Engineering Discovery: the Story of SKI

1945—Timeline of Progress

Click right to view major scientific milestones of the Sloan Kettering Institute.  

1945—The Sloan Kettering Institute is established

On August 8, 1945 — two days after the atomic bombing of Hiroshima — General Motors executive Alfred P. Sloan, Jr., and engineer Charles F. Kettering announce the creation of the Sloan-Kettering Institute for Cancer Research. The two founders seek to apply lessons gleaned from the automobile industry to cancer research.  

1948—The Sloan Kettering Institute opens its doors

As conceived by its founders, the Sloan Kettering Institute would be devoted solely to scientific research and would serve as both the physical and intellectual center of MSK. "The Sloan-Kettering Institute building will stand squarely in the middle of Memorial Cancer Center," Reginald Coombe, Memorial's president, said at the time. 

1953—First chemotherapy drugs developed

Between 1946 and 1959, Cornelius Rhoads and his colleagues at SKI test thousands of natural and synthetic chemicals that they hope might selectively kill cancer cells, while leaving normal cells unharmed. This large-scale screening program brings to oncology some of the first effective chemotherapy drugs, including 6-mercaptopurine and the nitrogen mustards. 

1957—Viral cause of leukemia discovered

Virologist Charlotte Friend identifies a virus that causes leukemia in mice. Her work lends strong support to the controversial idea that viruses can cause cancer. The virus she discovered is now known as the Friend leukemia virus.

1959—BCG found to boost immune response to cancer

Immunologist Lloyd J. Old discovers that certain bacterial products can boost an animal’s innate immunity to cancer. Mice injected with a weakened version of a bacterium called Bacillus Calmette-Guerin (BCG) are resistant to the growth of implanted tumors. This discovery marks the beginning of modern tumor immunology.

1960—Horsfall becomes SKI Director

Pioneering virologist Frank Horsfall becomes director of SKI. During his tenure, he encourages the study of virology and immunology.

1968—T cell subtypes identified

Geneticist Edward (Ted) Boyse and immunologist Lloyd Old use antibodies to identify surface markers on different functional subsets of T cells. This paves the way for the cluster of differentiation, or CD, system for identifying T cells, such as CD4 and CD8.

1973—Good becomes SKI Director

In 1968, physician-scientist Robert Good performed the first successful bone marrow transplant from a sibling, permanently curing a boy born with severe combined immunodeficiency. At SKI, he continues to research and develop the science of bone marrow transplantation.

1975—Role of interferons in cancer explored

Virologist and geneticist Mathilde Krim was influential in promoting the study of interferons and cancer. She was a member of SKI from 1962 to 1985. In 1983, she cofounded the AIDS Medical Foundation (later the American Foundation for AIDS Research, or amfAR) to raise money and support AIDS research.

1975—Cancer-killing immune molecule identified

Lloyd Old, Elizabeth Carswell, and colleagues identify tumor necrosis factor (TNF), a powerful immune system molecule that causes tumors to hemorrhage and die. This work provides a clear link between the immune system and cancer. 

1979—Flu virus replication unlocked

Molecular biologist Robert Krug, who was a member of SKI from 1967 to 1989, discovers the process of "cap-snatching," by which the influenza virus tricks a host cell into making new proteins from its messenger RNA. A drug targeting this process (Xofluza) was approved in 2018 as a treatment for the flu. 

1980—Marks named president of MSK

Basic science at SKI grows dramatically under the leadership of Paul Marks, who became president of MSK in 1980. In his own research, Dr. Marks made important contributions to the early understanding of epigenetic changes in cells. The FDA-approved drug vorinostat (Zolinza) is based on his work.  

1981—MYC oncogene discovered

Molecular biologist William Hayward, working with scientists at The Rockefeller University, discovers that mutations in a gene called MYC can cause cancer, pinpointing it as an oncogene.

1983—Rifkind becomes SKI Director

Richard Rifkind, who had been a colleague of Paul Marks when they were at Columbia University, becomes the fourth SKI director. He serves from 1983 to 1999.

1984—Expert in RNA polymerase joins SKI

Biochemist Jerard Hurwitz, who co-discovered RNA polymerase in 1960, comes to SKI in 1984 as part of an effort to grow the molecular biology program.  

1984—Human G-CSF purified

Physician-scientists Malcolm Moore and Karl Welte isolate a protein from human cells that stimulates new blood cell growth. Called G-CSF, this protein forms the basis of filgrastim (Neupogen), one of the most important cancer drugs ever developed.

1985—Gene for insulin receptor cloned

Biochemist Ora Rosen, working in collaboration with researchers at Genentech, clones the gene for the insulin receptor, the molecule to which the insulin hormone binds and through which it signals to the cell. 

1988—Process of DNA replication described

Molecular biologist Ken Marians, who arrived at SKI in 1984, makes numerous contributions to the understanding of how prokaryotes replicate their DNA. His research shows that the process is intrinsically tolerant of DNA damage, and that there are various ways to bypass it. 

1990—EGFR-targeted therapy pioneered

Physician-scientist John Mendelsohn, who co-led the SKI Molecular Pharmacology Program from 1985 to 1990, developed the concept of using antibodies to block the epidermal growth factor receptor (EGFR) as a way to treat cancer. At MSK, he conducts important laboratory research and, with MSK colleagues, spearheads pivotal clinical trials that spur the development of the EGFR-blocking drug cetuximab (Erbitux). This work blazes a path for other growth factor receptor-targeting drugs such as trastuzumab (Herceptin).

1994—TGF-beta pathway delineated

Cell biologist Joan Massagué delineates the TGF-beta signal transduction pathway from membrane receptors to nuclear targets, establishing the central concept for how this family of pleiotropic signals controls stem cell division, immunity, and metastasis. Dr. Massagué arrived at SKI in 1989, becoming chair of the Cell Biology Program.  

1994—Protein transport deciphered

Biochemist James Rothman teases apart the mechanism that cells use to package and transport proteins. For this work, he shared the 2013 Nobel Prize in Physiology or Medicine. Dr. Rothman was a member of SKI from 1991 to 2003 and founding chair of the Cellular Biochemistry and Biophysics Program. 

1996—BRCA2 mutation identified

Cancer geneticist Kenneth Offit, who has a joint appointment in the Cancer Biology and Genetics Program at SKI, discovers the most common mutation of BRCA2. This inherited mutation is associated with a much higher risk of breast and ovarian cancers in women. 

1996—Epothilones synthesized

Organic chemist Samuel Danishefsky synthesizes a type of cancer drug called an epothilone, which exhibits a manner of cell killing similar to that of the chemotherapy drug Taxol. 

1996—Signal for limb development discovered

Developmental biologist Lee Niswander shows that bone morphogenetic protein (BMP) controls the programmed cell death that occurs between the digits of the developing chick limb. Blocking BMP signaling results in chicks with webbed feet, similar to what is seen in ducks.

1996—Structure of p53 determined

Nicknamed the "guardian of the genome," the p53 gene is mutated in more than half of all cancers. Using X-ray crystallography, structural biologist Nikola Pavletich determines the structure of the p53 protein, showing how it binds to DNA, a major milestone in cancer research.

1997—Expert in gene regulation comes to SKI

Molecular biologist Mark Ptashne, who won the Albert Lasker Award for Basic Medical Research in 1997, joins SKI the same year. Through his work on the lambda repressor, conducted at Harvard, Dr. Ptashne showed how gene transcription — turning genes on and off — could be regulated by a simple "molecular switch" composed of proteins binding specifically to DNA.

1999—Role of BRCA1 gene established

Molecular biologist Maria Jasin uses a mouse model to show that the BRCA1 protein is necessary for the repair of double-strand breaks in DNA by homologous recombination. Inherited mutations in the BRCA1 and BRCA2 genes are responsible for a large share of familial cancers.

2000—Varmus becomes MSK President

As president of MSK from 2000 to 2010, physician-scientist Harold Varmus greatly expands the institution's research efforts. Dr. Varmus, together with J. Michael Bishop, discovered that the proto-oncogene src is a normal part of cellular DNA. For this work, they were awarded the Nobel Prize for Physiology or Medicine in 1989.

2001—Alpha particles harnessed as therapy

David Scheinberg and colleagues publish the first practical methods for selectively targeting highly potent alpha particles, derived from Department of Energy programs, to various cancers. Clinical trials in people with leukemia soon follow.

2002—Center for Experimental Therapeutics established

Founded and directed by molecular pharmacologist David A. Scheinberg, this center is the first and largest of several collaborative research centers to be established at MSK. Its purpose is to encourage drug development and speed the translation of discoveries from the laboratory to the bedside.

2002—Chimeric antigen receptor (CAR) T cells developed

Michel Sadelain, Renier Brentjens, and Isabelle Rivière develop genetically engineered T cells with a chimeric antigen receptor (CAR), now a powerful way to fight leukemia and other blood cancers. CARs are hybrid proteins made up of different immune molecules joined together. 

2002—Kelly becomes Director of SKI

Molecular biologist Thomas Kelly joins SKI as director after a 30-year career at the Johns Hopkins University School of Medicine. Dr. Kelly helps to strengthen the basic science programs at SKI by recruiting many new investigators to the institution. 

2003—Anderson becomes Chair of Developmental Biology

Kathryn Anderson, a prominent developmental biologist who had been at SKI since 1996, becomes the first female chair of an SKI program, Developmental Biology, in 2003. 

2004—Allison becomes Chair of Immunology

Immunologist James Allison joins SKI to help steer the clinical development of a new drug that blocks a molecule on immune cells called CTLA-4. Dr. Allison was the first to show, in 1996, that blocking CTLA-4 could cure cancer in mice. The new drug, called ipilimumab, opens up a whole new approach to cancer treatment geared toward “releasing the brakes” on the immune system. Dr. Allison, along with Tasuku Honjo, won the 2018 Nobel Prize in Medicine or Physiology for this work. 

2006—Adaptive resistance to signaling inhibition defined

Molecular pharmacologist Neal Rosen shows how inhibiting different parts of the RAS-RAF-MEK-ERK and PI3K-AKT-mTOR pathways with targeted drugs leads to feedback allowing cancers to adapt to these drugs.  

2006—First HDAC inhibitor approved

Former MSK President and physician-scientist Paul Marks conducts laboratory work leading to the development of the first HDAC inhibitor, called SAHA or vorinostat. This drug works by targeting an enzyme called histone deacetylease, altering the way DNA is wrapped around proteins called histones. Marketed by Merck as Zolinza, the drug was approved in 2006 for the treatment of advanced refractory cutaneous T cell lymphoma.

2007—Hedgehog signaling found to depend on primary cilium

Developmental biologist Kathryn Anderson shows that an important signaling protein in mammals, Hedgehog, depends on a cell structure called the primary cilium for its action.

2009—Structure of histone reader determined

Structural biologist Dinshaw Patel, working with David Allis at The Rockefeller University, determines the structure of a protein that binds to and reads the instructions imprinted on histones, DNA’s packaging proteins. The research reveals new mechanisms by which some diseases, including certain types of leukemia, may arise.

2009—Rudensky elucidates regulatory T cells

Immunologist Alexander Rudensky, who joined SKI in 2009, is a world expert on the biology and function of regulatory T cells (Tregs), an important subset of immune cells that help keep the immune system in check. Understanding Tregs has implications for treating cancer as well as autoimmune diseases.

2010—Thompson becomes president of MSK

Current MSK President and Member of the SKI Cancer Biology and Genetics Program Craig Thompson is recognized for having rekindled interest in cancer metabolism as a means to understand and treat the disease. 

2011—Ipilimumab approved for treatment of melanoma

Ipilimumab (Yervoy®), the first immune checkpoint inhibitor, is approved by the FDA for the treatment of advanced melanoma, based on clinical trials led by Jedd Wolchok, a joint member of the SKI Immunology Program. Patients at MSK began receiving ipilimumab in 2004, under the care of Dr. Wolchok. These patients are some of the earliest patients in the world to receive this drug, and a number of them are still alive today. 

2011—Lowe joins SKI

Biologist Scott Lowe joins MSK in 2011. While a graduate student at the Massachusetts Institute of Technology, together with his advisor, Tyler Jacks, Dr. Lowe showed that p53 is required for the cell-killing action of certain chemotherapy drugs. DNA damage triggers p53 to induce the cell to commit suicide.  

2014—Toll receptor code found to shape fly embryo development

SKI development biologist and Howard Hughes Medical Institute Investigator Jennifer Zallen discovers that receptor proteins of the Toll family direct the oriented cell rearrangements required for the elongation of the head-to-tail axis during Drosophila development.

2014—Massagué becomes SKI Director

Joan Massagué, who joined SKI in 1989, becomes its director in 2014. Dr. Massagué is internationally known for his work on the TGF-beta family of growth factors and his contributions to the growing understanding of the biology of metastasis. He launches new SKI programs and collaborative research centers and increases interactions between experimental and clinical researchers at MSK.

2015—Restoring a gene's activity found to turn cancer cells normal

Scott Lowe, an expert in genetic models of cancer, finds that restoring the activity of a gene called APC, which is often mutated in colorectal cancer, turns the cells to normal.

 

2016—Pe'er joins SKI

Dana Pe’er becomes Chair of the Computational and Systems Biology Program and launches a research program to decipher the identity and activity of thousands of individual cells, both cancerous and noncancerous, in human tumor samples.

2016—SKI acquires cryo-electron microscope

SKI purchases an FEI Titan Krios cryo-electron microscope with a Gatan K2 Summit detector. This powerful device promises to greatly enhance scientists’ ability to understand the structure and function of biological molecules, including those that malfunction in cancer.

2017—First CAR T therapies approved

The FDA approves two chimeric antigen receptor (CAR) T therapies for blood cancers. This approach was pioneered by SKI scientists Michel Sadelain, Isabelle Rivière, and Renier Brentjens.

2017—IDH inhibitor approved

The US Food and Drug Administration approves the drug enasidenib (Idhifa) for the treatment of IDH-mutant acute myeloid leukemia that has stopped responding to other therapies. MSK’s President and CEO, Craig Thompson, did much of the preclinical work deciphering the relationship between the IDH mutations and cancer, including work done while he was at the University of Pennsylvania. 

2017—Complete structure of mTORC1 determined

Using cryo-electron microscopy, and building on their earlier X-ray crystallography work, SKI scientists including Nikola Pavletich and Haijuan Yang solve the complete structure of mTORC1, a key regulator of cellular growth.