A controversial technique to develop body parts from stem cells

may someday save countless lives, but will society allow it?

By Tuan C. Nguyen  

smithsonianmag.com

January 17, 2014

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If all goes according to plan, professor Hiroshi Nagashima's genetically-engineered pigs will grow up with functional organs. A few of those body parts, though, will have the genetic makeup of a human. In essence, they'll be mostly swine, partly human.

         

After successfully cloning pigs in 2007, <http://usatoday30.usatoday.com/news/topstories/2007-08-08-2351463685_x.htm>  the Tokyo-based geneticist has made steady progress on perfecting a technique to produce animals from multiple, genetically-different cells—scientifically referred to as chimeras <http://en.wikipedia.org/wiki/Chimera_%28genetics%29> . His latest achievement <http://www.japantimes.co.jp/news/2013/02/20/national/breakthrough-in-pig-pancreas-regeneration/#.Utk55Rb_SfQ>  was to breed white pigs that possessed the pancreases of black pigs, a different breed, by injecting outside embryonic stem cells into their embryos. The procedure required that he first switch off the gene in the white pigs that instructs the embryo to develop its own pancreas before surgically implanting the modified embryos into the womb of a surrogate.

  

Now while all this sounds like the stuff of weird franken-science, keep in mind that the concept of chimeras, derived from the lion, snake and goat-mix of Greek mythology <http://en.wikipedia.org/wiki/Chimera_%28mythology%29> , occurs naturally as well. In extremely rare instances <http://www.academia.edu/202539/Which_Half_Is_Mommy_Tetragametic_Chimerism_and_Trans-Subjectivity> , non-identical twin zygotes somehow fuse together in the early phase of pregnancy. The babies are a combination of genetically distinct body parts. Some hermaphrodites, with both male and female sex organs, are the most apparent example of this phenomenon <http://boingboing.net/2009/05/01/the-mind-blowing-wor.html> .

  

The chimeras Nagashima and his collaborator, biologist Hiromitsu Nakauchi, envision do, however, blur the line between distant species. The Japanese researchers aim to grow human pancreases in pigs, harvest them and then implant them in humans in need. Down the road, medical researchers may someday be able to harvest from animals other human organs grown from the donors' own DNA. A breakthrough of such magnitude has the potential to save many lives, particularly those on a growing waitlist for a suitable donor. It’s estimated that 18 people in America die each day <http://www.organdonor.gov/index.html>  waiting for an organ. And even then, there’s always a concern over the complications of the body rejecting it as nearly half of the people who receive transplanted kidneys <http://www.roche.co.uk/portal/uk/transplantation_definition_organ_rejection>  experience a negative immune system response in the first few weeks.

    

So why pigs? Well, in an odd way, the size and function of their internal parts are quite similar to ours <http://web.hcpss.org/%7Ejason_piluk/AP_docs/Fetal%20Pig%20-%20Day%20One.pdf> . In fact, one experiment <http://www.newscientist.com/article/dn4558-pighuman-chimeras-contain-cell-surprise.html#.UtgM04UQQQk>  showed that pigs raised from fetuses with injected human stem cells had a variation of pig cells, human cells and the hybrid cells in their blood and organs. The genetic "intimacy" between the two species allowed cells to fuse together with a fair degree of ease. It may also explain why they've long been thought of as ideal candidates for "xenografting, <http://www.fas.org/biosecurity/education/dualuse-agriculture/2.-agricultural-biotechnology/pigs-source-of-replacement-organs-for-humans.html> " where tissues or organs are transferred from animals to humans. Heart valves are often grafted from pigs and implanted into humans, since the two species' hearts are similarly structured. In a report on WIBW.com <http://www.wibw.com/home/headlines/9302726.html> , Nagashima stated that he chose to focus his cloning efforts on pigs because of the uncanny degree in which pigs and humans are anatomically alike.

  

Nakauchi has developed a separate method for growing a brown rat pancreas inside a white mouse. Though rodents are much more distant to humans than pigs, Nakauchi's technique uses induced pluripotent stem cells (iPSCs) <http://stemcells.nih.gov/info/basics/pages/basics10.aspx>  rather than embryonic, which sidesteps the thorny issue of destroying fertilized embryos. Taken from adult skin tissue or blood, iPSCs can be programmed to function just like embryonic stem cells, developing into any variety of building block found in the body. The real challenge, though, is whether he can develop this technology so that it'll work for cultivating human parts in pigs. When pressed on the prospect, Nakauchi told the BBC <http://www.bbc.co.uk/news/world-asia-25550419>  that he was confident the day will come, though it is at least five years away, perhaps even longer.

  

However, controversy is simply unavoidable when you're talking about reducing an animal that some consider a beloved household pet into an organ factory. Discomfort ranges from the obvious concern over the inhumane treatment of animals to more perplexing dilemmas should the technology advance to the point where it's possible to nurture more sacred human parts, such as a homosapien brain.

  

Robert Streiffer, a bioethicist at the University of Wisconsin in Madison, points out that rearing bioengineered pigs specifically for the purpose of extracting an organ or two would mean they would be subject to pretty harsh interventions. They might undergo constant pumping of immune suppression drugs to prevent, for instance, a kidney from being rejected and be forced to live in confined spaces to minimize the risk of injury.

  

"You can't forget that pigs are smart, social animals that experience a wide range of emotions," he says. "In such austere isolated conditions, they'll be suffering for much of their lives. For sure, it would get a lot of attention from animal rights groups."

 

And then there are the more difficult philosophical questions. At what point would a pig be considered more than a pig? If so, what rights should such creatures be conferred? Streiffer sees the research being done in Japan is tailored narrowly enough that it's probably not going to be kicking open the door to any brave new worlds.

 

"Anytime you entertain scenarios made possible by biotechnology you get into these conundrums, like where enhancing the brain a certain way can enhance an animal's status in a certain way and what kind of cognitive abilities [intelligence or awareness] are needed to attain the status of being human beings," Streiffer adds. "But I just don't see that as the outcome in this case."

 

The biggest obstacles at the moment are legal ones. While Japan allows the mixing of human and animal genetic material in vitro, it has banned the subsequent creation of actual living chimeras. Nakauchi, who's currently lobbying the government to reconsider the law, has recently flirted with the idea of moving his research to the United States where, in many states, no such ban exists <http://www.popsci.com/science/article/2013-06/japanese-scientist-may-have-make-his-human-pig-organs-america> .

  

"Even though he would probably still face opposition, at least on a societal level, it's not illegal here," Streiffer says. "He should get a pass."

 

Tuan C. Nguyen is a Silicon Valley-based journalist specializing in technology, health, design and innovation. His work has appeared in ABCNews.com, NBCNews.com, FoxNews.com, CBS' SmartPlanet and LiveScience.

Does Chopping Down Forests

Spread Diseases?

A young scientist in Panama devises a novel way to study ticks and disease

By Paul Bisceglio

Smithsonian Magazine       

January 2014

   

Some people go to Panama for the seafood and sunshine. Helen Esser, a fellow at the Smithsonian Tropical Research Institute in Panama City, went for the bloodsuckers. She spent three months on the Panama Canal, dragging cotton cloths across forest floors to collect 20,000 ticks. After dropping them into alcohol-filled jars, she carried them back to the lab and cataloged them, tick by tick, to get at a pressing global-health question: Does chopping down forests spread deadly diseases?

         

Scientists have long observed that infectious-disease outbreaks sometimes occur where and when forest habitats are degraded. The most notorious example is the Ebola virus, which causes an often fatal illness in humans; it was first identified in Congo, whose forests have been heavily logged. Another thing scientists have documented is that forests divided by roads, farms and settlements tend to hold fewer mammal species.

  

Esser, a doctoral candidate at Wageningen University in the Netherlands, has come up with an innovative way to determine if that might be a key to human disease outbreaks.

  

Ticks can transmit infectious-disease agents to mammals, including people, while feeding on their blood. (U.S. residents may be most familiar with Lyme disease and Rocky Mountain spotted fever, which are both caused by tick-borne bacteria.) Some ticks feed exclusively on one or two animal species, while others, called “generalists,” feed on many. Esser and her colleagues speculate that when forests are degraded and mammal diversity declines, generalist ticks outcompete species with narrower diets; that, in turn, would increase the risk to humans because generalists are more likely to bite us as well as more likely to carry infectious agents.

  

“To really understand how diseases spread, you can’t just look at one species,” she says. “You have to consider the different interactions between species throughout an entire community.” Esser’s innovation was to devise a field test that would allow her to trace those interactions in different communities.

  

The ideal field test would be to compare separate but similar parcels of forest, each with a self-contained animal community—an arrangement that’s not easy to come by in nature. But at the heart of the Panama Canal, Esser has found what she calls “the perfect fragmentation study”: the islands within the Barro Colorado Nature Monument. Those environments, isolated by water, range from miles-wide forests, with howler monkeys in the canopy and brocket deer, peccaries and even jaguars roaming the verdant floor, to woods a few hundred yards in diameter that barely support rodents. All of them have ticks: Panama is crawling with more than 40 species.

  

By comparing the numbers and kinds of ticks in these environments, Esser and her colleagues should be able to show whether, as they suspect, those higher-risk generalist ticks prevail in places with less mammal diversity. That dynamic has been modeled mathematically, says Allen Herre, a STRI staff scientist who assisted Esser, “but ain’t nobody nowhere shown this.”

  

In addition to spotting the opportunity hidden on Barro Colorado’s islands, Esser figured out a better way to count the mammals on them: She attached motion- and heat-sensing cameras to trees. (Human observers, she says, are prone to error, and some “walk around like an elephant” and scare the animals away.) And of course, she collected ticks. “It involved a lot of climbing steep hills and grabbing onto roots and trees,” she says. And tick bites—on some days, dozens. “Bites are part of the job,” she says, laughing.

And worth it, she says, if her work helps preserve forests. “Habitat destruction, fragmentation...these things are backfiring on us,” she says, “because in many cases they’re paving the way for human infection.”

Paul Bisceglio is an editorial fellow at Pacific Standard and co-editor of the website "The Land That I Live." He was previously the editorial intern for Smithsonian magazine.