Dr. Andras Nagy
Senior Investigator, Samuel Lunenfeld Research Institute
Mount Sinai Hospital, Toronto

Dr. Andras Nagy keeps a dog-eared, coffee stained lunch menu from a restaurant outside of Munich, Germany close to him at his desk in a lab office in Toronto’s downtown Discovery District.

That menu – one side covered in crude circles and triangles, connected by crooked arrows and cryptic words like PiggyBac and Sox – represents little more than bored doodling to the untrained eye. But that menu is the genesis of what has become one of the most exciting scientific breakthroughs in stem cell research in recent years.

Nagy and his team of researchers at Mount Sinai Hospital’s Samuel Lunenfeld Research Institute have developed a safer way to reprogram ordinary skin cells into embryonic-like stem cells, also known as iPS (induced pluripotent stem) cells. It’s a major discovery that could eventually eliminate the need to use human embryos. Nagy’s work, published recently in the science journal Nature, significantly accelerates stem cell technology and provides a road map for new clinical approaches to regenerative medicine.

Nagy’s initial idea was sparked during a lecture in Germany in January 2008. He invited the speaker to lunch and Nagy’s ideas took shape on the back of his menu. “I drew him this plan. All the elements are here. See? My coffee spilled here,” he points out.

Dr. Nagy first came to Toronto from his native Hungary in 1988 on a three-month visiting scientist invitation from Dr. Janet Rossant, herself a pre-eminent stem cell researcher in the Developmental & Stem Cell Biology research program at Sick Kids Hospital. He returned the following year, stayed for a second, and he knew he was here to stay when “I bought a piano for my daughter. It’s pretty hard to move when you have a piano,” he says.

As a father, Nagy was enticed by the quality of life Toronto offered. “Toronto is a good place to live, it’s good for children, a place where my daughter can walk to her music lessons by herself.” As a scientist, Nagy was impressed with the “critical mass of scientists” clustered within Toronto’s Discovery District. It was an ideal setting to conduct cutting-edge research.

In fact, Ontario is well-known as a world leader in stem cell research. It was Ontario scientists – Doctors Ernest McCulloch and James Till of the University of Toronto – who discovered stem cells back in 1961. Ontario has built upon this discovery from Dr. Tony Pawson unlocking cell biology, to Dr. John Dick discovering cancer stem cells, to Dr. Janet Rossant deriving stem cells from early embryos.

Today Nagy is in good company as Senior Investigator at the Samuel Lunenfeld Research Institute of Mount Sinai Hospital, one of the world's leading centres in biomedical research. He is also an Investigator at the McEwen Centre for Regenerative Medicine, and holds a Canada Research Chair in Stem Cells and Regeneration.

Nagy’s discovery inserts four essential reprogramming genes (c-Myc, Klf4, Oct4 and Sox) into what’s commonly known as a "jumping gene" - a tiny piece of DNA called a transposon found in moths. The transposon Nagy used has been dubbed "piggyBac". This jumping gene can be pasted into the genome of a single skin cell and, once the cell is reprogrammed back to its embryonic state, the jumping gene can be easily and seamlessly removed to eliminate any potential damage.

His breakthrough builds on 2007 advancements by Japanese and U.S. scientists who were the first to create stem cells from a patient's skin. However, that technique used viruses to insert the four reprogramming genes into the genome of a mature skin cell. The problem is that the viruses could mutate and eventually cause cancer to develop in the tissue grown from iPS cells. Also, because Nagy’s stem cells are taken from the patient's own skin, they pose no threat of immune rejection, mitigating another medical drawback of embryonic stem cell use.

Because previous methods used embryos or women's eggs, Nagy’s discovery using skin cells to grow embryonic-like stem cells may help lay to rest many of the medical and ethical concerns of those who contend that stem-cell use is dangerous or immoral. Even some of the more vocal opponents of stem cell research have had positive things to say about Nagy’s work. “That’s very encouraging,” he says.

Nagy’s work was not conducted in isolation. His paper was published at the same time as a complementary paper by an Edinburgh team of scientists from the Medical Research Council Centre for Regenerative Medicine. “I was in Scotland at a seminar where we met up by chance. I didn’t know about the work they were doing, but discovered that one researcher there – Dr. Keisuke Kaji - had a genius idea.”

The two research centres combined their efforts using Edinburgh’s technique for combining the genes into one fragment of DNA and Nagy’s clean removal system. Before this study, non-viral methods for reprogramming skin cells had only worked on mice. This is the first time they worked on human skin cells.

And today he’s a very busy man. In addition to the many media interviews he’s conducted for articles that have appeared around the world, he has a full schedule of invitations to international conferences to present his findings. “My year is filled up,” he says. “It’s important to get out there and meet other scientists in my field. Personal contacts are very important to the work we do.”

This latest discovery is not Nagy's first stem cell breakthrough. In 2005, he developed Canada's first two human embryonic stem cell lines. At that time, he said he hoped to help bring "Canada and the world closer to treating or curing diseases such as multiple sclerosis, Parkinson's disease, Alzheimer's disease, diabetes and spinal cord injuries."

In fact, Nagy’s latest discovery brings that hope even closer to reality. 

At a Glance

The researcher: Dr. Andras Nagy, Senior Investigator at the Samuel Lunenfeld Research Institute of Mount Sinai Hospital in Toronto, Investigator at the McEwen Centre for Regenerative Medicine and Canada Research Chair in Stem Cells and Regeneration.

The Breakthrough:  Nagy and his team have developed a safer way to reprogram ordinary skin cells into embryonic-like stem cells. This discovery could eventually eliminate the need to use human embryos and provides a road map for new clinical approaches to regenerative medicine.

Worth Repeating:  Nagy’s discovery inserts four essential reprogramming genes (c-Myc, Klf4, Oct4 and Sox) into what’s commonly known as a "jumping gene" - a tiny piece of DNA called a transposon found in moths. The transposon Nagy used has been dubbed "piggyBac". This jumping gene can be pasted into the genome of a single skin cell and, once the cell is reprogrammed back to its embryonic state, the jumping gene can be easily and seamlessly removed to eliminate any potential damage.

Connect With the Researcher:  http://www.mshri.on.ca/nagy/