Infectious Disease Research and Treatment in the Genomics Era

In the Opening Plenary of IDWeek 2019, 2 bright lights in infectious disease research spoke on the sea-change brought by genomics to biomedicine and the response to infectious disease outbreaks.

Francis Collins, MD, PhD, director of the National Institutes of Health (NIH), was in on the first “enterprise of big biology,” the sequencing of the human genome. At the time there were skeptics who felt that computational power and biology were like oil and water. The ensuing few years quelled that storm. It was a dauntingly expensive enterprise, to the tune of about $100 million. With time and refinements, the cost nosedived. Today, the same sequence can be generated for about $500. “I know of no other technology in the course of history that has dropped in cost this rapidly. This was accompanied by the increased speed and accuracy of sequencing. This is one-time things got better, faster, and cheaper,” Collins said.

The success turned research thinking to the use of genomic applications in patient health, with infectious diseases topping the list. NIH was one of the agencies that helped assemble a battery of genomic databases of different diseases and made the data freely available. “A small laboratory did not have to do all the work to generate all this data. That meant a small laboratory could become a pretty big genomic engine in discoveries,” Collins said.

Collins selected 4 applications for comment—the human microbiome, rapid diagnostics, curing HIV, and NIH’s All of Us initiative. Within about 15 years, the human microbiome has gone from a distant curiosity to a fundamentally important contributor to health (and disease). It is still a bit of a black box, since many of the organisms cannot yet be cultured. But they can be sequenced, which may allow an understanding of the microbiome in times of good health and times of disease, the role that drugs like antibiotics play in altering the microbiome, and how the information can be used to track outbreaks of infection.

Rapid diagnostics is an issue that has dogged clinical microbiologists for decades. “When I was a medical student, I worked in a microbiology lab. I did the streaking of those plates and tried to figure out what it was that was there and then determine the antibiotic sensitivities using those little discs. And, it’s a bit odd, but even many years later, a lot of diagnostics haven’t gotten all that much better,” Collins explained. The need for swifter diagnosis is pressing. NIH is spearheading a competition that provides big cash to companies that can devise an accurate diagnostic test that delivers results within a working day. The 5 finalists are hard at work and the hope is that something good will emerge by the 2020 deadline.

Rapid diagnostics will surely benefit from the Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) technology. Although originally devised as a way of seeking out sequences to edit, the potential of the sequence recognition part of the technology in the diagnosis of microbes has been recognized, with basic and for-profit researchers diving in.

The CRISPR-Cas approach may also be useful to discover the currently unknown reservoirs of HIV in the body. Knowing these hiding places and eliminating the virus in them could be a real way to eliminate HIV infection. This research is in the early days, but results from mouse models are encouraging.

Finally, the All of Us initiative seeks to enlist 1 million Americans in a life-long commitment to being monitored to gauge the effects of lifestyle, diet, health, and a raft of other factors on, among other targets, their microbial content. The data could go a long way to realizing precision medicine.

The ability to acquire genomics information and share the information in real-time has opened the possibility of establishing communications networks that can monitor hotspots of infection around the world, and to rapidly respond when an infection appears to be gaining steam, as happened disastrously in the Ebola outbreak in Africa in 2014. Also, teasing apart the molecular details of a pathogen like the Ebola virus can reveal changes in the virus that can be used for better prevention and treatment strategies. These aspects of infectious disease genomics are what drives Pardis Sabeti, MD, PhD, a professor at Harvard TH Chan School of Public Health, who delivered the second talk in the plenary.

Work in her lab has aimed to harness genomics to provide information that can be used in real-time to inform the development of vaccines and other therapies, to identify variations occurring in the viral genome that could be fueling outbreaks, tracking and characterizing the transmission of the virus during outbreaks, and uncovering selection pressures.

Her talk centered around the 2014 Ebola outbreak, which spread to multiple countries in Africa with alarming swiftness and rapidly affected thousands. Data so far have confirmed the alarming tendency of the virus to mutate more quickly than had been noted in prior outbreaks and the very ominous finding that the virus appears to be rejigging its surface so that it is more capable of being transmitted person-to-person. “The acquisition of this mutation by the virus occurred near the inflection point of the outbreak, when the outbreak spread and the number of cases climbed rapidly. From then on, nearly all virus we sampled had the mutation,” Sabeti said.

Skipping the fairly hefty technical details, the CRISPR-Cas technology likely has a beneficial role in devising diagnostic tests that are portable, rapid, and inexpensive. Their deployment in Ebola outbreaks is envisioned. Such a test would also be an immense relief to pregnant women in regions affected by the Zika virus; currently results are available weeks after testing.

“We need to be able to move faster and better. We need to be able to rapidly detect emerging infections. We need to connect that information immediately, in real-time, across the involved area and across the world, and share this information so we can find out what caused this infection and deal with it,” Sabeti explained.

Carlos del Rio, MD, co-director of Emory Center for AIDS Research, reacted to the opening plenary session in a video interview with Contagion® (see video above).

"The opening plenary was fantastic, and it was fantastic just because we got the opportunity to listen to Dr. Collins, who is the director of NIH, but also got the opportunity to listen to an incredible researcher doing genetics from Harvard, and talk about how she uses genetics to to approach outbreaks like Ebola, and how she's looking at that and big data, etc."

Brian Hoyle, PhD, is a medical and science writer and editor from Halifax, Nova Scotia, Canada. He has been a full-time freelance writer/editor for over 15 years. Prior to that, he was a research microbiologist and lab manager of a provincial government water testing lab. He can be reached at hoyle@square-rainbow.com.