, I still don't want one of these things in my house.
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satadru
2 days ago
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😍. Seriously love this. Make this work with cameras in a room to control lights now please.
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These cloven toe pumps will make you look twice

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These puddy-colored pumps by Maison Margiela ($825) are described as "cloven toe." I might be 12, but wouldn't a better description be "camel toe"? A similarly racy shoe is available in red for $1080.

Thanks, Caroline B.!

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satadru
2 days ago
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That's one way to do toe cleavage...
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fxer
1 day ago
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ships of the desert
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Baby peacock shows off its tiny feathers for the first time

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Did you know a baby peacock is called a peachick? I didn't until I started writing this post up. I'm not even sure I had ever even seen a baby peacock, er peachick, before in my life. This peachick's name is Drew and he was rescued by the folks at Hairy Farmpit Girls in White Oak, Georgia. Last week, they captured him strutting around with his new big-bird feathers for the first time and it's really, really cute.

News4Jax reports:

"Drew was thrown in a garbage can out in Douglas, Georgia," Jennifer Evitts, owner of Hairy Farmpit Girls... "Someone saw what happened, grabbed him and then reached out to us to see if we would take him as she didn't know what to do with him."

...In addition to providing a safe haven for abused or neglected animals, the farm sells a range of goat milk-based products, from soap to lotion to lip balm, to support their cause.

https://www.instagram.com/p/Bk41xeMg50U/

(reddit)

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satadru
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Black man asked to leave his own pool by officer in viral video | TheHill

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satadru
4 days ago
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Swimming Pools and Segregation: A Long History

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The latest police incident caught on video captures a police officer outside a community pool who appears to be waving his gun at young partygoers who approached him as he tried to subdue and eventually hold down a teenage girl. She was wearing a bikini because she was at a pool party.

The party was held at the community pool in the Craig Ranch North subdivision, which is predominately white although McKinney, Texas is racially diverse. A group of African American teens heard about the party on social media. Not long after they arrived, allegedly a nearby white resident, began to harass the teenagers and one woman told them to “go back to Section 8 housing.” In a statement, the Police Department said officers arrived at the pool responding to a call about a “disturbance involving multiple juveniles at the location, who do not live in the area or have permission to be there, refusing to leave.” Several adults at the pool reportedly placed calls to the police.

After the incident, Eric Casebolt, the police officer, was placed on administrative leave and resigned a few days later. The video and story went viral. The significance and symbolism of it not only resonated because of the larger context of policing and race relations, but also because it revolved around a pool and Black and white people swimming together in that pool. It is a teachable moment.

Public swimming, race and segregation have a long and difficult history in this country, dating back to the early 20th century. Between 1920 and 1940, swimming as a pastime became increasingly popular and the number of public pools being built skyrocketed. By the 1960s, American use of public swimming pools declined dramatically. According to Jeff Wiltse, author of Contested Waters: A Social History of Swimming Pools in America, this decline was the direct result of desegregation.  Although some white people were comfortable with the desegregation of certain public domains, it seemed the majority of them—both from the North and South—shared the belief that swimming pools should be exempt from racial integration.

Swimming pools are unique in that they do not just require swimmers to share a space—rather, swimmers must share an intimate space. In addition to concerns of “contamination,” whites had a deep and widespread fear of interracial romance and dating. Despite laws against segregation, African Americans were often met with angry and sometimes violent crowds of white people when trying to use a public pool. Although these crowds had some initial success in deterring blacks from swimming, eventually integration laws were more strictly enforced and whites had to go elsewhere if they wanted to avoid swimming with African Americans. With this dramatic decrease in swimmers, many public pools closed and white Americans joined private pool clubs where the government did not yet enforce integration. However, even in 1973, when a court order mandated an end to racial exclusion at private clubs, white Americans continued to avoid swimming with blacks by building and solely using residential swimming pools.

Even though the United States has comprehensive civil rights legislation which deems segregation illegal, overt and implicit bias continues to make its way into our schools, voting places, residences and other public and private spaces.  Laws are critical but they are not enough to fundamentally impact the hearts and minds of our citizens.

For educators, families and others who interact with children and youth, you can:

  • Talk with young people about the history of racism, segregation and the struggle for equal rights, using the Civil Rights Movement as an example of how activism can bring about change through legislative means.  Talk with them about the civil rights issues today and what can be done to reverse those injustices.
  • Teach and talk about the ways that implicit bias continues to permeate our institutions, segregating people along racial lines and creating advantages for some and discrimination for others through policing and the criminal justice system, our schools, voting rights and more.
  • Find real opportunities for young people of different racial and ethnic groups to work, study and play together.  Research shows that when people of different racial/ethnic groups interact with each other regularly, stereotyping and prejudice are diminished. Similarly, exposing students to accurate information about other groups allows them to learn about similarities and differences and they are less likely to take on biased attitudes and beliefs. Therefore, it is important to include different people and perspectives in your classroom curriculum and expose children and teens to different kinds of people through books and other media.
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satadru
4 days ago
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A reminder that residential swimming pools arose in popularity due to the white fear of miscegenation caused by mixed-race pools.
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acdha
3 days ago
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