The story of the healing golden rice and the human-hearted bunny - or the benefits of genetic modification today

- You mentioned in a conversation that the public is, unfortunately, a good ten to fifteen years behind in terms of what is considered genetically modified. Let's start then by explaining what we mean by GMOs in the 21st century.

- People are as distrustful of GMOs as they were of mobile phones. A few decades ago, of course, genetic modification worked differently. Perhaps the best way to imagine its evolution is to compare it to fixing a broken kitchen cupboard. Whereas in the old days, if a cupboard door was broken, you had to buy another cupboard to replace it, today, if you have the same problem, you only have to replace the screw that caused the problem. I can understand why fifteen years ago people were terrified of genetic engineering, but nowadays it is more like genetic engineering than genetic modification. We can now achieve the desired change not only by introducing an external gene into the organism but also by tweaking the regulatory region of the genes in the plant. In other words, we are fine-tuning.

- What is the purpose of genetic modification in plants today?

- We produce such plants for several purposes. One version is when we genetically modify the plant to make it more resistant to various diseases, insects, pests so that ultimately fewer pesticides need to be used in its cultivation. Another genetic modification technique, often used, is to make the plant more resistant to the active ingredient of a spray. This method is used so that the useful grain that is sown can be easily sorted out from the various weeds and plants, as the agent kills the weed, but the valuable grain is unharmed by the genetic modification, so the end result is a much cleaner crop. In these cases, low environmental impact sprays are always used today.

Perhaps these examples already illustrate one of the benefits of genetic modification: it reduces the use of chemicals.

- As far as I know, feed imported from abroad by livestock breeders is not controlled, so it may contain GMO products. So a chicken breast may get a GMO-free label in the shop because it is a conventional chicken raised on Hungarian feed. But how verifiable do you think this is?

- It always makes me think about how "organic" bananas from Colombia, the home of the drug lords, can be. I wonder how much it costs there to buy a label like that and put it on a banana? Who can check it several continents away? One thing is for sure: I, who am familiar with these technologies, would never buy meat more expensive just because it is GMO-free. And it is important to emphasize once again that if a piece of meat is GMO-free it means that it is not organic because it may require more chemicals to treat it and it may have higher technical costs. And let's not deny the marketing value of the label: because GMO has become a pejorative term in the public consciousness, the GMO-free label has a good ring in the market. It is as if it was an adjective for the quality of meat, however, the meat itself can still be bad, label notwithstanding.

- Why aren't researchers like you lobbying to whitewash the term GMO?

- Genetic modification can be used to do a lot of good things, but because it is also done by humans, it is inevitably sometimes used for pointless or harmful purposes. Fifty years from now, there are likely to be private reproductive clinics where people go because they want glow-in-the-dark body parts. We can't do anything about stupid or self-interested people, but for the moment we researchers need to concentrate on how we can turn this knowledge to the benefit of humanity. In many cases, this is controlled breeding, which can achieve useful goals in five to ten years that would take decades using conventional methods.

We can hate GMOs, it is just important that we put the energy and attention into it so that we know exactly what we hate.

- Will we get to the point where we can eat better quality food thanks to genetic modification?

- Such attempts have been made and are still being made: the best known is the story of the so-called golden rice. In the Far East, many problems are caused by vitamin A deficiency, which in severe cases can lead to childhood blindness. Twenty years ago, researchers Peter Beyer and Ingo Potrykus used what was then considered a conventional genetic modification to 'breed' rice that produces beta-carotene, which gives it a slightly yellower colour - hence the name golden rice. It has no resistance to any pesticides, it is only considered genetically modified because it contains this extra substance that prevents the development of this typical deficiency disease, thus saving lives. At the time, the scientists who created the gold rice were driven by humanitarian concerns and gave up their copyright and patent rights. Unfortunately, however, gold rice has not been commercialized since then because it has been so fiercely opposed by various environmental lobby organisations that they have won the day - at the expense of the masses. Of course, we in the West may have unrealistic fears about genetic pollution, since we live in a place where vitamin A deficiency is a rarity, because carrots, spinach, and Brussels sprouts are among the foods we eat every day. But no one in the Philippines or Vietnam has asked people about this. In 2019, the Philippines finally allowed the public cultivation of golden rice.

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- But you're not genetically modifying plants, you're genetically modifying animals for a noble cause. Can you tell us about that?

- Of course! In my PhD project with the University of Szeged Medical School, we studied drugs that cause sudden cardiac death in animal experiments. As a PhD student at the well-remembered Institute of Agricultural Biotechnology, with a research group led by Dr Zsuzsanna Bősze, I contributed to this by creating a rabbit whose heart was engineered to produce a human ion channel protein.

The rabbit is a very good electrophysiological model, because its heart size and heart rhythm are the closest to those of humans among small animals.

In case of laboratory animals, it is important that they should be easy to keep, and that is why most of these experiments are done on mice, but the mouse heart is very different from the human heart in terms of electrophysiological properties. In the rabbit heart, thanks to our genetic modification, a human protein was produced alongside its own, so that human drugs could bind to this human protein, giving much more accurate clinical results. It was really complete research because we developed the animal and there was someone who was able to examine it immediately – the process did not die along its course but became practice-oriented.

- Yes, here genetic modification is taking place at quite different levels and for important causes.

- I wanted to choose a research topic that made sense, and these rabbits and our results are still being used and studied in Europe today. Sudden cardiac death often has no symptoms, or more precisely no identifiable symptoms, which is why it can happen that athletes who have undergone regular medical check-ups suddenly collapse and die on the field without any warning. Doctors cannot examine or reconstruct the events afterwards, because unfortunately the heart is no longer working, and the only way to find out whether the person had a gene mutation/defect that could have such drastic consequences is to check their DNA. So we have basically reproduced this gene defect in an animal and from then on we could continuously monitor the minimal abnormalities that can be detected in the heart. That is how different types of drugs were tested, because the other difficulty with this condition is that it is not only cardiac drugs that can cause this effect, but also certain antidepressants, anti-inflammatory drugs.

- Let's also reassure animal rights activists that you value the animals used in your experiments.

- Yes, obviously because they are very valuable, very important. The animal welfare standards are based on the 3Rs principle, to which another one has been added to in recent years. So the four R's are reduction, refinement, replacement and rehabilitation, which must be respected in all experiments. Reduction involves reducing the number of animals used in experiments as much as possible. Refinement means using methods that cause the animal as little suffering and pain as possible during the experiment, breeding and care. Replacement means that, where possible, instead of animal testing, a scientifically accepted method or test should be used that does not require the use of live animals. The fourth, rehabilitation, draws attention to the moral responsibility of all researchers in the aftercare and rehabilitation of animals used in experiments. Any experiment that causes more pain to the animal than a needle stick must obtain an animal protection permit. The ethical aspect of all animal experiments is crucial: we must demonstrate the purpose for which we want to carry them out.

Obviously, someone who wanted to use the results for entertainment purposes would not get a licence if the aim was to produce, say, a faster greyhound or a lighting horse.

But if we use it for purposes such as producing golden rice or medicine, or perhaps developing agricultural products, then perhaps it is more understandable for the readers why one can love biotechnology so much.

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- How much buzz is there in experiments around the world? Can Hungary keep up with the Western world? Or is it in the Far East that the latest technological innovations are being born?

- Scientists differentiate 16 different types of sudden cardiac death syndrome, and in 2013, we developed type 5, meaning we developed a rabbit that is apt to examine sudden cardiac death type 5. We met a Chinese researcher at a conference years later, and we were very happy when he told us that they too were developing this particular type of rabbit. We asked him which type of syndrome they were modelling and he said, with the utmost naturalness: all of them! This is a good example of the different possibilities we have. Obviously we cannot and should not compete with them.

- What does the future hold? Will we be less afraid of genetic modification? I hope that those who read this interview will...

- We are moving towards more and more gentle regulation. Already, there are treatments for plants that only make the leaves genetically more resistant to pests, and does not affect the crops, as pests leave that alone, too, and humans only eat the that part.  In case of farm livestock, it is now feasible to introduce a regulatory region into the animal which, once the animal is ready for slaughter, turns off the gene that was producing the protein that helps it grow. After the 'switch-off', these animals are kept for an additional month and when they are used as cooking material, they no longer contain any of the protein produced by the modified gene.

Our bunny was of the kind that only produced the human protein in its heart chamber, not in the whole bunny. It is even possible to assign a certain substance not to be produced in embryo phase but be produced in adolescence.

So, science is capable of more than we think, and is smarter with its power than we first think. It may be feared, but it is no more dangerous than any of the two-edged tools God has given to mankind.