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The Spark that Ignites Innovation

The architect of the Pediatric Cancer Genome Project reflects on the initiative’s origins and legacy.

James R. Downing, MD; Photos by Peter Barta and Sam Hurd

Think about the invention of the lightbulb. The creation of a vaccine. The mass production of the Model T. What is the spark that ignites innovation? It’s seldom a single point, but rather the convergence of ingenuity and imagination.

A decade ago, we had the talent, time and technology to launch a project that would transform how we understand and treat childhood cancer.

The Pediatric Cancer Genome Project (PCGP) began with simple sketches on envelopes and napkins. Those scribbles by scientists from St. Jude Children’s Research Hospital and Washington University in St. Louis would usher in the next wave of discovery.

In 2010, pediatric cancer survival rates hovered around 80%. Success had been incremental. Progress had plateaued.

Researchers worldwide had not yet uncovered the genetic changes that lead to cancer. As a result, the drivers of cancer remained elusive, especially in children. Genomic sequencing projects that were underway largely ignored childhood cancer. The void underscored the need.

James R. Downing, MD, and other leaders officially launch the PCGP.

Birth of the PCGP: James R. Downing, MD, and other leaders officially launch the project in January 2010 at the National Press Club in Washington, D.C.

Thanks to recent leaps in technology, the cost of whole-genome sequencing had dropped, and the speed had increased.

“What if” conversations gave way to formal proposals.

Timothy Ley, MD, a Washington University cancer genomics and leukemia researcher, as well as Richard Wilson, PhD, and Elaine Mardis, PhD, then co-directors of the university’s McDonnell Genome Institute, offered their expertise in high-speed, large-scale genomic sequencing. St. Jude would provide research and treatment experience — and access to one of the world’s largest collections of childhood cancer tissue.

With those pieces in place, St. Jude committed $65 million to a three-year collaboration with Washington University to uncover why childhood cancer arises, spreads and resists treatment. We unveiled the PCGP January 25, 2010, at the National Press Club in Washington, D.C.

As I traveled back to Memphis after that announcement, the weight of the task ahead set in. Many sleepless nights followed. At the time, scientists had not sequenced even one pediatric cancer genome. No one else had tried to conduct this level of sequencing on such a massive scale.

The collaboration among PCGP scientists made all the difference. The project included more than 150 faculty and staff at St. Jude and more than 200 people at Washington University.

In general, brain tumor doctors don’t work with leukemia doctors, and leukemia doctors don’t work with solid tumor doctors. People in computational biology don’t often talk with clinicians. But the PCGP brought everyone together. It transformed the culture of St. Jude and brought the power of collaboration to the forefront.

The first year, we sequenced the normal and cancer genomes of 50 patients, with another 250 in the second year. By the end, we had whole genome sequences from 800 cancer patients with 23 types of cancer.

 
 
 

The PCGP came into being because of the need to accelerate progress. It succeeded because we were willing to chase big ideas and make the most of a unique moment in history.

James R. Downing, MD

 
 

The project unearthed a treasure trove of discoveries in brain tumors, high-risk leukemias, solid tumors and even a non-cancerous disorder called Lou Gehrig’s disease. We also learned that about 10% of children with cancer are born with genetic changes that increase their cancer risk.

The PCGP generated new computational tools. Five of our new software applications helped identify key driver mutations that other methods had missed.

Based on the success of the first phase, St. Jude committed another $30 million to extend the project in 2014.

The PCGP served as a catalyst for a decade of transformative research. St. Jude Cloud, the world’s largest storehouse of childhood cancer genomics; pre-clinical resources such as PROPEL and the Childhood Solid Tumor Network; and the St. Jude Cancer Predisposition Clinic can all be traced back to the project.

Current clinical trials for children with cancer reflect insights gained from the PCGP. Those trials include SJMB12, an international study for young people with the brain tumor medulloblastoma, and TOTAL 17 for children with acute lymphoblastic leukemia.

An old adage tells us that necessity is the mother of invention. In many regards, the PCGP came into being because of the need to accelerate progress. It succeeded because we were willing to chase big ideas and make the most of a unique moment in history.

Scientists worldwide continue to make discoveries based on the project’s data. The beneficiaries are the children of today as well as the generations to follow.

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