June 5, 2020

The Niche

Knoepfler lab stem cell blog

Is monkey cloning a breakthrough or a bad idea?

Is monkey cloning a good idea? We’re about to find out.cloning monkeys

A new Cell paper today reports the first cloning of monkeys via somatic cell nuclear transfer (SCNT), raising many questions. The paper from a team led by Qiang Sun is entitled, “Cloning of Macaque Monkeys by Somatic Cell Nuclear Transfer.”

The highlight bullet points from the paper are the following:

“•Somatic cell nuclear transfer (SCNT) using fetal fibroblasts yielded two live monkeys

Epigenetic modulators promoted development and pregnancy rate of SCNT embryos

SCNT using adult cumulus cells yielded live births of monkeys that were short-lived

Genetic analysis confirmed the clonal origin of the SCNT monkey offspring”

On first glance my initial thinking is that I’m not sure why cloning monkeys would be a good thing to do as a researcher.

Is this technology useful?

Are the cloned monkeys themselves of some kind of special use for science?

The answers are not immediately clear.

While some have speculated that cloned monkeys could have uses for genetic disease research or other kinds of studies such as in human cancer, I’m not convinced.

monkey cloning
Zhong Zhong and Hua Hua. Photo by Qiang Sun and Mu-ming Poo / Chinese Academy of Sciences

There are also special bioethical considerations with work on non-human primates in general and when you combine that with cloning, it raises the stakes further with more questions.

Research on primates has been on the wane too in some countries like here in the U.S. so the idea that one might clone a bunch of monkeys and/or breed a large cohort of genetically identical monkeys for unique research could be going against the research tide at this point.

At the same time, questions are already being raised over whether this research could enable human cloning (see discussions on human cloning and genetic modification in my books Stem Cells: An Insider’s Guide and GMO Sapiens).

Even with some  reported new technological tweaks in the SCNT process (say compared to SCNT used to make the first mammalian clone Dolly), the new monkey cloning method still didn’t work well at all and led to the deaths of some primates.

The paper’s abstract itself points to the challenges and ethical issues here:

“Generation of genetically uniform non-human primates may help to establish animal models for primate biology and biomedical research. In this study, we have successfully cloned cynomolgus monkeys (Macaca fascicularis) by somatic cell nuclear transfer (SCNT). We found that injection of H3K9me3 demethylase Kdm4d mRNA and treatment with histone deacetylase inhibitor trichostatin A at one-cell stage following SCNT greatly improved blastocyst development and pregnancy rate of transplanted SCNT embryos in surrogate monkeys. For SCNT using fetal monkey fibroblasts, 6 pregnancies were confirmed in 21 surrogates and yielded 2 healthy babies. For SCNT using adult monkey cumulus cells, 22 pregnancies were confirmed in 42 surrogates and yielded 2 babies that were short-lived. In both cases, genetic analyses confirmed that the nuclear DNA and mitochondria DNA of the monkey offspring originated from the nucleus donor cell and the oocyte donor monkey, respectively. Thus, cloning macaque monkeys by SCNT is feasible using fetal fibroblasts.”

In theory, the reported epigenetic improvements (addition of the histone demethylase and the HDACi TSA, which as a scientist I find interesting) to the cloning process reported here could embolden some rogue to give that a try in humans.

Out of the large number of early embryos produced and using 21 surrogate mothers, only 2 healthy baby monkeys (Zhong Zhong and Hua Hua) were born when using fetal cells as a basis for the cloning. Starting with adult cells as donors, only 2 short-lived babies were born. Clearly, this work led to a lot of undesired developmental outcomes involving non-human primates.

Is this research ethical? Is it a big breakthrough?

I’m not sure one way or another yet. I need to think it through more, but it does make me stop and think with a feeling that this work may not be a great idea. What do you think?

An NPR piece by Rob Stein on this development both quotes Dieter Egli that this research is a breakthrough and also mentioned some difficult ethical issues including this quote from top bioethicist Insoo Hyun:

“People may wonder: Are human beings next?” says Insoo Hyun, a bioethicist at Case Western Reserve University. “People have always been worried about the possibility of human cloning. And this is just yet another step in that direction.”

Some others in media maybe are not doing such a thorough, balanced job of handling this story without hype such as referring to “cute monkey clones” and probably overstating the research potential here. For instance, one Verge piece on this new paper ended this way, “As Zhong Zhong and Hua Hua get older, the Chinese researchers will be monitoring their health and behavior. Hopefully that means lots more cute photos as they grow up.” So I’ll end my blog post this way, “Will monkey clones yield something uniquely valuable scientifically and for society…or mostly just more cute photos?”

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