Zvi Laron, MD: The man behind Laron syndrome

Zvi Laron, MD, is perhaps best known for the discovery of his namesake, Laron syndrome, and subsequent breakthroughs in growth hormone receptor defects and disorders.

Laron syndrome, also called Laron-type dwarfism, is an autosomal recessive disorder that is characterized by insensitivity to GH, caused by defects of the GH receptor. The syndrome is known to cause grossly impaired growth despite normal levels of serum GH.

Laron, an Israeli researcher, first reported the condition in 1966, based on unique observations that began in 1958.

“The drive for me was in the curiosity of discovering and observing a strange syndrome. It took us 20 years to really get to the etiology of it,” Laron said.

His 5-decade career extends past the discovery of Laron syndrome and travels across a wide range of accomplishments, including juvenile diabetes researcher, medical editor and writer, and founder of the Institute of Endocrinology and Diabetes in Israel.

Endocrine Today recently interviewed Laron, who shared the story of his journey, research, accomplishments and thoughts for the future.

War-fraught beginnings

Born in Cernauti, Romania, in 1927, Laron was thrown into the turmoil of World War II. As a child, he was sent to a Ukrainian concentration camp in war-devastated Transnistria.

For 4 years, Laron worked in a factory as an iron worker. He was able to survive because his uncle, Siegfried Sami Jagendorf, a Jewish entrepreneur, persuaded Nazi officials to allow him to recruit a task force to repair the city’s destroyed electrical system and iron works. Jagendorf’s efforts helped save the lives of more than 15,000 prisoners, including Laron.

Laron returned to Romania in 1944 after he was freed by the Russians. Despite having no previous draw to medicine, he began precursory studies in the field and continued for 2 years.

As a member of a Zionist youth organization, Laron planned a return to his spiritual homeland in the Middle East after the war. There, as a member of a kibbutz, he would live simply as a peasant and a farmer, he told Endocrine Today. He left Soviet-occupied Romania and traveled to Bulgaria, where he boarded a ship with 7,500 others, “packed together like sardines.”

Arrival in British-occupied Palestine was a rude awakening for the would-be immigrants, Laron said. Instead of finding a fresh start, they were detained by the British and shipped to Cyprus, Greece. There, Laron was placed in a refugee camp, which would be his home for the next year.

Zvi Laron, MD, and patient. Photo courtesy of: Zvi Laron, MD, and Howard Martell of Medical Photo Lab, Beilinson Hospital, Israel

Start of career

Upon the official establishment of Israel, the Cyprus refugees were released, but respite was short-lived. Entering Israel, Laron was immediately drafted into the armed forces and mobilized for the Arab-Israeli War of 1948, for which he served as a medic.

After his military service ended, Laron decided to continue his earlier work with medicine. He attended and graduated from Hadassah Hebrew University Medical School in Jerusalem. There, Laron became interested in the study of metabolism, through his experiences in the laboratory of hematologist André de Vries, a man he described as a major influence and mentor.

After graduation, Laron applied to Massachusetts General Hospital in Boston, where he was accepted and became a research and clinical fellow in pediatrics in 1954.

“This was a very interesting time in the development of endocrinology, and I feel lucky to have been a part of and contributed to it,” Laron said. “I met a lot of interesting people, and it allowed me to bring invaluable knowledge back home with me.”

Upon his return to Israel, Laron founded the Institute of Endocrinology and Diabetes, which is the largest of its kind in the country.

Laron syndrome

Laron said his life changed more than 40 years ago when he received a phone call from de Vries asking him to establish a pediatric endocrine clinic. He accepted and began his life’s work.

In 1958, Laron and colleagues began research on a group of short-statured patients with clinical and biochemical features of GH deficiency but with high concentrations of immunoreactive serum GH. Two variations of the disorder would later become apparent: the first, a defect in the GH receptor gene that prevents hormones from binding; the second, a fault in the biochemical processing of GH after the hormone has been bound to the cell surface.

For Laron, the highlight of his research with Laron syndrome was when parents of patients first allowed him to perform a biopsy of the children’s livers.

“This was what really allowed us to get at the underlying cause that this was a receptor defect. This was the defining moment for our team,” Laron said.

Laron syndrome is rare — just 250 cases have been described worldwide. However, this understanding of GH receptor defects opened many doors in endocrine research.

“We found one point in the axis of GH to insulin-like growth factor I where things go wrong. This is not only true for Laron syndrome, and through studying receptor defects, we now know that there are quite a few other diseases in which peptide hormones also have receptor defects.

“There is great satisfaction to know that we contributed to that knowledge and, most importantly, found the way to treat these patients by the administration of biosynthetic IGF-I,” he said.

Today, Laron said the largest issue surrounding Laron syndrome lies in patient obesity. It is known that long-term treatment of GH and IGF-I increases adiposity. For the first 1 or 2 years, treatment may reduce the adiposity and fat in the blood, but then these markers increase.

“We still do not know how to treat and prevent this. Finding a solution to this problem is one of my current tasks,” he said.

Beyond the syndrome

Laron may be best known for his research with the syndrome that bears his name, but his work does not end there. Throughout his career, thus far, he has written and edited about 30 books, published approximately 1,000 scientific articles and won numerous awards and honors for his research, including the Clinical Investigator Award of The Endocrine Society.

Laron has since given up daily administration tasks at the hospital and currently devotes his attention to the research unit.

Currently, Laron and his team have focused on the study of type 1 diabetes and are researching the possibility that the disease is caused by seasonal viral infections passed in utero from mother to child.

“The goal is to discover which viruses are the cause,” he said. “If we can prove that type 1 diabetes is of infectious origins, we may be able to potentially prevent it with a vaccine.”

Laron cites the introduction and implementation of a multidisciplinary team in the endocrine clinic he founded as another major accomplishment. He helped integrate social workers and psychologists to assist with the treatment of children.

Looking to the future

At the age of 83 years, Laron currently serves as the director of the Endocrinology and Diabetes Research Unit at Schneider Children’s Medical Center of Israel; head of the WHO Collaborating Center for the Study of Diabetes in Youth; professor emeritus of pediatric endocrinology at the Sackler Faculty of Medicine and Tel Aviv University; and is chief editor of Pediatric Endocrinology Reviews.

Laron lives with his wife, Tova, in Ramat Efal, Israel. They have four children and nine grandchildren.

“I feel that I can still contribute and that people are still interested in what I do, so that brings me a lot of satisfaction,” he said. “I’m fortunate to still be able to do what I love.” – by Matthew Brannon