William Herman Prusoff (June 25, 1920 – April 3, 2011) was a pharmacologist who was an early innovator in antiviral drugs, developing
idoxuridine
Idoxuridine is an anti-herpesvirus antiviral drug.
It is a nucleoside analogue, a modified form of deoxyuridine, similar enough to be incorporated into viral DNA replication, but the iodine atom added to the uracil component blocks base pairin ...
, the first antiviral agent approved by the
FDA
The United States Food and Drug Administration (FDA or US FDA) is a federal agency of the Department of Health and Human Services. The FDA is responsible for protecting and promoting public health through the control and supervision of food ...
, in the 1950s, and co-developing (with
Tai-shun Lin)
stavudine
Stavudine (d4T), sold under the brand name Zerit among others, is an antiretroviral medication used to prevent and treat HIV/AIDS. It is generally recommended for use with other antiretrovirals. It may be used for prevention after a needlestick ...
, one of the earliest
AIDS
Human immunodeficiency virus infection and acquired immunodeficiency syndrome (HIV/AIDS) is a spectrum of conditions caused by infection with the human immunodeficiency virus (HIV), a retrovirus. Following initial infection an individual m ...
drugs, in the mid-1980s.
Scientific career
William Prusoff attended the
University of Miami
The University of Miami (UM, UMiami, Miami, U of M, and The U) is a private research university in Coral Gables, Florida. , the university enrolled 19,096 students in 12 colleges and schools across nearly 350 academic majors and programs, incl ...
. After receiving his
undergraduate degree
An undergraduate degree (also called first degree or simply degree) is a colloquial term for an academic degree earned by a person who has completed undergraduate courses. In the United States, it is usually offered at an institution of higher e ...
in
chemistry
Chemistry is the science, scientific study of the properties and behavior of matter. It is a natural science that covers the Chemical element, elements that make up matter to the chemical compound, compounds made of atoms, molecules and ions ...
, he obtained his
PhD from
Columbia University
Columbia University (also known as Columbia, and officially as Columbia University in the City of New York) is a private research university in New York City. Established in 1754 as King's College on the grounds of Trinity Church in Manhatt ...
and later completed his
postdoctoral training
A postdoctoral fellow, postdoctoral researcher, or simply postdoc, is a person professionally conducting research after the completion of their doctoral studies (typically a PhD). The ultimate goal of a postdoctoral research position is to p ...
in the laboratory of professor
Arnold Welch
Arnold may refer to:
People
* Arnold (given name), a masculine given name
* Arnold (surname), a German and English surname
Places Australia
* Arnold, Victoria, a small town in the Australian state of Victoria
Canada
* Arnold, Nova Scotia
Uni ...
at
Case Western Reserve University
Case Western Reserve University (CWRU) is a private research university in Cleveland, Ohio. Case Western Reserve was established in 1967, when Western Reserve University, founded in 1826 and named for its location in the Connecticut Western Reser ...
. After Welch was recruited by
Yale
Yale University is a private research university in New Haven, Connecticut. Established in 1701 as the Collegiate School, it is the third-oldest institution of higher education in the United States and among the most prestigious in the wor ...
to head the
Medical School's pharmacology
Pharmacology is a branch of medicine, biology and pharmaceutical sciences concerned with drug or medication action, where a drug may be defined as any artificial, natural, or endogenous (from within the body) molecule which exerts a biochemica ...
department, Prusoff was invited to join the same department as an
assistant professor
Assistant Professor is an academic rank just below the rank of an associate professor used in universities or colleges, mainly in the United States and Canada.
Overview
This position is generally taken after earning a doctoral degree and general ...
and was subsequently promoted to the rank of
professor
Professor (commonly abbreviated as Prof.) is an Academy, academic rank at university, universities and other post-secondary education and research institutions in most countries. Literally, ''professor'' derives from Latin as a "person who pr ...
. This relationship at Yale would span over the next 58 years, with William Prusoff becoming one of Yale's most well respected scientists and teachers.
Prusoff spent most of his career studying
analog
Analog or analogue may refer to:
Computing and electronics
* Analog signal, in which information is encoded in a continuous variable
** Analog device, an apparatus that operates on analog signals
*** Analog electronics, circuits which use analog ...
s of
thymidine
Thymidine (symbol dT or dThd), also known as deoxythymidine, deoxyribosylthymine, or thymine deoxyriboside, is a pyrimidine deoxynucleoside. Deoxythymidine is the DNA nucleoside T, which pairs with deoxyadenosine (A) in double-stranded DNA. I ...
, a
nucleoside
Nucleosides are glycosylamines that can be thought of as nucleotides without a phosphate group. A nucleoside consists simply of a nucleobase (also termed a nitrogenous base) and a five-carbon sugar (ribose or 2'-deoxyribose) whereas a nucleotide ...
building block of
DNA, with an eye toward developing therapeutic agents. By exploring analogs to thymidine for use as
antiviral drug
Antiviral drugs are a class of medication used for treating viral infections. Most antivirals target specific viruses, while a broad-spectrum antiviral is effective against a wide range of viruses. Unlike most antibiotics, antiviral drugs do n ...
s, his research created a new
scientific paradigm
In science and philosophy, a paradigm () is a distinct set of concepts or thought patterns, including theories, research methods, postulates, and standards for what constitute legitimate contributions to a field.
Etymology
''Paradigm'' comes ...
for
antiviral drug
Antiviral drugs are a class of medication used for treating viral infections. Most antivirals target specific viruses, while a broad-spectrum antiviral is effective against a wide range of viruses. Unlike most antibiotics, antiviral drugs do n ...
development.
In the late 1950s, William Prusoff synthesized one of the first
thymidine analogs,
5-iododeoxyuridine. At the time, it was thought to be difficult to find antiviral drugs with a high
therapeutic index
The therapeutic index (TI; also referred to as therapeutic ratio) is a quantitative measurement of the relative safety of a drug. It is a comparison of the amount of a therapeutic agent that causes the therapeutic effect to the amount that causes ...
, but professor
Herbert E. Kaufman found that the compound could be used as an effective
topical
A topical medication is a medication that is applied to a particular place on or in the body. Most often topical medication means application to body surfaces such as the skin or mucous membranes to treat ailments via a large range of classes ...
treatment for
herpesvirus
''Herpesviridae'' is a large family of DNA viruses that cause infections and certain diseases in animals, including humans. The members of this family are also known as herpesviruses. The family name is derived from the Greek word ''ἕρπειν ...
keratitis
Keratitis is a condition in which the eye's cornea, the clear dome on the front surface of the eye, becomes inflamed. The condition is often marked by moderate to intense pain and usually involves any of the following symptoms: pain, impaired e ...
by disrupting the
virus's ability to reproduce. More significantly, though, this discovery was a scientific
game changer - it was the first time that a clinical antiviral drug had been shown to have selective antiviral activity if used properly. In the 1970s, Prusoff coformulated the
Cheng-Prusoff equation
The half maximal inhibitory concentration (IC50) is a measure of the potency of a substance in inhibiting a specific biological or biochemical function. IC50 is a quantitative measure that indicates how much of a particular inhibitory substance ...
to calculate the absolute inhibition constant
Ki.
In the 1980s, while the
AIDS
Human immunodeficiency virus infection and acquired immunodeficiency syndrome (HIV/AIDS) is a spectrum of conditions caused by infection with the human immunodeficiency virus (HIV), a retrovirus. Following initial infection an individual m ...
epidemic was spreading and found to be caused by
HIV
The human immunodeficiency viruses (HIV) are two species of ''Lentivirus'' (a subgroup of retrovirus) that infect humans. Over time, they cause acquired immunodeficiency syndrome (AIDS), a condition in which progressive failure of the immune ...
, William Prusoff and the late dr. Tai-Shun Lin discovered that a compound synthesized by dr.
Jerome Horwitz
Jerome Phillip Horwitz (January 16, 1919 – September 6, 2012) was an American scientist; his affiliations included the Barbara Ann Karmanos Cancer Institute, the Wayne State University School of Medicine and the Michigan Cancer Foundation.
...
had potent anti-HIV properties. The compound was originally named
D4T, and
Bristol-Myers Squibb
The Bristol Myers Squibb Company (BMS) is an American multinational pharmaceutical company. Headquartered in New York City, BMS is one of the world's largest pharmaceutical companies and consistently ranks on the ''Fortune'' 500 list of the lar ...
developed and marketed this drug under its more common name,
Zerit. It became a key drug as part of the first combination therapy for treating AIDS. Realizing that this treatment could provide great benefits to those struggling with the growing HIV crisis in impoverished
Africa
Africa is the world's second-largest and second-most populous continent, after Asia in both cases. At about 30.3 million km2 (11.7 million square miles) including adjacent islands, it covers 6% of Earth's total surface area ...
,
Doctors Without Borders
Doctor or The Doctor may refer to:
Personal titles
* Doctor (title), the holder of an accredited academic degree
* A medical practitioner, including:
** Physician
** Surgeon
** Dentist
** Veterinary physician
** Optometrist
*Other roles
** ...
and Yale students later lobbied Yale University and Bristol-Myers Squibb to make Zerit available at a low cost for the African market. Prusoff quickly joined the effort, even though it meant a loss of personal income. "We are not doing this to make money, we are interested in developing a compound that would be a benefit to society," he explained. The effort to make Zerit more affordable was a success: millions of people around the world benefited from Prusoff's research and humanitarian efforts.
Though William Prusoff officially retired at age 70, he never stopped working and continued to be industrious. Until his death, his work as
professor emeritus
''Emeritus'' (; female: ''emerita'') is an adjective used to designate a retired chair, professor, pastor, bishop, pope, director, president, prime minister, rabbi, emperor, or other person who has been "permitted to retain as an honorary title ...
concentrated on the potential for using
boron
Boron is a chemical element with the symbol B and atomic number 5. In its crystalline form it is a brittle, dark, lustrous metalloid; in its amorphous form it is a brown powder. As the lightest element of the ''boron group'' it has th ...
ated-thymidine analogs as
sensitizing cancer agents for
neutron therapy
Fast neutron therapy utilizes high energy neutrons typically between 50 and 70 MeV to treat cancer. Most fast neutron therapy beams are produced by reactors, cyclotrons (d+Be) and linear accelerators. Neutron therapy is currently available in ...
.
Prizes
Among his many accolades, Prusoff received the ''ASPET Award'' from the
and the ''Peter Parker Medal'', Yale School of Medicine's highest award. He also received the ''Inaugural Lifetime Achievement Award'' from the
Yale Comprehensive Cancer Center. His legacy was further solidified when the School of Medicine established an
endowed chair
A financial endowment is a legal structure for managing, and in many cases indefinitely perpetuating, a pool of financial, real estate, or other investments for a specific purpose according to the will of its founders and donors. Endowments are of ...
in his name and the Department of Pharmacology named one of its conference rooms after him. In addition, the
International Society for Antiviral Research
The International Society for Antiviral Research (ISAR) is a scientific society that focuses on the discovery and clinical application of antiviral agents. It was founded in 1987 to encourage the exchange of information and collaborative researc ...
established the ''William Prusoff Young Investigator Lecture Award''.
Prusoff established the
William H. Prusoff Foundation to support various programs, including the
United Way
United Way is an international network of over 1,800 local nonprofit fundraising affiliates. United Way was the largest nonprofit organization in the United States by donations from the public, prior to 2016.
United Way organizations raise funds ...
and the
Yale Initiative for the Interdisciplinary Study of Anti-Semitism. He dedicated his life to the service of others because he saw generosity and helping as a natural extension of the human condition.
References
*Cheng Y-C (2011) ''William H. Prusoff (1920–2011): Father of Antiviral Chemotherapy.'
PLoS Biol 9(11): e1001190. doi:10.1371/journal.pbio.1001190
External links
William Prusoff Young Investigator Lecture Award
{{DEFAULTSORT:Prusoff, William H.
University of Miami alumni
Case Western Reserve University alumni
1920 births
2011 deaths
HIV/AIDS researchers
American pharmacologists
Columbia University alumni