Scientists have created the first human-pig chimera. According to the IFLscience.com portal, an international team of researchers conducted an experiment in which they managed to obtain an embryo that is a hybrid of a pig and a human.

Human stem cells were introduced into early-stage pig embryos. As a result, more than two thousand hybrids were obtained, which were introduced into the sow’s body. 186 embryos developed into chimeras - organisms consisting of genetically dissimilar cells.

Only 1 cell in 10 thousand of the embryo was human, but the fact that human cells took root at all and functioned as part of a single organism is already a big step for science. Previously, scientists were unable to crossbreed a human with another large animal. This is hampered, in particular, by the different rates of development of organisms: for example, pregnancy in humans lasts 9 months, in pigs - on average 112 days.

There is a worldwide shortage of organs for transplantation. People wait for years for an organ transplant; some die without waiting for a suitable donor. Despite this, scientific experiments that can solve this problem are causing great public outcry and debate about ethics.

Because of this, the US National Institutes of Health (NIH), the leading government agency responsible for medical developments, refused to fund such experiments in 2015. In August 2016, the NIH proposed lifting the moratorium on these studies, but this has not yet happened.

The pig and human embryos were allowed to develop for 28 days (this period corresponds to the first trimester of pregnancy in a pig). Once they had proven viable, they were removed from the sow's body.

“This is long enough to understand how pig and human cells mix, but not long enough to raise ethical debate about adult chimera animals,” said lead author Juan Carlos Izpisua Belmonte, a professor at the Salk Institute for Biological Studies in California. USA.
The idea of ​​creating a human-pig hybrid to provide organ transplants to those in need is truly amazing. The debate over the ethics of such experiments will continue for a long time, if ever. After all, today people who consume meat products every day somehow coexist in the same world and those who consider it unnatural to raise animals for the sole purpose of eating them.

Based on materials from: iflscience.com

The world has moved closer to one of the ethical dilemmas we didn't want to think about. Scientists produced the embryos by combining DNA from pigs and humans to make a so-called chimera. They developed for several weeks before being destroyed. It's safe to assume that hybrid embryos will soon develop further, but technical problems have made their formation more difficult than scientists expected.

How do chimeras appear?

Chimeras are organisms formed from two fertilized cells, or zygotes, taken from different species. As the name suggests, they should remain in the pages of JK Rowling or ancient mythology, but there are good reasons why some scientists want to create them. In particular, people are dying from a lack of donor organs such as hearts and kidneys. Chimeras created by combining fertilized pig and human cells could be a solution to this problem, providing organs similar enough to our own to be effectively transplanted.

Ethical issues

Many people think the idea even sounds horrific, but others argue it's no worse than raising animals, often in horrific conditions, just to eat them. Moreover, it would be difficult to explain to a person whose only hope of survival is a chimera's liver that this idea seems too repulsive to implement. Science fiction writers and philosophers have tried to grapple with this ethical problem for a while, but political institutions and the general public have tended to relegate it to the basket of complicated things that we don't have to worry about just yet.

Therefore, the announcement of the successful creation of a hybrid embryo serves as a wake-up call that we can no longer delay solving this problem and must address it now.

The initial stage of the scientists’ work

The efforts of lead researcher Professor Juan Carlos Belmonte of the Salk Institute and his team showed that there are more than just ethical obstacles to this issue. “The ultimate goal is to grow functional and transferable tissues and organs, but we are far from there,” Belmonte said in a statement. “This is an important first step.”

Belmonte began by placing rat stem cells into mouse embryos. Other researchers have done this before. He then used gene-editing tools to remove genes responsible for the development of specific organs in the mouse and replaced them with rat equivalents. “Rat cells have a functional copy of the missing mouse gene, so they can displace mouse cells and fill vacated niches for organ development,” said first author Dr. Jang Wu, also of the Salk Institute.

Why are pig embryos used?

Human stem cells have also previously been injected into mouse embryos, but the results have been insignificant. Belmonte and Wu went further and tried to inject human cells into cow and pig embryos. Some of the work with cow embryos turned out to be more difficult and expensive, and so the choice was made in favor of pigs.

But even after this, the work was not easy. It takes less than four months from conception to birth of a pig, so their development is much faster than that of humans.

Although the team was able to obtain intermediate human pluripotent stem cells to form a chimera within a pig embryo, the hybrid looked more like an animal than a human. The authors consider this a good result, since many of the biggest ethical problems arise when creating a creature with a human brain.

The embryos were destroyed after 3–4 weeks and demonstrated viability at this stage. The authors are working to install specific human genes into subsequent chimeras (as was done with rats and mice) to create more human organs.

The embryo is a hybrid of a human and a pig. Biologists from the USA, Japan and Spain introduced human stem cells into a pig egg. Scientists named the embryo grown in the womb of an animal a chimera - in honor of a creature from ancient mythology. In the future, these studies will allow scientists to grow organs for transplantation and study the nature of genetic diseases. In order for research to move forward, scientists must not only prove the effectiveness of the experiments, but also their ethicality.

What is the essence of the experiment?

A group of American scientists from the Salk Institute for Biological Research in California injected human stem cells into a pig embryo at an early stage of development and placed it in the womb of the animal. A month later, the stem cells developed into embryos with the rudiments of human tissue: heart, liver and neurons.

Of the 2,075 embryos transferred, 186 developed to the 28-day stage. The resulting embryos were “extremely unstable,” scientists admit, but so far they are the most successful human hybrid. Scientists write that the resulting chimera is a critical step towards creating animal embryos with functioning human organs.

Source: Cell Press

The ultimate goal is to grow organs that are functional and ready for transplantation; these experiments are the first step towards this, WP writes, citing scientists from California.

The results of a similar study are reported in the first issue of the journal Nature in 2017. As follows from the publication, a group of scientists from Japan and the United States managed to grow a mouse pancreas inside a rat, and then transplant the insulin-producing organ into diabetic mice, which did not cause immune rejection. This was the first confirmation that interspecies organ transplantation is possible, writes Nature.

Why is this necessary?

The main goal of scientists is to grow human organs using embryos of large animals. According to the US Department of Health, 22 people die every day waiting for organs for transplantation. Scientists have long tried to grow artificial tissues outside the human body, but organs developing in a Petri dish (the so-called container for growing microorganisms) are very different from those grown inside a living organism.

The technology for growing artificial organs will most likely be similar to the experiment with mice and rats, writes The Washington Post. The rats that received new cells as part of the studies described in Nature were genetically modified. They couldn't grow their own pancreas, so stem cells "filled the empty space." Some of the glands that appeared in rats were transplanted into sick mice. After surgery, the mice lived with healthy glucose levels for a year—half their life in human terms, writes WP.

The study proved that cross-species transplantation is not only possible, but also effective, senior study author Hiromitsu Nakauchi from Stanford University commented on the results. Scientists managed to “grow” the heart and eyes in the same way.

What are the difficulties?

Scientists from California achieved the first results four years after the start of research. According to them, pigs are ideal animals for the experiment. Their organs are about the same size, but they grow much faster than humans. In further research, the time factor should become the main one, the researchers admit.

“So far, the number of human cells in the resulting embryo is very small, and the whole process takes place at the early embryonic stage, so it is too early to talk about creating a full-fledged chimera,” Nakauchi’s colleagues commented on the result. In the resulting embryos, there was only one human cell per 100,000 pig cells (efficiency 0.00001%). "It's enough to achieve an efficiency of 0.1% to 1% of cells," one of the authors of the Californian study explained to the BBC.

After four weeks of development, scientists from the Salk Institute, for ethical reasons, destroyed the resulting embryos to prevent the chimera from fully developing. “We just wanted to answer the question of whether human cells can adapt at all,” explained one of the authors.

Ethical issues

In 2015, the US National Institutes of Health imposed a moratorium on funding for research that involves crossing human and animal cells. Since stem cells can develop into any human tissue, an animal with a human brain could eventually be created, some bioethicists believe. Others point to the violation of the “symbolic boundary” between humans and animals, writes WP.

Californian scientists say fears surrounding "chimeras" are more like myths than controlled experiments, but admit the possibility of an animal being born with human cells is a concern.

In August, the US National Institutes of Health allowed funding for chimera research to return. The organization proposes to allow the introduction of human stem cells into embryos at an early stage of development of large animals, with the exception of other primates.

“We have finally been able to prove that this approach to creating organs is possible and safe. I hope people understand this. Many people believe that this is science fiction, but now it is becoming a reality,” Nakauchi commented on the possible lifting of the ban.

Daniil Sotnikov

Preview photo: still from the film “Chimera”

Header photo: WikiCommons

Geneticists have grown a 4-week pig embryo with the rudiments of human organs

• Biotechnology,
• Geek Health

Rat-mouse chimera shows normal development of the embryo (B) and internal organs: kidneys, heart, liver, lungs, pancreas and brain within the host organism (C)

Pluripotency is a unique property of embryonic stem cells that can turn into any of the 200 known types of somatic cells, in accordance with a given embryonic development program and other conditions. Scientists have learned to take these cells from human embryos and cultivate them in the laboratory. Numerous experiments have shown that pluripotent cells retain the ability to differentiate into any cell type, including sperm and eggs.

But in laboratory conditions it is very difficult to grow a full-fledged organ from stem cells, since human physiology is almost impossible to recreate from scratch. Scientists do not yet know how to program cells with such precision. We need a natural environment where the program for the development of cells into the desired organ is activated on its own. The ideal environment would be a human or primate embryo, but such testing is prohibited by law. Therefore, scientists have found a way out in using embryos of animals physiologically close to humans - pigs and cattle. In developed countries, experiments on these embryos are still allowed.

Chimeras - organisms consisting of genetically heterogeneous cells - are excellent for solving this problem. Chimeras can grow organs from another organism. A number of such experiments were carried out by a group of scientists from the Salk Institute for Biological Research (California). In particular, they managed for the first time to create a chimera of a pig embryo with the rudiments of human organs.

Chimeras are very interesting organisms from a scientific point of view. They could become a valuable tool for scientific research, with potential for use in clinical trials and organ transplantation.

Now the situation with donor organs is very tense. For example, the average waiting time for a kidney is about 10 years. The average life expectancy on dialysis is 5 years. If the technique for growing chimeras is perfected, then a suitable kidney can be grown much faster, while the person is still alive.

Using the CRISPR-Cas9 gene editing technique and the latest stem cell processing technologies, scientists successfully implanted stem cells into embryos and grew various rat organs - pancreas, heart and eyes - in the mouse. This experiment confirmed the conceptual feasibility of this method of obtaining donor organs.

The researchers then implanted pluripotent human cells into pig embryos, studying the development of human tissues and organs. This is the first step towards more detailed research into growing human organs in other organisms that are suitable in size, physiology and anatomy.

In 2015, a team of scientists led by Izpisua Belmonte created the first chimera by following the development of human cells in a nonviable mouse embryo. Now they have gone further, using the CRISPR-Cas9 gene editing technique to direct the development of pluripotent cells into specific organs.

Using CRISPR-Cas9 genetic editing, scientists changed the host embryo by turning off genes that are responsible for the development of a specific organ - for example, the pancreas. Stem cells from another animal (rat) with an active pancreatic gene are then placed into the embryo. The embryo itself develops absolutely normally in the body of the surrogate mother, except for the fact that it has a foreign pancreas.

Exactly the same experiments were carried out with other organs in the rat-mouse chimera - eyes and heart. The scientists also discovered that the rat's pluripotent cells unexpectedly formed a gallbladder in the mouse embryo, an organ that is absent in rats. This indicates that the pluripotent cells of the donor are strongly influenced by the host organism and adopt its developmental programs.

However, growing human organs from pigs will not be easy. Scientists are highlighting a number of difficulties that arise when crossing very different living organisms, such as humans and pigs. Such difficulties do not exist when growing organs in genetically similar organisms. For example, the gestation period for humans and pigs varies greatly (for pigs it is 112 days).

However, an experiment with human organs in pig embryos was carried out. Human tissue precursors began to be created and developed until the embryo was four weeks old, although not with the same success rates as the rat-mouse chimera. Only a small number of cells survived - and they clearly did not develop into anything viable. The experiment was stopped to evaluate the safety and effectiveness of the technology.

Scientists admit that the ultimate goal of research with chimeras may be the cultivation of human organs and tissues on an industrial scale, but this is a very distant prospect. In the coming years, research in this area will have theoretical rather than practical significance. They will provide a better understanding of human embryonic development and help study some diseases that cannot be studied in any other way.