Scientists looking for new tumor viruses have to keep an eye out for the virus genes rather
than the viral particles. 2017 winners of the Paul Ehrlich and Ludwig Darmstaedter
Prize were twice successful with this strategy.
Two Americans, Yuan Chang and Patrick S. Moore, received
the 2017 Paul Ehrlich and Ludwig Darmstaedter Prize in Frankfurt's Paulskirche for
their discovery of the tumor viruses HHV-8 and MCV by means of a clever subtraction
strategy. HHV-8 is the human herpesvirus 8, and MCV stands for Merkel cell polyomavirus.
"With their decision to search for the viral genes rather than the viral particles, the
prizewinners have taken a major step forward in the hunt for new human tumor viruses and
have laid the foundation for further discoveries. The discovery of further human tumor viruses
in future remains a distinct possibility," wrote the Scientific Council in substantiating its
decision. One in every six cancers in the world is related to a viral infection However, the risk
of cancer from a viral infection is lower in the Western industrial countries than in the
developing world. Yuan Chang is Professor of Pathology at the University of Pittsburgh
Cancer Institute. Patrick Moore is Professor and Director of the Cancer Virology Program at
the University of Pittsburgh Cancer Institute. They are a wife and husband team.
HHV-8 causes Kaposi's sarcoma, a tumor of the blood vessel cells, which can be seen on the
skin with the naked eye owing to its pronounced red or purplish spots. The tumor occurs
mainly in AIDS patients. In their search for HHV-8, Chang and Moore subtracted the entire
human genome from the genomic DNA of the tumor cells. The idea behind this approach was
that the remaining sequences would, in the best case, belong to the tumor virus and not to the
human genome. Following this strategy, the prizewinners isolated two small DNA fragments
that they were eventually able to assign to a new herpesvirus. When they published their
findings in 1994, they named the virus Kaposi's sarcoma-associated herpesvirus (KSHV). It
was later given the official name HHV-8.
MCV is responsible for causing Merkel cell carcinoma, an extremely rare, malignant skin
cancer. Chang and Moore refined their strategy in the search for the virus causing Merkel cell
carcinoma. Fourteen years after the discovery of HHV-8, their approach was no longer to
subtract the entire human genome from the tumor DNA but only the RNA sequences, thereby
greatly simplifying the search. In addition, the sequences were not subtracted in a laboratory
experiment but computationally, for which they used the published human genome sequences.
Chang and Moore not only discovered the viruses but also showed that they are in fact
responsible for the two types of cancer. All Kaposi's sarcomas everywhere in the world
contain HHV-8, in other words, not only those that occur in the context of AIDS but also the
rare sarcomas that occur sporadically in the USA, Europe and Africa. The infection also
precedes the tumor development. It was more difficult to demonstrate that MCV is the culprit
in Merkel cell carcinoma because the virus is present in humans' normal skin flora. Chang and
Moore showed that in all cells of a given Merkel cell carcinoma the virus is located at the
same site in the genome – although the sites will differ between different Merkel cell
carcinoma patients. The tumor must therefore have developed from a single cell with
integrated MCV, and this fact, along with further findings, confirmed its causal role.
If some tumor viruses are ubiquitous, why does not everyone fall ill? The tumor viruses first
have to overcome the cell's defenses – either by means of cancer genes that they bring with
them as with HHV-8 or through mutations as with MCV – and the immune system has to be
weakened for cancer to actually develop. Is there a vaccine or treatment for HHV-8 or MCV?
"The situation with Kaposi's sarcoma is disappointing for us," says Moore. "Although the
community of researchers has found candidates for a vaccine and target molecules for
therapy, there is little commercial interest in developing a vaccine or a specific drug therapy."
Chang adds: "For Merkel cell carcinoma, however, we're optimistic. Many patients respond to
checkpoint inhibitors, some even go into complete remission." Checkpoint inhibition is a
promising new therapeutic principle in cancer treatment.
The €120,000 Paul Ehrlich and Ludwig Darmstaedter Prize is among the most prestigious
international awards granted in the Federal Republic of Germany in the field of medicine. The
Prize will be presented by Professor Harald zur Hausen, Chairman of the Scientific Council.
Short biography of Prof. Yuan Chang
Yuan Chang is a virologist and pathologist. She was born in Taiwan and
grew up in Salt Lake City. She studied medicine at the University of Utah and holds a
Bachelor of Science degree from Stanford University. Chang worked at Stanford University
Medical Center, at the DNAX Research Institute of Molecular Biology in Palo Alto, and at
Columbia University`s College of Physicians and Surgeons in New York, before moving to
the University of Pittsburgh in 2002. She is currently American Cancer Society Research
Professor, Distinguished Professor of Pathology, and UPMC Endowed Chair in Cancer
Virology at the University of Pittsburgh School of Medicine. Yuan Chang has won numerous
awards. This year she will receive the 2017 Passano Foundation Award together with her
husband Patrick Moore.
Short biography of Prof. Patrick S. Moore
Patrick S. Moore is an epidemiologist and virologist. He studied biology at
Westminster College in Salt Lake City and completed his master's degree in chemistry at
Stanford University. He studied medicine at the University of Utah and obtained a Master of
Public Health at the University of California, Berkeley. He worked in Ghana in 1985 and then
in Liberia in 1986. He then joined the Centers for Disease Control and Prevention, where he
was involved in international public health interventions in Chad, Ethiopia, Saipan, Nigeria,
Nepal and Somalia. He worked for a short time as Deputy Commissioner of the New York
City Department of Health in 1993 before moving with his wife to Columbia University in
New York. Moore was Professor of Public Health Division of Epidemiology at Columbia
University until 2002, when he took up a position at the University of Pittsburgh. He is the
Director of the Cancer Virology Program at the University of Pittsburgh Cancer Institute,
American Cancer Society Research Professor, Distinguished Professor of Microbiology and
Molecular Genetics and the Pittsburgh Foundation Chair in Innovative Cancer Research at the
University of Pittsburgh School of Medicine. Patrick S. Moore has won numerous awards.