Zhong Zhong (, born 27 November 2017) and Hua Hua (, born 5 December 2017) are a pair of identical
crab-eating macaque
The crab-eating macaque (''Macaca fascicularis''), also known as the long-tailed macaque and referred to as the cynomolgus monkey in laboratories, is a cercopithecine primate native to Southeast Asia. A species of macaque, the crab-eating macaqu ...
s (also referred to as cynomolgus monkeys) that were created through
somatic cell nuclear transfer
In genetics and developmental biology, somatic cell nuclear transfer (SCNT) is a laboratory strategy for creating a viable embryo from a body cell and an egg cell. The technique consists of taking an enucleated oocyte (egg cell) and implanting a ...
(SCNT), the same
cloning
Cloning is the process of producing individual organisms with identical or virtually identical DNA, either by natural or artificial means. In nature, some organisms produce clones through asexual reproduction. In the field of biotechnology, cl ...
technique that produced
Dolly the sheep
Dolly (5 July 1996 – 14 February 2003) was a female Finnish Dorset sheep and the first mammal cloned from an adult somatic cell. She was cloned by associates of the Roslin Institute in Scotland, using the process of nuclear transfer from a ...
in 1996. They are the first cloned
primate
Primates are a diverse order of mammals. They are divided into the strepsirrhines, which include the lemurs, galagos, and lorisids, and the haplorhines, which include the tarsiers and the simians (monkeys and apes, the latter including huma ...
s produced by this technique. Unlike previous attempts to clone monkeys, the donated
nuclei came from
fetal cells, not
embryonic cells.
[Scholarly sources:
*
*][Popular sources:
*
*] The primates were born from two independent surrogate pregnancies at the Institute of Neuroscience of the
Chinese Academy of Sciences
The Chinese Academy of Sciences (CAS); ), known by Academia Sinica in English until the 1980s, is the national academy of the People's Republic of China for natural sciences. It has historical origins in the Academia Sinica during the Republ ...
in
Shanghai
Shanghai (; , , Standard Mandarin pronunciation: ) is one of the four direct-administered municipalities of the People's Republic of China (PRC). The city is located on the southern estuary of the Yangtze River, with the Huangpu River flow ...
.
Background
Since scientists produced the first cloned mammal
Dolly the sheep
Dolly (5 July 1996 – 14 February 2003) was a female Finnish Dorset sheep and the first mammal cloned from an adult somatic cell. She was cloned by associates of the Roslin Institute in Scotland, using the process of nuclear transfer from a ...
in 1996 using the
somatic cell nuclear transfer
In genetics and developmental biology, somatic cell nuclear transfer (SCNT) is a laboratory strategy for creating a viable embryo from a body cell and an egg cell. The technique consists of taking an enucleated oocyte (egg cell) and implanting a ...
(SCNT) technique, 23 mammalian species have been successfully cloned, including cattle, cats, dogs, horses and rats.
Using this technique for primates had never been successful and no pregnancy had lasted more than 80 days. The main difficulty was likely the proper
programming of the transferred nuclei to support the growth of the embryo.
Tetra
Terrestrial Trunked Radio (TETRA; formerly known as Trans-European Trunked Radio), a European standard for a trunked radio system, is a professional mobile radio and two-way transceiver specification. TETRA was specifically designed for use by go ...
(born October 1999), a female
rhesus macaque
The rhesus macaque (''Macaca mulatta''), colloquially rhesus monkey, is a species of Old World monkey. There are between six and nine recognised subspecies that are split between two groups, the Chinese-derived and the Indian-derived. Generally b ...
, was created by a team led by
Gerald Schatten
Gerald Schatten (born 1949) is an American stem cell researcher with interests in cell, developmental, and reproductive biology. He is Professor and vice-chair of Obstetrics, Gynecology and Reproductive Sciences and Professor of Cell Biology a ...
of the
Oregon National Primate Research Center
The Oregon National Primate Research Center (ONPRC) is one of seven federally funded National Primate Research Centers in the United States and has been affiliated with Oregon Health and Science University (OHSU) since 1998. The center is located ...
using a different technique, called "
embryo splitting". She is the first "cloned" primate by artificial twinning, which is a much less complex procedure than the DNA transfer used for the creation of Zhong Zhong and Hua Hua.
In January 2019, scientists in China reported the creation of five identical
cloned
Cloning is the process of producing individual organisms with identical or virtually identical DNA, either by natural or artificial means. In nature, some organisms produce clones through asexual reproduction. In the field of biotechnology, c ...
gene-edited monkeys, using the same cloning technique that was used with Zhong Zhong and Hua Hua, and the same gene-editing
CRISPR
CRISPR () (an acronym for clustered regularly interspaced short palindromic repeats) is a family of DNA sequences found in the genomes of prokaryotic organisms such as bacteria and archaea. These sequences are derived from DNA fragments of bacte ...
-
Cas9
Cas9 (CRISPR associated protein 9, formerly called Cas5, Csn1, or Csx12) is a 160 kilodalton protein which plays a vital role in the immunological defense of certain bacteria against DNA viruses and plasmids, and is heavily utilized in genetic e ...
technique allegedly used by
He Jiankui
He Jiankui (; ; born 1984) is a Chinese biophysics researcher who was an associate professor in the Department of Biology of the Southern University of Science and Technology (SUSTech) in Shenzhen, China. Earning his Ph.D. from Rice University ...
in creating the first ever gene-modified human babies
Lulu and Nana
The He Jiankui affair is a scientific and bioethical controversy concerning the use of genome editing following its first use on humans by Chinese scientist He Jiankui, who edited the genomes of human embryos in 2018. He became widely known on ...
. The monkey clones were made in order to study several medical diseases.
Process
Zhong Zhong and Hua Hua were produced by scientists from the Institute of Neuroscience of the
Chinese Academy of Sciences
The Chinese Academy of Sciences (CAS); ), known by Academia Sinica in English until the 1980s, is the national academy of the People's Republic of China for natural sciences. It has historical origins in the Academia Sinica during the Republ ...
in
Shanghai
Shanghai (; , , Standard Mandarin pronunciation: ) is one of the four direct-administered municipalities of the People's Republic of China (PRC). The city is located on the southern estuary of the Yangtze River, with the Huangpu River flow ...
, led by Qiang Sun and
Mu-ming Poo
Mu-ming Poo (; born October 31, 1948) is a Chinese-American neuroscientist. He is the Paul Licht Distinguished Professor Emeritus at the University of California, Berkeley and the Founding Director of the Shanghai-based Institute of Neuroscienc ...
.
They extracted nuclei from the
fibroblast
A fibroblast is a type of cell (biology), biological cell that synthesizes the extracellular matrix and collagen, produces the structural framework (Stroma (tissue), stroma) for animal Tissue (biology), tissues, and plays a critical role in wound ...
s of an aborted fetal monkey (a
crab-eating macaque
The crab-eating macaque (''Macaca fascicularis''), also known as the long-tailed macaque and referred to as the cynomolgus monkey in laboratories, is a cercopithecine primate native to Southeast Asia. A species of macaque, the crab-eating macaqu ...
or ''Macaca fascicularis'') and inserted them into
egg cell
The egg cell, or ovum (plural ova), is the female reproductive cell, or gamete, in most anisogamous organisms (organisms that reproduce sexually with a larger, female gamete and a smaller, male one). The term is used when the female gamete is ...
s (ova) that had had their own nuclei removed.
The team used two
enzyme
Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products. A ...
s to erase the
epigenetic
In biology, epigenetics is the study of stable phenotypic changes (known as ''marks'') that do not involve alterations in the DNA sequence. The Greek prefix '' epi-'' ( "over, outside of, around") in ''epigenetics'' implies features that are "o ...
memory of the transferred nuclei of being
somatic cell
A somatic cell (from Ancient Greek σῶμα ''sôma'', meaning "body"), or vegetal cell, is any biological cell forming the body of a multicellular organism other than a gamete, germ cell, gametocyte or undifferentiated stem cell. Such cells compo ...
s. This crucial
reprogramming
In biology, reprogramming refers to erasure and remodeling of epigenetic marks, such as DNA methylation, during mammalian development or in cell culture. Such control is also often associated with alternative covalent modifications of histones.
...
step allowed the researchers to overcome the main obstacle that had precluded the successful cloning of primates until now.
They then placed 21 of these ova into surrogate mother monkeys, resulting in six pregnancies, two of which produced living animals.
The monkeys were named Zhong Zhong and Hua Hua, a reference to ''Zhonghua'' (, a
Chinese name for China). Although the success rate was still low, the methods could be improved to increase survival rate in the future.
By comparison, the
Scotland
Scotland (, ) is a country that is part of the United Kingdom. Covering the northern third of the island of Great Britain, mainland Scotland has a border with England to the southeast and is otherwise surrounded by the Atlantic Ocean to the ...
-based team that created Dolly the sheep in 1996 required 277 attempts and produced only one lamb.
The scientists also attempted to clone macaques using nuclei from adult donors, which is much more difficult. They implanted 42 surrogates, resulting in 22 pregnancies, but there were still only two infant macaques, and they died soon after birth.
Implications
According to
Mu-ming Poo
Mu-ming Poo (; born October 31, 1948) is a Chinese-American neuroscientist. He is the Paul Licht Distinguished Professor Emeritus at the University of California, Berkeley and the Founding Director of the Shanghai-based Institute of Neuroscienc ...
, the principal significance of this event is that it could be used to create genetically identical monkeys for use in
animal experiments. Crab-eating macaques are already an established
model organism
A model organism (often shortened to model) is a non-human species that is extensively studied to understand particular biological phenomena, with the expectation that discoveries made in the model organism will provide insight into the workin ...
for studies of
atherosclerosis
Atherosclerosis is a pattern of the disease arteriosclerosis in which the wall of the artery develops abnormalities, called lesions. These lesions may lead to narrowing due to the buildup of atheroma, atheromatous plaque. At onset there are usu ...
,
though Poo chose to emphasize
neuroscience
Neuroscience is the scientific study of the nervous system (the brain, spinal cord, and peripheral nervous system), its functions and disorders. It is a multidisciplinary science that combines physiology, anatomy, molecular biology, development ...
, naming
Parkinson's disease
Parkinson's disease (PD), or simply Parkinson's, is a long-term degenerative disorder of the central nervous system that mainly affects the motor system. The symptoms usually emerge slowly, and as the disease worsens, non-motor symptoms becom ...
and
Alzheimer's disease
Alzheimer's disease (AD) is a neurodegeneration, neurodegenerative disease that usually starts slowly and progressively worsens. It is the cause of 60–70% of cases of dementia. The most common early symptom is difficulty in short-term me ...
when he appeared on the radio news program ''
All Things Considered
''All Things Considered'' (''ATC'') is the flagship news program on the American network National Public Radio (NPR). It was the first news program on NPR, premiering on May 3, 1971. It is broadcast live on NPR affiliated stations in the United ...
'' in January 2018.
[*]
The birth of the two cloned primates also raised concerns from bioethicists. Insoo Hyun of
Case Western Reserve University
Case Western Reserve University (CWRU) is a private research university in Cleveland, Ohio. Case Western Reserve was established in 1967, when Western Reserve University, founded in 1826 and named for its location in the Connecticut Western Reser ...
questioned whether this meant that human cloning would be next. Poo told ''All Things Considered'' that "Technically speaking one can clone human
nbsp;... But we're not going to do it. There's absolutely no plan to do anything on humans."
See also
*
List of animals that have been cloned Banteng
*A Javan banteng calf was cloned from frozen cells using a cow as a surrogate, delivered via c-section on April 1, 2003, then hand raised at the San Diego Wild Animal Parks Infant Isolation Unit. It died due to an injury when it was less ...
References
External links
*
*
{{DEFAULTSORT:Zhong Zhong (Monkey)
2017 animal births
2017 in biology
2017 in China
Cloned animals
Identical twins
Individual animals in China
Individual monkeys
Macaca
Science and technology in China