The Part that’s Not Funny about Cloning Macaques

On January 25th 2018, CNN.com announced a striking scientific breakthrough in biotechnology with the painful headline “Monkey See, Monkey 2.”

A technique known as somatic cell nuclear transfer (SCNT) had been used successfully by Chinese researchers to create two genetically identical long-tailed macaque monkeys. This was the first time that SCNT, a technique that arrived on the scene in 1996 when Ian Wilmot created a sheep named “Dolly,” had been used successfully on a primate. January’s success with the monkeys became international news not just because the two identical macaques were incredibly photogenic. It became international news because, if this technique could be used on monkeys, it could presumably also be used on people.

Qiang Sun and Mu-ming Poo Chinese Academy of Sciences
Image by Qiang Sun and Moo-ming Poo, Chinese Academy of Sciences

Although this was the first case of a primate being cloned using SCNT, it was not the first time that scientists had created genetically identical monkeys. Back in the dark ages – a full decade before the release of the first iPhone – two rhesus monkeys were successfully cloned using a nuclear transfer technique. An Oregon research group removed a number of nuclei from a female rhesus’ eggs that had been fertilized in vitro using a male rhesus’ sperm and placed them into evacuated rhesus monkey ova. They applied a small electric shock to each cell to fuse the nucleus to its new host. The cells were then placed in a chemical soup that encouraged them to start dividing. After a period of normal cell division, the embryos were placed into surrogate rhesus monkey mothers for gestation.

Just two of the many cells that were fused were carried successfully to term. When these two rhesus monkeys were born in 1997, they were named, presumably by people with identical humor genes to the science reporters at CNN, “Neti” (Nuclear Embryo Transfer Infant) and “Ditto.”

Critics complained – and the researchers themselves conceded – that these weren’t real clones but siblings. Although their DNA was close to identical, the cell nuclei had been taken from different developing embryos and implanted into different ova. Same parents, similar genes, but quite different individuals.

Clones or not, Neti and Ditto demonstrated that a whole primate could be intentionally created by stuffing a string of DNA from one source into an evacuated egg from another. The scientists were clearly conducting some highly synthetic parenting shenanigans.

A breakthrough that came a bit closer to cloning occurred in 1999. This time it involved a practice called “embryo splitting.” This technique involves breaking up an eight cell embryo into pairs of cells and encouraging the four resulting units to keep dividing so that they can be implanted into surrogate parents.

A rhesus monkey named Tetra was born at the same Oregon research center as Neti and Ditto using this technique but she was the only one of the four split embryos to survive. Although Tetra would have been a clone of the three others had they made it, in the event she was a clone of nobody in particular. Showing the same knack for word plays as CNN, researchers from the group that produced Tetra made plans to name the first two artificially twinned monkeys that made it to term ‘Romulus and Rhesus’ after the famous twins of Roman fable.

Detractors again found Tetra’s appearance a little underwhelming. Not only did Tetra have no surviving clones with which to compare her, at the end of the day, she was no more than an artificially produced identical twin. Instead of nature alone causing the first few cells to split and implant as separate embryo’s, researchers were making it happen through a carefully timed intervention.

The achievement this January brings to the table a third technique for creating monkeys with identical genomes. The technique has created great excitement among those interested in doing medical research on monkeys. If you can create new monkeys whose genomes you know to be identical to a given test subject, you are in a much better position to advance your research when the first monkey dies. You are also in a better position to run multiple versions of a test on genetically similar research subjects.

Unlike Neti, Ditto, and Tetra, the two rhesus monkeys produced in China, Hua Hua and Zhong Zhong, were not produced from embryonic cells but somatic cells. This matters because embryonic cells have always been considered “easier.” They have not started to differentiate into the specialized cells of the body and hence still contain unrestricted potential. If somatic cells are going to be used to create babies, the DNA has to be reprogrammed in order to take it back to an earlier stage of its development.

But if you can reprogram them, as the Chinese research demonstrates, you have developed a much more potent research tool.  You know what the adult organism looks like and what its characteristics are.  You also have a virtually unlimited number of adult cells available to create more clones. Unlike work that starts with embryos and their nuclei, you are not restricted to a small number of available cells.

Despite being an impressive technical achievement, there is one feature of the Chinese work that does not yet fit the idea of a clone that lurks in the darkest corners of the imagination. The researchers found that they could not take an adult rhesus somatic cell and successfully encourage it to grow in an evacuated ovum. They had to take cells from rhesus monkey fetuses if the cloned embryos were to develop. Cells taken from adult monkeys yielded individuals that died at birth.

From the point of view of the “shudder factor” this makes a huge difference. It means there is no adult monkey walking around that can be compared to Hua Hua and Zhong Zhong. Although they are genetically identical to each other, they are not clones of any other living individual. As much as they are clones, Hua Hua and Zhong Zhong might also be thought of artificially produced, genetically identical (and orphaned) twins.

Still, the achievement is notable. Even though they are arguably still a long way from getting there, it is clear that researchers are chipping away at the technical barriers that stand in the way of creating a human baby that has been cloned from cells taken directly from an adult human.

Caroline DavisFor most people, it is only this end point that gives them the creeps. It is as if the only moral line in the sand worth talking about involves the cloning of a Homo sapiens.

Yet there is ethics loaded into all of the intervening steps. Other species are being radically manipulated, subjected to highly invasive and dangerous procedures, and are losing their lives to test out a technique. (In January’s success, seventy-nine embryos were implanted into twenty-one surrogate rhesus monkey mothers with only Hua Hua and Zhong Zhong surviving). Furthermore, it is a technique whose primary purpose is to provide suitable subjects for even more testing.

These concerns about animal well-being, serious as they are, have been well rehearsed and are not my focus here.

I suggest we come at the ethics from an even wider angle. We might think of the moral lines in the sand as not only being about how to treat particular species. We might think of them as being about how to treat biological processes themselves. Biotechnology is providing humans with increasing power to replace natural processes with artificial or synthetic ones.

Humans have long participated in egregious manipulations of other species to serve their own interests. More and more they are carrying out these manipulations on some of the bigger forces that shape the world in which we live. Climate, DNA, atomic structures, and evolution are all being opened up for the production of synthetic versions of themselves. These, in the end, might turn out to be the most radical manipulations of all.

This is a big deal and it may end up being not in the least bit funny. “Monkey See, Monkey 2” may pale in significance compared to “Biology as We Knew It” and “Biology 2.”

 

Second image by Caroline Davis

 

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