Why three little virus-free pigs matter – The Messenger (subscription)

Posted: August 20, 2017 at 1:40 am

We've done some genetics. We've done DNA. We've done GMOs. We've done some immunology. We've done science literacy. Now, let's get down in the weeds a little bit and put all of that together to look at just exactly why virus-free piglets are news.

Aren't piglets just the cutest things? The three particular precious petite porkers in the picture have recently been making the rounds of the national news, usually under a headline that says something like "Scientists create virus-free pigs." This is an excellent example of a headline that really fails to do what a headline is supposed to, which is capture the reader's interest. Virus-free pigs. Big whoop.

If, however, you got past the lame headlines and you've read any of those stories, you know that this is sort of a big deal, on several different levels, and we'll use what we've already talked about in some of my earlier articles about genes, viruses, DNA, genetic engineering, and the value of science literacy to explore why these three little pigs are important.

These pigs are really just like any other pigs, except they were born without any genes in their genomes that code for a number of viruses found in all other pigs, called porcine endogenous retroviruses, or PERVs (yeah, I know. Not that kind of perv). Let's talks about what the term means and what PERVs are. The word "porcine" just means "related to pigs." "Endogenous" means "something that is normally found in or originating from within an organism." For instance, insulin is an endogenous human hormone, because it is produced by the pancreas and is normally present in people. "Retroviruses" are a group of viruses that use RNA (ribonucleic acid) instead of DNA (deoxyribonucleic acid) as their genetic material.

When a virus of any kind infects a cell, the reproductive machinery of the cell, which is normally used to make proteins and copy the DNA of the cell so that the cell can divide and reproduce, is hijacked by the virus. The virus causes the cell to make new copies of the viral genome and then to use the viral genes to make viral proteins. When the cell makes the new viral proteins, they are assembled into new viruses and the new viruses then can go out to infect other cells. Usually, the cell is destroyed in the process. Sometimes, though, the viral genes just get integrated into the genome of the infected host cell and the cell goes on living and reproducing as normal, only now, every time the cell divides, the new cell also has a copy of the viral genes in its DNA.

Sometimes, the viral genes just sit there, causing no

problems. This is called a "latent virus." It may sit there forever doing nothing, or sometimes, something happens to activate the latent virus and the viral genes start to be reproduced, viral proteins start to be made by the infected cells and that may cause disease. The Herpes simplex family of viruses is an example of latent viruses. Other examples of latent viruses are called retroviruses. In a retrovirus, the RNA from the retrovirus is used as a template to make DNA in the infected cell, and then the DNA becomes integrated into the host cell's genome. HIV is an example of a retrovirus that affects humans.

If you look at the genome of almost any organism, particularly complex organisms, like most of us, there is a lot of what is called "non-coding DNA." Non-coding DNA is exactly that -- it doesn't code for any specific proteins. There is some disagreement on whether this non-coding DNA has any function at all, but the amount of it is pretty amazing. Somewhere between 80 percent and 98 percent of the human genome is non-coding. This was a bit of a surprise when the Human Genome Project was going on in the 1990s.

The Human Genome Project was a very ambitious, very wide-ranging effort to identify all the genes in the human genome and map the location where each gene would be found on our chromosomes. The early expectation was that the human genome, based on the amount of DNA it contains (along with human ego), would contain hundreds of thousands of, possibly a million, individual genes. After all, something as marvelous as we are would obviously have the most genes of any creature, right? Wrong. The initial findings of the genome project was that humans have about 30,000 individual genes that code for proteins. This low number was quite the surprise. After all, there is a single-celled protozoan that has over 60,000 genes. There is a plant that has a genome almost three times the size of the human genome. Talk about you rude awakenings! Here we are, thinking how complex and wonderful we are, and there are flowers and pond scum with larger, more complex genomes than ours!

So, what does this have to do with our story today? Well, with the discovery that the vast majority of the human genome, and the genomes of most complex organisms, for that matter, doesn't code for proteins, it begs the question, "then why is it there and where did it come from?" Both of those are good questions that haven't been fully answered, but part of that "extra" DNA is probably DNA that originated long, long ago in our evolutionary history as viral DNA that got integrated into our own genome. The same is likely true for much of the PERV DNA in pigs.

In the case of PERVs, the viruses are found in most of the pig's cells, including the sperm and egg cells used in reproduction. Because they are in the reproductive cells, newborn pigs are already infected with the virus. The PERVs don't normally cause any disease in the pigs, as they usually remains latent in pig cells. The problem with PERVs is that they can be transferred to humans and infect human cells when pig organs or tissues are transplanted into people and PERVs can potentially cause disease in humans.

This is why scientists bothered to try to make virus-free pigs. Pigs have long been used as a source of organs and tissues for transplantation into humans. One reason for this is that the anatomy and physiology of pigs is very similar to that of humans, and so many of their organs and tissues are very similar to those of humans. Pigs and people are also of similar size, so swapping out parts works pretty well because, for instance, a heart valve from a pig is just about the same size as a heart valve from a human. Producing pigs that have tissues free of PERVs is a big step into making pig organs more available and safer for transplantation into humans.

The cute little virus-free piggies in the picture were created using a couple of genetic engineering techniques that are both revolutionary and controversial. The first technique is a new technology called CRISPR (pronounced "crisper"). It stands for "Clustered, Regularly Interspaced Short Palindromic Repeats." I'm not going to go into what all that means. What I will say is that it takes advantage of a genetic mechanism used by bacteria to avoid being infected by viruses. Yes, bacteria can be, and often are, infected by viruses. The CRISPR technology allows scientists to target specific gene sequences in the DNA of a cell, cut it out and replace it with a new gene sequence. CRISPR is hugely valuable in genetic research and has great promise in therapeutic use to treat genetic diseases. Theoretically, CRISPR could be used to cut out defective genes in a patient with a genetic disease and replace the bad gene with a good one. That sort of application is quite a way off. In the case of our pigs, however, CRISPR was used to cut out the genes for all the PERVs found in pig cells that were grown in a dish. The result of that was pig cells that were completely free of PERVs.

The second controversial technique that was used is called "somatic cell nuclear transfer." A somatic cell is just a term for any of the regular, non-reproductive cells found in an organism. In this technique, the nucleus of a cell, where all the genetic material is located, is removed. That nucleus is then transferred into another cell, from which the nucleus has also been removed, essentially turning the recipient cell into a genetic copy of the donor cell. If the recipient cell is a reproductive cell, like an egg cell, and the egg is fertilized, the genes contained in the donor cell will be present in all the cells that develop from the fertilized egg. In this case, the nuclei from the cells grown in the dish that were modified to be PERV-free were injected into fertilized pig eggs. The eggs were then implanted into surrogate mother pigs and they developed into our piglets.

This technology has incredible potential in transplant therapeutics, as well as gene therapy to correct some horrible diseases. Somatic cell nuclear transfer also has another name -- cloning. Dolly the Sheep, if you remember her, was the first mammal to be produced through cloning. The term "cloning" brings up all sorts of late-night horror movie terrors and visions of genetically engineered babies and so on. In reality, cloning is not fearsome or evil. It is just a fairly simple, very powerful tool in the field of genetic research.

However, here is where the science literacy part of the story comes into play. These techniques were used, in this case, as a step toward improving options for transplanted organs and tissues. It is theoretically possible, however, that these same techniques could be used for less clearly beneficial ends. It could, for instance, be further developed and adapted to be used to modify human embryos to create "designer babies." Clearly, this is an issue with profound bioethical considerations. It is important that we, as a human society, understand this science, and that includes you.

This technology, like other forms of genetic engineering, stem cell-based therapeutics, artificial intelligence, GMOs, and other equally powerful, potentially transformative science, could be hugely valuable in improving the human condition if used properly, but the consequences of abuse of the technology are also huge. We must be part of a well-informed populace to make reasoned, rational decisions on how we want our science to be used.

Already, the scientific communities of the U.S., UK, China, and others have set strict guidelines on what types of research along the lines of that which produced our virus-free pigs is permissible, but as science moves forward, there will need to be more discussion. The benefits and consequences of these technologies are so huge that we must discuss them from a position of knowledge and understanding, not from one of fear, ignorance and emotion. This is why it is so vitally important for everyone to be scientifically literate.

Michael J. Howard, Ph.D., is the vice president fo education and research at Baptist Health Madisonville. He can be reached by email at madisonvillescience@gmail.com or via Twitter at @madville_sci.

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