History of the Discovery of the Thymosins

Abstract

From a historical perspective, the studies that led to the isolation and characterization of the thymosins began in earnest in the early 1960s in the laboratory of Abraham White at the Albert Einstein College of Medicine in New York. In a 1966 paper in the Proceedings of the National Academy of Sciences, U.S., we first named these thymic-derived factors "Thymosins." By 1972, the thymosin team had moved to the University of Texas Medical Branch in Galveston (UTMB) where an extremely talented group of young scientists and students succeeded over the next 6 years in preparing and testing a highly active partially purified calf thymus preparation, termed thymosin fraction-5 (TF5), which was amenable for scale-up and suitable for clinical use. In 1974, we received the first IND for a thymic hormone preparation from the FDA to begin a phase-I study with TF5 in children with primary immunodeficiency diseases at the University of California Medical Center in San Francisco. The immunorestorative and potentially life-saving properties of TF5 in clinical medicine were first documented in a landmark paper in 1975 by Drs. Arthur Ammann and Diane Wara in the New England Journal of Medicine. TF5 consists of a family of at least 40 mostly small acidic polypeptides, with molecular weights ranging from 1000 to 15,000 Da. This article will identify the key scientists and the milestones involved in the initial studies with TF5 that have led to the chemical characterization of the thymosins and to translational studies from the lab bench to the clinic.

Characterization of two thymosins as immune-related genes in common carp (Cyprinus carpio L.)

“…These small proteins have been well studied as particularly attractive molecules for stimulating immune responses in mammals thereafter, and some of which have already progressed from the laboratory to the clinic (Goldstein, 2007;Goldstein and Badamchian, 2004). Until now, the roles and functions of thymosins in teleost are still poorly explored.…”

Longitudinal system-based analysis of transcriptional responses to type I interferons

“…The hub gene PTMA is small, highly acidic thymic peptide that affects a diverse array of cellular function including DNA packaging, apoptotic regulation, cell proliferation, and both the innate and adaptive immune responses (28,68). PTMA can upregulate MHC class II molecules on monocytes (5) and inhibit tumor growth (61) and, in combination with IFN-␣, has been used to effectively treat various cancers and chronic hepatitis B and C (23).…”

Thymosin Apha 1–A Peptide Immune Modulator with a Broad Range of Clinical Applications

“…A number of previous review articles [71][72][73][74][75][76][77][78][79][80] address the history, biological effects, and potential therapeutic indications for Ta1.…”