Jim Allison, immunotherapy researcher at MD Anderson and Nobel Prize recipient, is the subject of a new film that premiered at SXSW. Photo courtesy of MD Anderson Cancer Center

For most of his career, James Allison has been a cancer research wildcatter fighting an oftentimes lonely battle for the advancement of immunotherapy. The medical community has historically been skeptical of the science, but nonetheless Allison dedicated his life to developing a better treatment to the disease that has claimed so many lives — including his mother's.

Last year, Allison, the chair of Immunology and executive director of the Immunotherapy Platform at MD Anderson, won the 2018 Nobel Prize in medicine, and Breakthrough, a film about Allison's progression from early researcher to Nobel Prize recipient, premiered on March 9 at the 2019 SXSW Interactive festival.

But despite the Nobel Prize and the new film both validating the science to the public, Allison says there's a lot more work to be done in immunotherapy. Allison, his colleague, Padmanee Sharma, and the filmmaker for Breakthrough, Bill Haney, hosted a discussion at SXSW about the future of immunotherapy.

"It's a time of considerable optimism — and we're just at the beginning," says Allison.

The film focuses on the man behind the science — a 70-year-old, harmonica-playing researcher from small-town Alice, Texas. It's both an ode to Allison's career and a thought-provoking take on all the work left to be done in the industry.

Immunotherapy is the process of targeting one's immune system's T-cells, infection-fighting white blood cells, to attack cancer cells. Sharma, a fellow MD Anderson oncology expert and clinician, says their work has received clinical approvals for treating Melanoma, kidney cancer, lung cancer, and bladder cancer. The scientists are now focused on expanding that treatment to other cancer types and building upon the established platform they've created, while also making sure nothing comes in the way of the facts of the science.

"It really requires that we dedicate ourselves to the basic science, understanding it and educating people about it, so we don't allow the facts and science get muddied by things that are political or nonfactual," Sharma says.

In a lot of ways, this is what Breakthrough has been able to do — communicate the facts on a platform where anyone can understand the science.

"We have a revolution on our hands, and thankfully we have people like Bill who can really tell the story well, because maybe as a scientist and a clinician, we're not always equally talented on telling the story to laypeople," Sharma says.

Moving forward, Allison says he's focused on finding out why the treatment fails in some instances, and he's determined to progress immunotherapy's success rate from the 20 to 40 percent rate he says he sees it at now to 100 percent.

"We've got all the basic tools, and we know what the main issues are," Allison says. "There's still a lot to do, but we need to be smart and do fact-based and mechanism-based combinations."

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Houston doctor wins NIH grant to test virtual reality for ICU delirium

Virtual healing

Think of it like a reverse version of The Matrix. A person wakes up in a hospital bed and gets plugged into a virtual reality game world in order to heal.

While it may sound far-fetched, Dr. Hina Faisal, a Houston Methodist critical care specialist in the Department of Surgery, was recently awarded a $242,000 grant from the National Institute of Health to test the effects of VR games on patients coming out of major surgery in the intensive care unit (ICU).

The five-year study will focus on older patients using mental stimulation techniques to reduce incidences of delirium. The award comes courtesy of the National Institute on Aging K76 Paul B. Beeson Emerging Leaders Career Development Award in Aging.

“As the population of older adults continues to grow, the need for effective, scalable interventions to prevent postoperative complications like delirium is more important than ever,” Faisal said in a news release.

ICU delirium is a serious condition that can lead to major complications and even death. Roughly 87 percent of patients who undergo major surgery involving intubation will experience some form of delirium coming out of anesthesia. Causes can range from infection to drug reactions. While many cases are mild, prolonged ICU delirium may prevent a patient from following medical advice or even cause them to hurt themselves.

Using VR games to treat delirium is a rapidly emerging and exciting branch of medicine. Studies show that VR games can help promote mental activity, memory and cognitive function. However, the full benefits are currently unknown as studies have been hampered by small patient populations.

Faisal believes that half of all ICU delirium cases are preventable through VR treatment. Currently, a general lack of knowledge and resources has been holding back the advancement of the treatment.

Hopefully, the work of Faisal in one of the busiest medical cities in the world can alleviate that problem as she spends the next half-decade plugging patients into games to aid in their healing.

Houston scientists develop breakthrough AI-driven process to design, decode genetic circuits

biotech breakthrough

Researchers at Rice University have developed an innovative process that uses artificial intelligence to better understand complex genetic circuits.

A study, published in the journal Nature, shows how the new technique, known as “Combining Long- and Short-range Sequencing to Investigate Genetic Complexity,” or CLASSIC, can generate and test millions of DNA designs at the same time, which, according to Rice.

The work was led by Rice’s Caleb Bashor, deputy director for the Rice Synthetic Biology Institute and member of the Ken Kennedy Institute. Bashor has been working with Kshitij Rai and Ronan O’Connell, co-first authors on the study, on the CLASSIC for over four years, according to a news release.

“Our work is the first demonstration that you can use AI for designing these circuits,” Bashor said in the release.

Genetic circuits program cells to perform specific functions. Finding the circuit that matches a desired function or performance "can be like looking for a needle in a haystack," Bashor explained. This work looked to find a solution to this long-standing challenge in synthetic biology.

First, the team developed a library of proof-of-concept genetic circuits. It then pooled the circuits and inserted them into human cells. Next, they used long-read and short-read DNA sequencing to create "a master map" that linked each circuit to how it performed.

The data was then used to train AI and machine learning models to analyze circuits and make accurate predictions for how untested circuits might perform.

“We end up with measurements for a lot of the possible designs but not all of them, and that is where building the (machine learning) model comes in,” O’Connell explained in the release. “We use the data to train a model that can understand this landscape and predict things we were not able to generate data on.”

Ultimately, the researchers believe the circuit characterization and AI-driven understanding can speed up synthetic biology, lead to faster development of biotechnology and potentially support more cell-based therapy breakthroughs by shedding new light on how gene circuits behave, according to Rice.

“We think AI/ML-driven design is the future of synthetic biology,” Bashor added in the release. “As we collect more data using CLASSIC, we can train more complex models to make predictions for how to design even more sophisticated and useful cellular biotechnology.”

The team at Rice also worked with Pankaj Mehta’s group in the department of physics at Boston University and Todd Treangen’s group in Rice’s computer science department. Research was supported by the National Institutes of Health, Office of Naval Research, the Robert J. Kleberg Jr. and Helen C. Kleberg Foundation, the American Heart Association, National Library of Medicine, the National Science Foundation, Rice’s Ken Kennedy Institute and the Rice Institute of Synthetic Biology.

James Collins, a biomedical engineer at MIT who helped establish synthetic biology as a field, added that CLASSIC is a new, defining milestone.

“Twenty-five years ago, those early circuits showed that we could program living cells, but they were built one at a time, each requiring months of tuning,” said Collins, who was one of the inventors of the toggle switch. “Bashor and colleagues have now delivered a transformative leap: CLASSIC brings high-throughput engineering to gene circuit design, allowing exploration of combinatorial spaces that were previously out of reach. Their platform doesn’t just accelerate the design-build-test-learn cycle; it redefines its scale, marking a new era of data-driven synthetic biology.”