First published December 2, 2020.
In 2020, researchers in Germany and Japan gave marmoset monkey fetuses a gene found only in humans, ARHGAP11B, and found that the animals’ developing neocortex became larger and more folded. The study did not create “super-intelligent” monkeys. The fetuses were examined before birth, no behaviour or intelligence was tested, and headlines claiming the brains doubled in size went beyond the published results. Here is what the experiment did, what it showed and why it sparked an ethical debate.
Who did the study and what they did
The work was led by Wieland Huttner at the Max Planck Institute of Molecular Cell Biology and Genetics in Dresden, with first author Michael Heide. It was carried out in Japan with the Central Institute for Experimental Animals in Kawasaki, including Erika Sasaki, and Keio University in Tokyo, where Hideyuki Okano had pioneered methods for creating transgenic primates. The paper, “Human-specific ARHGAP11B increases size and folding of primate neocortex in the fetal marmoset”, appeared online in Science on 18 June 2020 and in print on 31 July 2020.
The team introduced the human gene, under the control of its own human promoter, into marmoset embryos so that it would be active in the developing brain at roughly the levels seen in humans. Earlier experiments in mice and ferrets had used unnaturally high levels of the gene, which made the results harder to interpret. The pregnancies were ended at day 101, about 50 days before marmosets would normally be born, and the fetal brains were studied.
What ARHGAP11B is and why it matters
ARHGAP11B arose a few million years ago when part of an older gene, ARHGAP11A, was duplicated in the human lineage. It exists in humans but not in chimpanzees or other primates. Earlier research by the same group showed it boosts the number of basal progenitors, the stem-like cells in the developing cortex that generate neurons.
The neocortex is the outer layer of the brain involved in reasoning, language and planning. Humans have a particularly large and deeply folded neocortex, and scientists want to know which genetic changes helped produce it. Marmosets are useful for this question because their brains are small and almost smooth, so any increase in folding is easy to see.
What the researchers found
Compared with normal marmoset fetuses of the same age, the transgenic fetuses showed:
- a larger neocortex and a thicker cortical plate;
- folding of the brain surface, which is normally smooth in marmosets;
- more basal radial glia, progenitor cells in the outer subventricular zone;
- more upper-layer neurons, a type that has expanded during primate evolution.
The authors concluded that ARHGAP11B may have contributed to the expansion of the human neocortex during evolution. That is a claim about developmental mechanisms, not about how clever the animals would have been.
What the study did not show
Several claims that circulated online need correcting.
The brains did not double in size. Popular reports said the monkeys’ brains were twice their normal size after 100 days. The paper and the institute’s press release describe an enlarged neocortex and induced folding, not a doubling of the whole brain.
No intelligence or language was measured. The animals were never born, so nothing about behaviour, memory or language could be tested. Saying the brains became “more advanced in language and complex thinking” confuses anatomy with ability.
The fetuses were not born for ethical reasons. Huttner explained that the team limited the work to fetuses because the effects on brain function after birth were unknown, and that it was ethically necessary to study fetal development first. Japan’s rules for animal research are broadly comparable to Germany’s.
Earlier primate gene studies
This was not the first experiment to put a human brain gene into monkeys. In 2019, researchers at the Kunming Institute of Zoology in China, working with colleagues including the University of North Carolina, reported in National Science Review that they had created 11 rhesus monkeys carrying human copies of MCPH1, a gene linked to brain size. Those monkeys were born and tested. They showed slower, more human-like brain maturation and performed better on some short-term memory and reaction-time tasks than unmodified monkeys. That study was criticised by some scientists, who questioned both its ethics and how much small groups of animals can tell us about human evolution.
The ethical debate
Studies like these raise real questions, and the debate is more nuanced than “playing God” headlines suggest.
Arguments for the research
Supporters say primate models can reveal how the human brain evolved and how developmental disorders arise, such as conditions involving abnormal cortex size or folding. Mice and ferrets differ too much from humans to answer some of these questions.
Arguments for caution
Critics worry about animal welfare and about changing the minds of animals that are already highly social and cognitively complex. If an engineered primate developed abilities closer to ours, its moral status and appropriate treatment would become harder to settle. Many researchers, including some involved in this field, argue that primate experiments touching on human-specific brain genes need especially strict oversight and public discussion.
What about human embryos?
Some coverage suggested the work points toward “super-intelligent” designer babies. Nothing in this study involved human embryos, and heritable genetic modification of human embryos for reproduction is prohibited or tightly restricted in most countries.
The bottom line
The 2020 marmoset study is a careful piece of developmental biology. It showed that a single human-specific gene, expressed at natural levels, can enlarge and fold a primate’s fetal neocortex in ways that resemble human development. It did not produce intelligent monkeys, did not double brain size and did not involve live births. The real story is about how the human brain came to be, and about how far scientists should go in asking that question with other primates.
Sources: Heide et al., Science 369:546 (2020): Human-specific ARHGAP11B increases size and folding of primate neocortex in the fetal marmoset; Max Planck Institute of Molecular Cell Biology and Genetics press release via EurekAlert (June 2020); China Daily: Monkeys with human gene (MCPH1) study (April 2019).
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