A deadly virus created by genetic engineers breaks out of a test tube...

How to create a killerAlexey Torgashev, Russian Reporter magazine

"I was shocked," says Professor Evgeny Kandel.

He discovered that the method, which is used in thousands of biological laboratories, is capable of generating new viruses. The new disease may be comparable to cancer or AIDS. But technologies that pose a threat can be a salvation for millions of patients

A deadly virus created by genetic engineers breaks out of a test tube. A terrible disease affects experimenters, their relatives and residents of a defenseless town in the heart of America. An epidemic is about to sweep the planet. And the worst thing is that millions of future victims have no idea about anything…

Such a Hollywood beginning will do honor to any tabloid publication, only it will have a very indirect relation to reality. Because the discovery, which will be discussed, just allows you to prevent a biological threat. And because scientists are mostly sane people, and for more than thirty years of gene manipulation, not a single Hollywood plot has happened. There are security problems, sometimes with a tragic outcome, but new technology is a risk, and it is important to properly assess this risk.

The medicine of the futureSo, we are talking about genetic engineering, as well as about gene therapy – the introduction of new genes into human cells.

Let's say you have a suspicion that a certain mutant gene causes cancer. What does a researcher do? Transfers a piece of DNA with this gene into healthy cells, where it is embedded in the chromosome. These cells are specially grown outside the body in a so-called cell culture in Petri dishes. Then we look at what changes in the cell – for example, whether cancer occurs or not.

In this way, most of the information about how genes control our body and how the body controls our genes is obtained.

Gene therapy is even more promising. Cancer, diabetes, immunodeficiency, myodystrophy – almost all diseases can be treated if healthy genes are injected into a sick person. Scientists and doctors predict that gene therapy is the future of medicine. But…

– For me, it all started about two years ago, – says Evgeny Kandel, professor of oncology at the Roswell Park Institute in the American city of Buffalo.– My friend Robert Silverman studied prostate cancer and discovered a new virus in several patients. This virus turned out to be very similar to what I used in the lab every day – the mouse leukemia virus. I was shocked.

Virus as a means of transportationMice with leukemia virus are working in hundreds of laboratories around the world.

More precisely, they work not with the virus itself, but with gene constructs based on it – the so-called vectors. They are needed in order to transfer individual genes into mammalian cells and observe how they work there.

A gene is not a crate of beer that can be moved from one place to another to continue the party. This is a section of a DNA molecule with a beginning, an end, a certain sequence of elements, and so on. To transfer it from cell to cell, special methods are needed. When these methods were invented thirty years ago, the idea arose to use the mechanisms that nature had already invented.

The most famous of them are retroviruses (for example, HIV belongs to this family). It works like this: a viral particle merges with the cell membrane and spills its contents into a human or animal cell. The main thing in this content is the genes of the virus, which are first embedded in the chromosome, and then multiply, forcing the entire biochemical machine of the cell to work for itself, to collect new viral particles. Eventually, these particles leave the cell and infect neighboring ones. This is how the infection spreads.

When retroviruses were studied, it turned out that only a few genetic elements are enough for successful infection, and any other genes can be embedded between them. All other virus genes are deleted. That is, the virus ceases to be an "infection" and becomes nothing more than a vehicle.

This is how they learned to make viruses transfer useful "cargo" into cells. The convenience is that, having suffered once with the creation of such a hybrid molecule, then you can quickly infect many cells. Which they began to do.

A mouse and human mixture

The most studied was the mouse leukemia virus (MLV) – many vectors were made and are being made on its basis. To keep the process under control, the genes that are responsible for assembling new particles are removed from the virus. Special packaging cells are used to propagate such a virus. But when this vector penetrates into an ordinary cell, it no longer has the ability to reproduce.

That is, the system is triggered once, and the vector embedded in a new cell behaves simply as another one of tens of thousands of host genes. Fast, convenient, safe.

The main thing is that there is no other virus in the new cell that got there naturally: it can provide our vector with the missing reproduction mechanisms. Until recently, such a meeting in human cells was considered unlikely – where would a mouse virus come from in them?

Vectors carry a lot of genes in many laboratories, recently they have been used in gene therapy, that is, injected into patients for therapeutic purposes.

– The new virus discovered by Silverman was named XMRV. It was discussed mainly among oncologists, and its similarity to the mouse leukemia virus did not arouse much interest. But I've been creating vectors all my life," says Professor Kandel. – And I had a suspicion that a new virus could help our vectors multiply and produce viral particles. We immediately set up experiments that simulated the situation when a retroviral vector enters a cell where there is already XMRV.

During the experiments, the results of which were recently published in the journal PloS ONE, it turned out that yes, the vector begins to multiply actively and can infect new cells. And that's the problem.

To be treated for cancer, to die from infectionImagine a situation: a person is undergoing gene therapy.

For example, to fight blood cancer, healthy cells are injected that contain a gene for enhanced protection against chemotherapy. Vectors with transgenic material are used for this. Then "chemistry" is carried out in huge doses, all cancer cells die, and healthy and protected ones multiply and take the place of patients.

Now imagine that this person is infected with the XMRV virus. The resistance vector multiplies and is transmitted to neighboring cells, including cancer cells. Those accordingly become insensitive to any chemistry. And instead of recovery, we get a completely incurable option. And even with the risk of transmission to others.

Another example is accidental infection in the laboratory. It's even difficult to say what exactly a person can pick up, since the genes inside the vectors are absolutely any. If a laboratory vector gets to a human carrier, then he will not only get sick himself, but can also transmit it to others.

How will the new virus spread – during sex, with blood, through food? – no one knows that. Similarly, it is unknown what scale the epidemic may be.

"Potentially, a dangerous hybrid virus can also arise," says Kandel. – Artificial vectors often enhance the work of genes. For example, our constructions can function in those cells in which the usual "wild virus" is powerless. Such changes are useful for the vector to work, but if it gets into a cell with XMRV, a much more dangerous hybrid can come out.

Genetic Security ServiceThere are many such scary, but realistic scenarios that can be thought of.

It is clear that some kind of protection is needed from them. But how to defend yourself? After all, genetic engineering is good, and no one is going to give it up.

Professor Kandel claims that there is a defense, and not very complicated. For example, you can make "self-inactivating" vectors in which the ability to reproduce is blocked, even if they encounter a "wild" virus. With vectors based on the human immunodeficiency virus, for example, this is how you have to work. It's time to do the same with the mouse leukemia virus: what previously seemed like an unnecessary precaution has become a necessary security measure.

Of course, not everyone liked Dr. Kandel's discovery: many laboratories and biotech companies must now review their arsenal of genetic engineering "tools". And it costs money, and a lot of it.

Protection during gene manipulation works is not bad, especially where really dangerous viruses are used. But it has not yet been sufficiently studied which artificial gene constructs have already penetrated into nature – and whether they have. And there is very little information about how such structures can interact with natural organisms and viruses that inhabit them.

It seemed to many that the question was removed by itself after the Asilomar conference in 1975, when geneticists developed safety rules. But time goes on, new threats appear. Here there is another problem: you can only defend yourself from what the potential danger of which is already known. As in the case of vectors based on the mouse leukemia virus.

Portal "Eternal youth" www.vechnayamolodost.ru26.03.2009