Top Trends in Health and Science for 2014

The marketplace is awash in wearable medical technology, but these devices won’t really help doctors treat their patients until we figure out how to manage all that data.

At the level of design, that means wearable heart rate monitors that don’t merely mimic the look of an EKG, but also collect clinically usable data on heart signals. At the level of organization, it means collecting the kind of data that a physician finds meaningful, and not just what seems cool to consumers.

Figuring all this out is the next big challenge for digital health.

The Center for Digital Health Innovation (CDHI) is creating an open platform that integrates the data from patients' sensors and devices into their electronic health records. Patients with insulin-dependent diabetes will soon be able to use Tidepool's Blip app to aggregate glucometer, insulin pump and continuous blood glucose monitor data and transmit it to their providers via the CDHI platform.  

“The new frontier in cancer treatment is getting a person’s own immune system to eliminate tumors, rather than targeting the cancer cells with chemotherapy. In contrast to conventional cancer treatments, immunotherapies can lead to long-lasting clinical responses.” 

— Lawrence Fong, MD, associate professor of medicine

Conventional chemotherapy for cancer leaves much to be desired.

Currently available compounds kill normal cells as well as cancer cells, leading to serious side effects. The immune system, meanwhile, is remarkably effective at combatting bacterial and viral invaders while sparing normal cells, but the goal of coaxing immune cells to target cancer has eluded researchers for decades.

But the field has turned a corner over the past several years, as researchers have identified receptors expressed on immune system cells, such as CTLA4 and PD-1, that put the brakes on the immune response. In recent clinical trials of antibodies that block these receptors, doctors have seen unprecedented responses in metastatic melanoma and lung cancer, both of which are almost always fatal with conventional treatments.

Because the immune system has a “memory,” these responses have proven far more durable than those to targeted cancer drugs: Some patients treated at UCSF with anti-CTLA4 therapy for late-stage metastatic prostate cancer are still living more than six years later.

“A system known as CRISPRs gives us unprecedented ability to reach in and surgically alter and manipulate the genome. Their impact on basic discovery and on biotechnology and medicine will be revolutionary.”

— Wendell Lim, PhD, professor of cellular and molecular pharmacology and Howard Hughes Medicine Institute investigator

The 1998 discovery of RNA interference (RNAi) provided scientists with a powerful tool to target and switch off the expression of particular genes to unravel their function.

But RNAi can be imprecise, causing unintended “off-target” silencing of genes, and the technique can be time-consuming and cumbersome to employ in experiments. Other methods, such as zinc-finger proteins, have similar limitations.

To the rescue come CRISPRs (Clustered Regularly Interspaced Short Palindromic Repeats), a gene-editing system that could revolutionize everything from disease treatment to plant biology. The technique involves programming an RNA guide molecule to target a section of defective DNA and replace it with “good” DNA.

CRISPRs are simple and inexpensive to use, and can precisely and reversibly suppress the expression of multiple target genes in human cells with 99.9 percent efficiency. Lim, Jonathan Weissman, PhD, and their colleagues in UCSF’s Department of Cellular and Molecular Pharmacology are at the forefront of CRISPR research.

“Microbiome research is rapidly identifying relationships between the bacterial ecosystem in the human gut and an ever-expanding range of diseases. This field of research will prove transformative in the development of novel microbiome-based therapies to treat or prevent respiratory, gastrointestinal and even neurological disorders." 

— Susan Lynch, PhD, associate professor of medicine

Though scientists have long known that bacteria reside in and on our bodies, it is only over the past few years that research has unveiled the staggering scale of these populations and their crucial importance to our health.

There are as many as 1,000 bacterial species known to live in the human gut alone, and all told, these organisms – collectively known as the microbiome – outnumber our own cells by a factor of 10 and account for 1 to 3 percent of our total body mass.

Disturbances in these microbial communities have now been associated with a range of serious chronic diseases, such as inflammatory bowel disease, allergies, obesity, cancer, and even psychiatric and neurological disorders.

The emergence of new therapies targeting the microbiome is one of the most exciting frontiers in medicine. Lynch has recently shown how having a dog in the home alters the gut microbiome, which in turn modulates the immune system to lower the risk of asthma and respiratory infection.

“Primary care is not a new idea. What has changed is that everyone from the President to hospital CEOs to individual patients has now recognized that high quality, affordable health systems all share a common characteristic – a robust foundation of family physicians and other primary care clinicians who serve as patients’ entry point and the medical 'home' for personalized care.” 

— Kevin Grumbach, MD, chair of the Dept of Family and Community Medicine

What medical discovery has definitively proven to improve quality of care and the health of the public while lowering health care costs? The answer is primary care.

We are experiencing an unprecedented era of innovation in primary care. The term “patient-centered medical home” describes new models of care that can include same-day appointments and “virtual visits” using digital forms of communication; emphasizing wellness and prevention; addressing patient’s comprehensive care needs by integrating nurses, pharmacists, counselors and other health professionals into the primary care team; and coordinating care provided by specialists, hospitals, home care services and other sectors to keep a focus on the whole person.

UCSF faculty members are not only performing cutting edge research on primary care innovations, but are leading implementation of these advanced models in its own practices at UCSF Medical Center, San Francisco General Hospital and Trauma Center and the San Francisco Veterans Administration and training our future health professionals to become leaders in the transformation of primary care.

“We now have the technology to be able to generate stem cells from a sample of a patient’s skin, correct the genetic mutation in those cells and return the ‘gene-corrected’ cells back to the patient for therapy. These cells have the advan- tage of containing the patient’s own genetic code, so they escape rejection by the body’s immune system.” 

— David Rowitch, MD, PhD, professor of pediatrics and neurological surgery 

For years, investigators have worked to enable gene therapy to correct mutations resulting in human disease – but successfully delivering repaired genes into cells has been a formidable challenge.

The discovery of induced pluripotent stem cells, or iPS cells, by Nobel laureate Shinya Yamanaka, MD, PhD, and his colleagues in 2006 has brought new hope to the field by making a cell-based approach to gene therapy possible.

>Researchers can now use a patient’s skin cells to create iPS cells that then can be induced to differentiate into the specialized cell types that make up the various organs of the body. Faulty genes can be corrected in these differentiated cells, which can then be placed directly into affected organs. 

“Translating a discovery to practical application is hard work. It's perhaps one of the most important challenges that academia, funding agencies and industry need to address together, particularly in the life sciences. By ensuring that high-potential discoveries are identified and receive focused support, we can accelerate translation and enhance the discovery’s impact on human health.”

— June Lee, MD, of UCSF’s Clinical and Translational Science Institute

So often, promising research doesn’t ever see the light of day. Researchers typically lack access to experts and resources that allow them to rethink and reimagine their work, or to navigate common product development challenges.

More than ever before, academia has a crucial role in addressing the widening translational gap to ensure that the important research happening in our institutions lead to benefitting people. 

At UCSF, the CTSI Catalyst Awardscombine expert feedback with funding to help drive promising early-stage research through the lengthy and complex process of translating ideas into patient benefit. The awards connect researchers with the expertise that’s missing within academic institutions, leveraging the extensive network of biotech/life science industry experts in the Bay Area to address product development-related issues early and in context.

"Consumers are more responsible for managing their own health care expenses, so demand will be higher than ever for greater transparency about quality, safety and cost.  The health care industry needs to be more aggressive in streamlining processes, increasing collaboration and consistently delivering higher value." 

— Mark Laret, CEO of UCSF Medical Center

The entities comprising our nation's health care delivery system will need  to focus on two areas: becoming more efficient and working together in new ways.

For example, UCSF has a number of evidence-based initiatives under way that are increasing patient comfort while reducing costs. These include eliminating unneeded lab tests, reducing inhaled nebulizer use for hospitalized patients and more quickly switching patients from medications delivered intravenously to orally.

We'll also see more linkages among doctors, hospitals, and health plans, who traditionally have competed with each other or spent time buying each others' practices. Collaboration will be key, as we develop partnerships that combine individual organizations' strengths, to create more integrated and comprehensive networks that will provide better access for patients.