New drug is born that uses evolutionary theory to fight cancer and pandemics | Health and Wellness
If God were a 19th century physicist he would not play dice, but as a biologist he would always be a gambler. Living things are the result of a random combination of genetic variants that produce individuals trying to survive in a mutant world. What is an advantage in one circumstance may condemn us later. A big person may have more sex appeal than a small person, or be more likely to win a fight, but they also have a higher risk of dying earlier. Elephants have no predators, but they reproduce very slowly and, as a species, are more fragile than the delightful gazelles. All the chaotic diversity of life would be meaningless, as the evolutionary biologist Theodosius Dobzhansky said, if it were not the light of evolution. This light has given meaning to life and can now also illuminate health and illness.
The world’s first collaborative research program in evolutionary medical genomics (EvoMG) was unveiled in Barcelona this week. The initiative, with initial funding of one million euros from the Generalitat of Catalonia, is the result of a collaboration between the Center for Genomic Regulation (CRG), the University of Pompeu Fabra (UPF) and the CSIC-UPF Institute of Evolutionary Biology (IBE). Its goal: to apply the principles of evolution to understand the causes of disease and improve human health. “Part of this concept is what we call therapy that is resistant to evolutionary processes, including cancer, bacteria, viruses or any pathogens that mutate and adapt to the treatment you give,” explains the project’s promoter, ICREA. Research Professor Manuel Irimia (Maputo, Mozambique, 43 years old).
Cancer follows the same evolutionary rules as living things, but with fewer restrictions; It’s nature gone crazy. In living things, mutations offer alternatives that improve survival when situations change, such as the ability to better utilize oxygen, which Tibetans have due to a genetic variant. Tumor cells mutate at an astonishing rate, which explains the rapid emergence of resistance to drugs that initially work but become ineffective as resistant cells multiply. One of the groups participating in EvoMG, led by CRG researcher Donate Weghorn, studies cancer as an evolutionary system; and there are other groups of scientists trying to push cancer into an evolutionary dead end.
Another area where evolutionary understanding is most evident is antibiotic resistance. After success in recent decades in fighting bacteria, drugs to combat them are losing effectiveness as the microbes adapt. “This is one of the biggest public health problems, and it is an evolutionary problem: we are fighting pathogens that are evolving very quickly. We’re pitting the chemical and pharmaceutical industries against bacterial evolution, and I think that’s a bad idea,” says Irimiya.
Compared to trial-and-error discovery of antibiotics, the use of evolutionary and mathematical models has the potential to produce more effective drugs. “UPF has a virologist, Juana Diez, who is involved in the program and is developing a treatment that attacks the secondary structures of the virus. From an evolutionary point of view, it is much more difficult for the virus to adapt to such treatment, because one mutation is not enough, it needs a mutation in two places at the same time, and there are mathematical models that show this. this makes it much more difficult for resistance to arise. These are the ideas we want to promote with this program,” continues Irimiya.
According to this scientist, one of the main advantages of this initiative is that it offers a new perspective for biomedical researchers: “These are people who are working on very diverse problems and have not even thought about applying these evolutionary principles. With this program, they can do that and come up with solutions they wouldn’t have thought of otherwise,” says Irimiya.
He knows the way, even though he went the other way. As an evolutionary geneticist, he spent years studying how the same gene can produce different proteins with different functions. It seems that our genome is written by an author of riddles who alternates understandable words with meaningless ones. To extract useful information for protein production, there is a splicing system known as splicewhich combines meaningful phrases and allows the same gene to have different readings. This means that in our body, cells produce different proteins with different functions, and also that there are so many different living things.
By studying this genome system, Irimiya discovered small pieces of information known as microexons that regulate neuronal function. “When I compared the results from humans and mice, I saw that they were the same, that they were very evolutionarily conserved – they appeared 550 million years ago – and that made me think that this was something important,” he says. Then he saw that in people with autism, microexons are often deregulated because their neurons don’t make enough of the protein SRRM4, a tool that neurons have that allows microexons to be inserted into the right place. A similar effect was observed with changes that cause diabetes.
“We can now use non-coding RNAs to manipulate the process splice and it has incredible therapeutic potential for correcting what is wrong in the body. splice and, for example, modify those microexons that are involved in diabetes and force beta cells to produce more insulin. You start trying to understand the origins of vertebrates, how genomes evolve, and you discover that processes like splice They have implications for disease. There are already treatments splice which save children’s lives, and I think that in five years there will be a real boom in this type of treatment,” Irimiya predicts.
The capricious balance of life
In the long term, one of the main interests of evolutionary medicine is to understand why we age, a process that underlies all disease. There is a genetic program that causes mice to live for a couple of years and humans for 80, or that produces strange phenomena such as small and long-lived mice that live many decades longer than similar species and seem to be immune to cancer. Because organisms are the result of a series of choices aimed at achieving the best outcome with limited resources, they exist in a balance that makes it difficult to modify undesirable aspects without affecting others that we like as they are.
Some time ago, the length of telomeres—a kind of protective shell at the ends of chromosomes that store information that tells our bodies how to stay alive—was linked to the rate of aging. Telomeres that are too short are associated with accelerated aging and diseases such as pulmonary fibrosis, and it has been suggested that treatments aimed at lengthening them may slow aging. But it has also been observed that excessive length increases the risk of certain tumors.
Irimiya believes that it is not yet possible to say whether our aging program can be manipulated without side effects, whether life can be extended indefinitely, or whether biology has intrinsic limits. “Typically, animals that live a long time reproduce little, and vice versa, because if you live long and reproduce a lot, you will use up environmental resources. This is what we humans do now. This may be seen as an imbalance, but people live out of balance. You may think that people break the rules, but these are also the rules of the evolutionary process: the emergence of new living creatures creates new rules,” the researcher warns. And he concludes: “When cyanobacteria appeared and filled the atmosphere with oxygen, they destroyed everything that was there before and thanks to this we can breathe. People are going to change the rules, and in thousands of years the Earth will be unrecognizable; But this is evolution, and we are part of it.”