A Progression of Science
By: Caroline Trent-Gurbuz
Allan Goldstein’s office, a narrow room with a bank of windows overlooking the George Washington University (GW) campus, is a tribute to the octogenarian who occupies it. A bulletin board displays a collage of photos of the well-known researcher shoulder to shoulder with scientific greats — Jonas Salk, for one. Framed photos on the wall above his desk and on his window ledge, meanwhile, show him paired with political heavyweights — members of the Bush and Clinton dynasties — and his family. Another wall holds a collection of books and papers, many he authored himself. His topic of choice: thymosins, small proteins isolated from the thymus gland, which Goldstein discovered.
Thymosins “have been my life’s work, starting with being a postdoc at the Albert Einstein College of Medicine,” explains Goldstein, PhD, Professor Emeritus in Residence in the Department of Biochemistry and Molecular Biology at the GW School of Medicine and Health Sciences. “What is that, 53 years working on the same thing?”
Goldstein, who joined the GW faculty in 1978, has authored about 430 papers. One of the most recent, a study on thymosins’ impact on cystic fibrosis (CF), carried out in collaboration with colleagues Luigina Romani and Enrico Garaci from Italy, is making considerable waves in the scientific community after its publication in Nature Medicine.
CF, according to Goldstein, is a genetic disorder that affects not only the lungs, but also the gastrointestinal tract and other parts of the body. Those with CF have a limited life span and must deal with a host of medicinal interventions.
“Over the years, there’s been a bunch of drugs developed that can treat one or more [aspects] of the disease, but not really stop the progression,” Goldstein says. “Individuals, in addition to having to take 40 or so different drugs a day — picture taking 40 different pills — have to spend 12 to 15 hours a day on different physical therapy and machines. It’s horrendous, and it’s really challenging.”
CF also presents two major problems: first, because it’s an autosomal recessive mutation, a protein necessary to keep the chloride channels open in cells is missing an amino acid, resulting in the protein being misfolded; second, because the chloride channel isn’t working properly, there’s immune dysregulation. “A lot of the immune system is out of whack, basically,” Goldstein says.
Using an established mouse model, Goldstein tested thymosin α1 (Tα1), which is produced naturally in the body, to see if it could correct the immune system defect. “Lo and behold, we started administering Tα1 to these mice, and not only did it correct the immune problem, but it also corrected this misfolded protein,” Goldstein says. “We thought, ‘This is truly amazing.’ ”
In other words, Tα1 treated the symptoms while also halting the progression of the underlying disease. The next step, Goldstein says, was to test Tα1 on human cells from patients with CF. “We sprinkled in Tα1, and it corrected it in humans. Now we’re able to stop the progression in animals and also in vitro in human cells,” he said.
Tα1, whose drug version, Zadaxin, has been approved in Europe, though not yet in the United States, is now the main focus of a planned Phase I trial in Italy. It is a concrete result of his life’s work, and Goldstein hopes to see it improve the lives of thousands.
“I’ve been here a long time, but what’s wonderful, as a scientist and a teacher, is to see the progression of science,” he adds. “It is really, really amazing.”