Robert Lefkowitz

2.1. Birth and Education

Robert Joseph Lefkowitz was born on April 15, 1943, in The Bronx, New York City. He grew up in a Jewish family; his parents, Max and Rose Lefkowitz, had families that immigrated to the United States from Poland in the late 19th century. He attended the Bronx High School of Science, graduating in 1959. Following high school, Lefkowitz enrolled at Columbia College, where he earned a Bachelor of Arts degree in chemistry in 1962. During his time at Columbia, he studied under the notable chemist Ronald Breslow. He continued his medical education at Columbia University College of Physicians and Surgeons, from which he received his M.D. degree in 1966.

2.2. Early Career and Research Foundations

After completing his M.D., Lefkowitz undertook an internship and a year of general medical residency at the College of Physicians and Surgeons. From 1968 to 1970, he served as a clinical and research associate at the National Institutes of Health (NIH). This period was particularly influential, as it ignited his lifelong passion for research, initially fulfilling a draft obligation during the Vietnam War as part of the United States Public Health Service, humorously known as the "Yellow Berets" of the NIH. Subsequently, from 1970 to 1973, he conducted research on cardiovascular diseases at Massachusetts General Hospital which is affiliated with Harvard University, further solidifying his foundational experience in medical research.

3.1. Affiliations and Research Institutions

Upon completing his medical residency and research training in 1973, Robert Lefkowitz was appointed as an associate professor of medicine and assistant professor of biochemistry at the Duke University Medical Center. His dedication and contributions led to rapid advancements; he was promoted to professor of medicine in 1977 and, in 1982, achieved the distinguished title of James B. Duke Professor of Medicine at Duke University. He also holds professorships in biochemistry and chemistry at Duke. Since 1976, he has been a prominent Investigator with the Howard Hughes Medical Institute. Earlier in his career, he was also an established investigator of the American Heart Association from 1973 to 1976, reflecting his early engagement with cardiovascular research.

3.2. Research on G protein-coupled Receptors (GPCRs)

Lefkowitz's research primarily focuses on receptor biology and signal transduction, elucidating how cells sense and respond to their environment. He is most renowned for his extensive and detailed characterizations of the sequence, structure, and function of the β-adrenergic receptor and related receptors. A pivotal contribution came in the mid-1980s when he and his colleagues successfully cloned the gene for the β-adrenergic receptor. This achievement was swiftly followed by the cloning of genes for a total of eight adrenergic receptors, which are receptors for adrenaline and noradrenaline.

This work led to the seminal discovery that all G protein-coupled receptors, including the β-adrenergic receptor, possess a remarkably similar molecular structure. This structure is defined by an amino acid sequence that weaves back and forth across the plasma membrane exactly seven times. Today, it is understood that approximately 1,000 different receptors in the human body belong to this same family. Furthermore, Lefkowitz's team also identified and characterized two crucial families of proteins that regulate these receptors: the GPCR kinases and β-arrestins. The significance of these findings lies in the revelation that all these receptors operate using the same fundamental mechanisms, providing pharmaceutical researchers with a comprehensive understanding of how to effectively target the largest receptor family in the human body.

3.3. Impact on Pharmacology and Medicine

The discoveries made by Robert Lefkowitz regarding GPCRs have had a profound and widespread impact on drug development and medical treatment. His research has enabled the design of numerous prescription drugs, as it is now known that as many as 30 to 50 percent of all prescription medications are specifically engineered to interact with the similarly structured "locks" of these GPCRs. These drugs effectively "fit" into the receptors like keys, modulating cellular responses.

The range of conditions addressed by these GPCR-targeting drugs is extensive, including everything from antihistamines for allergies to drugs for ulcers. Crucially, his work has facilitated the development of beta blockers, which are vital in treating hypertension (high blood pressure), angina, and various coronary diseases. Beyond these, his insights have also significantly advanced the creation of treatments for serious conditions such as heart disease, Parkinson's disease, and migraines, by illuminating the molecular mechanisms involved in cellular communication and drug action.

3.4. Academic Achievements and Influence

Robert Lefkowitz's extensive contributions to scientific literature and his broad academic influence are widely recognized. He is consistently listed among the most highly cited researchers across multiple fields, including biology, biochemistry, pharmacology, toxicology, and clinical medicine. This high citation count reflects the fundamental and far-reaching impact of his research on the scientific community and its subsequent application in various areas of biological and medical inquiry.

4.1. Family and Relationships

Robert Lefkowitz is married to Lynn (née Tilley). He was previously married to Arna Brandel. Together, he has five children and six grandchildren, forming a large and supportive family.

4.2. Memoir Publication

In 2021, Lefkowitz published his memoir titled A Funny Thing Happened on the Way to Stockholm: The Adrenaline-Fueled Adventures of an Accidental Scientist. The book was co-authored by Randy Hall, who had been a post-doctoral fellow in Lefkowitz's laboratory in the 1990s. The memoir provides a detailed account of Lefkowitz's early life, his rigorous training as a physician, and his tenure in the United States Public Health Service. This period, which began as a way to fulfill his draft obligation during the Vietnam War, ultimately ignited a profound and lasting passion for scientific research. The latter half of the book chronicles his distinguished research career and various notable experiences, both before and after his momentous Nobel Prize win. Upon its publication in February 2021, the memoir garnered significant attention, being named "New & Noteworthy" by The New York Times and recognized as "one of the week's best science picks" by the prestigious journal Nature.

5.1. Nobel Prize in Chemistry

In 2012, Robert Lefkowitz was awarded the Nobel Prize in Chemistry, an honor he shared with Brian Kobilka. The prize recognized their pioneering discoveries concerning the inner workings of G protein-coupled receptors (GPCRs). Their research illuminated how billions of cells in the human body are able to sense and respond to their surrounding environment, a fundamental aspect of cellular communication crucial for life. This recognition highlighted the transformative impact of their work on scientific understanding and drug development.

5.2. Other Major Awards and Recognitions

Lefkowitz's significant contributions to science have been acknowledged through a multitude of other esteemed awards and honors:

• 2014: Golden Plate Award of the American Academy of Achievement
• 2011: George M. Kober Medal
• 2009: BBVA Foundation Frontiers of Knowledge Award in the Biomedicine Category
• 2009: Research Achievement Award from the American Heart Association
• 2007: National Medal of Science
• 2007: Shaw Prize in Life Science and Medicine
• 2007: Albany Medical Center Prize in Medicine and Biomedical Research
• 2006: George M. Kober Lectureship
• 2003: Fondation Lefoulon - Delalande Grand Prix for Science from the Institut de France
• 2003: Endocrine Regulation Prize
• 2001: Jessie Stevenson Kovalenko Medal of the USA - The National Academy of Sciences
• 2001: Fred Conrad Koch Award
• 2001: Pasarow Award
• 1992: Bristol-Myers Squibb Award for Distinguished Achievement In Cardiovascular Research
• 1988: Gairdner Foundation International Award
• 1978: John Jacob Abel Award in Pharmacology
• 1978: Pasarow Award Young Scientist Award