Desperate times call for desperate measures

The field of stem cell research began in 1981 with the discovery of embryonic stem cells by Martin Evans at Cardiff University, the U.K. In 1998, stem cell 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 much 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? It led the U.S. government to limit the federal funding of research on human embryonic stem cells because these embryos were destroyed.

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 In-Vitro Fertilization (IVF). It 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 to overcome 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 created embryonic-like cells from adult (mature) cells. This breakthrough was a game changer because it meant that embryos from abortions and IVF would 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 produce any cell or tissue the body needs to repair itself. This type of cell came to be induced pluripotent stem cells (iPSCs or iPS).

Time went by, and scientists continued to discover new ways to gain complete control of stem cells and turn them into any cell in the body. Thanks to the latest 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 feel 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 federal funding for human embryonic stem cell research.

The beginning of a 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 four months after receiving 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.

Adult vs. Embryonic stem cells

It is essential 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 a 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 with its genetic material removed. The unfertilized egg cell then develops and eventually produces stem cells. It was a giant leap! But there was one problem: an egg was involved in the process. We want to avoid using eggs for stem cell research to keep everyone happy and to avoid controversy.

Turning skin cells into egg cells and sperm

In 2016, researchers converted mouse skin cells into viable, fertile, mature eggs for the first time. Then, these same eggs were fertilized to create seemingly healthy pups. To achieve it, the researchers converted skin cells first into embryonic stem cells, then programmed these cells to become egg cells. It brings me back to the importance of embryonic stem cells. They have more potential and 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 more to it! Instead of extracting eggs from females to create stem cells, we could create an unlimited supply of eggs from as many skin cells as possible.

But egg cells alone are not enough. We still need sperm. Although males have an unlimited supply that 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 produced new healthy generations.

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

Artificial Embryos from stem cells

If you thought sperm and egg cells must make contact to create an embryo, then you probably haven’t heard of the extraordinary breakthrough made at the University of Cambridge. The researchers developed artificial embryos using two types of stem cells: embryonic stem cells and extra-embryonic trophoblast stem cells. The extra-embryonic trophoblast stem cells are typically 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 scaffold cells began forming what looked like a natural mouse embryo. If such embryos could function as much as natural ones, it would be possible to create an unlimited supply of human embryos from scratch without needing sperm and eggs. Moreover, identical embryos could eventually grow into human beings with a new process.

CRISPR and stem cell research join forces

Existing research showed us that turning skin cells into functional embryos that could be used to create whole organisms is not so complicated. 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. So we’re looking for something more! Something extraordinary! Luckily, this problem is solvable thanks to the power of genetic engineering.

You can genetically engineer human embryos in China if you follow certain guidelines. Because the rules and regulations are not as strict as in Europe and the U.S., 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 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 also becoming acceptable in other countries. For example, earlier in 2016, the U.K. granted scientists 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!

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 created from human skin cells. In other words, we will turn human skin cells into fully grown genetically engineered humans 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 birth.

Genetically engineered humans

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. We could enhance our intelligence, become more resistant to diseases and provide our bodies with new capabilities to counter challenging environmental problems. Imagine having the absolute power to fully control what your baby would look like before his or her birth! And that is just the tip of the iceberg!

Let’s take a simple case of something rather astonishing. Tardigrades (or water bears) are tiny creatures renowned for their ability to withstand extreme conditions such as space radiation and 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 human cells. The results were incredible! Human cells have become more resistant to X-rays and can now suppress X-ray-induced damage by about 40 percent. If we could integrate this ability into 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.

It seems that we will eventually be able to create human beings who combine the best genetic traits of other species. The scientists created the first human-pig hybrid embryos in 2016. They called them interspecies chimeras. Researchers hope these chimeras will eventually allow growing human organs in other animal species before transplanting them into those needing them. We have to consider, though, that these interspecies chimeras will someday be useful in creating humans with capabilities beyond what nature intended, and these capabilities will come from other species.

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 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 effort. However, adult humans already have trillions of cells (37.2 trillion cells), and it is nearly impossible to edit them simultaneously with our current technologies. And it probably won’t be achievable for many decades to come.

In addition, editing embryos is 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 in the long term.

The artificial womb

There is no doubt that creating functional and 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 complete human without needing a mother? Let’s find out.

There is a unique field called ectogenesis, where researchers attempt to replicate the exact conditions inside the uterus to allow 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 in 1955.

In terms of design, the artificial womb consists of two main sections: a nutrient supply chamber and a waste disposal chamber. The nutrient supply chamber is filled with artificial amniotic fluid, which usually 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 birth. The womb provides the ideal temperature for the fetus to develop and grow. Special pumps maintain warm water circulation to achieve a constant body temperature. All sounds exciting, but would it ever work?

In the 1990s, Tokyo University’s medical department researchers tested the artificial womb to see if it worked. First, 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.

In April 2017, researchers at the Children’s Hospital of Philadelphia (CHOP) repeated the same experiment with 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 grew 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 an artificial womb. So far, researchers have successfully used 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. Then, on day 14, the embryos were destroyed because the rules generally don’t permit growing human embryos for scientific research beyond that stage. Although the 14-day rule has been revisited by the International Society for Stem Cell Research to allow research on human embryos beyond 2 weeks, the new guidelines do not grant a permission to grow an entire human being from an embroyic cell. Keeping lab-grown embryos alive outside the uterus is the first step toward 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 womb’s lining. 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 this was done almost 20 years ago, the same cells extracted from the womb’s lining could be recreated from stem cells with our current technology. This will ensure an unlimited supply of such cells to build as many artificial support systems as possible. In addition, 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 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 the 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 sperm, while the other will be converted into egg cells. The sperm will 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 created from skin cells will be converted directly into embryos. The embryos will then be engineered using CRISPR-cas9, and we will continue the same procedure as in option 1.

As you can see, every step of this procedure has already been achieved. The remaining question is, when will we test this on humans? It may have already been tested, but we don’t know the results yet. It’s just a matter of time.

EctoLife Artificial Wombs

I recently released my concept for the world’s first artificial facility. It is called EctoLife and it can incubate up to 30,000 lab-grown babies per year. You can watch the video where I highlighted how how concept works. It is 100% based on scientific research that has been conducted for over 50 years.

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 routine as we look at babies born using IVF procedures. Yes, it faced huge resistance in the beginning, and 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?

There are around 35 billion skin cells in your body. The fact that these cells could be converted into human beings is 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.

REFERENCES:

1. Hansen, T., The Nobel Prize in physiology or medicine 2007. Scandinavian journal of immunology, 2007. 66(6): p. 603-603.
2. Jones, P.B., Funding of human stem cell research by the United States. Electronic Journal of Biotechnology, 2000. 3(1): p. 15-20.
3. Takahashi, K. and S. Yamanaka, Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. cell, 2006. 126(4): p. 663-676.
4. Holden, C., A first step in relaxing restrictions on stem cell research. Science, 2009. 323(5920): p. 1412-1413.
5. Schwartz, S.D., et al., Embryonic stem cell trials for macular degeneration: a preliminary report. The Lancet, 2012. 379(9817): p. 713-720.
6. Stuckey, D.W., et al., Engineering toxin‐resistant therapeutic stem cells to treat brain tumors. Stem cells, 2015. 33(2): p. 589-600.
7. Uth, K. and D. Trifonov, Stem cell application for osteoarthritis in the knee joint: A minireview. World journal of stem cells, 2014. 6(5): p. 629.
8. Mozid, A.M., et al., Stem cell therapy for heart diseases. British medical bulletin, 2011. 98(1): p. 143-159.
9. Vawda, R., J. Wilcox, and M. Fehlings, Current stem cell treatments for spinal cord injury. Indian journal of orthopaedics, 2012. 46(1): p. 10.
10. ME Abdel-Salam, O., Stem cell therapy for Alzheimer’s disease. CNS & Neurological Disorders-Drug Targets (Formerly Current Drug Targets-CNS & Neurological Disorders), 2011. 10(4): p. 459-485.
11. Pino, C.J. and H.D. Humes, Stem cell technology for the treatment of acute and chronic renal failure. Translational Research, 2010. 156(3): p. 161-168.
12. Hikabe, O., et al., Reconstitution in vitro of the entire cycle of the mouse female germ line. Nature, 2016. 539(7628): p. 299-303.
13. Zhou, Q., et al., Complete meiosis from embryonic stem cell-derived germ cells in vitro. Cell Stem Cell, 2016. 18(3): p. 330-340.
14. Harrison, S.E., et al., Assembly of embryonic and extraembryonic stem cells to mimic embryogenesis in vitro. Science, 2017. 356(6334): p. eaal1810.
15. Araki, M. and T. Ishii, International regulatory landscape and integration of corrective genome editing into in vitro fertilization. Reproductive biology and endocrinology, 2014. 12(1): p. 108.
16. Liang, P., et al., CRISPR/Cas9-mediated gene editing in human tripronuclear zygotes. Protein & cell, 2015. 6(5): p. 363-372.
17. Kang, X., et al., Introducing precise genetic modifications into human 3PN embryos by CRISPR/Cas-mediated genome editing. Journal of assisted reproduction and genetics, 2016. 33(5): p. 581-588.
18. Callaway, E., UK scientists gain licence to edit genes in human embryos. 2016.
19. Ma, H., et al., Correction of a pathogenic gene mutation in human embryos. Nature, 2017. 548(7668): p. 413-419.
20. Jönsson, K.I., et al., Tardigrades survive exposure to space in low Earth orbit. Current biology, 2008. 18(17): p. R729-R731.
21. Boothby, T.C., et al., Tardigrades use intrinsically disordered proteins to survive desiccation. Molecular Cell, 2017. 65(6): p. 975-984. e5.
22. Hashimoto, T., et al., Extremotolerant tardigrade genome and improved radiotolerance of human cultured cells by tardigrade-unique protein. Nature communications, 2016. 7: p. 12808.
23. Wu, J., et al., Interspecies chimerism with mammalian pluripotent stem cells. Cell, 2017. 168(3): p. 473-486. e15.
24. Bianconi, E., et al., An estimation of the number of cells in the human body. Annals of human biology, 2013. 40(6): p. 463-471.
25. Artificial uterus. 1955, Google Patents.
26. Partridge, E.A., et al., An extra-uterine system to physiologically support the extreme premature lamb. Nature communications, 2017. 8.
27. Aach, J., et al., Addressing the ethical issues raised by synthetic human entities with embryo-like features. Elife, 2017. 6: p. e20674.
28. Bulletti, C., et al., The artificial womb. Annals of the New York Academy of Sciences, 2011. 1221(1): p. 124-128.