What exactly is a chimera?
The concept of chimeras predates human attempts to artificially create them, and at a basic level refers to an organism with tissue that comes from two or more different zygotes, the little cells that form after sperm fertilizes egg (in mammals).
Chimeras occur in nature -- two eggs can be fertilized by two separate males, for example, then merge into one individual in the womb. This is called tetragametic chimerism, and when it happens in humans, the chimera can have organs with different sets of DNA. Think of a chimera as twins that melded together at a very early stage of development. Sometimes life is stranger than fiction.
Lab-developed chimeras are a more recent phenomenon; the first rat-mouse chimera was created a decade ago. But combining human cells with those of another large mammal is proving to be quite the formidable challenge.
How do you go about creating a human-pig chimera?
Chimera experiments are a complex (obviously) blend of stem cell therapy and gene editing; the basic idea is that you want to put the stem cells from a donor species into an embryo of a different host species, then selectively turn off the genes in the host that make whatever organ(s) you're trying to grow, while simultaneously coaxing the stem cells to become those organs.
In layman's terms, the result should be that a pig grows human lungs, for example, instead of pig lungs, or a human liver instead of a pig liver, and so on.
Does this mean there are human-pig hybrids running around secret labs?
The short answer is: No. The slightly longer answer is… the science is still developing; the most recent experiment only succeeded in demonstrating human cells growing in a pig embryo, a far cry from on-demand pancreas.
MIT Technology Review reported that in 2015 about 20 pregnancies of pig-human and sheep-human chimeras were gestated in labs in Minnesota and California. So far, none of the animals has been brought to term, and very little peer-reviewed research has been published on the results of these experiments.
More recently, the Salk Institute in San Diego published data about its pig-human embryo, which developed for 28 days -- the first trimester of a pig's pregnancy -- before being terminated.
Perhaps at this stage you're wondering, "Why pigs?" While some research has focused on sheep, pigs happen to make excellent hosts for human organs. Which sounds gross and creepy, but there it is.
"Due to its resemblance to humans in anatomy, physiology, organ size, and development, the pig is considered a good host animal," says Dr. Jun Wu, a scientist at Salk and the lead author of the institute's paper, which was published in Cell. "Success of this approach hinges on the [host having] two critical components: zygote gene editing to knock out genes involved in lung development in the developing pig embryo, and establishing appropriate conditions for human stem cell introduction."
The institute also created mouse-rat chimeras, proving that rat cells implanted in mouse embryos could develop other organs, such as gallbladders -- an organ that rats stopped producing in the 18 million years since separating in evolution from mice. That was the critical step showing researchers it was possible to grow another species' organs in a host body.
"We have discovered which mouse genes are necessary to remove to stop the development of the pancreas, eye, liver, kidney, blood vessels, and heart," Dr. Wu says. "And by adding in rat-induced pluripotent stem cells, we have succeeded in creating mice with a functional rat pancreas and heart."
Rats and mice are relatively close genetically, as you can tell just by looking at them. Humans and pigs are another ballgame, last sharing an ancestor nearly 90 million years ago. One of the biggest challenges is that pig pregnancy only lasts about 112 days, meaning that bun's done in the oven at a much quicker rate.
Scientists haven't figured that out yet, and doing so anytime soon would be, as Dr. Wu puts it, "far-fetched."
"The breakthrough can come in a few months or a few years," he says. "It's hard to see."
How ethical is creating pigs with human organs?
According to Dr. Wu, the experiment is a means of "taking advantage of in vivo developmental principles perfected by millions of years of evolution" and using them to better people's lives -- whether it’s genetically matching organs for patients or testing new medicines safely with no human guinea pig necessary. In other words, the ultimate goal is to improve human life, and chimeras are a new technique that might be useful for our continued survival as a species.
But the National Institutes of Health (NIH), which controls access to government-supplied research funding, isn't on board. Pro-life groups and animal rights activists in particular are worried about the implications of creating pigs bred exclusively for organ harvesting.
There's also a concern based more in science fiction than reality, but here goes: What if those human cells somehow migrate to the developing pig's brain and make it more human? Like, pigs with human hair, reproductive cells, or the most extreme scenario, a real Babe?
In 2015, the NIH banned taxpayer funding for chimera research, which it moved to lift in 2016 -- predictably, groups like the US Conference of Catholic Bishops and PETA aren't keen on the idea.
Dr. Wu says the funding ax has greatly affected chimera research. Getting enough functional cells for clinical use is often costly, and therefore impractical.
"Working with large animals such as the pig is rather expensive, and continued funding will greatly facilitate our project," he says. "We have to resort to other funding sources for continued research."
He claims the team is working responsibly, reassuring the skeptics that creating the pig from Animal Farm is just as crazy as it sounds.
"At this stage, we only allow the gestation to continue no more than four weeks, when the pig brain is far from fully developed and therefore the chances of an animal gaining human consciousness is basically zero," he explains. "Besides, the human cell contribution to the whole pig embryo at this stage is very low, less than 0.01%. The NIH's concern is only valid if a significant amount of human cells can contribute to pig brain development and, based on our preliminary results, this outcome is unlikely."
Human cells could also be engineered to prevent them contributing to the chimera brain, but again, that's way down the line.
Is creating human-pig chimeras worth it if it means saving lives?
Chimeras might be the answer to one of medicine's biggest shortfalls -- an overwhelming organ shortage worldwide. In the US alone, nearly two dozen people die every day needing a transplant. Since 1999, waiting lists have nearly doubled.
That shortage is only set to get worse with self-driving cars, free from human error, coming down the pipeline. To go ahead and get morbid, road accidents are a main source of healthy donor organs and transplants. One in five donations comes from the victim of such an accident.
Researchers also believe that chimeras could potentially hold the cure to various diseases, including diabetes and Parkinson's.
"Pluripotent stem cells can proliferate indefinitely in culture, and under proper cues might be able to differentiate into all cell types in the adult body," Dr. Wu says, "thus providing an unlimited source material." This "source material" could potentially be used to test drugs and other novel treatments without risking human life.
There's still a lot of work needed before human-pig chimeras grow to full term
According to Dr. Wu, chimera research is still "more questions than answers."
"With our current technology, we can only have a glimpse of this possibility at best," he points out. "And we really need another breakthrough to make this practical so that it can make a difference in people's lives."