Cloning: Philosophical, Technological and Medical Challenges and Opportunities – Rustam Gilfanov’s Opinion

Science came very close to making human cloning technically possible. But does it mean this technology will soon be institutionalized?

Rustam Gilfanov is a private investor, philanthropist and a venture partner of the LongeVC fund.

The famous Dolly sheep was cloned 25 years ago; even back then, it was clear this experiment would mark a milestone for biomedicine.

Since that, people introduced commercial cloning of pets, learned how to recover endangered species, and decided that cloning human embryos is absolutely (or almost absolutely) unethical.

Here we explain how modern cloning methods can help people to live longer and what pitfalls this technology may have.

Natural, molecular, and multicellular cloning

The term “clone” was originally used to describe plants propagated from the same original by vegetative methods. Eventually, it began to be applied to bacteria cultivation as well.

Apart from plants and bacteria, natural cloning is also present among some animals. It occurs during apomictic parthenogenesis when egg cells develop into mature organisms without fertilization. Another example is polyembryony, the phenomenon of two or more embryos developing from one zygote. As we know, this “splitting” can happen among people in the case of monozygotic twins, who are identical to each other.

The second type of cloning distinguished by scientists is molecular cloning, made possible after tissue cells, nucleus structure, chromosomes, DNA, and genes were discovered. Researchers even learned to duplicate complete DNA molecules: genes, their combinations and fragments, and DNA sequences. Molecular cloning methods have been adopted to study the expression of genes and the synthesis of recombinant proteins, as well as develop genetically modified organisms and gene therapy methods.

Finally, the third type is related to multicellular organisms and became possible thanks to gene engineering achievements. Scientists create specific conditions to interfere with the nuclear structure of the cell, forcing it to transform into a certain tissue or a full-fledged organism.

Full (also known as reproductive) and partial cloning can be distinguished: the former produces a copy of a whole organism, while the latter — specific tissues or organs.

The most successful method of cloning higher animals is nuclear transfer that involves removing an enucleated cell and replacing its DNA with the DNA of another organism. After multiple divisions, the new cell becomes a blastocyst — an early-stage embryo consisting of hundreds of DNA, almost identical to the prototype.

The classic example of nuclear transfer is the creation of Dolly, a genetic copy of a dead sheep, in the late 1990s. For that experiment, scientists used the prototype cells that had been frozen and stored in liquid nitrogen.

As for human cloning, no human clones exist in the world at the moment. The technology behind human cloning, to put it simply, would involve creating an embryo and developing it into an individual with the same genotype as their prototype.

Therapeutic cloning

Therapeutic cloning, used in biomedicine to culture stem cells and discover therapies for incurable diseases, deserves special attention. This cloning type is called this way because, throughout the first two weeks, embryonic cells can transform into specific tissue cells of the heart, liver, pancreas, kidneys, and other organs. Those tissues can be used for treating insulin-dependent diabetes, Parkinson’s, Alzheimer’s, heart, kidney, liver, bone, blood disorders, and other diseases.

For instance, this technology makes it possible to transfer the nucleus of a somatic cell (any cell not involved in reproduction) to a donor egg cell, that will divide into a blastocyst. The embryonic cells comprising the inner layer can eventually form the fetus; however, affecting certain growth factors would enable it to generate artificial skin or an artificial thyroid gland.

Therapeutic cloning is already applied for human treatment, but only a few countries (notably Australia, the UK, and the US) explore this breakthrough technique. In the UK, scientists are allowed to conduct stem cell research for medical purposes.

By the way, therapeutic cloning of animals can be coupled with genome editing methods. For example, two genetically modified Labradors with a reduced risk of hip dysplasia were generated in South Korea.

The geneticists working on this project combined cloning and prime editing mechanisms to correct the mutations that had accumulated throughout the selection process. Before that, Korean researchers integrated cloning and gene editing tools to generate beagles for modeling the progression of Parkinson’s.

Reproductive cloning 

Reproductive cloning is a laboratory method of creating a genetically identical copy of any organism. The first cloned big animal was Dolly, who we mentioned earlier.

This type of cloning can be of real practical value. In agriculture, for instance, it enables farmers to get animals or plants with the right parameters, such as potatoes resistant to Colorado beetles, wheat that can be harvested several times a year, or cows producing record amounts of milk. Besides, cloning experiments help to treat various animal or plant diseases, as new vaccines and medications can be tested on the artificial “doubles”.

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 been gaining popularity among pet owners, who always wish their animals had a longer lifespan. In the US, several laboratories can recreate (for a good amount of money) your favorite cat, dog, or guinea pig in case they pass away. The first commercial clone of this kind was Little Nicky, a “successor” to a 19-year-old cat. For $50,000, Genetic Savings & Clone company granted the kitty a second life.

Technological aspect

Scientists also perform cloning experiments on monkeys: in China, for example, two healthy macaques were created via somatic cell nuclear transfer. Previous attempts turned out to be less successful, with embryos failing to develop and certain genes being already “preset” to do specific biological tasks. Still, Chinese researchers managed to “override” those settings by initiating a chemical cell reaction that modified the DNA-folding proteins and eventually deactivated unwanted genes.

For a long time, scientists struggled with another challenge: they were looking for ways to transform one “adult” cell into several cell types (e.g., embryonic and extraembryonic) and then put them together as a whole.

In 2019, Spanish biologist Juan Carlos Izpisua Belmonte became the first researcher who managed to resolve this task and created chimeric human and monkey embryos. The researcher reprogrammed an adult mouse cell and multiplied it to get a culture of embryonic stem cells.

After that, the culture was reprogrammed again and returned to the state, from which it could develop into either embryonic or non-embryonic cells. Belmonte then applied a signaling pathway that dictated to the cells what to do; the resulting formation — a blastocyst-like blastoid — was successfully implanted into a mouse uterus. In other words, the Spanish scientist demonstrated the third type of animal cloning.

Belmonte’s method was adopted (this time using human cells) by researchers from Australia and Texas and scientists at the California Institute of Technology; the latter published the preprint of their study on the biorXiv portal. All those groups successfully developed structures with morphology and gene expression similar to human blastocysts.

Since the law forbids implanting those formations into a living woman’s uterus to analyze their viability, the scientists performed their tests in vitro. The observation took only fourteen days, but it revealed that artificial embryos undergo the same development stages as live ones.

Philosophical challenges of human cloning

Human cell cloning remains a complicated issue: opponents of biotechnology keep saying that it results in ending a new life. Besides, nuclear transfer produces a living organism, whose status has not been defined in any legal system in the world.

As for therapeutic cloning, nowadays scientists are allowed to grow a human embryo for fourteen days only. After that, the embryo develops the primitive streak, considered to be the precursor to the central nervous system.

An important nuance is that biologists do not treat embryos as separate organisms, as they depend on external conditions and cannot survive outside their environment. Religion, on the contrary, claims that embryos have a mind and a soul from the moment of conception, so it is a crime to kill or experiment on them. Furthermore, the church, as an institution, finds the idea of creating artificial humans extremely concerning.

Almost all religions (e.g., Islam, Catholicism, and Orthodox Christianity) unyieldingly condemn cloning technologies. In August 2000, Pope John Paul II harshly criticized cloning in his speech at the 18th International Congress of the Transplantation Society in Rome. Judaism and Buddhism, however, have a somewhat more loyal attitude to biotechnologies.

In 1998, twenty-four out of forty-three Council of Europe member states signed the Additional Protocol to the Convention for the Protection of Human Rights and Dignity of the Human Being that imposed a stringent ban on human cloning. As of now, this is the only international legal act regulating that matter. Meanwhile, legislative restrictions on human cloning are provisioned in more than seventy countries.

Thus, creating human clones is not allowed anywhere in the world; cloning of organs also remains forbidden in most countries. In any case, before the first human clone is born, humanity will need to address numerous ethical and legal dilemmas, while keeping in mind that there is the treatment of severe diseases and extension of human life on the other side of the scale.

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