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, 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. His latest achievement 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, occurs naturally as well. In extremely rare instances, 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.
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 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 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. In fact, one experiment 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," 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, 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) 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 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.
"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."