Endless curiosity, admits Professor Howard Cedar, has driven him to investigate some of the most fundamental questions in human genetics — questions about the mechanisms that control the development of the incredibly diverse collection of cells that constitutes the human body. His research, first published back in the late 1970s, not only identified how cells control their development but also initiated a whole new field of science known as epigenetics. And what began as fundamental research over three decades ago is now beginning to yield profound insights into the causes of cancer, as well as understanding about a range of genetic diseases.
Cedar immigrated to Israel with his young family just two months before the Yom Kippur War broke out in 1973. He joined the Department of Biochemistry at the Hebrew University-Hadassah Medical School and, during his ensuing career, has received many awards including the Israel Prize and the Wolf Prize in Medicine. In 2008, he was appointed the University’s first Edmond J. Safra Distinguished Professor.
Cedar regards his life’s research as being “focused on one central idea” concerning how cells select the genetic information they need to function and ignore the rest of the genetic package. He describes the genetic information, or DNA, contained within every cell of our bodies as “an instruction booklet”; his challenge has been to understand how any particular cell uses only a few relevant pages of the book and ignores the rest.
Prof. Cedar’s pioneering work in the 1970s — done in collaboration with his current research partner and colleague in the Institute of Medical Research Israel-Canada (IMRIC), Professor Aharon Razin — showed that the DNA becomes partly modified by another chemical, a process known as methylation. This results in only one part of the DNA code being available for the cell to read; in a skin cell, for example, only the instructions for making skin cells are available while the rest of the instructions are methylated and unavailable.
“It took time,” he says, “to put the whole story together to understand how methylation controls human development.” The work has also thrown light on how cells take on specific functions at the very beginning of life. When a human egg cell is fertilized the first bundle of cells produced have the potential to develop into any cell in the human body (none of the DNA is methylated). However, at some stage the cells begin to assume the particular functions that they will have in the new baby — some become liver cells, others become skin, hair, blood, bones. In a paper published in late 2008 with Faculty of Medicine colleague Professor Yehudit Bergman, the gene that initiates this entire process was identified.
Of course, hand-in-hand with understanding how the mechanism functions in normal cells have come insights into how it fails in some genetic diseases such as Fragile-X syndrome. Cedar’s most recent work has also discovered that methylation plays an essential role in the development of all cancers. His work may not lead to a cure-all pill but it can no doubt help identify those most at risk and ensure they get the necessary screening and preventative measures.
For British Medical Journal interview with Prof. Cedar, click here