CAMBRIDGE, MA – Why are some people overweight, no matter what they try, whereas for others, being slim and trim comes naturally? An international team of researchers led by Greek-born Prof. Manolis Kellis, PhD, at the Massachusetts Institute of Technology (MIT) may have found the answer. Collaborating with Dr. Kellis in leading the other researchers was Dr. Melina Claussnitzer – a professor of medicine at Harvard University, who, like Kellis, is also of Greek descent – wrote an article published August 19 in the New England Journal of Medicine titled: “FTO Obesity Variant Circuitry and Adipocyte Browning in Humans.” He described this groundbreaking discovery to The National Herald.

CITIZEN OF THE WORLD

Born in Athens to John and Anna Kamvyselis, Dr. Kellis spent his childhood years in the center of the city, complete with a view of the Parthenon, and summers in Sounion. At age 12, Kellis and his family moved to France, which broadened his horizons to a completely different culture. And at 16, the family headed to New York City. His father, who traveled the world many times over, realized that Greece was part of the global economy and that his children needed to have opportunities abroad and to speak numerous languages in order to thrive, and what better way to learn a language than to live where it is predominant? Kellis’ studies, in the United States, culminated with a PhD from MIT, where he is currently a professor.

GENETICS GENESIS

“In the last few years, a revolution in human genetics has revealed that small changes in our DNA can lead to significant differences, in our health, our bodies, our brains, and even our personal choices, Kellis told TNH.

“Countless genetic studies have given us more than a thousand regions in the human genome that predispose us to disease,” he explains. “We can now, through genetic mapping, observe common variables that influence cancer, diabetes, and obesity.

“Translating these discoveries into therapeutics can transform medicine, enable personalized treatments, and lead to therapeutic avenues that were previously unsuspected.”

SHEDDING CASSANDRA

Dr. Kellis says genetics, unfortunately, has suffered from the Cassandra syndrome – referring to the Greek mythological figure who could see into the future, but was cursed in that no one would believe her predictions.

Similarly, he says that genetics was able to deliver bad news about predispositions to diseases and conditions, without providing the good news of resolution.

“But genetics over the past dozen years of so have given us a large number of regions in the human genome associated with disease,” he explains. “We can now, through genetic mapping, observe common variables that influence cancer, diabetes, and obesity.

OBESITY GENETICS

“We now know that 90% of the genetic differences that predispose us to disease or to almost any other trait do not affect the protein sequences of our genes,” Dr. Kellis says. “So, we need systematic ways to understand what these variants are actually doing.
“As we point out in our paper, they affect the ‘switches’ that alter the expression of these genes. These switches can determine whether a fat cell will specialize in storing energy or burning it.” He emphasized that both of these functions are necessary, but to different extents. The importance of fat cells that store energy should not be underestimated, because it is essential to human survival in times of scarcity. It is energy held in reserve, when the supply is limited or depleted. On the other hand, too much energy storage and not enough burning leads to obesity. Burning energy is involved in using muscles (exercising) or heating the body in case of cold climate. Hence, the importance of the switch in regulating between the two functions.

For the last decade or so, Kellis says, scientists have known that white cells store fat while brown cells burn them, but recently they have discovered the exciting development that there are beige fat cells, which have the characteristics of both white and brown ones. Kellis believes that if fat cells can be controlled to store at times and burn at other times, then human metabolisms can be regulated.

EDITING DNA

This explains why some people are obese while others are not. But what can we do about it? Kellis explains how amazing it is that nowadays. We not only “fixed the broken switch,” but we were able to repair the genes. It would be like fixing a light switch on a wall so that it properly turns on and off, but also repairing the lightbulbs themselves.

We can now provide therapy to individuals, regardless of whether their condition is genetic or environmental (such as, they live next door to a fast-food restaurant, or an injury limits their ability to exercise). “All human beings have that type of circuit, regardless of their genetic background. And we have the option of editing the genome (fix the switch) or changing the expression of the cells (fixing the lightbulbs). This offers new hope in a field that has always focused on how to trick people into feeling less hungry, or focusing them on exercising more.”

Dr. Kellis reiterates that this phenomenal medical and scientific breakthrough doesn’t just apply to obesity – he reminds that the possibilities of curing a myriad of other ailments are limitless.

NOW WHAT?

So when can we expect to put this into action? “In the grand scheme of things, it will be in the blink of an eye,” he says, but then adds in real time, probably within a decade, and maybe even sooner than that.

Thus far, the process has been tested successfully in the laboratory, on mice, but not on humans. There have been no negative side effects – the mice are thinner, which was the desired goal, but have not experienced related health issues. Kellis describes this type of “precision medicine” as going in with a “specialized commando unit” instead of dropping a heavy-duty bomb from above. This, continuing the analogy, prevents collateral damage – “civilian casualties” so to speak.

Nonetheless, Kellis emphasizes that despite the promising results thus far, there have been no tests on actual human beings yet.
And when shall we expect those to happen? “As soon as possible,” he says.