Gabriel Perna | July 14, 2021
In 2018, the University of California at San Francisco (UCSF) Health named Aleksandar Rajkovic, MD, PhD as the system’s first-ever Chief Genomics Officer. It was a telling designation for a health system that was increasingly using genomic medicine across different clinical specialties.
“It’s becoming clear to everyone that more and more medicine will be tailored to the individual and less to larger groups of individuals. Genomics plays a huge role in who is predisposed to certain diseases and who is not. COVID has been a big example of that,” says Rajkovic. “The position of a Chief Genomics Officer was created to help the organization figure out where to allocate resources in precision medicine and genomic health.”
Of course, the number of Chief Genomics Officers is not quite yet on par with the number of Chief Medical Officers. And not everyone has UCSF’s level of commitment, which includes a Center for Clinical Genetics and Genomics (UCCGG), which operates several genomics laboratories across different specialties, and the Institute for Human Genetics that offers research, training and clinical application in human genetics.
However, Rajkovic sees it becoming more commonplace and the role of CGO (or some kind of genomics director) increasingly necessary as academic medical institutions invest large sums into precision medicine and genomics. A report from the American Society of Human Genetics found that the annual impact on the U.S. economy from genomics has grown five-fold in the last decade, adding $265 billion to the U.S. economy in 2019 and 850,000 American jobs. An August 2020 report from University of Pittsburgh Medical Center’s Center for Connected Medicine found that two-thirds of health systems have—or will have—an enterprise-level strategy in place for genomics and nine-out-of-10 organizations are offering or planning to offer genome sequencing.
The reports were largely tabulated before COVID showed the potential of genomic sequencing with the creation of mRNA-based COVID-19 vaccines (both Pfizer and Moderna) and the PCR COVID-19 rapid test, both brought to market in a short amount of time. Many in the field believe that the pandemic will be a catalyst for health care organizations to further invest in genomics and precision medicine programs. Steve Smith, MD, Chief Science Officer at AdventHealth Research Institute, says consumers have seen firsthand how powerful genomics can be and there is more of an appetite for it than ever before.
“COVID provided an opportunity for our patients to become familiar with genomics technologies. I can pretty much tell you a lot of people didn’t pay attention to sequencing, strain typing or PCR tests two years ago. COVID has brought that into the forefront of discussions with the patients in our communities. That’s a real inflection point for us in clinical genomics, to have this appreciation from patients that not only can they get a PCR test, but they can explore their health,” says Smith.
Opportunities in genomics
Across California, Rajkovic says UCSF and other University of California health systems are collaborating together to sequence the genomes of symptomatic and non-symptomatic individuals that come into their hospitals. He says interesting data has emerged from this initiative in terms of discovering which parts of the genome are responsible for the viral entry.
Last year, UCSF started to offer genome sequencing to all adult patients as part of its precision medicine efforts. The ultimate goal is to build a genomic database that matches the diversity of UCSF Health’s patient population to help scientists better understand genomic variations underlying health and disease impacting these people.
“It’s only through having millions of genomes do we begin to understand our predisposition to certain diseases,” says Rajkovic. However, he notes that this effort has received skepticism among racial minority groups that have dealt with structural racism in medicine for decades. “What we have found to be extremely important is to engage the community who would benefit from getting their genome sequenced, stored and used to identify their predispositions to infections and diseases. It’s important that we’re transparent with them on what will happen with their information.”
Beyond individual sequencing efforts, UCSF has genomics projects around polygenic risk scores for diabetes, cardiovascular, cancer, and heart disease. UCSF is also implementing pharmacogenetics into the EHR to study genomes to determine people’s responses to certain drugs.
In Orlando, AdventHealth recently announced a major genomics and precision medicine initiative with Sema4, an AI and machine learning company based in Stamford, Connecticut. The partnership will aim to bolster AdventHealth’s Genomics and Personalized Health Program by offering clinic-ready sequencing with strong bioinformatics support, Smith says. The partnership will help Advent, with more than 20 hospitals and emergency departments in the Orlando area alone, amp up its research efforts.
“We want to have standardized genomics services with the appropriate medical interpretation and communication with our patients,” says Smith. “We want to provide whole-person care to our patients and genomics is part of that. Patients need more than just a test and a report, they need outstanding medical interpretation along with the appropriate counseling and communications of genetics reports.”
While consumer-focused companies in this space have moved genomics into the public conversation, Sema4 CEO Eric Schadt, PhD, says provider-led efforts can go even further. “When you have a relationship with the physician and the provider, they can use the information to guide you in the right direction. The provider has to engage the information in the right kind of way to make it have value,” Schadt says. In this regard, Smith adds that physicians have been on board and seem ready to move in this direction.
Of course, even with the recent excitement in genomics, there is still a cold hard reality: A lack of serious uptake in clinical practice. Mayo Clinic researchers recently wrote an article in the Journal of Personalized Medicine reporting that adoption of genomic data into clinical decision making remains a “work in progress,” with barriers including the inability to integrate this data into the workflow, and an overall lack of knowledge about genomics by clinicians. There is also the National Human Genome Research Institute finding that it takes on average 17 years to translate a novel research finding into clinical practice.
One of the challenges, according to Clay Smith, MD, Director, Blood Disorders and Cell Therapies Center and Medical Director, University of Colorado Health and CU Innovation Centers, is that the sheer amount of data produced by precision medicine initiatives requires a shift to an informatics-based medicine approach in delivering care.
Steve Smith, MD, Chief Science Officer at AdventHealth Research Institute
“You have to figure out how to take this complex data and the analysis of it and turn it into something that’s very simple and efficient. When I’m in clinic, I have 30 minutes with a patient. I have to decide on something very quickly. Condensing that complicated data into something that I can act upon in a 30-minute visit is another challenge,” Clay Smith says.
Managing petabyte scales of data is a tremendous challenge, says Schadt, and it’s not as easy as pulling these insights out of the EHR. “It requires annotation, curation and taking unstructured data like physician notes, and applying AI-based NLP to extract knowledge and understanding from what the physician is writing down and do it in a way that allows you to share the data. The engineering component is very significant,” says Schadt, who is also the Dean for Precision Medicine at Icahn School of Medicine at Mount Sinai.
Yet another challenge in adoption is unclear regulation. Even with recent developments in FDA approval for genome sequencing, and the emergency use authorizations related to the COVID innovations, many genetic tools remain unregulated. Without regulation, it’s difficult for health care provider organizations to determine how this data should be governed and how tools can be utilized in the safest manner possible.
“From a regulatory standpoint, we need to do a better job of understanding how things are safe, but also ensuring it’s approved [for usage] in an efficient manner. A lot of the diagnostics around this take a long time to get reviewed,” Clay Smith adds. Without clear regulation, health payers are not always reimbursing patients for these tests.
These breakthroughs are moving faster than the regulatory bodies can react, according to Roy Smythe, MD, CEO of SomaLogic, which offers diagnostics tools based on the analysis of cell proteins. Moreover, he says that the American payment structure is antiquated and too focused on acute conditions such that precision medicine tools for disease prevention can often get left behind.
“The payment structure in North America is focused on putting fires out,” says Smythe. “The bulk of investment in biotechnology still goes into acute-care problems. Health care providers want those tools because they get paid to use them. Investors and entrepreneurs are going to make those tools. It’s a cycle that goes on and on. If we said that 50 percent of health care reimbursement in 2023 will be based on management and prevention, you’d see a lot of innovation in those areas.”
Challenges aside, there is as much excitement about genomics in 2021 as there was in 1990 when the Human Genome Project began. In the next five years, Rajkovic predicts there will be significant genome sequencing being done in a variety of settings. He sees it becoming a standard of care for cancer screenings, tumor testing, prenatal and neonatology carrier screenings, and for other diseases.
“The question will become ‘will health systems be able to manage all that information themselves or will they partner with someone to provide that?’ Like anything else, you’ll have different models. There are commercial companies interested in managing certain aspects of genetics. Probably the biggest uses of genetics right now are tumor testing, cancer predisposition and carrier screening for reproductive decision making. Many health systems will probably be partnering with these individual companies to form certain alliances,” Rajkovic says.
He also says there will be more studies being done to prove whether or not these types of genomics can lead to improved outcomes and lower costs of care. There will also be more efforts, Rajkovic says, to integrate this data within the EHR so it becomes less of a workflow challenge.
Clay Smith at UCHealth says that future of precision medicine will be driven by more dynamic tests that go beyond analyzing fixed DNA. He points to new-generation technologies that look to DNA, RNA and protein within individual cells as important.
“With cancer, we now know that every leukemia is different from one person to the next. When we look at the single cell level within leukemia, every cell is different. The old way of doing things with genomic testing is all of those would look the same,” says Smith. “With these single-cell technologies, you’re getting a much more detailed picture. That’s important in cancer because only a small number of cells are causing most of the problems and you have to find those within the larger tumor.”
AdventHealth’s Smith says consumer interest will continue to drive the investment in this space as people are looking to health care organizations to provide cutting edge technology and breakthroughs. He says the real-time insights this kind of data offers providers, as evidenced during COVID, will help the industry reach the “learning health system” concept that the Institute of Medicine introduced more than a decade ago.
“We’ve been talking about creating these loops that allow us to learn from aggregate data that can be applied to one patient at a time. That is the reality of how genomics can work because of the rapid cycle times combined with data quality and integrity. It can really lead us to these new insights and fulfill the promise of a learning health system. It’s clear genomics is the tip of the sphere for that learning health system,” Smith says.