From Michael Belkin
http://www.nytimes.com/2004/01/22/nyregion/22CHAS.html

January 22, 2004
Merrill W. Chase Is Dead at 98; Scientist Who Advanced Immunology

By ANAHAD O'CONNOR

Dr. Merrill W. Chase, an immunologist whose research on white blood cells helped undermine the longstanding belief that antibodies alone protected the body from disease and micro-organisms, died on Jan. 5 at his home in New York City, according to the Rockefeller University, where he worked for 70 years. He was 98.

Dr. Chase made his landmark discovery in the early 1940's while working with Dr. Karl Landsteiner, a Nobel laureate recognized for his work identifying the human blood groups. At the time, experts believed that the body mounted its attacks against pathogens primarily through antibodies circulating in the blood stream, known as humoral immunity.

But Dr. Chase, working in his laboratory, stumbled upon something that appeared to shatter that widespread tenet. As he tried to immunize a guinea pig against a disease using antibodies he had extracted from a second pig, he found that blood serum did not work as the transfer agent. Not until he used white blood cells did the immunity carry over to the other guinea pig, providing solid evidence that it could not be antibodies alone orchestrating the body's immune response.

Dr. Chase had uncovered the second arm of the immune system, or cell-mediated immunity. His finding became the groundwork for later research that pinpointed B cells, T cells and other types of white blood cells as the body's central safeguards against infection. "This was a major discovery because everyone now thinks of the immune response in two parts, and in many instances it's the cellular components that are more important," said Dr. Michel Nussenzweig, a professor of immunology at Rockefeller. "Before Chase, there was only humoral immunity.  After him, there was humoral and cellular immunity."

Dr. Chase's breakthrough generated little interest at the time, but it set in motion the research that helped redefine the fundamental nature of the immune system. "So many areas of medicine rely on this type of reaction that he clearly distinguished as not being antibody mediated," said Dr. Ralph Steinman, a professor of cellular physiology and immunology at Rockefeller. "People never anticipated that there would be something other than antibodies. It was an amazing finding."

Born in Providence, R.I., in 1905, Merrill Wallace Chase earned his bachelor's degree and doctorate from Brown. He taught biology there for a year, before joining the faculty at Rockefeller in 1932 as an assistant to Dr. Landsteiner. He has published at least 150 scientific papers.  In 1975, he was elected to the National Academy of Sciences. Dr. Chase, who lived in Manhattan, was married twice, first to Edith Steele Bowen, who died in 1961, and then to Cynthia Hambury Pierce, who died in 1997. He is survived by a son, John, of West Hills, Calif.; a daughter, Nancy Chase Cowles, of Redding, Conn.; five grandchildren; and four great-grandchildren.

For some antigens, the duration of humoral immunity after infection or vaccination is measured in decades, rather than in months or years.


How long does humoral immunity last after infection or vaccination? This question is germane, considering the ever-increasing number of novel vaccines and the ongoing occurrence of vaccine-preventable diseases in both developed and developing countries,

To explore this issue, researchers performed a longitudinal analysis of serum antibody titers specific for eight antigens, using 630 serum samples collected over an extended period (up to 26 years) from 45 Oregon National Primate Research Center workers. Samples were retrieved from the center’s serum bank or taken from scheduled blood draws. (Employees had at least 1 sample drawn annually as part of the center’s program to test humans who work in close proximity to nonhuman primates.) In addition, participants completed a detailed medical-history questionnaire. Most had received a smallpox vaccination during childhood and had experienced a variety of viral infections; the average age was 52.

The half-lives of antibody responses to six viruses (vaccinia, measles, mumps, rubella, varicella-zoster, and Epstein-Barr) were 50 years. Moreover, many of the antibody titers to viral antigens did not decrease over time. The estimated half-lives of antibody responses to two other antigens (tetanus and diphtheria) were <20 years.

Comment: These findings suggest that antigen-specific mechanisms are largely responsible for the duration of humoral immunity. The longevity of antibody responses varied among the participants, however, suggesting that other factors (perhaps including presentation of the antigen) also affect response to viral antigens. Because participants’ average age was 52, immunity to many of the viral antigens was induced by natural infection. Whether vaccine-induced immunity is as long-lived as natural infection–induced immunity remains unknown.

— Larry M. Baddour, MD

Dr. Baddour is a Professor of Medicine at the Mayo Clinic College of Medicine, Rochester, Minnesota.

Published in Journal Watch Infectious Diseases November 7, 2007

http://infectious-diseases.jwatch.org/cgi/content/full/2007/1107/3
 

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