Its name is deoxyribonucleic acid, but it is better known as DNA. Imperceptible to the human eye, this substance is responsible for us being what we are. It is present in almost everything and defines each of its characteristics. The science that studies and works with him is genetics. That is why, on DNA Day, Infobae spoke with four specialists about the milestones that marked the history of humanity thanks to their “partnership”.
Less than 100 years have passed since, on April 25, 1953, biologist James Watson and physicist Francis Crick published an article where they presented the double helix of DNA, thanks to experiments carried out by chemist Rosalind Elsie Franklin. However, summarizing these almost 70 years may be whimsical, since this science, in a few years, proved that it will be able to change the present and future of humanity.
1 - A finding that would change the history of humanity, albeit with some controversy
The first step in the “science of DNA” was to describe its structure: two chains that meander around each other. Currently referred to as the “double helix”. “More than 50 years ago, Watson and Crick described the DNA chain and, through it, were able to explain, basically, what humans and other species of living things are made of,” Pablo Kalfayan, a medical specialist in Medical Clinic and Medical Genetics (MN 122,754) and member of the National Cancer Program, told Infobae Family, National Cancer Institute, Ministry of Health of the Nation of Argentina
“In 1952, Rosalind Franklin photographs, for the first time, the DNA fiber. Then Watson and Crick publish the double helix. But the story of this woman, who worked a lot, was tarnished because some say that her credit was stolen. Some say that she showed them a photograph in a corridor and, since it was something they were working on, they found the logic of it,” said Dr. Soledad Kleppe, a physician specializing in Genetics and Metabolic Diseases at the High Complexity Medical Institute of the Italian Hospital. “For decades it was tried to elucidate and it was not achieved, but after this publication the pyramidal bases of genetics were known,” he added.
In 1962, James Watson, Francis Crick and Maurice Wilkins, leader of the laboratory where Rosalind Franklin worked, received the Nobel Prize in medicine. The woman behind the X-ray image that showed the double helix was not recognized, since at that time these prizes were not awarded posthumously.
2- With Dolly began a change that today is counted in dozens
For “mere mortals” who didn't know the world of DNA, cloning was closer to a science fiction film than a fait accompli. However, Dolly showed that it was not only possible, but that it was a path that had a lot ahead of me. On July 5, 1996, this little sheep greeted the world and positioned itself as the first mammal cloned from an adult cell.
Its “creators” were Ian Wilmut and Keith Campbell, from the Roslin Institute in Edinburgh (Scotland), who chose to make their existence known 7 months after their birth. She was the mother of 6 young and 7 years after her birth, she was sacrificed for a progressive lung disease. Although her life can be considered as fleeting, Dolly began a journey that would change the world. An example of this is the project led by CONICET researcher Andrés Gambini, in producing the first embryos clones of zebras (some species are threatened) using mare eggs (a species belonging to the same family).
“This technology has allowed the generation of embryos, pregnancies and births, from Dolly the sheep in 1996 to the present day, more than 20 species of mammals were cloned,” Gambini told Infobae, who is also a member of the Department of Animal Production of the Faculty of Agronomy of the UBA (FAUBA) and a specialist in this technical. “The cloning of organisms is an artificial form of asexual reproduction where genetically identical individuals are produced and in which there is no fertilization, that is, spermatozoa do not participate in the process of generating genetic copies,” he said.
In the words of the expert, this technique has several lines of application, one of which is aimed at the conservation of endangered species. “Cloning by transferring DNA from cells is a biotechnology with great potential because it allows the maintenance of biodiversity through species recovery, nuclear reprogramming for the production of stem cells and the study related to embryonic development,” said the expert.
Meanwhile, Hernán Dopazo, PhD in Biological Sciences, independent researcher at CONICET and Scientific Director of Biocodices, said: “Today what we do with cloning and all the possibilities that come from it 'come' from Dolly. Stem cells, de-differentiation of any cell and the production of cells is part of the whole path that came along it.”
“Dolly was the first cloning of mammals, but before that minor organisms, such as bacteria, had been cloned. Dolly was not made from embryonic cells, but from DNA that was already differentiated, albeit with all information. In this case, the development features were made available and that code was reused. In other words, DNA worked again 'from scratch, 'and they created a living being with the same information,” Kleppe summarized.
3- PCR: a technique that changed diagnoses
The pandemic put the acronym PCR in the mouths of hundreds of millions of people. However, few know about its origin or how much genetics had to do with its evolution. Its real name is 'Polymerase Chain Reaction' and it is a diagnostic method that allows the detection of a fragment of the genetic material of a pathogen.
“Today, practically, we couldn't do anything without PCR, which allows DNA to multiply thanks to enzymes that were discovered and that are polymerases. It's a great discovery, but clearly it's also a fundamental tool for biology, laboratories and medicine in general,” said Dopazo. “PCR allows you to detect a genetic disease, such as Mendelian diseases (NDer: known by that name because they are inherited to offspring according to Gregor Mendel's laws, there are about 6,000 of this class),” he added.
In this regard, the scientist explained that, at present, “couples are analyzed to find out if the combination between them will not give children with diseases that can be genetically prevented. To detect the embryo that does not have these diseases, PCR and (Frederick) Sanger's method are used”. At the same time Kleppe added: “It is the amplification of certain specific areas. You have the whole chain of DNA and with PCR you indicate from where and how far it should be amplified. The PCR locates the section and makes many copies of that DNA that is very small and difficult to find.”
4- Human Genome Project: a decade, a future with a new horizon
What are we? What defines us as human beings? Why does each individual have a particular characteristic? These questions and many more were answered thanks to the Human Genome Project (HGP). Initiated in October 1990, this collaborative international research program aimed to generate a map and achieve a complete understanding of all human genes. In just 13 years, humanity managed to know more than 90% of the genome and a few days ago it reached 100%.
“The human genome project was completed in 2003, although some 'acceptable' errors remained. There were 6 international groups that worked together on a project that cost 3 billion dollars, and they found that same number of letters in the genome. It is an advance that will last a lifetime and that was not all, because one of the most relevant points is the advancement of technology that came hand in hand with this project,” explained Dopazo. According to the expert, by analyzing both aspects, humanity managed to make progress in this matter. “Today, making a genome costs you a thousand dollars,” he said.
The CONICET researcher also stressed that “in 20 years there was a change in all technology and this was one of the points of the projects, because when they are of this size they end up being technological projects. We went from doing the sequences manually and even by hand, to sequences 500 genomes in a week, for which we need multiprocessing, miniaturization, parallelism and massive data analysis: all advances generated by the Human Genome Project.” He clarified: “In 2004, only 8% of the genome was missing and they were very difficult and short regions. In 2022 it was completed.”
“This advance and the discoveries that followed it, and the detection of different genes allowed the cause of many diseases that can occur in families to be searched; give them a nomenclature, a name or an association. It can be identified when DNA 'does not work well', increasing the risk of diseases such as cancer and other non-cancer diseases. In short, through genetic studies and knowledge of the genome we find genetic alterations that one may suspect, but which are confirmed by these technologies. And that, even, they can be studied and analyzed both in the patient and in their family group,” Kalfayan said.
For his part, Kleppe explained: “A pattern DNA was taken from a group of supposedly healthy people and the work was divided so that 6 centers from different parts of the world could analyze it. Six years after its inception, scientists working on the Human Genome Project agreed that the information had to be freely accessible to make the data available to anyone who wants to advance that research. In 2003, the first part of the Human Genome Project was completed, earlier than had been thought, which was 15 years old.”
“Until about 2000, it was a constant and interesting growth in gene discovery. But between 2000 and 2010 there was an explosion; these advances are truly overwhelming and exponential. In 2022, the first complete human genome was officially published, although between 1% and 2% of the genome has different structures, on different sides. The future is huge, because through what we know we can predict and not just talk about family history,” added the expert from the Italian Hospital.
5- From “à la carte” births and prevention of hereditary diseases to treatments
From 2000 to the present day, fertilization faced several advances. From the first child named as “a la carte” until today, with the technique called “son of three parents”, advances in this matter were meteoric. But that's not all, a range of diagnoses and treatments were also opened up, as well as strategies to prevent some diseases from arising and even developing.
“In prenatal medicine, possible changes in pregnancy are evaluated and components are evaluated at the management level, and pathologies can be diagnosed and addressed during this same period of time. Some specific syndromes can also be detected, and these aspects can be analyzed in both early and second childhood,” Kalfayan explained. But that's not all, according to the expert, after a birth, “you can evaluate different pathologies in children and assess the degree or risk of recurrence, for a future pregnancy.”
For his part, Dopazo added: “In genetic screening we analyze embryos to find out which one can transfer and thus avoid these diseases in adulthood. Thanks to HPG, progress was made in the knowledge of diseases and in the prediction of risks. Even, now these pathologies can be predicted as soon as a person is born. Knowing which embryo to transfer or what are the risks of developing a disease changes the whole picture and, even, in a few years, some diseases can be eliminated.”
“It is not used to choose physical traits or characteristics. If not with a severe risk of a disease. Before they had to continue having children and with low survival rates or no more children, but with this technique the treatment is done in vitro and the embryo is diagnosed before it is implanted. Only embryos that do not have the risk of disease are implanted. In Argentina it is used a lot and the truth is that it allows people to have a family who otherwise could not,” added Kleppe.
Finally, Kalfayan elaborated on diagnostic techniques: “My specialty is oncological genetics and thanks to new technologies, which allow people and their families to evaluate, the chances of developing cancer can be analyzed. In 1994, the first gene associated with breast cancer was discovered, then the other (BRCA1 and BRCA2) was found. We now know that when we detect these mutated genes, the risk of developing cancer increases, although this does not mean that it will actually develop.”
“This technique applies to cancer, but it can also be applied to other non-oncological pathologies. The implications of these advances are enormous, in addition to detecting alterations and defining more effective treatments according to its DNA or the mutation it presents, and medicine is already accurate, because it targets these pathologies and the genes that present specific mutations,” added the expert from the Italian Hospital.
6- CRISPR: a technique, a new future
The last milestone of this review comes from the hand of two scientists who were also awarded the Nobel Prize in Chemistry 2020. They are Emmanuelle Charpentier and Jennifer Doudna, who were awarded “for the development of a method for genome editing”. Called as “the CRISPR/Cas9 genetic scissors,” this technique has “had a revolutionary impact on the sciences, is contributing to new cancer therapies and can make the dream of curing hereditary diseases a reality”, as noted by the Royal Swedish Academy of Sciences.
“This technology allows us to cut DNA in a specific position, so that we can edit, based on and in certain positions, to cure Mendelian diseases and other ailments can be corrected,” Dopazo explained. In this regard, he clarified that with this technique “it is not possible to work on a complete organ, although at least to correct some aspects. CRISPR is going to change everything. We can now diagnose, change, observe, read and edit. It is unthinkable what can be done from now on, it has many edges”, he added.
While Kleppe added: “CRISPR is a technique for editing genetic information. Before, you gave a virus a gene to get inside the DNA, but it got anywhere and could break it and cause a genetic disease. This technique comes from bacteria and is used to be able to enter genetic information in a specific place, so there is very little chance of error.”
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