In the latest developments that sound like they came straight from a science fiction novel, or maybe the start of a horror movie, scientists have tweaked monkey brains using human brain genes. The experiment involved transgenic rhesus monkeys, which were genetically engineered to carry human copies of MCPH1, a gene important for brain development.1
While the researchers claim the study provides value “in understanding human unique traits” in brain development, at least one of them — University of North Carolina computer scientist Martin Styner — seems to be having second thoughts and even considered removing his name from the study. Styner told MIT Technology Review:2
“Now we have created this animal which is different than it is supposed to be. When we do experiments, we have to have a good understanding of what we are trying to learn, to help society, and that is not the case here … They are trying to understand brain development. And I don’t think they are getting there.”
Transgenic Monkeys With Human Brain Genes Have Improved Short-Term Memory
In what was “the first attempt to experimentally interrogate the genetic basis of human brain origin using a transgenic monkey model,”3 researchers used 11 monkeys, six of which died during the experiment. The five surviving animals, however, had better short-term memory and shorter reaction times compared to nonengineered monkeys.
In human babies, MCPH1 is expressed in abundance during development, a phenomenon not seen to the same extent in nonhuman primates.4 When the researchers engineered the monkeys to carry human copies of MCPH1, no difference in brain size was found, but the monkeys performed better on memory tests and took longer to develop, similar to brains in humans.
The study was published in a Beijing journal after reportedly being rejected by Western publishers. Other experts, including James Sikela, a geneticist at the University of Colorado, also called the study risky and unethical. He told MIT Technology Review:5
“The use of transgenic monkeys to study human genes linked to brain evolution is a very risky road to take. It is a classic slippery slope issue and one that we can expect to recur as this type of research is pursued.”
Concerns have been raised, including by the study’s own authors, that similar experiments should not be conducted in apes, as they are too closely related to humans. To alter their brains would be unethical, as making them more “human” would raise questions of whether they could lead meaningful lives.
One study author says monkeys have enough genetic differences from humans that introducing only a few human genes shouldn’t cause ethical concerns. But they’re already tinkering with another gene, SRGAP2C, which has been called the “humanity switch” in its role in emerging human intelligence millions of years ago. The team has already added such genes to monkeys, with unknown consequences.6
Chinese Researchers Creating Gene-Edited Babies
While scientists have made great strides in mapping out genomes of entire organisms, much remains unknown about the purpose of individual genes and how they interact with one another. As such, making tweaks to genes, even those intended to be precise, often leads to surprising and unintended consequences.
This is what makes the rapidly moving field both fascinating and terrifying, especially when it involves adding human genes to nonhuman animals — or tinkering with human genetics directly. In 2015, Chinese researchers used the gene-editing technology known as CRISPR/Cas9 to edit human embryos — a first.7
Then, in 2018, He Jiankui, a Chinese scientist, claimed to have created the world’s first gene-edited babies. Although the claims haven’t been vetted, Jiankui says he modified the DNA of human embryos during in vitro fertilization by disabling a gene called CCR5, which could potentially make the babies resistant to infection with HIV.8
While the U.S. National Institutes of Health does not provide funding for studies on gene-editing technologies in human embryos, some scientists believe clinical trials of human germline editing should proceed, provided they are for purposes of treating series diseases or disabilities.
Already, in one study researchers corrected a pathogenic gene mutation in human embryos 67 percent of the time9 and, in another, used CRISPR/Cas9 to investigate gene function in the earliest stages of human development.10
CRISPR technology has also been used to edit human embryos made from sperm from men carrying inherited disease mutations. The researchers successfully altered the DNA in a way that would eliminate or correct the genes causing the inherited disease.11
If the embryos were implanted into a womb and allowed to grow, the process would result in the first genetically modified children — and any engineered changes would be passed on to their own children.
FrankenPig: Dead Pig Brain Cells Restored
Adding even more questions about the possibilities of tinkering with the brain, researchers from Yale University have restored some function to dead pigs’ brain cells, making them neither dead nor alive but rather “partly alive.”12
“We had clear lines between ‘this is alive’ and ‘this is dead,'” Nita A. Farahany, a bioethicist and law professor at Duke University, told The New York Times. “How do we now think about this middle category of ‘partly alive’? We didn’t think it could exist.”13
It’s long been believed that that brain cells die quickly when deprived of a blood supply. However, the study involved brains from pigs that had been killed for their meat, which had been clinically “dead” for four hours.
An experimental solution was then pumped into the brains for six hours, bringing oxygen to the tissue and blocking nerve signals in order to keep the cells inactive. Researchers believed they might be preserved better this way, but also wanted to circumvent the possibility of the unthinkable, The New York Times reported:14
“[T]he investigators also did not want to take a chance that the brains might regain consciousness, unlikely as that seemed. Had the team seen electrical activity suggesting actual consciousness, they planned to give the brains anesthetic drugs and cool them immediately to stop the process.”
After treating the brains with the solution, they showed some function was restored, including blood vessel functioning and electrical activity in some neurons. While it’s too soon to speculate on what this could mean for humans, the meaning of brain death and the future for recovery from brain injuries, it’s possible that one day brain resuscitation could become commonplace.
Human-Pig GMO Also Exists
Researchers from the Salk Institute for Biological Studies in La Jolla, California, made history in 2017 by creating a human-pig hybrid, a task achieved by injecting days-old pig embryos with human pluripotent stem cells.15 Such cells, like embryonic stem cells, are able to divide indefinitely and become any type of cell in the body.
The human-pig embryos were then transferred into adult pigs and allowed to grow for up to four weeks, before they were “removed and analyzed.”16 The study noted that more than 2,000 hybrid embryos were transferred into surrogate sows, but only 186 later-stage chimeric embryos survived the process, each with about one in 100,000 human cells.
The long-term goal of such research is to figure out if it’s possible to grow human organs inside other species, like pigs. Human embryo development, drug development and disease processes could also be studied using chimeras.
Researchers have also genetically engineered rat embryos to not produce a pancreas (which controls blood sugar levels), then injected mouse stem cells into them, which resulted in the growth of pancreatic tissue. They were then able to treat diabetes by transplanting parts of the healthy organs into diseased mice.17
Aside from the glaring ethical considerations of creating animal-human hybrids, these types of experiments have been ineligible for public funding in the U.S., which is why the Salk Institute had to rely on private funding for the study.18 There’s also the question of, if organs can one day be grown inside animals, can and should this — raising animals for the sole purpose of organ harvesting — be done, ethically speaking,
Gene-Edited Food Is Already on the Market
Genetic tinkering is becoming commonplace not only in the world of science but also in the food supply. In 2019, a gene-edited soybean oil created by biotech company Calyxt, was picked up by its first user — a Midwest company with both restaurant and foodservice locations, which is using it for frying as well as in dressings and sauces.19
Calyxt’s soybean oil, Calyno, contains two inactivated genes, resulting in an oil with no trans fats, increased heart-healthy oleic acid and a longer shelf life — but with unknown effects on human health. Although they’re genetically engineered, gene-edited foods are not marketed as GMOs, nor are they labeled as such.
In fact, because they contain no foreign genetic material, foods produced via gene-editing are not subject to regulation by the U.S. Department of Agriculture (USDA) — although an advisory board recommended gene-edited foods could not be labeled organic — or other regulatory agencies.
Gene-edited chickens also exist, although they haven’t yet entered the food supply. For now, the best way to avoid gene-edited foods, if you so choose, is to purchase organic.
What Does the Future Hold?
Gene-editing and similar technologies often fall into the realm of research moving full-steam ahead before we’ve adequately stopped to consider whether we should move forward at all. In the case of adding human brain genes to monkeys, “yes, it’s as scary as it sounds,” news outlet Vox quipped, citing Barbara J. King, emerita professor of anthropology at the College of William and Mary, who called the experiment “an ethical nightmare.”20 Vox added:
“… [T]here are ‘tens of millions of differences’ between humans and monkeys. But [t]his transgenic study is definitionally aimed at eliminating a few of those differences. After how many eliminated differences does a monkey shade into a human being? There’s no clear answer to that question.”
As for the function being restored to dead pig brain cells, it adds even more questions than answers to current knowledge of the brain and what it means to be alive. Scientifically, the researchers noted:21
“These findings demonstrate that under appropriate conditions the isolated, intact large mammalian brain possesses an underappreciated capacity for restoration of microcirculation and molecular and cellular activity after a prolonged post-mortem interval.”
Ultimately, such studies highlight how much we don’t know, and the unexpected consequences that can occur when dabbling in genetics. We’re only beginning to understand even the questions that need to be asked in order to proceed safely and ethically, but, as is often the case with technology, science is moving faster than the moral implications can be considered, much less understood.