20 Years of Translational Research

20 Years of Translational Research


20 Years of Translational Research

There is a photograph of Felix Baumgartner, the daredevil skydiver, crouched on a platform 24 miles above the Earth, moments before his record-breaking freefall at more than 800 miles per hour from the edge of space. Our planet dominates most of the image. Just over his shoulder, the vastness of space stretches infinite. The image is arresting. At once, it is knee-buckling and awe-inspiring.

“That is what it felt like to start TGen,” quips Dr. Jeffrey Trent, the founding President and Scientific Director of the Translational Genomics Research Institute (TGen).

 Nonprofits are a risky business. Over half of them fail within the first few years. Startups are even more so, with a failure rate of around 90 percent. TGen was a combination of both based on relatively unknown science. 

“No one knew what genomic research or precision medicine or translational sciences really was twenty years ago,” he explains. “We had to do a lot of educating before we could show what was possible.”

TGen represented more than new terminology. It meant a paradigm shift in genomic research. The Institute facilitated a move from discovery to diagnosis, treatment, and prevention of disease. It represented the transition from expanding our knowledge and understanding of human biology to applying it directly. That was the promise and possibility just over the horizon—all it required was a leap of faith.

 

Diving into New Frontiers

“If we are not helping people, why are we doing this work?” asked Dr. Trent over the din of party chatter in a packed Phoenix living room. It was 2001, TGen was more vision than reality, and the question was one he often asked in those days.

The cocktail party drew out civic leaders and socialites from around the state. At the time, Trent served as the founding Scientific Director of the NIH Institute overseeing the world’s largest collaborative biological undertaking— the Human Genome Project—a 13-year effort to determine the complete sequence of DNA bases in the human genome.

The result was a mosaic of the central ingredients that make up human beings. For the first time, all the estimated 20,000-25,000 human genes were accessible for further biological study.

This was important work, no question, but Trent felt an urgent need to apply this knowledge. 

“We need to do something with these findings,” he found himself saying. This party was a step toward that something. To build an institute that would translate the blueprint for understanding human biology to advance the diagnosis and treatment of various cancers, neurologic, and metabolic diseases, such as Alzheimer’s and diabetes.

Trent envisioned a partnership between public and private sectors aligning industry, academia, and government. “University research is focused on educating and informing,” he says, elaborating on his perspective. Government knows population and scale, they foster great work, but they are conservative in their approach. They swim in their own lane. Confined.

Industry provides the opportunity to scale. Realistic applications. They know how to do that.”

Bringing these approaches together could focus efforts on the individual patient.

Even if the science wasn’t completely understood that evening, its significance was almost palpable to some of the guests. History was being made. The kind of history that comes along maybe once in a lifetime — an epoch-altering event —ushering in the genomic era of biomedical research. An approach to treating and preventing disease based on an individual’s genomic makeup — which would later come to be known as precision medicine.

Bennett Dorrance, Managing Director and co-founder of DMB Associates, a Phoenix-based real estate firm, was among the guests that night. He sensed the possibilities.

“I didn’t know a lot about the science, but I was convinced that TGen was onto something,” he explains.

Initially, for Dorrance, it was about jobs. Bringing opportunity to the state. He and his wife, Jacquie, had attended the University of Arizona. After graduation, they settled in Phoenix. They started a family, built a business, made a life. Arizona was their home.

The economic downturn in the early aughts hit the state hard. Bringing TGen here could mean establishing the epicenter of an emerging industry. Phoenix could be a real hub for biomedical research.

“To his credit,” Jacquie says of her husband, “Bennett was so convinced this was something he wanted to support, absolutely convinced, that he didn’t even listen to the naysayers. There were a lot of naysayers in the early days.”

By summer the following year, it was official that TGen would headquarter in downtown Phoenix. The summer after that, June 2003, they broke ground on a six-story, $46 million facility to house TGen laboratories and administrative offices.

Bennett’s convictions and those early contributions from the Dorrance family have been vindicated several times over. The Phoenix Bioscience Core is on track to have a $3.1 billion economic impact generating 22,132 jobs by 2025.

In 2004, Trent would get his first proof points to scientifically validate his leap of faith. In a small Old Order Amish community in central Pennsylvania, nine families across two generations lost twenty-one infants to a newly described form of sudden infant death syndrome. TGen scientists helped identify the genetic basis for the syndrome.

Over the decade that followed, TGen had a series of remarkable successes. TGen researchers contributed to the discovery of Kibra, a gene that plays a significant role in memory performance in humans. In 2006, TGen announced findings from the first genome-wide linkage study of prostate cancer in African Americans. They contributed to the discovery of the genes that contribute to melanoma risk in 2008, co-developed individualized-therapies for pancreatic cancer patients in 2009, and licensed a unique compound that targets cancer tumors by modifying the actions of proteins in 2011.

For Bennett Dorrance, reflecting on the progress since that initial gift, what first began as an investment to bring economic prospects has evolved. It is no longer just about jobs and opportunities. “I see this more as a gift to the world,” he says of TGen’s work.

 

Lessons from COVID  

When the COVID virus first emerged more than two years ago, TGen went into action. In 2007, TGen North opened to focus on detecting and preventing biological threats and viral outbreaks. Now, they joined a growing number of facilities concentrating on the virus. As the pandemic spread, TGen pivoted to combat COVID head-on.

TGen applied the tools, technologies, and approaches that drove its many successes in cancer and infectious disease research full force to the genome of the virus. The results: a blood plasma test that looked for antibodies in those individuals exposed to the virus, a saliva-based test, methods for tracking how the disease moves and mutates, and contributions toward the development of treatments.

Dr. Michael Berens, Director of the Cancer and Cell Biology Division at TGen, who focuses primarily on malignant brain tumors, points out the hidden value of understanding COVID. “If COVID has taught us anything,” he explains, “it is how differently we are all experiencing the same disease.”

Some cases put patients on a respirator, while others reacted as if it were just a cold. More than 40% of COVID survivors are estimated to have developed “Long COVID,” with complications outlasting the virus. We see the variance in how the disease is expressed from person-to-person that answers to larger, often unspoken, questions in the medical community.

Over the last two decades, the terminology that made TGen seem so foreign has experienced an uptake. Nearly every research university in the country now has a translational sciences department. Genomics is no longer a strange idea but is now routinely applied. Precision medicine as a concept is better understood and more well known. Still, while the terminology has been embraced, some of the most fundamental ideas underlying this work are slow to take root.

 “My own research is to bring new treatments to brain tumors.” Dr. Berens explains. “What is true for one person’s tumor may not be true for another. That can pose a significant challenge to the work.”

Scientifically, it means understanding each unique patient. Systemically, it means disrupting a traditionally conservative medical establishment. Trent observed, “Today, less than 1 in 10 physicians are comfortable sharing genetic information.” For TGen’s practices to be more commonplace and readily adopted, that figure must be higher.

Berens is optimistic. He believes that one of the longer-term lessons that will take root after COVID is the broader recognition that no two people experience the same disease in the same way.

 

Moving from Promise to Practice

Imagine building a boardwalk backward across a shifting dune in the dark. You are twice blind. The terrain is unknown and constantly changing. Ground that was stable moments ago now completely vanishes in an instant.

Berens presents this vivid metaphor. Overseeing the Brain Tumor Unit at TGen, he has helped build a lot of boardwalks.

“This is explosive, exciting work,” he says. “We are learning how to help patients’ own immune system go after their cancer. Brain cancer is such a devastating disease. It is aggressive and moves quickly. In the last 13 years, there hasn’t been a new drug developed for treatment in this area. The blood-brain barrier is frightening,” he says, referring to the unique properties possessed by blood vessels that vascularize the central nervous system (CNS). “Most try to avoid it because we don’t want to run the risk of side effects happening in the brain. My lab races into that fire. It is something we try to use to our advantage.”

Dr. Daniel Von Hoff, TGen Distinguished Professor and Executive Vice President of the Molecular Medicine Division, focuses on equally exciting work in oncology—specifically pancreatic cancer. His ceaseless efforts to create drugs and treatments that extend quality of life often aim to keep his patients alive until the next breakthrough. His cases are some of the toughest and most persistent. After conventional treatments have failed, targeted medicine has become a last resort. 

“TGen is a major contributor in this area. Of the five drugs approved by the FDA for advanced pancreatic cancer, TGen has done pre-clinical trials in three of them. This is on Stage 4 patients.” Von Hoff’s clinical trial work has led to the approval of three of the four drugs approved by the FDA for the treatment of patients.

This remarkable work would not have been possible if not for the unique environment TGen provides.

“Our medical establishment is conservative. Do no harm. Science is a high-risk endeavor. Experimentation. In order to have success, to build the boardwalk, the conservative medical establishment must meet high-risk startup culture,” Berens explains. 

This circles back to Trent’s original vision of taking the best elements of the public and private sectors. Aligning industry, research, and government. Making knowledge actionable because if we are not helping, what is the point?

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