We’ve Sequenced the Human Genome. So Why Haven’t We Cured More Diseases?
An emergency room doctor, initially unable to diagnose a disoriented affected person, finds on the affected person a wallet-sized card offering entry to his genome, or all his DNA. The doctor rapidly searches the genome, diagnoses the downside and sends the affected person off for a gene-therapy treatment. That’s what a Pulitzer prize-winning journalist imagined 2020 would seem like when she reported on the Human Genome Project again in 1996.
A New Era in Medicine?
The Human Genome Project was a global scientific collaboration that efficiently mapped, sequenced and made publicly accessible the genetic content material of human chromosomes – or all human DNA. Taking place between 1990 and 2003, the challenge induced many to invest about the future of drugs. In 1996, Walter Gilbert, a Nobel laureate, mentioned, “The results of the Human Genome Project will produce a tremendous shift in the way we can do medicine and attack problems of human disease.” In 2000, Francis Collins, then head of the HGP at the National Institutes of Health, predicted, “Perhaps in another 15 or 20 years, you will see a complete transformation in therapeutic medicine.” The identical yr, President Bill Clinton said the Human Genome Project would “revolutionize the diagnosis, prevention and treatment of most, if not all, human diseases.”
It is now 2020 and nobody carries a genome card. Physicians usually don’t study your DNA to diagnose or deal with you. Why not? As I clarify in a current article in the Journal of Neurogenetics, the causes of widespread debilitating ailments are advanced, in order that they usually should not amenable to easy genetic remedies, regardless of the hope and hype to the opposite.
Causation is Complex
The concept that a single gene may cause widespread ailments has been round for a number of many years. In the late 1980s and early 1990s, high-profile scientific journals, together with Nature and JAMA, introduced single-gene causation of bipolar dysfunction, schizophrenia and alcoholism, amongst different circumstances and behaviors. These articles drew huge consideration in the fashionable media, however had been quickly retracted or failed makes an attempt at replication. These reevaluations fully undermined the preliminary conclusions, which frequently had relied on misguided statistical exams. Biologists had been typically conscious of those developments, although the follow-up research obtained little consideration in fashionable media.
There are certainly particular person gene mutations that trigger devastating problems, similar to Huntington’s illness. But most typical debilitating ailments should not attributable to a mutation of a single gene. This is as a result of individuals who have a debilitating genetic illness, on common, don’t survive lengthy sufficient to have quite a few wholesome youngsters. In different phrases, there’s robust evolutionary strain towards such mutations. Huntington’s illness is an exception that endures as a result of it usually doesn’t produce signs till a affected person is past their reproductive years. Although new mutations for a lot of different disabling circumstances happen by probability, they don’t change into frequent in the inhabitants.
Instead, most typical debilitating ailments are attributable to combos of mutations in lots of genes, every having a really small impact. They work together with each other and with environmental elements, modifying the manufacturing of proteins from genes. The many sorts of microbes that dwell inside the human physique can play a task, too.
A silver bullet genetic repair continues to be elusive for many ailments. (Credit: drpnncpptak/Shutterstock)
Since widespread critical ailments are not often attributable to single-gene mutations, they can’t be cured by changing the mutated gene with a standard copy, the premise for gene remedy. Gene remedy has steadily progressed in analysis alongside a really bumpy path, which has included by chance inflicting leukemia and a minimum of one demise, however medical doctors just lately have been profitable treating some uncommon ailments through which a single-gene mutation has had a big impact. Gene remedy for uncommon single-gene problems is more likely to succeed, however should be tailor-made to every particular person situation. The monumental price and the comparatively small variety of sufferers who will be helped by such a therapy might create insurmountable monetary limitations in these circumstances. For many ailments, gene remedy might by no means be helpful.
The New Biology
The Human Genome Project has had an infinite influence on nearly each discipline of organic analysis, by spurring technical advances that facilitate quick, exact and comparatively cheap sequencing and manipulation of DNA. But these advances in analysis strategies haven’t led to dramatic enhancements in therapy of widespread debilitating ailments.
Although you can not deliver your genome card to your subsequent physician’s appointment, maybe you’ll be able to deliver a extra nuanced understanding of the relationship between genes and illness. A extra correct understanding of illness causation might insulate sufferers towards unrealistic tales and false guarantees.