Creating Human Beings From Skin Cells Is Possible

Stem cell research is one of my absolute favorite topics. This amazing field does not only reveal to us how our bodies function and develop, but also holds promising future applications that could help us treat severe diseases, which would not be treated otherwise. However, stem cell research can do more than just treat diseases. In this article, I will highlight the latest scientific breakthroughs to show you how we can turn a simple skin cell into a fully-grown genetically-engineered human being all thanks to the power of stem cells and genetic engineering.

Desperate times call for desperate measures

The field of stem cell research began in 1981 with the discovery of the embryonic stem cells by Martin Evans at Cardiff University, UK. In 1998, stem cells research became a hot topic in the mainstream media after scientists isolated human embryonic stem cells and grew them in the lab for the first time. Due to this breakthrough, stem cell research faced a lot of resistance from the general public. It raised questions about life, consciousness and human rights. At what point does one consider life to begin? If an embryo can develop into an individual, is it justifiable to destroy it or even use it for scientific research? This led the U.S. government to limit the federal funding of research on human embryonic stem cells because these embryos were destroyed in the process.

News headlines from 2001

In the late 1990s, human embryos for stem cell research were either obtained from elective abortions or donated by couples undergoing treatment for infertility In-Vitro Fertilization (IVF). This sparked a lot of controversy among anti-abortion activists who believed that human embryos should be off limits.

Scientists began to look for other ways to create stem cells in order to overcome the ethical concerns and make everyone happy. They were confident about the therapeutic applications of stem cells, so they were determined to keep this field going despite all the restrictions.

Endless supply of stem cells

In 2006, Japanese scientist Shinya Yamanaka managed to create embryonic-like cells from adult (mature) cells. This breakthrough was a game changer because it meant that embryos from abortions and IVF will no longer be needed to create stem cells. Instead, we can turn any adult cells into stem cells. By feeding these adult cells a small set of transcription factors (proteins) or reprogramming them genetically, it was possible to revert them to a pluripotent state. A pluripotent state means that these new cells can potentially produce any cell or tissue the body needs to repair itself. This type of cells came to be known as induced pluripotent stem cells (iPSCs or iPS).

This revolutionary technique allowed scientists to turn any cell in the body into induced pluripotent stem cells (iPS) with simple reprogramming techniques. The iPS cells could then be reprogrammed to become certain types of cells in the body. Credit: Genetic Science Learning Center

Time went by and scientists continued to discover new ways to gain full control of stem cells and turn them into any cell in the body. Thanks to the new methods of creating stem cells and the advocacy of their therapeutic applications, the general public began to understand the importance of this field. Because iPS cells are derived from different types of cells in the body, some people felt that genetic reprogramming is more ethical than creating embryonic stem cells from embryos or eggs. In 2009, the U.S. government lifted the 2001 restrictions on the federal funding for human embryonic stem cell research.

The beginning of a new revolution

In 2012, researchers announced that they had treated blindness with the help of human embryonic stem cells. Two patients with eye degeneration had their vision improved in the four months after they received implants of retinal pigment epithelial cells made from human embryonic stem cells. That was the tip of the iceberg of what stem cells could offer. More therapeutic applications followed and new treatments were devised for different diseases including – but not limited to – joint injuries, heart disease, spinal cord injury, diabetes, Alzheimer’s disease, kidney disease, brain tumors, and other types of cancer. Just as scientists predicted, stem cell therapy does indeed work! And right now it is becoming a standard procedure to treat different diseases in countries across Europe and Asia.

As soon as the general public, including media, witnessed the wonders of stem cell therapy, they became more supportive to the field.
Adult vs. embryonic stem cells

It is very important to understand the difference between adult stem cells and embryonic stem cells. Stem cells are divided into two types in terms of their development potential. Embryonic stem cells are generally more flexible and versatile than adult stem cells. In other words, embryonic stem cells can develop into almost every type of cell in the human body while adult stem cells can give rise to a limited number of cell types. So, embryonic stem cells are the great deal here! If we can create them in the lab, that would change everything forever! Why this is important will come later.

In 2013, scientists converted human skin cells into embryonic stem cells for the first time! The researchers used a cloning technique called Somatic Cell Nuclear Transfer (SCNT), which involves transplanting the nucleus of one cell, containing an individual’s DNA, into an egg cell that has had its genetic material removed. The unfertilized egg cell then develops and eventually produces stem cells. This was a giant leap! But there was one problem: there is an egg involved in the process. We want to avoid using eggs for stem cell research to keep everyone happy and to avoid the controversy.

Later on scientists used a technique called Somatic Cell Nuclear Transfer (SCNT) to create embryonic stem cells, which can develop into almost every type of cell in the human body.  Credit: Genetic Science Learning Center
Turning skin cells into egg cells and sperms

In 2016, researchers converted mouse skin cells into viable, fertile, mature eggs for the first time! These same eggs were fertilized to create seemingly healthy pups. In order to achieve this, the researchers converted skin cells first into embryonic stem cells, then programmed these cells to become egg cells. This brings me back to the importance of embryonic stem cells. They have more potential and they can give rise to almost any cell type, including egg cells.

Although researchers hope their breakthrough could help us eradicate infertility and allow couples to become the true biological fathers of their babies, there is actually more to it! Instead of extracting eggs from females to create stem cells, this meant we could create unlimited supply of eggs from as many skin cells as possible.

Scientists converted skin cells into egg cells and then used them to create functional embryos, which then developed and gave rise to 6 healthy pups. Credit: Orie Hikabe et al.

But egg cells alone are not enough. We still need sperms. Although males have unlimited supply which they’re prepared to donate for science, it’s best to stay away from all the controversy and keep looking for alternatives. In 2016, scientists created functional sperms from embryonic stem cells. The sperms were then used to fertilize mouse egg cells before implanting the embryos into female mice. The resulting mice appeared healthy and normal, and went on to produce new healthy generations.

Scientists converted embryonic stem cells into functional sperms, then used them to create healthy pups which went on to produce new healthy generation. Credit: Quan Zhou et al.

There is just one limitation here: they directly used embryonic stem cells instead of using skin cells, but that’s okay. In 2016, researchers managed to convert human skin cells into sperms. The skin cells were reprogrammed with the help of a cocktail of genes. Within a month the skin cells were transformed to become a germ cell, which can develop into either a sperm or an egg depending on what you feed them. Their promising study shows that we could actually create functional sperms from skin cells, which can be used to fertilize egg cells.

Artificial embryos from stem cells

If you thought sperms and egg cells must make contact to create an embryo, then you probably haven’t heard of the extraordinary breakthrough that was made at the University of Cambridge earlier this year. The researchers were able to create  artificial embryos using two types of stem cells: the embryonic stem cells and extra-embryonic trophoblast stem cells. The extra-embryonic trophoblast stem cells are normally found in the placenta. The mice embryos were created by placing the two types of stem cells onto a specially-designed 3D scaffold. Four and a half days later, the cells on the scaffold began to form what looked like a natural mouse embryo. If such embryos could ever function as much as natural ones, it would be possible to create unlimited supply human embryos from scratch without the need for sperms and eggs. The same embryos could eventually be used to grow human beings with a completely new process.

An artificially created three-dimensional model of a mouse embryo at 96 hours, left, and then an embryo cultured in a test tube for 48 hours from the blastocyst stage, right. The red colour denotes the embryo-like structure while the blue shows extra-embryonic material that would form the placenta. Credit: Sarah Ellys Harrison et al.
CRISPR and stem cell research join forces

Existing research showed us that turning skin cells into functional embryos that could be used to create full organism is not so complicated after all. But these embryos will still have the same problems that every other ordinary embryo has: they’re susceptible to genetic diseases, they could mutate and eventually experience serious health problems after birth. They may also give rise to ordinary human beings. We’re looking for something more! Something extraordinary! Luckily, this problem is solvable thanks to the power of genetic engineering.

In China you can genetically engineer human embryos if you follow certain guidelines. The rules and regulations there are not as strict as in Europe and the U.S. (see the map below), which is why some scientists migrate to China to take advantage of this situation. Chinese researchers engineer human embryos with the help of CRISPR-cas9, a revolutionary technique that can edit the genome of any cell with a high precision and accuracy.

In 2015, Chinese researchers announced that they had modified a gene linked to a blood disease in human embryos. This was the first time we learned about editing human embryos using CRISPR-cas9. Well, at least the one that was announced. And in 2017, another team in China reported introducing HIV-resistance mutation into human embryos. 4 out of 26 embryos were successfully modified, which proves that editing human embryos might actually work! It could eventually help us fix genetic disorders before a baby is born.

It’s not just in China, it’s actually becoming acceptable in other countries too. Earlier in 2016, the UK granted a group of scientists a permission to edit human embryos. And recently in the U.S., scientists reported the first ever U.S.-based successful attempt at engineering human embryos. They used CRISPR-cas9 to correct a gene mutation that causes a heart condition called hypertrophic cardiomyopathy, and it was a resounding success!

This map shows the legal restrictions on editing human embryos in different countries across the globe. Some countries allow editing human embryos if you follow certain guidelines while some others have ambiguous rules. Source: Araki and Ishii, Reproductive Biology and Endocrinology, 2014.

With all these amazing breakthroughs that we continue to learn about, it shouldn’t take too long before we master the science of re-engineering human embryos. And when that happens, the same techniques could be applied to embryos that have been created from human skin cells. In other words, we will manage to turn human skin cells into fully grown genetically engineered human beings with incredible capabilities beyond our imagination. The common term for them is “designer babies” because they have been customized or “redesigned” to possess certain genetic traits that have been precisely controlled before their birth.

Genetically engineered human beings

So, why exactly would we want to genetically engineer the human body? Simple answer: to overcome the limitations of nature and accelerate the new stage of human evolution, one that is controlled by our species itself. We could enhance our intelligence, become more resistant to diseases and provide our bodies new capabilities to counter the challenging environmental problems. Imagine having the absolute power to fully control what your baby would look before his or her birth! And that is just the tip of the iceberg!

Let’s take a simple case of something rather more astonishing. Tardigrades (or water bears) are tiny creatures renowned for their ability to withstand extreme conditions such as space radiation, extreme pressure (six times the pressure of water in the deepest point of the ocean, the Mariana trench). In addition to surviving in the vacuum of space, these creatures can turn themselves into glass to survive complete dehydration. Scientists discovered that these organisms produce a protein that protects them against damaging X-rays. They identified the gene responsible for synthesizing this protein and introduced it to humans cells. The results were incredible! Human cells became more resistant to X-rays and can now suppress X-ray induced damage by about 40%. If we could integrate this ability to a fully grown human being, we would overcome the danger of space radiation and travel to the farthest regions of the cosmos with minimal risks.

By entering a state known as ‘cryptobiosis’, tardigrades become nearly impossible to kill. Credit: Eye of Science

It seems that we will eventually be able to create human beings who combine the best genetic traits of other species. Earlier this year, scientists created the first human-pig hybrid embryos. They called them interspecies chimeras. Researchers hope that these chimeras would eventually allow growing human organs in other animal species before transplanting into those who need them. We have to take into consideration, though, that these interspecies chimeras will someday prove to be useful in creating humans with capabilities beyond what nature intended, and these capabilities will come from other species.

This pig embryo was injected with human cells during its early stage of development and grew to be four weeks old. The success demonstrates a step towards human organs in large animals. Credit: Jun Wu et al.
Why embryos?

If we are very serious about making humans more intelligent, why don’t we do it now? If we can create genetically engineered humans who can survive climate change, why don’t we do it on the existing 7.5 billion people? Spoiler alert: it doesn’t work that way.

There is a huge difference between engineering an embryo and engineering an adult human being. Genetic engineering works best on embryos because the number of cells is so low that you can edit all of them with minimal efforts. However, adult humans already have trillions of cells (37.2 trillion cells), editing all of them at once with our current technologies is near impossible. And it probably won’t be achievable for many decades to come.

In addition to that, editing embryos is also better and far more efficient because genetic information can pass through generations. If you genetically engineer an embryo to become someone intelligent, the intelligence will pass from generation to generation. Assuming that you did this to an adult, which is impossible, the intelligence would remain with that particular individual and will die as soon as s/he dies. That’s why we should work with embryos because any genetic traits introduced here will affect the entire species for a very long term.

The artificial womb

There is no doubt that creating functional developing human embryos from skin cells is indeed possible. But let’s take this one step further. Would it ever be possible to implant such embryos into an artificial support system that could replace the mother’s uterus? In other words, allowing the embryo to develop into a full human being without the need for a mother? Let’s find out.

There is a special field for this called ectogenesis where researchers attempt to replicate the exact conditions inside the uterus with the hope of allowing human embryos to develop in similar but completely artificial environments! And the concept isn’t really new. The growth pod where the embryo will develop is called the Artificial Womb, and it was first patented by Emanuel M. Greenberg back in 1955.

The first concept of the artificial womb was designed and patented by Emanuel M. Greenberg back in 1955.

In terms of design, the artificial womb consists of two main sections: nutrient supply chamber and waste disposal chamber. The nutrient supply chamber is filled with artificial amniotic fluid, which normally surrounds the fetus inside the mother’s uterus. It is needed to sustain the unborn fetus inside the womb. The device is also equipped with a container that provides the fetus with a constant stream of pure oxygenated blood until the moment of birth. The womb provides the ideal temperature for the fetus to develop and grow. Special pumps maintain the circulation of warm water to achieve a constant body temperature. All of this sounds exciting, but would it ever work?

In 1990s, researchers at Tokyo University’s medical department tested the artificial womb to see if it works. They removed a goat fetus from its mother by Caesarean section after 120 days’ gestation, about three-quarters of the way to its full term. Then they placed it in a rubber womb filled with artificial amniotic fluid, and the little guy was delivered 17 days later. You can see footage of the experiment below.

And earlier this year, researchers at the Children’s Hospital of Philadelphia (CHOP) repeated the same experimentwith a modified version of the old design of the artificial womb. They placed a premature lamb fetus inside the womb and kept it in the womb for four weeks. After four weeks, the lamb started to grow a wool coat, gained weight, and even opened its eyes. They successfully conducted this experiment on eight lamb fetuses and the results were promising. You can see the footage below.

The artificial womb is mainly designed to help premature babies to continue their development inside an artificial environment that simulates the mother’s uterus. And that’s great! But there is a big difference between placing a premature baby and an embryo in the artificial womb. So far researchers demonstrated success of using the artificial womb to host premature fetuses, what about embryos?

In 2016, researchers managed to keep lab-grown human embryos alive and active beyond the stage when they would naturally implant in a mother’s womb. The developing embryos were intact for 13 days. On day 14, the embryos were destroyed because the rules generally don’t permit growing human embryos for scientific research beyond that stage. Keeping lab-grown embryos alive outside the uterus is the first step towards finding a way to implant them in an artificial womb. So, we will just need one final factor: an artificial support system. Something that can hold the embryo in place. Guess what? It has already been done.

In 2002, researchers built mini artificial wombs that allow embryos to attach themselves and continue to develop. The prototypes were made out of cells extracted from the endometrium, the lining of the womb. These cells were grown into layers that were then used to coat scaffolds of biodegradable material. The scaffolds were modeled into shapes mirroring the interior of the uterus. The experimental embryos successfully attached themselves to the walls of these laboratory wombs and began to grow. However, the experiments were terminated 5 days later due to ethical concerns and “to comply with the In-Vitro Fertilization (IVF) regulations.” Considering that this was done 15 years ago, the same cells that were extracted from the lining of the womb could be recreated now from stem cells with our current technology. This will ensure unlimited supply of such cells to build as many artificial support systems as possible. These mini artificial wombs could be scaled up and integrated into the main growth pod where the fetus will develop; allowing embryos – instead of just premature babies, to take advantage of the system.

A modern design of the artificial womb. Credit: 2070: Edge of Science
A new way to create humans

Everything looks great so far. So, let’s put everything together and devise a new procedure to create human babies. First, you start by extracting skin cells from a single human. Age, sex and gender don’t matter. We just want the skin cell. The skin cell will then be cultured in the lab to obtain maximum number of cells. Then we use genetic reprogramming to turn skin cells into embryonic stem cells. Now we have two options:

Option 1: The embryonic stem cells will be divided into two groups. One group will be converted into sperms while the other group will be converted into egg cells. The sperms will be used to fertilize the egg cells to create viable embryos. We screen for the healthiest embryos before moving to the next step. Once we choose healthy embryos, we use CRISPR-cas9 to upgrade their genome and design them according to our own will. We remove the genes that are responsible for diseases and introduce genes that are responsible for good traits. After engineering the embryos, we screen them once again to ensure only a healthy embryo will be chosen. The healthiest embryo will then be implanted directly into the artificial womb. We keep it alive and active until a fully grown human being is ready to be reborn.

Option 2: The embryonic stem cells that were created from skin cells will be converted directly into embryos. The embryos will then be engineered using CRISPR-cas9 and from there we continue the same procedure as in option 1.

A summary of the procedure.

As you can see, every single step of this procedure has already been achieved. The remaining question is, when are we going to test this on humans? It is possible that it had already been tested but we don’t know about the results yet. It’s just a matter of time.

We can do it, but should we?

If you are now in your mid 50s, you will live long enough to see the world’s first synthetic human being come into existence. Creating customized humans will eventually become as normal as the way we look into babies born using IVF procedures. Yes, it will face a huge resistance in the beginning, so did IVF. And where is IVF now? Anyone can do it as long as they can afford it. But the question is, should we really do this? I will answer this question in part 2 of this article series. The second article will go beyond the ethical concerns to discuss whether or not we should do this.

There are around 35 billion skin cells in your body. The fact that these cells could be converted into human beings is really scary! But as long as we have ethical concerns with such techniques, it’s still a while before this procedure becomes normal and widely accepted by most people. And one last thing, the first synthetic human being would probably be born in China where embryonic stem cell research is flourishing thanks to minimal legislative restrictions.

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