Nature, the First Genetic Engineer

Agrobacteria know-how

The mastermind of modern genetic engineering has become a modest bacterium, which induces crown galls in plants whose effect is analogous to the effect of tumors on animals. About 30 years ago scientists became aware that this agrobacteria possesses a marvelous capability of incorporating its genes into plant genomes. It does this using a plasmid (a circular piece of DNA) comprising two blocks of genes. One of them provides transportation and incorporation of another one, which carries the so-called oncogenes. The oncogenes begin to operate in a plant cell and give rise to galls, a kind of ‘food factories’ for bacteria.

Genetic engineering technologies are one of the most striking and challengeable scientific chievements of the XX century. “Hypotheses and Facts” section of this issue discusses transgenesis as a natural technique that is important for evolution and was borrowed from nature.
Progress in this field cannot be stopped even for safety reasons.
Billions of humans need GMO-based foods, medications and materials. There is no way back...

The natural technique for the transformation of the genetic material was borrowed from bacteria under laid the creation of transgenic plants. Scientists just replaced the block of oncogenes by various ‘helpful’ genes, which improve the quality of resulting transgenic plants. These are not the only examples of the activity of mother Nature as a genetic engineer. With advancements in molecular genetics and rapid accumulation of data on the structure of genomes of microorganisms, plants and animals, it has become clear that the exchange of genes between unrelated organisms is an everyday occurrence that plays its role in evolution. For more detail on the role of the horizontal transfer of genes in the course of evolution, the reader is referred to Transgenic Relatives by S. Shestakov.

There is an evident similarity between horizontal gene transfer, which is an evolutionary phenomenon, and transgenesis that occurs in laboratories. In both cases, alien genetic information is transferred to a donor organism’s genome and is expressed (works) there. But in the second case, the experiment is run and assessed by man, while in the other, natural selection is the arbitrator.

A trip that took thousands of years

Humans changed to settled lifestyle and to plant and animal breeding about 10—12 thousand years ago. At first they dealt with wild plants and animals, the products of natural evolution. Using that material, man started his own selection, which, as N.I. Vavilov put it, is yet another kind of evolution, the one controlled by man to serve his purpose.

Horizontal gene transfer, which is an evolutionary phenomenon, and transgenesis, which is confined to laboratory settings, have much in common

Today’s plant cultivars and animal breeds bear little resemblance with their wild ancestors and contemporaries. Moreover, some plant and animal species only occur as cultivars and breeds, for their ancestors have long been gone. Over 10 thousand years of plant and animal breeding the structure and function of the genetic material of these organisms have undergone rearrangements much more dramatic than those produced by genetic engineers who have only been on the scene for 30–40 years.

Advances in molecular genetics made it clear that the exchange of genes between the organisms that belong to different systematic categories is a commonplace

The only thing that the experimenters added to the ‘habitual’ affair of genome transformation was loosening or removal of some taxonomic limitations on genetic material transfer. New organisms emerge not only by selection of useful mutants or closely related crosses, but also by direct gene transfer to different genera, families, domains, and even kingdoms! This opened fantastic opportunities for obtaining plants, animals, and microorganisms with improved or novel characters and thus a new era for breeding was proclaimed.

DNA with all the trimmings

The development and use of transgenic or—as the media put it—genetically modified organisms (GMOs) have given rise to heated discussion, in particular, about transgenic plants, which have increasingly been used in foods. The dispute is fueled by those poorly informed persons who consistently argue that consumption of GM plants is harmful.

Although pig is considered among the animals closest to man, a half-pound pork chop contains about 0.5 gram of alien DNA

“To eat or not to eat” alien DNA? To answer this question, let us remind simple but seldom remembered biological axioms. As all animals and many microorganisms, man is a heterotroph. This means that, unlike plants, which are autotrophs, we need more than just water, solar energy and carbon dioxide to carry on, we need organic matter! And this matter is mostly contained in the cells and tissues of particular organisms, that is, is consumed in the form of meat, vegetables, eggs, and the likes.

Fried locust, pickled jellyfish, frog’s legs, blue-veined Roquefort…
The human stomach is able to digest all these, no matter how unique their DNA is

Any live cell contains genetic material in the form of DNA, and that is why the food we consume contains about 0.1 % of alien DNA. For thousands of years man’s ration has included representatives of all the kingdoms — from bacteria and fungi upward. Apart from animal, avian and fish DNA, we consume plant DNA and microorganisms’ DNA (yogurt, beer, to name a few).

Our encounters with nucleic acids are not limited to the kitchen, however. We deal with genetic material of viruses, bacteria, protozoa and fungi in tremendous amounts all the time both as our friendly symbionts and disease agents. We get bacterial DNA in with the air and dust we inhale. Myriads of microorganisms—up to 6 kg per capita!—inhabit our skin, mucous coats and intestines—and normally the coexistence is peaceful and mutually beneficial. Moreover, our little tenants can share their genetic material between themselves — thus, for instance, a gene for resistance to an antibiotic can be transferred— through ‘legal’ natural transgenesis. To say nothing of viruses, who incorporate their genetic material into our genome as a matter of course.

Fear me not

Might alien DNA be a threat? Might transgenic DNA be a threat? Higher organisms—especially animals and man—have developed, in the course of evolution, impressive means of neutralizing alien DNA. Special enzymes—nonspecific nucleases—split them into smaller non-functional fragments, which are later used as material for building functional molecules the organism needs.

Zounds of microorganisms (each — with its own DNA!) inhabit our skin, mucous coats and intestines, and normally our coexistence is peaceful and mutually beneficial

The share of transgenes in alien DNA consumed by man in tremendous amounts is infinitesimal: as a droplet of water added to a cask of water! Before being brought to the market, GMOs are checked for allergenicity, mutagenicity, carcinogenicity, etc. In all legally permitted cases, transgenes only encode the proteins that can do no harm to human health. The genetically modified organisms that fail to comply with the requirements are banned from use. It is therefore extremely difficult to figure out what ‘devastating effects’ can GMO possibly have on us — to date no such occurrences have been documented.

It is true that we have limited knowledge of the implications of exposure of human and animal intestinal cells to alien DNA and how these DNA are utilized. This, however, seem to be a general problem of our coexistence with a large pool of alien DNA belonging to hundreds of plant, animal and microbial species. This problem did not arise yesterday and it is not connected with the emergence of genetic engineering technologies. The development and use of transgenic organisms just fuel genetic engineering research, but do not change the situation qualitatively.

A ban against GMOs will not solve the problem of genetic safety, because it is very complex and the issue of genetically modified organisms only makes up a scanty share of it. Nevertheless, we emphasize that it is extremely important to study the implications of alien DNA ingress into human organisms with food to improve the test systems used to check the safety of ingredients obtained from transgenic plants.

Future world?

Due to improved quality — including better pest/disease resistance and technological effectiveness of cropping — transgenic plants are now being used in exponentially growing amounts. Imparting pest resistance — for instance, potato resistance to Colorado potato beetle — removes the need for pesticides, which are by themselves harmful for animals and man.

If I were to choose between transgenic plants and pesticides, I would select the former, because their ill effects are only being hypothesized about, whereas for the latter they are real. However, ungrounded acceptance or rejection of either way are equally unscientific. Instead, all the implications of the use of new foods, medications, materials, chemicals should be closely studied, which is being done in many laboratories worldwide. This is a long-term, difficult and expensive process, which should not be interfered with. Moreover, because lot of foods contain transgenic products harvested from millions of hectares, the process is irreversible.

Why waste effort trying to stop technological progress (by which we mean here genetic engineering-based breeding) in biology and agriculture? Is the matter really worth making a fuss about? After all, we only updated our collection of usual breeding tools—mutagenesis, polyploidy, gene shuffling, remote hybridization — by adding the transfer of genes from taxonomically more distant organisms using techniques learnt from nature. No big deal by itself, but what fantastic prospects!

True issues

Since all transgenic products are thoroughly tested for safety, real issues their use might have are not connected with their use for foods. I would mention two major problems ignored by the public or media. One is a possible escape of transgenes to wild conspecifics, which could lead to upset ecology in biocoenoses; another is coevolution of pest and host organisms.

Main risks related to genetically modified organisms are not those of their use for foods and fodder. More important biosafety issues escape the attention of the public and mass media

As far as transgene escape is concerned, the chances of it are low. In one of our experiments we assessed natural hybridization rates in cultured and wild soy, which is a self-pollinating plant. Even when pollen was applied artificially, we obtained only single seeds and no ‘working’ transgenes were detected in plants grown from them. Still, the escape issue should be seriously examined. Moreover, in some cases depending on the function of a particular transgene and the plant species, growth in isolation may be required.

Coevolution, — that is cooperative evolution, — of pest and host organisms represents a somewhat more difficult issue. Whenever we develop pest-resistant plants, pests undergo selection for more successful forms (like those with tolerance to plant toxins). As a result, pests become more resistant and plant breeders’ whole effort is eventually negated. When it takes place, a new strategy should be developed and new agents introduced.

Probably there are other issues related to the use of transgenic plants. Whatever they are, they all need to be thoroughly studied.

Awareness versus ignorance

Transgenic plants may have a lot of applications. They are considered not only as food plants, badly wanted in the current demographic situation, but also as potential suppliers of biologically active compounds. They are not yet widely used as such suppliers; however, in a long term, this trend may prove important, especially in the context of the so-called edible vaccines.

Development of new materials, including ultrahard ones, on the basis of transgenic plants, holds promise too. With the progression of scientific research, the field of application of transgenic plants will grow as well.

With the progression of science, fears of transgenic organisms should be eased to a great extent

The use of transgenic animals shows good promises. Cows and goats can be used as ‘bioreactors’ whose milk can provide unique biologically active compounds for medicine purposes… In this series of publications, however, we decided to focus on plants, because today they are in greater demand.

The attentive reader will wholly understand the role of gene shuffling and gene transfer run by nature via evolution and by the humankind via artificial selection. Some recent studies have shown that microorganisms have up to 20 % of their genomes shared! You will never learn this from a beer can or a yogurt bottle. And when we are eating or drinking whatever comes from transgenic plants, we should understand that this is just a speck of a droplet in uncharted waters churned up by genetic engineer Nature. Researchers still play with a very small set of pre-selected target genes, whose products humankind needs.

In the future, fears of transgenic organisms should be eased to a great extent. The attitudes will certainly change with the advent of improved biosafety tests and a better understanding of how alien DNA is utilized by animals and man. Trivial as it may seem, a special role should be attached to public awareness programs, for it is about time for the community to do a reality check.