Accelerating Discovery

Accelerating Discovery Scientific achievements and milestones at St. Jude Children’s Research Hospital®

Explore More To learn more about the history of St. Jude, our in-depth scientific accomplishments and the profound impact of our research enterprise, use the QR codes below.

Table of Contents A Message from James R. Downing, MD .............................................. 5 Introduction................................................................................................... 6

St. Jude Research

1960s ............................................................................................................... 8

Setting the Standard for Research and Discovery stjude.org/research

Scientific Report Translating Science into Survival stjude.org/scientificreport

1970s ................................................................................................................ 8 1980s ................................................................................................................ 8 1990s .............................................................................................................. 10 2000s ............................................................................................................. 12

Accelerating Discovery Bringing Science to the Forefront stjude.org/scientific-milestones

Neighborly A Magazine about Life in Memphis stjude.org/neighborly

2010s .............................................................................................................. 14 2020s .............................................................................................................. 16 Vision for the Future ................................................................................. 18

A Message from James R. Downing, MD Each day at St. Jude Children’s Research Hospital, thousands unite in the mission to advance the research and treatment of pediatric cancer and other life-threatening diseases. This sense of shared purpose has led to unprecedented gains in how childhood catastrophic diseases are understood and treated.

From its start, St. Jude has been a place of discovery and collaboration. Information flows freely from the lab to the clinic.

Insights gained shape new knowledge, forming the basis of the next iteration of improvements in care. Creativity is cultivated and compassion prioritized. The speed of research moves forward irrespective of funding cycles, grants or bureaucracy.

This model has served science and medicine well, but work remains. Childhood cancer continues to be the leading cause of death from disease among U.S. children ages 1 to 14.

Globally, 80% of children with cancer will perish. Cures for sickle cell disease and many pediatric neurological disorders remain elusive. The devastating effect of infectious diseases has been brought into sharp focus with the COVID-19 pandemic.

With considerable investments in talent, programs and resources, we are poised to unearth transformative ideas, push the bounds of exploration, better inform care and make a lifesaving difference for children in Memphis and far beyond.

James R. Downing, MD President and Chief Executive Officer St. Jude Children’s Research Hospital

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A History of World-class Science and Compassionate Care St. Jude was founded on big dreams and a trailblazing spirit. From the beginning, the premise was daring. In 1962, when the hospital opened, a mere 20% of those with pediatric cancer survived. Children with sickle cell disease lived from pain crisis to pain crisis.

Donald Pinkel, MD, the first medical director of St. Jude, placed doctors, scientists and patients under one roof, allowing discoveries to move quickly from the lab to the clinic.

Pinkel and his colleagues created a culture of extraordinary science and compassionate care that endures to this day.

The hospital has grown exponentially since its opening, but the urgency of the work remains the same.

In this booklet, explore the scientific milestones in our journey to advance cures and means of prevention for pediatric catastrophic diseases through research and treatment.

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19601960 19701970 19801980 1960s

1965

St. Jude develops the first immunologic method to diagnose solid tumors in children.

1962

Rudolph Jackson, MD — one of the first Black doctors at St. Jude — helps establish the sickle cell program at the hospital.

The hospital opens in Memphis, Tennessee, before a crowd of 9,000 people.

1966

1969

St. Jude initiates the Total Therapy approach to acute lymphoblastic leukemia (ALL) treatment. The four-component approach still forms the backbone of ALL treatments today.

A group of St. Jude patients with ALL are the first to be successfully taken off therapy, based on evidence that remission can be sustained.

St. Jude enrolls thousands of local infants in a successful nutritional program, which serves as the prototype for WIC, the federal health and nutrition program for women, infants and children.

1970s

1972

1977

The hospital publishes a study that shows a 50% survival rate for ALL using a combination of chemotherapy and radiation. The achievement revolutionizes leukemia therapy worldwide.

1975

1980s

The hospital launches the first major effort to understand the lifelong progression of sickle cell disease, the Cooperative Study of Sickle Cell Disease.

1976

St. Jude becomes the first to identify important subtypes of ALL, including T-cell leukemia. The finding leads to better risk classifications, new research directions and improved treatment.

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1968

1984

1983

St. Jude opens the After Completion of Therapy Clinic, the world’s largest long-term follow-up clinic for pediatric cancer patients.

A St. Jude patient with sickle cell disease is the first to be cured with a bone marrow transplant.

Researchers pinpoint the first two specific genetic translocations known to cause ALL.

Scientists find evidence that some patients have a mixture of two acute leukemias: myeloid and lymphoid.

World Health Organization (WHO) designates St. Jude as a Collaborating Center for the study of influenza transmission from animals to humans.

Clinicians develop a treatment that is effective for 55% of patients with neuroblastoma, the second most common solid tumor in children.

1985

The hospital’s brain tumor program, which opened the previous year, begins accepting patients. Unlike other hospitals, St. Jude provides an integrated and personalized treatment plan for each child.

1987

The hospital institutes a clinical program to seek a cure for pediatric AIDS.

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1990s

1990

1995

St. Jude is the first to use gene marking to follow the course of bone marrow transplantation in children.

St. Jude is among the first to incorporate a computer-based, 3-D radiation therapy technique into pediatric brain tumor treatment.

St. Jude scientists discover that an antimalarial drug can prevent or effectively treat a life-threatening form of pneumonia in patients with AIDS.

1996

1991

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Peter Doherty, PhD, St. Jude Immunology chair, is awarded the Nobel Prize for Physiology or Medicine. He and Rolf M. Zinkernagel, MD, PhD, of the University of Zurich, share the prize for their pioneering research that explains how the immune system recognizes and kills virus-infected cells.

Scientists identify and associate mammalian G1 cyclins (types of proteins involved in initiating cell cycles) with the development of certain cancers.

By measuring the number of copies of the N-myc gene in neuroblastoma patients, St. Jude researchers individualize chemotherapy for those children.

By opening vector production labs, St. Jude becomes one of the few centers in the world with a comprehensive cell and gene therapy program.

1992

1998

St. Jude forms a Pediatric AIDS Clinical Trial Unit with two other Memphis area hospitals.

By individualizing chemotherapy dosage, scientists discover they can increase survival rates for children with acute lymphoblastic leukemia (ALL) without causing excessive toxicity.

1993

Arthur Nienhuis, MD, establishes an experimental hematology program with a focus on developing gene therapy for blood disorders.

1994

The Pediatric AIDS Clinical Trial Unit publishes evidence that shows HIV infections are preventable by chemotherapy treatment.

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1999

In a landmark study, pharmacists at St. Jude demonstrate the importance of pharmacogenetics and drug interactions.

Scientists identify a genetic defect that can predispose pediatric leukemia patients to secondary brain tumors.

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2000s

2006 St. Jude reports a 94% survival rate for patients with acute lymphoblastic leukemia (ALL) using therapy that does not include radiation.

2001

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Scientists at St. Jude conduct the first measurements of radiation’s impact on the pediatric brain.

The multi-institutional Childhood Cancer Survivor Study (CCSS) publishes a seminal report describing the magnitude of therapy-related chronic health conditions experienced by long-term survivors of childhood cancer. Learn more: stjude.org/ccss

Researchers find that cranial artery damage in patients with sickle cell disease may be reversed by bone marrow transplantation.

Subtypes of medulloblastoma, which was previously thought to be one disease, are defined.

2007

2002

The hospital initiates the St. Jude Lifetime Cohort Study (SJLIFE) to evaluate long-term survivors of childhood cancer via comprehensive health assessments. Learn more: stjude.org/sjlife

Scientists unveil a genetic screening technique that uses microarray chips to diagnose and treat acute lymphoblastic leukemia (ALL) while improving diagnostic accuracy and identifying new prognostic details.

Scientists identify the specific cell that causes retinoblastoma, disproving a long-held theory.

2003

2004

Investigators develop a laboratory model that closely mimics the human eye cancer retinoblastoma, providing scientists a way to test new therapies in the lab.

2008

St. Jude becomes the nation’s first pediatric cancer research center to open a Good Manufacturing Practices (GMP) facility to produce vaccines, proteins, gene-based molecules and other biopharmaceuticals.

St. Jude physicians demonstrate children with bilateral Wilms tumor can retain normal function in both kidneys by undergoing bilateral nephron-sparing surgery, even when scans suggest the tumors are inoperable.

A St. Jude study that compares long-term outcomes of children treated for ALL shows Black children do as well as white children if given equal access to the latest treatments.

St. Jude is designated as a National Cancer Institute Comprehensive Cancer Center, making St. Jude the first and only pediatric cancer center to receive this distinction.

An initial study from St. Jude researchers demonstrates preventative antibiotics can reduce the potential for infection in patients with acute myeloid leukemia (AML).

2005

Researchers find certain traits inherited from parents can reduce the effectiveness of some chemotherapy drugs in children with ALL.

Investigators discover a specific pattern of gene expression in leukemic cells that links to their resistance to anti-leukemic drugs. The discovery helps explain why standard therapies fail to cure about 20% of children with ALL.

2009

St. Jude announces that with effective personalized chemotherapy, cranial irradiation can be eliminated from the treatment of children with acute lymphoblastic leukemia (ALL).

A comprehensive genomic analysis of childhood AML finds remarkably few gene alterations, distinguishing it from other cancers.

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2010s

2015

2010

To train the next generation of scientists in a one-of-a-kind interdisciplinary setting, St. Jude establishes the St. Jude Graduate School of Biomedical Sciences.

St. Jude and Washington University launch the Pediatric Cancer Genome Project to uncover why childhood cancer arises, spreads and resists treatment.

Learn more: stjude.org/pcgp Acute myeloid leukemia (AML) survival rates rise to 71% for children treated on a St. Jude protocol.

2016 2017

St. Jude is named a trial site for an HIV Prevention Trials Network study that compares methods of preexposure prevention of HIV in young men.

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2012

Work at St. Jude identifies genetic factors that make Hispanic children more likely to receive fatal acute lymphoblastic leukemia (ALL) diagnoses.

The Pediatric Cancer Genome Project announces the largest-ever release of comprehensive human cancer genome data for free access.

2014

2013

St. Jude creates the Cancer Predisposition Program to evaluate and care for children at increased genetic risk for cancer.

The Pediatric Cancer Genome Project identifies drugs that enhance oxidative stress as a possible treatment against rhabdomyosarcoma, the most common pediatric soft-tissue tumor.

St. Jude creates the Sickle Cell Clinical Research and Intervention Program to study a large group of patients with sickle cell disease over time.

The Pediatric Cancer Genome Project offers new leads for improved outcomes in children with high-grade glioma brain tumors.

St. Jude and the Howard Hughes Medical Institute create the Childhood Solid Tumor Network, which provides preclinical research and fuels research worldwide.

2015

St. Jude opens the world’s first proton therapy center for children with cancer.

A study from the Pediatric Cancer Genome Project suggests that comprehensive genomic screening may be warranted for all pediatric cancer patients, not just those with family histories of cancer.

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St. Jude researchers and clinicians show the use of a preventative antibiotic treatment during the initial phase of chemotherapy lowers infection risk, broadens protection and reduces Clostridium difficile infection in patients with acute lymphoblastic leukemia (ALL).

2018

St. Jude-led research offers the most comprehensive analysis yet of the genomic alterations that lead to cancer in children and affirms the need for pediatric-specific precision therapies.

St. Jude Cloud, the world’s largest public repository of pediatric cancer genomics data, launches in collaboration with Microsoft and DNAnexus.

Learn more: stjude.cloud St. Jude joins in the effort to eliminate human papillomavirus (HPV)-related cancers and establishes the St. Jude HPV Cancer Prevention Program. Learn more: stjude.org/hpv

St. Jude is designated as the first World Health Organization Collaborating Center for Childhood Cancer. The collaboration is a worldwide effort to advance cure rates to at least 60% in children with six of the most common cancers by 2030.

2019

In collaboration with investigators at the National Institutes of Health and UCSF Benioff Children’s Hospital San Francisco, the St. Jude gene therapy vector cures eight infants with X-linked severe combined immunodeficiency (SCID-X1).

St. Jude acquires the nation’s largest and most powerful nuclear magnetic resonance spectrometer to visualize protein structures that cannot be detected with other technology.

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2020s

2020 St. Jude launches the Pediatric Translational Neuroscience Initiative to bring promising treatments to children with neurological diseases.

Learn more: stjude.org/ptni

In a report published from the Childhood Cancer Survivorship Study (CCSS), researchers at St. Jude demonstrate the importance of a healthy lifestyle for childhood cancer survivors, showing that it can lower early-mortality risk.

02 02

An international collaboration led

by St. Jude shows therapy-induced mutations can drive about 25% of relapsed acute lymphoblastic leukemias.

2023

2021

Scientists develop the Childhood Solid Tumor Network (CSTN) data portal on St. Jude Cloud.

Developed in 2013, the CSTN includes wide-ranging data on 170 patient-derived samples that represent 21 types of childhood solid tumors.

St. Jude scientists identify how the SARS-CoV-2 virus activates inflammatory cell death pathways. They find that drugs already used to treat some inflammatory diseases could be repurposed for COVID-19.

Scientists from St. Jude perform the largest study yet examining drug sensitivity in pediatric acute lymphoblastic leukemia (ALL) across genomic subtypes and its association with treatment response.

By adding a molecular anchor to chimeric antigen receptors (CARs), investigators at St. Jude increase the anti-cancer activity of cellular immunotherapies in cancer models.

In a collaboration between St. Jude and Rockefeller University, scientists reveal how the cystic fibrosis transmembrane conductance regulator (CFTR) functions and how disease mutations and potentiators affect CFTR function, providing insights into potential new therapies for cystic fibrosis.

By October 2021, the Global COVID-19 Observatory and Resource Center for Childhood Cancer has tracked 1,775 COVID-19 positive cases from 51 countries.

This project provides an unparalleled resource for understanding how the SARSCoV-2 virus affects children undergoing cancer treatment around the world.

2022

Researchers at St. Jude find the cellular response to low oxygen also increases fetal hemoglobin expression in adults, which could lead to novel treatments for some common genetic anemias, such as sickle cell disease.

Scientists at St. Jude develop a method that may be able to improve chimeric antigen receptor (CAR) T-cell therapies by identifying the early cells that become the most effective cancer killers.

The Broad Institute of MIT and Harvard, Dana-Farber Cancer Institute and St. Jude announce the largest academic collaboration of its kind to transform and accelerate the identification of vulnerabilities in pediatric cancers and translate them into better treatments. Learn more: stjude.org/pediatriccancer-dependencies-announce

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Vision for the Future In the 60 years since its opening, St. Jude has been at the forefront of discoveries that have transformed how the world treats childhood cancer and other life-threatening diseases. We freely share our discoveries so that more children can be saved. But we don’t stop there.

Approximately 400,000 children develop cancer each year.

More than 90% of those live in low- and middle-income countries where they have little or no access to adequate diagnosis and treatment. Most of those children will die from their diseases. Launched in 2018, St. Jude Global focuses on raising pediatric cancer survival rates around the world. The program unites health care providers through a global alliance, with the goal of one day ensuring children everywhere have access to quality care.

At St. Jude, we continue to look toward the future. But how can we leverage decades of incredible achievements to further accelerate progress and maximize impact?

The 2022–27 St. Jude Strategic Plan answers this lofty call with a bold vision: a $12.9 billion committment aimed at accelerating progress globally.

Our plan concentrates on five areas: fundamental science, childhood cancer, pediatric catastrophic diseases, global impact, and workforce and environment. This ambitious plan will allow us to significantly influence the way the world understands and treats childhood cancer, sickle cell disease, neurological disorders and infectious diseases.

At its heart, our plan for the future is a call to accelerate progress for children with catastrophic diseases on a global scale.

Learn more at stjude.org/strategic-plan.

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