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A Half Century in Science, Ruddle Narrates a “Yale Story”

February 25, 2020
by Michael Greenwood

Nancy Ruddle’s career as a scientific researcher began in 1963, more than 50 years ago, when she enrolled in graduate school in Yale’s Department of Microbiology, a time when there were relatively few women in the field.

Ruddle was training as an immunologist and was drawn to the study of inflammation. She quickly made a mark.

Her work examined the proteins that control inflammation in response to invading pathogens (bacteria and viruses), autoimmune diseases and cancer. Much of her research has concentrated on a molecule known as lymphotoxin (LT) which she identified. While still a graduate student, she succeeded in describing LT’s ability to kill tumor cells in a tissue culture system. The finding had a range of important health implications. She completed her PhD in 1968 and has been at Yale ever since.

Ruddle gave a sweeping overview of her scientific career on Thursday (February 20) as the featured speaker of the school’s annual Frank Black Memorial Lecture sponsored by the Department of Epidemiology of Microbial Diseases, supported by a gift from the late William Prusoff. She likened her journey to that of the characters in the Wizard of Oz movie. As it was for them, there have been ups and downs over a half century, but it's been mostly ups for Ruddle, who is now a professor emerita and widely recognized in her field and a senior and distinguished member of the Yale School of Public Health’s faculty.

“Things have continued to move along pretty well,” Ruddle, PhD, said with typical understatement to the large gathering of faculty, students and members of Frank Black’s and William Prusoff’s families.

Moving quickly through the highlights of her career, she touched on how she and colleagues showed that LT and a similar molecule, tumor necrosis factor (TNF), were important in a model of multiple sclerosis, prompting the development of treatments for autoimmune diseases, such as rheumatoid arthritis, psoriasis and inflammatory bowel disease.

In order to distinguish LT from TNF they genetically engineered models that lacked LT. These models had severe problems in their immune system in that they lacked lymph nodes and Peyer’s patches (lymphoid accumulations on the gut) and a disorganized spleen. These so-called secondary lymphoid organs are where pathogens are usually encountered. Models deficient in TNF had normal lymphoid organs, demonstrating that LT alone has an important role in lymphoid organ development, in addition to inflammation.

She and others also directed overexpression of the LT gene to the pancreas or salivary glands of mice and showed inflammation that had all the characteristics of lymphoid organs, including special blood vessels and lymphatic vessels. These are known as Tertiary Lymphoid Organs, important components of many autoimmune diseases, responses to bacteria and viruses, and cancer, where they are beneficial or harmful, depending on the context. More recent studies have involved tools for the visualization of the immune system in models, taking advantage of genes uniquely expressed in high endothelial venules and lymphatic vessels.

Last year she co-edited and co-authored a book, Immunoepidemiology, with several other Yale scientists. The textbook focuses on how differences in immune responses among human populations affect the epidemiology of infectious diseases, cancer, hypersensitivity and autoimmunity.

This year’s Frank Black Memorial Lecture was also tied to the school’s celebration of the 50th anniversary of coeducation in Yale College and the 150th anniversary of women students at the university that are going on throughout Yale this academic year.

“I knew Frank Black from the time I was a graduate student. He was a wonderful teacher, colleague, role model and mentor,” said Ruddle.

Black, Ph.D., was a member of the Yale School of Public Health faculty from 1955 until his retirement in 1996. He was only the third scientist to use the measles vaccine in humans and pioneered the in-vitro cultivation of the virus and tested the efficacy of measles vaccines in susceptible populations in both the United States and abroad. He passed away in 2007.

Professor Albert Ko, MD, chair of EMD, welcomed members of the Black and Prusoff families to the lecture and said the event was a celebration of the school’s and department’s rich histories. Black made major contributions to virology and to the understanding of genetics and infections. Vaccinations, as a result, are much safer today.

Dean Sten Vermund described Ruddle as a “renowned scientist” who significantly influenced the school and generations of its students.

Submitted by Sayuri Gavaskar on February 25, 2020