Pentagon Plan to Regrow Limbs: Phase One, Complete
- Danger Room
- By Noah Shachtman
- March 25, 2009
The Defense Advanced Research Projects Agency (DARPA) has just given Massachusetts' Worcester Polytechnic Institute (WPI) a $570,000, one-year contract to get a mammal, preferably a human, to regenerate a large body part such as a finger or even a limb.
That's Phase
II of DARPA's "Restorative Injury Repair"
project, which according to the DARPA Web page
"will culminate in the restoration of a
functional multi-tissue structure in a mammal."
WPI's CellThera for-profit unit has already achieved Phase I, which according to the school's press release "succeeded in reprogramming mouse and human skin cells to act more like stem cells, able to form the early structures needed to begin the process of re-growing lost tissues."
"The goal is to genuinely replace a muscle that's lost," WPI bioengineering researcher Raymond Page told Wired News. "I appreciate that's a very aggressive goal."
Some salamanders can regrow lost limbs, and some lizards lost tails. But humans can generally regrow only their livers, and have to have at least one-quarter of the previous one still intact for it to happen.
_____________________________
The first phase of the Pentagon’s plan to regrow soldiers’ limbs is complete; scientists managed to turn human skin into the equivalent of a blastema — a mass of undifferentiated cells that can develop into new body parts. Now, researchers are on to phase two: turning that cellular glop into a square inch of honest-to-goodness muscle tissue.
Cellthera
Inc. and the Worcester
Polytechnic Institute (WPI)
just got a
one-year, $570,000 grant
from Darpa, the
Pentagon’s blue-sky
research arm, to grow
the new tissues. "The
goal is to genuinely
replace a muscle that’s
lost," biotechnology
professor
Raymond Page
tells Danger Room. "I
appreciate that’s a very
aggressive goal." And
it’s only one part in a
larger, even more
ambitious Darpa program,
Restorative Injury
Repair, that
aims to "fully restore
the function of complex
tissue (muscle, nerves,
skin, etc.)
after traumatic injury
on the battlefield."
Muscles are, of course, famous for their ability to regenerate; they’re broken down and rebuilt with every gym workout. But when too much of a muscle is lost — either from injury or illness — "instead of the regenerative response, you get scarring," Page says. He’s hoping to get a different result, by carefully growing fresh muscle, outside the body.
Step one will be trying to get those undifferentiated cells to turn into something like muscle cells. That means making sure the cells have myosin and actin — two proteins that are key to forming the cellular cytoskeleton, and to building muscle filaments. Then, Page and his team will try to get those cells to form around a scaffolding of tiny threads, made of biomaterial. Exactly what will be in thread, Page isn’t quite sure — maybe collagens, maybe fibrinogens. It’s one of many mysteries to unravel, as his team tries to grow body parts from scratch.
____________________
Rearming America
The military's plan to regrow body parts.
April 18, 2008,
The regeneration of lost body parts has just moved from science fiction to U.S. military policy.
Yesterday the Department of Defense announced the creation of the Armed Forces Institute of Regenerative Medicine, which will go by the happy acronym AFIRM. According to DOD's news service, AFIRM will "harness stem cell research and technology … to reconstruct new skin, muscles and tendons, and even ears, noses and fingers." The government is budgeting $250 million in public and private money for the project's first five years. NIH and three universities will be on the team.
The people who brought you the Internet are about to bring you replacement fingers.
If you've been following Human Nature for the past three years, you know that tissue regeneration is well underway. The military has been working on regrowing lost body parts using extracellular matrices. Scientists in labs have grown blood vessels, livers, bladders, breast implants, and meat. This year they announced the production of beating, disembodied rat hearts. At yesterday's press conference, Army Surgeon General Eric Schoomaker explained that our bodies systematically generate liver cells and bone marrow and that this ability can be redirected through "the right kind of stimulation."
Now that the regeneration fantasy is becoming real, it's worth pausing to notice how we're absorbing it culturally. This is extremely freaky stuff. Just a few days ago, my wife and I were explaining to our 5-year-old daughter that she needs to take good care of her adult teeth because they're the last real teeth she'll ever have.
That's just not true anymore. It's not true of her fingers and toes, either. And why stop there? Schoomaker points out that salamanders can regenerate whole limbs. He asks: "Why can't a mammal do the same thing?"
When technology transforms humanity in such a fundamental way, it's best to start with a context that feels normal. Today, that context is what every American politician now calls "our brave men and women in uniform." The wars in Iraq and Afghanistan, waged in large part through improvised explosive devices, have produced nearly 1,000 U.S. military amputees. Many other service members have lost eyesight or suffered burns or spinal-cord damage. We all want to help these young people recover. We've seen inspiring stories of doctors outfitting them with prosthetic limbs. If only we could make them truly whole again. And now we can.
At the press conference, Schoomaker displayed pictures of a wounded Marine whose disfigured features could be restored only through tissue regrowth. He vowed to "redefine the Army and military medicine." The Defense Department's assistant secretary for health declared a goal of "getting these people up to where they are functioning and reintegrated, employed, [and] able to help their families and be fully participating members of society."
It's a familiar and worthy goal. And it has to be, because in the larger context of human history, its job is to ease us across the mind-blowing threshold of human regeneration. If my daughter loses a tooth, she may be able to grow it back. If my son loses a finger, the work pioneered by AFIRM early in his life may be able to help him.
Warfare will never be the same again, either. American military medicine is already saving the lives of soldiers who would have died in previous conflicts. Yesterday's death is today's wound. Now we're raising the ante: Today's permanent wound will be tomorrow's bad memory. Blow off our fingers, and we'll grow them back.
Further down the road, other possibilities will emerge. If we can restore a soldier's original muscle strength, we can probably add to it. The military is already encouraging soldiers to get LASIK, which improves some people's eyesight beyond 20/20. It's hard to believe we won't continue to improve that surgery and systematize it across the armed forces. Most of us civilians will face these revolutions when we're ready. By then, like AFIRM, they'll already be here.
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When a hobby-store owner in Cincinnati sliced off his fingertip in 2005 while showing a customer why the motor on his model plane was dangerous, he went to the emergency room without the missing tip. He couldn't find it anywhere. The doctor bandaged the wound and recommended a skin graft to cover the top of his right-middle stub for cosmetic purposes, since nothing could be done to rebuild the finger.
Months later, he had regrown it, tissue, nerves, skin, fingernail and all.
This particular hobbyist happened to have a brother in the tissue-regeneration business, who told him to forego the skin graft and instead apply a powdered extract taken from pig's bladder to the raw finger tip. The extract, called extracellular matrix, lays the framework that cells use to generate any given body part. It's like a cellular scaffolding, and all animals have it. It holds the signals that direct cells to divide, differentiate and build themselves into a specific form.
Extracellular matrix is a component of body tissue that functions outside of the body's cells (thus the "extracellular" designation). It's made up mostly of collagen, a type of protein. So extracellular matrix extracted from the bladder of a pig does not actually have any of the pig's cells in it.
In human fetuses, the substance works in concert with stem cells to grow and regrow everything from heart aortas to toes. Fetuses can regrow almost anything that gets damaged while in the womb. Scientists have long believed that when a fetus reaches full development, this extracellular matrix stops functioning. But with evidence that applying extracellular matrix from a pig can initiate certain types of regeneration in humans, they're wondering if they can trigger human extracellular matrix to start working again. After all, according to regeneration researcher Dr. Stephen Badylak of the University of Pittsburgh, children up to the age of two have been known to regrow fingertips with no outside help.
Pig-extracted extracellular matrix is already used by veterinarians to help horses repair torn ligaments. In people, it's used to treat ulcers, closing a hole in the tissue that lines the stomach. It employs an entirely different process than the typical mammalian healing mechanism. Let's take the case of a person who loses the tip of a finger. When the finger is severed, the cells die, and their contents seep into the surrounding tissue. This alerts the immune system to a problem. The immune system's response to cell death is inflammation and scar tissue. The formation of scar tissue prevents any future cellular development in the area. That's why scars last -- cells are prevented from doing a repair job on that skin.
But when extracellular matrix is applied to a wound, it doesn't trigger an immune response. Instead, when it begins to break down into surrounding tissue, it causes the cells in that tissue to start repairing the damage the way they would in a developing fetus (or a salamander that loses a limb) -- they divide and rebuild, creating new, normal tissue, not scar tissue.
Combined with developments in stem-cell research, this extracellular matrix may work miracles in the area of regeneration science. As of early 2007, testing of the effects of extracellular matrix is being carried out on a military base in Texas. Scientists are using the powdered pig extract on Iraq War veterans whose hands were damaged in the war. They're opening the wounds and applying the component to finger stubs in an attempt to regrow them. The researchers conducting the study say they don't expect to regrow the entire finger, but are hoping to regrow enough of a finger to allow for some utility. They don't believe it will regenerate bone, but nothing is for sure right now. That man in Cincinnati had only lost his finger tip, at the lower part of the nail; he hadn't lost the entire finger.
Help from pigs aside, many wonder if the extracellular matrix in humans is unable to function or is simply in a latent state, awaiting some sort of trigger. Do humans in fact have the same regenerative capacity as salamanders, which can regrow an entire limb, and researchers just haven't found a way to activate the mechanism? It's not just amphibians that can regrow body parts: Deer regularly regrow lost antlers, composed of bone, tissue, cartilage and skin -- the same things that make up human limbs. Could there possibly be an internal switch that would reactivate the regeneration capacity that humans possess in the womb? Regenerative medicine is actively pursuing answers to these questions. And in the meantime, if applying powdered pig extract to a snipped finger can in fact facilitate regrowth, the possibilities for medicine are startling. Spinal injuries, amputated limbs and damaged organs could all be coaxed back into a complete, healthy state if science finds the right combination of treatments.
- Assignment Discovery: Growing a New Bone
- These days, if you lose a thumb, a new one can be regenerated in a lab. Learn how studying marine life led to this discovery on Discovery Channel's "Assignment Discovery." (October, 2008)
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