How does cloning work? | Live Science

The idea of human cloning was science fiction when it was first imagined. But in the last few decades, technological and scientific advances have made this a real possibility. Although the ethics of cloning a human are questionable, the technology has led to some promising reproductive and health therapies.

The most basic definition of cloning is the creation of an exact genetic copy of an organism, tissue, cell or gene, according to the U.S. National Library of Medicine. The how and why of cloning really depends on what is being cloned. There are three main types of cloning: Gene cloning, reproductive cloning and therapeutic cloning.

Related: How stem cell cloning works (infographic)

The most commonly applied type of cloning is gene cloning. At its most basic, gene cloning is a biochemical reaction that takes place in every single cell in every organism. It's the creation of a copy of genetic material from an existing strand of genetic material. This natural reaction can be recreated in the lab and is an essential tool for many aspects of biological research.

The most commonly discussed and debated type of cloning is reproductive cloning. This type of cloning creates genetic duplicates of whole organisms from the genetic material of an already-existing organism. A cloned organism is very similar to being an identical twin to the parent organism, just born later.

And perhaps the most medically applicable type of cloning for humans is therapeutic cloning, which creates cloned embryonic stem cells of a patient to create genetically identical cells that can treat a medical condition. "Therapeutic cloning refers to the use of embryonic stem cells that in our lab we derive from somatic cells from a patient's skin," Shoukhrat Mitalipov, an embryologist at Oregon Health & Science University in Portland, told LiveScience in an email. "In our research lab we can develop [these cells] into different kinds of cells in the body such as neurons or cardiovascular cells."

Yes, cloning is real, but it may not look like it does in science fiction stories.

Some types of cloning occur in nature regularly. For example, bacteria can reproduce asexually, essentially cloning themselves all the time. Similarly, parthenogenesis is a unique biological phenomenon that results in the spontaneous creation of natural clones it happens in some species of sharks, amphibians, lizards and snakes. In humans, every cell in the body is a clone of the first embryo cell created when the father's sperm fertilized the mother's egg, and identical twins are natural clones.

Related: Rare 'virgin birth' of shark in Italian aquarium could be first of its kind

Cloning is also very real in the biology lab researchers worldwide use gene cloning in many ways. For example, it can create large amounts of proteins for medications like insulin or be used to detect the presence of specific strands of DNA, like in the COVID-19 PCR test.

It has been more than a quarter of a century since researchers first cloned animals from adult cells. The most well-known animal clone is Dolly the sheep, created in 1996 at the University of Edinburgh. While not the first cloned mammal, Dolly was the first created from an adult cell, rather than an embryonic or fetal cell.

To create Dolly, researchers needed to clone 277 embryos, 29 of those were healthy enough to implant, but only one survived until birth. In those early years, cloned embryos faced many failures, and the animals born alive sometimes died prematurely. According to the National Human Genome Research Institute, sheep and other cloned mammals have had various organ defects, including the heart, brain and liver. Other reports suggest issues with premature aging, increased birth size and immune system issues.

Related: 20 years after Dolly the sheep, what have we learned about cloning?

The success of Dolly brought a flurry of media attention to cloning both its potential benefits and the world's fears. As a result, many countries rushed to ban cloning of all kinds.

Nevertheless, in the decades since Dolly, animal cloning has come a long way. Some services will clone pets, as Barbra Streisand had done with her pet, Smithsonian Magazine reported. Some companies will even clone an entire polo team. Polo team La Dolfina, and world-class player Adolfo Cambiaso, have for several years used cloned horses, according to a 2016 article in Science magazine.

Related: Cloning mammoths is still a dream.

The work to clone other animals has been a slow, uphill battle but over the past few decades, researchers have been working their way toward cloning humans.

In 2007, Mitalipovs research team cloned the first primate embryos rhesus macaque and used them to create embryonic stem cells, publishing the process in the journal Nature. But it took until 2018 for these technologies to result in a living cloned monkey, achieved by a team of Chinese scientists and described in their paper published in the journal Cell, Live Science previously reported. The researchers made about 80 cloned embryos, ending up with six pregnancies and just two live births.

Six years after cloning the monkeys, Mitalipovs team created embryonic stem cells from cloned human embryos, research he published in 2013 in the journal Cell. At this point, many of the technologies needed to create human clones exist, but there are still many roadblocks and ethical arguments against using them to clone a human.

As cells grow and divide, they naturally create clones using cellular division, a process called mitosis. The cells use proteins and enzymes coded in their genes to copy their genetic material. As researchers developed an understanding of how cells reproduce their genes, scientists began recreating these reactions in the lab. Now, cloning genes in the lab is as easy as mixing a drink combining the proteins that cells use to copy their DNA and adding a gene to copy.

"Cloning DNA or cells is simple; it's the nature of DNA to replicate itself," Mitalipov said. "But when we say cloning of an entire organism, that's much more complex."

Most multicellular organisms replicate themselves through sexual reproduction. This process takes half of the genetic code from one organism (an egg) and half from another (a sperm). It remixes them, creating a single cell that can turn into a whole new being an embryo that might grow into a new organism if it implants in the right uterus.

But the goal of cloning is to create an embryo without remixing the genome. To do this, the researchers first start with a body cell, called a somatic cell. Somatic cells make up the majority of the body the skin, internal organs, brain cells. A somatic cell's genome has been "set" like jello into a specific shape.

Differences in the structure of somatic cell DNA dictate what genes the cell can express, according to the U.S. National Libraries of Medicine. The differences in gene expression, dictated by chemical changes called epigenetic modifications, determine how the cell looks, how it acts, and what it does in the body. And that process is limiting that cell then can't do anything else in the body. It will just age and die, and be broken down into parts to be reused.

Embryonic cells, or stem cells, on the other hand, have the potential to become any type of cell in the body because the genes they can express aren't locked in like they are in somatic cells. Researchers use both types of cells to create clones. The process originally used to create Dolly the sheep is called somatic cell nuclear transfer, as described in a 2015 review in the journal Philosophical Transactions of the Royal Society B. In this process, scientists remove the nucleus, or genetic hub, of a somatic cell and insert it into an egg cell that has had its genome removed.

If successful, this process will reset the somatic genome's epigenetics, and result in a cloned embryo with an exact copy of the genome of the somatic cell without the epigenetic modifications. It sounds straightforward, but the process is incredibly finicky to be successful the egg needs exactly the right conditions, and these conditions differ with every species. So, when scientists attempt to clone a new animal, they're faced with making many adjustments to the general process, Mitalipov said.

"You'd have to resolve lots of mysteries and there's no standard protocol to do it," Mitalipov said. "Everything needs to be tweaked a little bit depending on the difference in species."

These might have to do with the chemical environment (including the presence of caffeine in the petri dish for human embryos) that the experiment is performed in, the application of a jolt of electricity, the timing of the steps and even how forcefully the embryo is touched while removing and inserting the somatic cell nucleus.

In his 2013 Nature paper, Mitalipov and his colleagues showed that they had found the conditions to successfully clone a human somatic cell into an embryo, which was then used to create a human embryonic stem cell line.

Following the Mitalipov team's breakthrough in 2013, and the first cloned primates in 2018, the world has been waiting to see if anyone would actually clone a human. But this hasn't happened yet.

But is it possible? The short answer is likely yes. The technology exists and there's nothing significantly different about how human genes or genetics work compared with those of other animals that have been cloned. But, based on the difficulties experienced in developing cloned animal embryos into living, full-term births, there's no saying what types of conditions or diseases a human clone might have if one was born. We also know that it would likely require creating many many embryos to get one live birth a very ethically murky proposition.

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Additionally, humans (and other animals) are more than their DNA. The environment human bodies and brains are exposed to in the womb, during development and extending through childhood and young adulthood, plays a big part in creating who a person is. And just as epigenetic modifications alter how genes are expressed to create specialized somatic cells, they also reflect the things cells and bodies have gone through adding another major layer of complication into the question.

families, many others believe this kind of research is ethically problematic.

The creation and destruction of human embryos is a sticking point for many major religions, and others worry about the potential diseases and conditions that this process might inflict on a cloned baby.

Related: Human cloning? Stem cell advance reignites ethics debate

For these reasons and more, many countries and U.S. states have put bans on human cloning experiments. In the U.S., there are no federal laws against cloning humans, but multiple states have laws prohibiting cloning for any purpose. Multiple others prohibit funding of human cloning. According to intellectual property attorneys Knobbe Martens, 10 states allow the creation of human cloned embryos but prevent them from being implanted researchers can destroy them to create embryonic stem cell lines.

The use of three-parent IVF is illegal due to a 2015 amendment introduced by Rep. Robert Aderholt, a Republican from Alabama, to the 2016 appropriations bill. The amendment forbade clinical trials of heritable genetic modifications. However, patients and scientists are pushing to change that, according to STAT News.

More than 30 countries ban human cloning experiments, according to a 2007 review published by Rice University. In 15 countries, there are bans on human reproductive cloning but not on the creation of cloned embryonic stem cells. Other countries do not have any specific legislation banning human cloning.

While polo ponies are no doubt important to some, there are several other ways that technologies developed through these cloning experiments may be important in the future, Mitalipov said.

Mitalipov's work on somatic cell nuclear transfer in humans has led directly to the development of reproductive technologies that allow women with mitochondrial diseases (which these women pass down to offspring through their eggs) and infertility issues to have healthy children that are genetically related to them. Previously, women with mitochondrial diseases had no recourse other than to pass their condition on or not have biological children.

Now, technology developed by Mitalipov's lab is used to strip donor eggs of their DNA and move the nucleus from the mother's egg, resulting in a healthy embryo that is genetically related to the mother, according to a 2014 review in the journal Fertility and Sterility. Multiple "three-parent babies" have been born using these methods at clinics in the Ukraine and Greece, according to STAT News.

Related: Prenatal genetic screening tests: Benefits & risks

The ability to create cloned embryonic stem cells using somatic nuclear transfer is also promising for developing therapies that a patient's immune system wouldn't reject. These clonal stem cell therapies could create new organs or cells for people that could replace damaged ones.

"You can theoretically use those cells to treat a patient with a neurodegenerative disease or a cardiovascular disease," Mitalipov said. These cells "could, in theory, lead to the development of stem cell therapies treating neurodegenerative diseases like Parkinson's, cardiac disease and spinal cord injuries."

The cloned stem cells can be created now, but there are roadblocks on the research and clinical end to developing these therapies.

"Unfortunately, no therapies have been developed yet," Mitalipov said. "We can grow neurons in a petri dish, but how do you integrate neurons into the brain or other types of cells into relevant organs like the heart? It's going to be very difficult."

In the future, Mitalipov hopes that some of the technologies he's working on now can help create genetically related babies for same-sex couples or infertile couples. For example, his lab is currently figuring out how to remove half of the DNA from a cloned embryonic cell to create an egg cell.

If researchers create a cloned egg cell from the somatic cells of a man or infertile female, it could then be fertilized with the sperm from another man, creating an embryo. Using the cloning technology this way would give same-sex or infertile couples a way to have genetically related babies.

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How does cloning work? | Live Science