If the Human Genome Project (HGP) was an actual human, he or she would be a revolutionary whiz kid. A prodigy in the vein of Mozart. One who changed the biomedical universe forever as a teenager, but ultimately has much more to offer in the way of transforming mankind.
It’s been 20 years since scientists published the first draft of the human genome. Since its launch in the 90s, the HGP fundamentally altered how we understand our genetic blueprint, our evolution, and the diagnosis and treatment of diseases. It spawned famous offspring, including gene therapy, mRNA vaccines, and CRISPR. It’s the parent to HGP-Write, a global consortium that seeks to rewrite life.
Yet as genome sequencing costs and time continue to dive, the question remains: what have we actually learned from the HGP? After two decades, is it becoming obsolete, with a new generation of genomic data in the making? And with controversial uses such as designer babies, human-animal chimeras, organs-in-a-tube, and shaky genetic privacy, how is the legacy of the HGP guiding the future of humanity?
In a special issue of Science, scientists across the globe took a deep dive into the lessons learned from the world’s first biomedical moonshot. “Although some hoped having the human genome in hand would let us sprint to medical miracles, the field is more an ongoing relay race of contributions from genomic studies,” wrote Science senior editor Laura Zahn.
Decoding, reworking, and potentially one day augmenting the human genome is an ultramarathon, buoyed by potential medical miracles and fraught with possible abuses.
“As genomic data and its uses continue to balloon, it will be critical to curb potential abuse and ensure that the legacy of the HGP contributes to the betterment of all human lives,” wrote Drs. Jennifer Rood and Aviv Regev at Genentech in a perspectives article for the issue.
An Apollo Program to Decode Life
Big data projects are a dime a dozen these days. A global effort to solve the brain? Yup. Scouring centenarians’ genes to find those that lead to longevity? Sure! Spitting in a tube to find out your ancestry and potential disease risks—the kits are on sale for the holidays! Genetically engineering anything—from yeast that brew insulin to an organism entirely new to Earth—been there, done that!
These massive international collaborations and sci-fi stretch goals that we now take for granted owe their success to the HGP. It’s had a “profound effect on biomedical research,” said Rood and Regev.
Flashback to the 1990s. Pulp Fiction played in theaters, Michael Jordan owned the NBA, and an international team decided to crack the base code of human life.
The study arose from years of frustration that genetic mapping tools needed better resolution. Scientists could roughly track down a gene related to certain types of genetic disorders, like Huntington’s disease, which is due to a single gene mutation. But it soon became clear that most of our toughest medical foes, such as cancer, often have multiple genetic hiccups. With the tools that were available at the time, solving these disorders was similar to debugging thousands of lines of code through a fogged-up lens.
Ultimately, the pioneers realized we needed an “infinitely dense” map of the genome to really begin decoding, said the authors. Meaning, we needed a whole picture of the human genome, at high resolution, and the tools to get it. Before the HGP, we were peeking at our genome through consumer binoculars. After it, we got the James Webb space telescope to look into our inner genetic universe.
The result was a human “reference genome,” a mold that nearly all biomedical studies map onto, from synthetic biology to chasing disease-causing mutants to the creation of CRISPR. Massive global consortiums, including the 1000 Genomes Project, the Cancer Genome Atlas, the BRAIN Initiative, and the Human Cell Atlas have all followed in HGP’s steps. As a first big data approach to medicine, before the internet was ub...