Three-year-old rhesus monkey was cloned using 'Dolly method'

A rhesus monkey has been successfully cloned and has become the first of its kind to reach adulthood, Chinese scientists have revealed.

The researchers cloned the rhesus monkey using somatic cell nuclear transfer (SCNT) – the same technique used to clone Dolly the Sheep more than 25 years ago (see BioNews 1131) – in combination with trophoblast replacement (TR). ReTro, named after the new TR technique, is now three and a half years old, making him the first cloned rhesus monkey to have lived beyond birth in good health.

'We have achieved the first live and healthy cloned rhesus monkey, which is a big step forward that has turned impossible to possible, although the efficiency is very low compared to normal fertilised embryos,' said Dr Falong Lu, joint supervisor of the research at the Chinese Academy of Sciences in Shanghai, China.

The researchers published their work in Nature Communications, a few years after the birth of ReTro in July 2020. They described how they used SCNT, which involved transferring the nucleus from skin tissue of a 62-day-old monkey fetus into an egg cell that had had its nucleus removed. The developing embryo was then implanted into the uterus of a surrogate where it grew into a fetus, which was a clone of the skin cell donor.

ReTro is not the first monkey to be successfully cloned using SCNT. In 2018, the same team reported that Zhong Zhong and Hua Hua, two macaque monkeys who are still alive today, were the first monkeys cloned from fetal cells using SCNT (see BioNews 935).

Rhesus monkeys, however, are notoriously difficult to clone. In an attempt to minimise developmental abnormalities that can impede embryo survival, such as defective placentas, researchers developed trophoblast replacement.

Before implantation they removed the outermost layer of the developing embryo, named the trophoblast, which is responsible for placenta formation. It was replaced with a healthy layer taken from an IVF-generated embryo. This meant that the cloned fetus developed inside a non-cloned placenta, but researchers confirmed that this did not impact the genetic integrity of the clone.

The process of cloning has inherently been a controversial topic. Despite the researchers having followed Chinese laws and scientific guidelines, the creation of ReTro has resurfaced concerns surrounding animal welfare, ethical issues and implications for human reproduction.

'The methods do not get us any closer to reproductive cloning in humans – which has always been a nonsense idea. It would be unethical purely on grounds of safety,' said Professor Robin Lovell-Badge, group leader at the Francis Crick Institute in London and chair of trustees at PET (the Progress Educational Trust – the charity that publishes BioNews).

Rhesus monkeys are commonly used as experimental animals in clinical research, particularly for conditions like depression and anxiety. The creation of ReTro and other clones, will offer the use of genetically-identical animals for modelling of human diseases and evaluating the effectiveness of new drugs, while eliminating the impact of natural genetic variation.