Why genomics pioneer Lee Hood hopes the Covid-19 pandemic will make precision medicine based on personalized patient data a reality


Davis believes the key to understanding why covid affects people in such diverse ways is to identify the differences between the immune systems of those who successfully fight the disease and those who die. These differences could range from simple, for example if someone has been exposed to other coronaviruses in the past, to factors as complex as genetically determined variations in the way certain cells present fragments of viral proteins on their surfaces. for inspection by circulating immune cells. These proteins can influence the likelihood that the immune cell will recognize the presence of a dangerous pathogen, sound the alarm, and mobilize an army of antibodies to launch the attack.

“Now there’s a flood of data, and it’s the highest quality we’ve ever had, and also the greatest we’ve ever had,” Davis says.

A godsend for science, of course. But will the ISB study change the way patients are treated and help us prepare for future pandemics? Hood is optimistic. “It validates absolutely everything I have supported for 20 years,” he says.

The necessary tools

Hood made a major contribution to immunology at the start of his career, after attending medical school and obtaining his doctorate from Caltech. He helped solve the mystery of how the body can produce around 10 billion varieties of antibodies, Y-shaped proteins that can bind to the outer surface of a distinctly shaped invading pathogen and destroy it. with the specificity of a guided missile.

Despite his early successes, Hood recognized early on that without major technological advancements, he would never answer the most intriguing biological questions that remained about the immune system: those revealing how it coordinates its remarkably complex collection of cell types and proteins. If immunologists were ever to understand how all of these parts worked together, Hood realized, they would first have to recognize, characterize, and measure them.

Jim Heath, President of the Institute for Systems Biology

IAN ALLEN

Hood’s Caltech lab has played a key role in the development of a wide range of tools, including instruments for biologists to read and write amino acid sequences and machines capable of stringing nucleotides together. DNA (the letters of the genetic code). Perhaps most famous, in 1986 he helped invent the automatic DNA sequencer, a machine capable of quickly reading nucleotides in the genome and determining their order; he paved the way for Human genome project, the $ 3 billion effort over 13 years to produce the first draft of a complete human genome.

In the years that followed, Hood advocated for a reinvention of modern healthcare that relied on new tools in molecular biology to collect data from individual patients: genomic sequences and comprehensive inventories of proteins circulating in the blood. . This data could then be analyzed, using early machine learning and pattern recognition systems to extract interesting patterns and correlations. The knowledge could be harnessed to maximize a person’s health and prevent disease much sooner than possible.

It all made perfect scientific sense. But nearly two decades after the completion of the Human Genome Project in 2003, and despite many advancements in genomic as well as data science, Hood’s predicted revolution in healthcare is still not arrival.

Hood says one of the reasons is that the tools were expensive. Now, however, a genome can be sequenced for $ 300 or less. And, he says, researchers have had access to computational tools “that can really integrate data and turn data into knowledge.”

But the biggest obstacle is that the health system is inefficient and resistant to change. There is a “lack of understanding of the importance of getting various types of data and integrating it,” Hood says. “Most doctors went to medical school five, 10, 20 years ago, and they never learned anything about it.”

“Everyone is very busy and change takes time, so you have to persuade leaders as well as doctors that it is in their best interest,” he says. “It all turned out to be a lot more difficult than I ever thought.”

Pandemic course

These days, Hood is still pushing hard, and despite years of frustration, he’s a distinctly optimistic one. One of the reasons for his renewed hope is that he finally has easy access to patients and the money to start his next big experiment.

In 2016, ISB merged with Providence Health & Services in Seattle, a massive network with 51 hospitals, billions of dollars in cash and a thirst to develop a more robust research agenda.

Shortly after the merger, Hood was talking about an incredibly ambitious campaign to launch what he calls the Million Person Project. He would apply phenotyping and genetic analysis, yes, to a million people. In January 2020, Hood launched a pilot project, having recruited 5,000 patients and started sequencing their genomes.



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