A Rich Scientific History

BARUCH S. BLUMBERG, MD, PHD

A Nobel Prize for the Discovery of the Hepatitis B Virus

Although all scientific research is valuable in its own way, few scientists live to see their discoveries potentially save millions of lives and enhance many others. 

But Baruch S. Blumberg, MD, PhD, achieved just that with his 1967 discovery of the hepatitis B virus and the development, with other Fox Chase Cancer Center researchers, of a vaccine against the disease. When approved by the Food & Drug Administration in 1981, it was the first vaccine capable of preventing a human cancer.

Blumberg received the 1976 Nobel Prize in Medicine for his discovery of the virus. He came to Fox Chase in 1964 and served as Associate Director for Clinical Research at the Institute for Cancer Research, a position he held until 1986. He was Vice President for Population Oncology from 1986 to 1989. He served as Senior Advisor to the president from 1989 until his death in 2011.

Blumberg was responsible for major insights into the pathogenesis and prevention of hepatitis B infection, endemic in many populous nations, especially in Asia and Africa, and the fatal liver diseases associated with it. These include primary cancer of the liver, or primary hepatocellular carcinoma, one of the world’s three most deadly cancers. 

Initially, Blumberg was interested in inherited variations in individual susceptibility to disease. But during his analysis of blood samples from various countries, he stumbled upon a mysterious protein that later proved to be the outer coat of the long-sought hepatitis B virus.

Blumberg and his colleagues at Fox Chase promptly developed sensitive blood tests that allowed blood banks to screen for hepatitis B and prevent transfusion-related cases. They also devised a new way to make a vaccine against the virus, harvesting its outer protein from the blood of chronic carriers. 

This approach was critical to the development of a hepatitis B vaccine at that time, since the virus could not be grown in tissue cultures until Fox Chase researchers invented a new technique in the 1980s.

IRWIN A. 'ERNIE' ROSE, PHD

A Nobel for Furthering Understanding of Protein Degradation

Fox Chase Cancer Center researcher Irwin A. “Ernie” Rose, PhD, won the 2004 Nobel Prize in Chemistry for a series of epoch-making biochemical studies on the breakdown of proteins within cells, findings that led to the development of a drug that was the first of its kind.

He received the Nobel along with Avram Hershko, MD, PhD, and Aaron Ciechanover, PhD, both from the Technion-Israel Institute of Technology in Haifa, Israel. Starting in the late 1970s, much of their work was conducted during a series of sabbatical leaves that Hershko and Ciechanover spent as visiting scientists in Rose’s laboratory at Fox Chase.

At that time, many scientists were researching how proteins are made within cells. Rose and Hershko were independently studying the other end of the protein’s life cycle — degradation, the process through which cells mark proteins for destruction, then destroy and dispose of them. A chance meeting at a scientific conference at the National Institutes of Health led to their groundbreaking work.

The focus of the Nobel Prize-winning research was the regulatory protein ubiquitin — so named because it is ubiquitous in the cells of animals and plants. Ubiquitin serves as each cell’s internal garbage disposal, using an enzyme system to target unwanted proteins for breakdown and recycling once their specific task within the cell is done. Along with recycling products the cell no longer needs, ubiquitin helps regulate the important proteins that control cell reproduction.

In decoding this process, Rose, Hershko, and Ciechanover helped future researchers understand how cancers develop when the degradation cycle is disrupted. 

The implications of the discovery weren’t fully realized until 2003, when a drug came to market that harnessed the power of ubiquitin.

Bortezomib, known commercially as Velcade, interferes with the proteasome to help destroy tumors in multiple myeloma, a cancer of the bone marrow. It was the first medication based on the award-winning team’s research to be approved by the Food and Drug Administration. 

In 2024, Fox Chase’s Center for Immunology celebrated the 20th anniversary of this Nobel Prize and the science that it catalyzed at its 14th Annual Scientific Symposium. Rose worked at Fox Chase from 1963 until his retirement in 1995. He died in 2015.

Mintz is responsible for developing many scientific tools and techniques that have changed how science is conducted. Among the most important is her mouse model of malignant melanoma.

BEATRICE MINTZ, PHD

A Basic Science Pioneer

Aprofessor in the Cancer Biology Program at Fox Chase Cancer Center, Beatrice Mintz, PhD, left behind a 60-year legacy that is punctuated not only by her strides in basic science research but her lasting impact on those she worked with.

Mintz came to Fox Chase in 1960 to pursue her research in Philadelphia after holding a teaching position at the University of Chicago. Her work at Fox Chase included several areas of science, including developmental genetics, gene-transfer technology, epigenetics, and the tumor microenvironment, which consists of normal cells and other components that surround tumor cells. 

Mintz was known by colleagues for her innovative thinking and ability to pose the simplest, yet toughest questions. One of her most well-known experiments began with a simple question: How does a complex organism, with its diverse tissues and structures, arise from a single fertilized egg?

She was able to demonstrate that just a handful of embryonic stem cells were able to generate a fully developed animal. Additionally, her work manipulating mouse embryos led Mintz to address questions surrounding the tumor microenvironment, a field that is now being studied aggressively as an essential element in cancer development.

Mintz is responsible for developing many scientific tools and techniques that have changed how science is conducted. Among the most important is her mouse model of malignant melanoma.

Among some of the highlights of a storied career is the list of recognitions and awards Mintz received. She was an elected member of the National Academy of Sciences since 1973 and an elected fellow of the American Association for the Advancement of Science since 1976.

Mintz was the first recipient of the Genetics Society of America Medal in 1981 and became an elected fellow of the American Academy of Arts and Sciences in 1982. In 1990, she was the first recipient of the Ernst Jung Gold Medal for Medicine, and in 1997, she was awarded the National Medal of Honor for Basic Research by the American Cancer Society. 

Mintz died in 2022 at the age of 100 and is remembered not only as an inspirational researcher but as a pivotal figure in Fox Chase’s history.

ALFRED J. KNUDSON, JR., MD, PHD

A Fundamental Shift in Understanding the Origins of Cancer

In 1971, Alfred G. Knudson Jr., MD, PhD, published research that would make him one of the true giants in oncology, a scientist who completely and fundamentally changed the way the world thinks about the origins of cancer. 

His “two-hit” hypothesis provided a unifying model for understanding cancer that occurs in individuals who carry a “susceptibility gene” and cancers that develop because of randomly induced mutations in otherwise normal genes. Tumor-suppressor genes, in particular, are important targets for cancer prevention research since they normally function to apply the brakes to cellular growth.

Like many significant conceptual leaps in science, Knudson’s “two-hit” hypothesis was met with skepticism when he first published it, yet his powerful insights into the development of cancer held implications for both cancer treatment and prevention.

Defects in tumor-suppressor genes permit abnormal, cancerous growth, so devising ways to remedy such flaws or replace the gene’s missing product through medication are of interest to researchers. 

A geneticist and physician, Knudson was internationally recognized for his theory of cancer causation and its explanation of the relationship between the hereditary and non-hereditary forms of cancer. This now-confirmed theory has advanced understanding of errors in the genetic program that turn normal cells into cancer cells.

Knudson first became affiliated with Fox Chase in 1970 as a member of its scientific advisory committee and joined the staff in 1976. In his time at Fox Chase, Knudson served as Director of its Institute for Cancer Research from 1976 until 1982, center President from 1980 to 1982, and Scientific Director from 1982 to 1983.

Throughout his career, Knudson received numerous prizes and honorary doctorates, including the 1998 Albert Lasker Award for Clinical Medical Research, the 1999 American Society of Pediatric Hematology/Oncology Distinguished Career Award, the 2005 American Association for Cancer Research Award for Lifetime Achievement in Cancer Research, the Charles S. Mott Prize of the General Motors Cancer Research Foundation, the John Scott Award from the City of Philadelphia, and the 2004 Kyoto Prize in Life Sciences and Medicine. He died in 2016.

ANNA MARIE 'ANN' SKALKA, PHD

Shattering the Glass Ceiling

When she was recruited to become the Director of the Institute for Cancer Research at Fox Chase Cancer Center in 1987, Anna Marie “Ann” Skalka, PhD, already had nearly 20 years under her belt as an accomplished basic science researcher and scientific administrator at the Roche Institute of Molecular Biology. She went on to serve as Senior Vice President for Basic Science at Fox Chase from 1987 until 2008 and is now Professor Emerita and Senior Advisor to the President.

Over the course of her career, Skalka has become internationally known for contributions to understanding how retroviruses replicate and insert their genetic material into the host genome. Although the most well-known retrovirus, HIV, causes AIDS, many retroviruses cause cancer in animals and some cause cancer in humans. Skalka’s work has greatly informed the study and treatment of both diseases.

She is also the co-author of “Principles of Virology,” the leading virology textbook for undergraduate and graduate students studying how viruses reproduce and cause disease, and is the author of “Discovering Retroviruses: Beacons in the Biosphere.”

Skalka began her research as a postdoctoral associate at the Cold Spring Harbor Laboratory in New York from 1964 to 1969 before being invited to be part of a new basic research institution, the Roche Institute, funded by the pharmaceutical company Hoffmann-LaRoche. Skalka was the only woman on the faculty for quite some time. Starting as a junior member, she was eventually promoted to laboratory chief and finally chair of the Department of Molecular Oncology.

Skalka was recruited to Fox Chase in 1987 as Director of the Institute for Cancer Research, which was the basic research arm of the center at that time. A group of scientists from the Roche Institute came with her and helped her set up her own laboratory at Fox Chase. It focused on retroviruses and oncogenes, research that hadn’t been going on at the center before she arrived.

In addition to being the former W.W. Smith Chair in Cancer Research, in 2023 she received the Stanley P. Reimann Honor Award, Fox Chase’s highest distinction. Skalka is also an elected member of the American Academy of Arts and Sciences and was awarded the 2018 Sigma Xi William Procter Prize for Scientific Achievement and Communications.