Thursday, September 23

20 years after the sequencing of the human genome, dangerous genetic myths abound | Philip Ball

TMany years ago, the scientific journal Nature published the first draft of the human genome: the sequence of chemical “letters” in the gene-carrying DNA of our chromosomes. The Human Genome Project (HGP) had worked for a decade to read this coded information. At a press conference at the White House in 2000, Francis Collins, who led the project as director of the US National Human Genome Research Institute, went biblical and called the human genome “our own instruction book, that before only God knew ”.

HGP has huge potential benefits for medicine and our understanding of diversity and human origins. But a storm of deceptive rhetoric surrounded the project, contributing to the widespread and sometimes dangerous misunderstandings about genes that now plague the genomic age.

So far, there have been few attempts to clear things up. Even now, the National Human Genome Research Institute calls HGP an effort to read “nature’s complete genetic blueprint for building a human being,” the “instruction book” that “determines our particular traits.” A genome, says the institute, “contains all the information necessary to build and maintain that organism.” But this deterministic “instruction book” picture is precisely the fallacy that genomics has overturned, and the information in the genome is demonstrably incomplete. However, no one associated with genomic research seems concerned with correcting these false claims.

In an area as promising and dangerous as genomics, clear communication is essential. The ability to sequence our full complement of genes has enabled great advances in medicine, but it has not yet been as transformative as initially promised. Successes in gene therapy remain rare and medicine tailored to people’s individual genetic makeup has yet to materialize. Meanwhile, a deterministic view of genes has helped the arguments about eugenics and “innate” racial characteristics to rejoin public discourse. The first gene-edited babies were born in 2018 through a case of scientific misconduct that landed the Chinese scientist responsible for the work, He Jiankui, in prison. Meanwhile, genome sequencing companies like 23andMe seduce us with the cursory promise of analyzing the DNA in your saliva to reveal “what makes you who you are.”

Gene hype has been with us since James Watson apocryphally stated in his 1968 book The Double Helix that his collaborator Francis Crick told each and everyone in a crowded Cambridge pub that “We have found the secret of life! ! ” shortly after the couple discovered the chemical structure of DNA in 1953. In 1995, sociologists of science Dorothy Nelkin and Susan Lindee argued that DNA had become a scientific surrogate for the soul, a kind of mystical essence imprinted on a molecule. By reading the “language in which God created life,” as President Bill Clinton he said grandly From the HGP in 2000, it seemed that we were on the verge of understanding life at its most fundamental level.

Many geneticists say that the story has turned out to be more complicated than they anticipated: genes are not exactly what we think (in fact, there is no consensus on what they even are). However, many are still happy to spread the misleading idea that we are “gene machines“And our DNA is ours”Flat”. It’s no wonder that public understanding of genetics is so ruined by notions of genetic determinism, not to mention the now ridiculous (but lucrative) idea that DNA genealogy tells you what percentage of you are “Scottish,” “African. Sub-Saharan “or” Neanderthal “. Such genetic nativism is catnip for the far right. Watson himself, a leading proponent of the HGP, has He suggested (no credible evidence) that there may be a genetically average difference based on IQ between racial groups.

HGP deserves a share of the blame for such problems, as it promoted and upheld a misleading view of genes. When the project began, an earlier notion that human traits like hair color or cognitive abilities each had a dedicated gene no longer seemed tenable. Still, the scientists thought that genes and traits could easily be combined, like those children’s puzzles in which intricate links are drawn between two sets of elements. That misconception explains why most geneticists overestimate the total number of human genes by a factor of several times, an error that is now usually presented with a smiling “Whoops!” rather than as a sign of a fundamental error about what genes are and how they work.

It is now clear that traits such as height, as well as susceptibility to many common ailments such as type 2 diabetes, cancer, and heart problems, have a genetic component that is immensely complicated. Perhaps hundreds of genes could be involved, each with only a small influence. Environmental or just random factors are also important. As a result, it is often difficult to identify effective genetic targets for drugs, and it is of little value to do so if we do not know how a particular gene actually influences. healthy conditions.

There have been some successes in genetic medicine. Some medicines used to treat rheumatoid arthritis, one of the what is now being study have a Potential Covid treatments emerged from genome studies that identified two possible target genes. But the most common medications for this condition, such as TNF inhibitors, it was not based on genetic data at all. Even in the case of diseases that have a clear genetic component, the genes may not be the appropriate level to intervene. “In some cases,” a group of experts in genetic medicine wrote in 2013, “an approach that relies on human genetics can slow down a drug discovery program.”

The real value of HGP is not in answering questions about “what does a gene do,” but rather in showing how small variations in the genomic sequence of each of us lead to tremendous variations in human attributes. Of course, there is no unique “human genome”, each of us has our own. By analyzing the genome sequences of hundreds and thousands of people, it is possible to identify what are the small differences that make us different. One message from such studies is that “race” is a social construct that does not have its roots in biology: there is much more genetic variation within conventional racial groupings than between them.

These comparisons of many genomes are based on perhaps the most important reward of HGP: the sequencing technology itself. The rapid genome analysis that has made it possible for the Covid-19 Genomics UK Consortium to identify and track new coronavirus variants is just one of the benefits of the increasingly cheap and rapid sequencing technology developed as a result of the project. In the same way, we can expect to know more soon about how our own genetics affect our individual. susceptibility to severe covid.

In addition to offering such valuable resources and technologies for healthcare, the HGP paradoxically revealed the limitations of a gene-centered view of life. After all, we don’t come with instructions included: you are not programmed into your chromosomes. Life is not a gene reading, it is a much more interesting, subtle and contingent process than that.

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