After years of trial and error, scientists have finally done something incredible: They have successfully grown human stem cells in a pig embryo. Why would anyone do this? Image: Chinese sculptor Liu Xue combines a human with an animal
The Chimera was, according to Greek mythology, a monstrous fire-breathing hybrid creature of Lycia in Asia Minor, composed of the parts of more than one animal. It was usually depicted as a lion with the head of a goat arising from its back, and a tail that might end with a snakes’s head, and was one of the offspring of Typhon and Echidna and a sibling of such monsters as Cerberus and the Lernaean Hydra. The seeing of a Chimera was also an omen for disaster.
The term chimera has come to describe any mythical or fictional animal with parts taken from various animals, or to describe anything composed of very disparate parts, or perceived as wildly imaginative, implausible, or dazzling. However, a genetic chimerism or chimera (also spelled chimaera) is a single organism composed of cells from different zygotes. This can result in male and female organs, two blood types, or subtle variations in form. Animal chimeras are produced by the merger of multiple fertilized eggs. In plant chimeras, however, the distinct types of tissue may originate from the same zygote, and the difference is often due to mutation during ordinary cell division. Normally, genetic chimerism is not visible on casual inspection; however, it has been detected in the course of proving parentage.Another way that chimerism can occur in animals is by organ transplantation, giving one individual tissues that developed from two genomes. For example, a bone marrow transplant can change someone’s blood type.
In a remarkable—if likely controversial—feat, scientists announced that they have created the first successful human-animal hybrids. The project proves that human cells can be introduced into a non-human organism, survive, and even grow inside a host animal, in this case, pigs. Turns out, many scientists have been working on growing the organs of one animal inside of a different type of animal. For example, scientists recently reported the successful growth of mouse pancreases inside of rats. The ultimate goal of this type of work is to grow human organs inside of other animals as a means to ending the organ shortage that is costing thousands of Americans — who need a transplant — their lives each year.
This biomedical advance has long been a dream and a quandary for scientists hoping to address a critical shortage of donor organs. Every ten minutes, a person is added to the national waiting list for organ transplants. Despite advances in medicine and technology, and increased awareness of organ donation and transplantation, the gap between supply and demand continues to widen. While national rates of donation and transplant have increased in recent years, more progress is needed to ensure that all candidates have a chance to receive a transplant. And every day, 22 people on that list die without the organ they need. What if, rather than relying on a generous donor, you could grow a custom organ inside an animal instead?
Image from the 1978 film Coma, based on the 1977 novel by Robin Cook. In the film a surgical resident discovers a front for black-market organ sales, where the patients’ organs are sold to the highest bidder. Boston Memorial is in on this, purposely inducing comas in patients whose organs match those of potential buyers.
Now, using similar methods as the mouse-rat hybrid, scientists have produced the first human-pig hybrid embryo, which is more difficult than you might think. Getting cells from one species to survive in an entirely different species is extremely tricky and has eluded scientists for years.
That’s now one step closer to reality, an international team of researchers led by the Salk Institute reports in the journal Cell. The team created what’s known scientifically as a chimera: an organism that contains cells from two different species. Even now, this breakthrough is preliminary. Only about one out of every 100,000 cells in the hybrid embryos was human. If the scientists had grown the embryos to maturity (which they did not), the organs would probably not have enough human cells in them for a human body to recognize — resulting in the human body rejecting the organ and potentially killing the patient. This is why more research is critical to improving the techniques, and hopefully, one day, paving the way for the first human transplant with a human-pig hybrid organ. But that day is years, possibly decades, off.
In the past, human-animal chimeras have been beyond reach. Such experiments are currently ineligible for public funding in the United States (so far, the Salk team has relied on private donors for the chimera project). Public opinion, too, has hampered the creation of organisms that are part human, part animal.
Chimera, Louis Jean Desprez (French, Auxerre 1743–1804 Stockholm), The Metropolitan Museum of Art
A revolutionary new technology called CRISPR-Cas9 with a natural system known as a gene drive, theory is rapidly becoming reality. CRISPR places an entirely new kind of power into human hands. For the first time, scientists can quickly and precisely alter, delete, and rearrange the DNA of nearly any living organism, including us. In the past three years, the technology has transformed biology. Working with animal models, researchers in laboratories around the world have already used CRISPR to correct major genetic flaws, including the mutations responsible for muscular dystrophy, cystic fibrosis, and one form of hepatitis. Recently several teams have deployed CRISPR in an attempt to eliminate HIV from the DNA of human cells. The results have been only partially successful, but many scientists remain convinced that the technology may contribute to a cure for AIDS.
In experiments, scientists have also used CRISPR to rid pigs of the viruses that prevent their organs from being transplanted into humans. Ecologists are exploring ways for the technology to help protect endangered species. Moreover, plant biologists, working with a wide variety of crops, have embarked on efforts to delete genes that attract pests. That way, by relying on biology rather than on chemicals, CRISPR could help reduce our dependence on toxic pesticides.
No scientific discovery of the past century holds more promise—or raises more troubling ethical questions. Most provocatively, if CRISPR were used to edit a human embryo’s germ line—cells that contain genetic material that can be inherited by the next generation—either to correct a genetic flaw or to enhance a desired trait, the change would then pass to that person’s children, and their children, in perpetuity. The full implications of changes that profound are difficult, if not impossible, to foresee.
“This is a remarkable technology, with many great uses. But if you are going to do anything as fateful as rewriting the germ line, you’d better be able to tell me there is a strong reason to do it,” said Eric Lander, who is director of the Broad Institute of Harvard and MIT and who served as leader of the Human Genome Project. “And you’d better be able to say that society made a choice to do this—that unless there’s broad agreement, it is not going to happen.”
“In ancient civilizations, chimeras were associated with God,” he says, and our ancestors thought “the chimeric form can guard humans.” In a sense, that’s what the team hopes human-animal hybrids will one day do.
There are two ways to make a chimera. The first is to introduce the organs of one animal into another—a risky proposition, because the host’s immune system may cause the organ to be rejected. The other method is to begin at the embryonic level, introducing one animal’s cells into the embryo of another and letting them grow together into a hybrid.
It sounds weird, but it’s an ingenious way to eventually solve a number of vexing biological problems with lab-grown organs.
When scientists discovered stem cells, the master cells that can produce any kind of body tissue, they seemed to contain infinite scientific promise. But convincing those cells to grow into the right kinds of tissues and organs is difficult.Cells must survive in Petri dishes. Scientists have to use scaffolds to make sure the organs grow into the right shapes. And often, patients must undergo painful and invasive procedures to harvest the tissues needed to kick off the process. At first, Juan Carlos Izpisua Belmonte, a professor in the Salk Institute’s Gene Expression Laboratory, thought the concept of using a host embryo to grow organs seemed straightforward enough. However, it took Belmonte and more than 40 collaborators four years to figure out how to make a human-animal chimera.To do so, the team piggybacked off prior chimera research conducted on mice and rats.
The group of scientists published their work on Thursday, Jan. 26, in the prestigious science journal Cell.