Science has made a step forward by making human cloning technically possible. However, is this a guarantee that this technology is going to be institutionalised?
Rustam Gilfanov is an investor, philanthropist and a partner of the LongeVC fund.
It was 25 years ago when Dolly, the famous sheep, was cloned. Even at that time, it was vivid that this experiment would be an essential step forward for biomedicine. Since then, people have experienced commercial cloning of pets, managed to recover endangered species, and came to the conclusion that it was entirely unethical to clone human embryos.
This article explains in what way modern methods of cloning can help people live longer and what pitfalls this technology may have.
Types of cloning: natural, molecular, and multicellular
The term “clone” was initially used to denote plants proliferated from the same original by vegetative methods. With time, it started also being applied to bacteria cultivation.
Unlike plants and bacteria, natural cloning is also related to some animals. It happens during apomictic parthenogenesis at the time when egg cells develop into mature organisms without fertilizing. There is another example: polyembryony. This is the phenomenon when two or more embryos develop from one zygote. This “splitting” is known to happen among people in the case of monozygotic twins, who are identical to each other.
Another type of cloning recognized by scientists is molecular cloning. It became possible as soon as nucleus structure, tissue cells, DNA, chromosomes, and genes were discovered. Scientists even learned how to duplicate complete DNA molecules: genes, their combinations and fragments, as well as DNA sequences. Methods of molecular cloning were adopted to study the behavior of genes and the synthesis of recombinant proteins. Scientists learnt how to develop genetically modified organisms and apply gene therapy methods.
The third type of cloning is related to multicellular organisms. It became possible due to achievements in gene engineering. Scientists make up specific conditions to interfere with the nuclear structure of the cell by forcing it to transform into a certain tissue or a full-fledged organism. Full (or reproductive) and partial cloning can be singled out: the first one produces a copy of the whole organism, while the second one — specific tissues or organs.
The most successful method of cloning is nuclear transfer. It involves removal of an enucleated cell and replacement of its DNA with another organism’s DNA. After numerous divisions, the new cell becomes a blastocyst which is an early-stage embryo that consist of hundreds of DNA that are almost identical to the prototype.
The nuclear transfer can be introduced with the aid of a classical example: the creation of Dolly which was a genetic copy of a dead sheep. It happened in the late 1990s. Conducting that experiment, scientists used the prototype cells that had been frozen and kept in liquid nitrogen.
As far as human cloning is concerned, at the moment there are no human clones. The technology of human cloning would require creating an embryo and developing it into an individual with the same genotype as their prototype.
Therapeutic cloning
Therapeutic cloning is used in biomedicine for culturing stem cells and discovering therapies for incurable diseases. It deserves certain attention. This cloning type is called therapeutic because during the first two weeks, embryonic cells can change into specific tissue cells of the heart, kidneys, pancreas, liver, and other organs. These tissues can be used to treat Alzheimer’s, insulin-dependent diabetes, kidney, blood disorders, Parkinson’s, heart, liver, bone, and other diseases.
For example, this technology enables scientists to transfer the nucleus of a somatic cell (that is any cell not involved in reproduction) to a donor egg cell that will divide into a blastocyst. The embryonic cells that comprise the inner layer can subsequently form the fetus. Although affecting certain growth factors would enable it to create artificial skin or an artificial thyroid gland.
Therapeutic cloning is already actively applied for human treatment. True, this happens only in a few countries (notably the UK, Australia, and the USA), where this technique is explored. In the UK, scientists are permitted to carry out stem cell research for medical purposes.
At the same time therapeutic cloning of animals can be united with genome editing methods. For instance, two genetically modified Labradors with a decreased risk of hip dysplasia were created in South Korea. The geneticists that go on working on this project combined cloning and prime editing mechanisms for correcting the mutations accumulated throughout the process of selection. Before that, Korean scientists integrated gene editing tools and cloning for generating beagles to model the progression of Parkinson’s.
Reproductive cloning
Reproductive cloning is another type of cloning. This is a laboratory method focused on creating a genetically identical copy of any organism. The first big animal that was successfully cloned was Dolly mentioned earlier.
Reproductive cloning can be of great practical value. For example, in agriculture it enables farmers to get animals or plants with the required parameters, e.g., potatoes resistant to Colorado beetles, cows producing record amounts of milk, wheat that can be harvested several times a year, etc. In addition to that, cloning experiments are helpful in treating various plant or animal diseases, because new medicines and vaccines can be tested on the artificial “copies”.
This biotechnology can also assist with restoring the population of extinct or endangered species. In 2020, for example, the San Diego Zoo announced the birth of Kurt, the world’s first cloned Przewalski’s horse, created from the cells that had been frozen 40 years ago.
The technology has also become popular among pet owners always wishing their animals to have a longer lifespan. Thus, several US laboratories can recreate a cat, a dog, or a guinea pig if they pass away. Little Nicky, a clone of a 19-year-old cat was the first commercial clone. It cost the owner $50,000 to grant the kitty a second life. It was done by Genetic Savings & Clone company.
Technological aspect
Sometimes scientists carry out cloning experiments on monkeys. For example, in China two healthy macaques were cloned via somatic cell nuclear transfer. Some attempts happened to be less successful, because embryos failed to develop, and some genes had already been “preset” to perform certain biological tasks. At the same time Chinese scientists managed to “override” those settings. They initiated a chemical cell reaction that changed the DNA-folding proteins and finally deactivated undesired genes.
It was another challenge scientists had to struggle with: they were searching for ways to change one “adult” cell into several cell types (e.g., embryonic and extraembryonic) and then unite them as a whole.
In 2019, Juan Carlos Izpisua Belmonte, a Spanish biologist, became the first scientist who succeeded in resolving this task and generated chimeric human and monkey embryos. The scientist reprogrammed an adult mouse cell and multiplied it to get a culture of embryonic stem cells. Afterwards, the culture was reprogrammed and returned to the condition it could develop from into embryonic or non-embryonic cells. After that Belmonte applied a signaling pathway dictating the cells what to do. As a result, a blastocyst-like blastoid was formed and successfully implanted into a mouse uterus. In this way the Spanish scientist showed the third type of animal cloning.
The Belmonte’s method was adopted by scientists from Texas and Australia, as well as by those at the California Institute of Technology who published the preprint of their study on the biorXiv portal. All of them successfully developed structures with morphology and gene expression that were similar to human blastocysts.
According to the law, implanting those formations into a living woman’s uterus to analyze their viability is prohibited, the scientists performed their tests in vitro. They were observing them for only fourteen days, but it showed that the artificial embryos underwent the same development stages as live ones.
Philosophical issues of human cloning
Cloning a human cell is still a complicated issue. Biotechnology opponents go on saying that it results in finishing a new life. Moreover, nuclear transfer makes up a living organism, whose status has not been defined in any legal system in the world.
As for therapeutic cloning, now scientists are permitted to grow a human embryo for only fourteen days. After that, the embryo develops the primitive streak, considered to be the precursor to the central nervous system.
There is an important point: biologists do not perceive embryos as separate organisms, because they depend on external conditions and cannot survive outside their environment. On the contrary, religion states that embryos have a soul since conception, and thus it is a crime to kill or experiment on them. Moreover, the church as an institution thinks the idea of creating artificial humans to be extremely concerning.
Almost all religions (e.g., Islam, Orthodox Christianity, and Catholicism) completely criticize cloning technologies. In August 2000, Pope John Paul II severely criticized cloning in his speech at the 18th International Congress of the Transplantation Society in Rome. At the same time, Buddhism and Judaism have a more loyal attitude to biotechnologies.
In 1998, twenty-four out of forty-three Council of Europe member countries signed the Additional Protocol to the Convention for the Protection of Human Rights and Dignity of the Human Being. According to it, a stringent ban was imposed on human cloning. Now, this is the only international legal act that regulates the matter of cloning. At the same time, legislative restrictions on human cloning are stated in more than seventy countries.
Therefore, it is not permitted to create human clones anywhere in the world. Organ cloning is also forbidden in most countries. At any rate, before the first human clone is born, humanity will need to solve a lot of ethical and legal dilemmas. At the same time, it is necessary to keep in mind that it can solve the problem of treating severe diseases and extend human life.
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