Ukrainian Scientist Oksana Piven, “We Are Planning to Develop a New Approach that Would Help to Restore and Improve Heart Function after a Heart Attack”
What are the prospects of gene editing technology? Is it possible to achieve longevity thanks to the correction of lifestyle? Oksana Piven (Ph.D. in biology) explained in the interview for Biohacking Conference Kyiv.
Oksana is a leading research worker at the Institute of Molecular Biology and Genetics at the National Academy of Sciences of Ukraine. Her scientific work relates to cell reprogramming and the use of CRISPR technology.
Read more about the prospects and possibilities of CRISPR/Cas technology, as well as the factors that influence life expectancy in our interview.
Interviewer: Biohacking Conference Kyiv (BCK)
Respondent: Oksana Piven (O. P.)
BCK: Tell us about the results of your research on genes that are essential for cardiac performance.
O. P.: In short, we learned about the new functions of these genes during the research. This fundamental work allowed us to understand how important such genes are for the development of an embryonal heart and its performance in adult age.
BCK: What is the main idea of your scientific work related to cell reprogramming and the use of CRISPR technology? What research stage are you at now?
O. P.: The main idea of our work lies in the fact that we are planning to develop a new approach that would help to restore and improve heart function after a heart attack.
We hope that using the CRISPR/Cas strategy, we will manage to make fibroblasts – connective tissue cells that replace the cardiac myocytes lost after the heart attack – to become similar to cardiac myocytes. In other words, we are reprogramming cells to make another job and they will be functioning, supporting cardiac performance in a way that cardiac myocytes do.
Currently, the research is undergoing an experimental stage. For now, we are working on rat models. We are selecting, testing, and cloning the guide RNA. We are checking them in isolated rat cells.
BCK: What are the prospects of gene editing technology?
O. P.: The technology has colossal prospects. It is already in use today, starting from agriculture and the national economy to human-related medicine.
Gene editing technology is used to create new organisms with advanced characteristics, all things relating to the GMO of plants and animals. For example in the USA, organisms created using CRISPR/Cas, i.e. modified, are not treated as GMO, as they did not acquire foreign genes but experienced a mutation of their own gene. In other words, the thing that could happen spontaneously in natural conditions, and we are just speeding up the process.
China will most probably come to the same decision as the USA has taken. The EU is also reconsidering their attitude to organisms created using CRISPR/Cas. The technology is giving less cause for concern there.
Talking about agriculture, organisms created with CRISPR/Cas have much more chances to enter the national economy and to get to our tables, as they cause far fewer concerns from the standpoint of bioethics.
Besides, of course, the creation of a basis for the development of organ transplantation. For example, Qihan Biotech that closely works with Cambridge-based eGenesis carries out research in Hangzhou, creating genetically modified pigs that can serve as potential human organ baths. Today, those are the most advanced pigs, improved thanks to genetic engineering. They have a hybrid immune system – half-human, half-piggish. This should reduce the potential load on the recipient’s immune system (the person that acquires an organ from such an animal).
This direction is actively developing. We are not talking about regenerative medicine and transplantology here. Recalling that every country has colossal patient lists for the transplantation of kidneys, heart, and other organs, it is an important direction.
Besides, gene editing technology is promising for the therapy of viral infections such as AIDS, Epstein-Barr virus and others. There is quite interesting preliminary data showing that the technology can be efficiently used to overcome these viral infections, reduce their load on the body, and improve the wellbeing of patients. And, of course, a lot of breakthroughs and interesting things are done in the oncology field.
BCK: Back in 2017, biohacker Joshua Zeiner attempted to edit genes. How safe is that?
O. P.: I think it was reckless behavior. Taking into account that he did it several years ago when CRISPR was poorly researched and had higher off-target effects. Today we know that there are many ways to overcome the off-target effect, i.e. mistakes.
The point is that CRISPR is not a flawless system. It can make mistakes. The consequences of these mistakes are very unpredictable, as we do not perfectly know how the system works and what consequences its use may bring.
For this reason, I think that the biohacker’s actions were untimely and unreasonable.
BCK: How do you assess the prospects of using CRISPR/Cas technology to change genes of an adult person and embryos?
O. P.: Speaking about editing or changing the genes in an adult body, one can use CRISPR/Cas to “cut off” AIDS, Epstein-Barr virus, to edit cells of the immune system to make it better recognize malignant cells and help to fight against cancer.
This one story. Here, we help the person. We are developing things that can help to increase the effectiveness of the existing therapy and to advance life quality and expectancy. If we talk about a big, global scientific and medical goal, it is difficult to find arguments about why one should not try this technology. Moreover, if we are discussing possible negative consequences, studying the effect, and trying to give a weighted assessment.
Another issue is whether one should use CRISPR and other genome editing systems, for example, TALEN, zinc finger proteins, as well as other systems and their combinations, with the aim to manipulate genes at the level of an embryo. This issue has to be considered from another viewpoint. Even if we do not take into account its ethical feasibility but look from the perspective of genetics, reasonability, and biological safety of the organism itself, embryo, and potential person that will grow out of it, everything needs to be thoroughly thought through.
CRISPR/Cas has an off-target effect and can make mistakes. We do not know what consequences these mistakes may have for the edited embryo and the potential person. It is unknown what other mutations we can add, how it will influence the person’s life expectancy, health state, and many other things.
Besides, using the CRISPR/Cas system, we increase the mosaicism level in the body. I am not talking about the creation of designer children now – how ethical, moral, and fair it is from the standpoint of the equality of people. I am talking solely about genetics now. We do not know what dangers we impose on such children.
Let us recollect the case of Chinese children Nana and Lulu. Firstly, they are children with mosaicism. Secondly, the gene that was edited for them provides genetic resistance to HIV, but at the same time, it imposes them to different dangers. As it is an important component of the immune system, sensitivity to the flue, yellow fever, dengue, and many other diseases increases.
This brings up the question about the viability of inducing the mutation in children, providing them with this kind of immunity in exchange for endangering them to face many known and unknown problems. Moreover, today there are other strategies of treating and inhibiting viral infections and people that suffer from them can live, bear children and feel well during many years.
This is the reason why it is important to know the function of every gene, the interconnection between the function and structure of the gene and between gene functions and embryonic development, as each of them can have different performance features in different tissues and in different processes of the ontogeny.
One should also take into account the complicated regulation of gene functions, changes in which can lead to unintended consequences that can outbalance the evident benefits that genome editing systems bring.
BCK: Is it possible to change your genes by correcting the lifestyle?
O. P.: Such notions as health state, intelligence, mental activity, cognitive functions, talent and creativity depend on many factors. Talking solely of intelligence, there are over 100 genes related to neuron function.
The same goes for health. Levels of mitochondrial genes, the state of mitochondria, etc. have an impact on physical well-being. In other words, thousands of genes influence metabolic processes in human cells and the presence of mutations.
For example, single nucleotide substitutions can bring about cancer. One person has this variant of gene and the other does not have it. The one with such a variant of gene risks having breast cancer 60% oftener. Let us take the case of Angelina Jolie, who had her breasts removed when she found out that she had such variants of genes. Her mother, grandmother, and aunt suffered cancer.
However, the presence of such genes does not mean that you are going to die from breast cancer. For example, a falling brick, blood stroke, or something else can kill you.
In fact, those are difficult things that depend on different factors such as genetics, the place where you work, and how you take care of yourself. You could have a bad genetic background and your relatives lived no longer than 65 years. However, if you give up on smoking and problem drinking, have enough sleep, a healthy diet, follow the well-known concepts intended to improve wellbeing, for example, avoid overeating and consuming much sugar, you will obtain a result. You will manage to prolong your probably genetically restricted 65 years of life by 10 or even 20 years. Everything depends on the way you take care of yourself. But you will not correct your genes, as their structure will not change.
You can change the load of behavior patterns such as the consumption of heavy food, smoking. By getting rid of this load, you can live longer. Other people may be luckier, as they have a good genome. They can live longer than you can, even not leading a healthy lifestyle.
BCK: Is it possible to prolong life to 200 and more years from the viewpoint of science?
O. P.: I do not think that now it is possible to prolong life to 200, 250 years. In my opinion, we have many restrictions. Our cells cannot live forever – they die. With every cell division, our chromosomes become shorter, etc.
I think that one can live up to 100 years and more. People actually live for so long today. We can advance the system of medicine and diagnostics, provide more modern treatment protocols, and improve wellbeing and life expectancy of people.
But for me, the most important thing is not just to live up to 100 years but to have a good quality of life and to feel well. If we can provide this kind of health state, it is cool and it is worth doing.
On the other hand, I cannot see any point in living forever or up to 200, 250 years. It seems to me that it will be a little boring. Or maybe not.
BCK: What will you discuss in your report at Biohacking Conference Kyiv?
O. P.: I will be talking about the CRISPR/Cas system, how it works, what potential it has for people. I will explain how this system can help to overcome very unpleasant diseases such as cancer, some genetic illnesses, for example, Duchenne muscular dystrophy, etc.
Oksana is making a presentation at Biohacking Conference Kyiv. The speaker will discuss “CRISPR genome editing technology”.