A team from the United States demonstrates a technique that allows editing the genome at an unprecedented level.

A photograph of the legendary physicist Richard Feynman’s chalkboard, taken in 1988, the year of his death from cancer, is preserved in the archives of the California Institute of Technology. On one corner of the board, he had written: «What I cannot create, I do not understand.» Years later, a select group of researchers applied this maxim to biology: humans will only understand their nature when they can create their own genome from scratch. Achieving this continues to be one of the greatest challenges of science. Recently, a study was published that marked a significant step towards this goal. Researchers from the University of Pennsylvania in the United States have created an artificial human chromosome that can integrate into human cells, join the existing chromosomes, and be passed from generation to generation. Chromosomes are the large volumes in which our genome, a chaotic and repetitive sequence of 3 billion chemical letters, is grouped; they are key in evolution, as they determine genetic inheritance and decide the sex of babies. Each of our cells contains 23 pairs of chromosomes that in turn contain smaller units, the genes, responsible for producing all the proteins we need to stay alive. Being able to write whole chromosomes or parts of them opens the door to creating microbes, animals, and human cells with new properties. The artificial human chromosome presented in this study solves a problem that arose in 1997, when a U.S. team introduced reduced versions of a human chromosome into human cells. This was a scientific triumph, but the therapeutic applications were frozen when, for unknown reasons, the small artificial chromosomes began to multiply uncontrollably, creating completely aberrant and potentially carcinogenic genomes. The researchers created the artificial chromosome within yeast cells and focused on reproducing the centromere, the central part that is crucial for a chromosome to divide correctly and pass to the next generation. Once the artificial chromosome was assembled, a technique was used to merge the yeast cell with a human one. For the first time, the artificial chromosome joined the rest of the chromosomes without causing aberrant multiplications, remained stable, and was passed from mothers to daughters with high efficiency. The discovery, published in the journal Science, also involved scientists from the Craig Venter Institute, one of the pioneers who led the Human Genome Project, the first effort to read our entire genetic code, in the 1990s. The new artificial chromosomes allow for genomic editing at a higher level. CRISPR and quality editing allow for making specific changes in the genetic sequence. This new system would allow for rewriting genes or even groups of genes; equivalent to changing entire chapters. The artificial chromosome presented in the study has only 750,000 DNA letters. The smallest of the human chromosomes, 21, which when tripled causes Down syndrome, has 46 million. In addition, only 182,000 letters of the artificial chromosome are of human origin; the rest are of bacterial origin. These latter sequences provide stability and prevent aberrations. The new technique allows for the creation of «larger therapeutic loads» and the creation of organs for transplants with large sections of their genome previously designed. This technology could also improve and expand the possibilities of cell therapy, for example in treatments that genetically modify the patient’s blood cells to treat cancer. Before being able to write a genome, one must learn to read it. Even though this project of more than a decade was concluded in 2003, the truth is that the complete genome of a specific person could not be read until two years ago. Francisco Antequera, an expert in synthetic biology from the University of Salamanca, values the new work, but warns that it is only a first step. «The fragments of human DNA are still very small. But it is true that this method could be used to build increasingly larger chromosomes. I believe that in the future it will be possible to obtain entire chromosomes, but that will pose a new challenge, as handling such gigantic molecules in the laboratory is very, very difficult,» he explains. Beyond creating our own genetic code is the challenge of being able to manipulate it without producing nightmares.