Jeffrey Friedman discusses research on leptin and obesity

Jeffrey Friedman discusses research on leptin and obesity

So people have noted that I won two really wonderful awards. One from Hong Kong and one from Japan, in short order. I tell them that “At least I’m hot in Asia. Here, not so much.” The reason I say that is
not long ago I wrote an editorial for Newsweek and it put forth the point of view that I hold true, which is that body weight is
to a very large extent biologically regulated and that stigmatizing the obese probably can’t be
defended, at least based on the science as we understand it. So I wrote this editorial and for about
a week or two it was one of the hottest uploads, hottest downloads from
the Newsweek site and was the most commented upon article. Almost all the comments were negative. My favorites were one in which the writer kept referring to me as Dr. McQuack, and in another of the notes, a writer called Smokescreen made the comment that “I doubt anyone
will ever nickname Dr. Friedman skinny.” And then one of the my defenders on the
site wrote “I doubt anyone ever called Smokescreen
smart.” So it turns out they were 78 pages in Microsoft Word of comments to date and a Yahoo! chatroom. And what I found most amusing was that I
was pilloried from both sides. I was pilloried by people who believe
the obese should be responsible and now shared some of their vitriol for the
obese with me, but also from obese people who felt that
I was victimizing them when they don’t want to be victimized,
understandably. Everyone has a personal set of
experiences with eating and food, and more than half the population has
also an experience with dieting and what they believed to be their own
efforts to manage their own weight. And so because of that, everyone has such
a rich set of personal and anecdotal experiences, that they immediately filter anything I might say
through their own personal experiences or the people around them. And so for that reason, it is quite a bit different trying to explain
our science to people than it is perhaps for other scientists. On the other hand, it is a topic about which
people are interested. I think to a large extent they’re interested
mainly insofar as they could tell me why I’m wrong. In 1951, a genetically obese mouse was identified
at the Jackson Laboratory in Maine. They breed millions of mice a year and because all the mice are maintained
by brother/sister matings, you often see recessive mutations popping up. They have very skilled animal handlers
there and so whenever a new phenotype, they call them a deviant, arises they put these animals out on the shelf
and ask investigators if they’d like to work on them. This obese animal weighs three times
more and has five times as much fat as compared to a normal animal. All as a result of a single defective
gene. People have been interested for decades
in what the nature of that gene product might be and no one was ever able to deduce
what it was. There was, however, prior evidence that
the defective gene might encode a novel hormone that regulates weight. And so we set out to clone the mutant gene with the hope, or expectation, that it would encode a
novel hormone In the 1980s, a new technology
developed that made it possible to identify defective genes not based on any a priori knowledge of
the function of that gene, but rather simply by knowledge of its
detailed position on a genetic map. And that’s the basic approach now known
as positional cloning that we employed to identify it. I’d befriended several years before
we found the gene a famous scientist who studies the hypothalamus named Roger Guillemin. And Roger won the Nobel Prize
some number of years ago for studying hypothalamic releasing factors and I gave a talk about our own ongoing
efforts to find this obesity gene, as the ob gene was often referred to and after hearing my talk, Roger wrote me
a letter and said they liked my talk very much
but that he didn’t think i should refer to
it is an obesity gene because the normal gene keeps you thin.
It’s only in its absence that you become fat and suggested that I start referring to it
as a thin gene. He then went on to say that “thin gene” didn’t sound very good and so he
proposes an alternative that I call it a lepto gene, from the Greek root lepton (λεπτός), meaning
thin. And so when we found the gene and had occasion to name it, that’d stuck with me and so that’s where the name leptin came from. So we identified the gene for mice, but quickly identified the homologous gene from human. The main reason I was interested in
doing that was just to confirm that we had the reading frame correct. But it was also gratifying to know that
the human gene was as similar to the mouse gene as we now know it to be. Most of our work through the years – almost
all of our work – is focused on animal experimentation. However, after the identification
of leptin, several of the groups embarked on trying to find patients with leptin mutations. And one group in particular that
led by Steve O’Rally in Cambridge so identified leptin-deficient children. Such cases are relatively rare, but the absence of leptin in human also
causes massive obesity and leptin treatment of these children
or adults has just dramatic effects. In one case, a patient described going to get
their leptin injections for the first time [as] riding
two seats on an airplane and going home in one seat. I never thought leptin as a therapeutic
would be a magic bullet of sorts that would treat everyone and partly, part of
the reason for that, is that we have done animal experiments early on that predicted almost completely what’s
subsequently been seen in human. And so I think there was an expectation on my
part that it would prove to be a useful means for treating some patients with
obesity and some patients with other conditions and that’s turned
out to be true. I think part of the reason, however, other people might have expected
otherwise had to do with how dramatic the pictures were. When you take this
unbelievably obese mouse and make him skinny… And we were incredibly excited about that result because of the science it foretold. And the fact that it proved
all of our work, proved that all of our work had
been correct. For the rest of the public, though,
however, the power of that image created an expectation that leptin would work that well in all settings and that hasn’t turned out to be the case. So I think that while perhaps
leptin suffered from excessive expectations you know more broadly when it was first
identified, I think it’s gone overall as well or better than I
could have hoped and we’ve learned a lot more. Now when we say the system that leptin regulates is complex, in a sense what we’re saying is behavior
is complex because leptin is not the only thing that drives feeding behavior. On the other hand the ability now to
study a behavior in response to a single stimulus, like getting leptin, gives us an opportunity in the future
perhaps to really dissect in greater detail and with a greater level of
understanding how we decide whether or not to go foraging. One of the things that resonated
with me about the Keio Prize is their stated wish to develop ways by which science can improve the
greater good and that resonated for me a little bit because
I’ve become aware of the last year or so of a variety the early figures from Rockefeller’s
history, one of whom, Samuel Meltzer, in 1914, on the eve of World War I, formed the society for
experimental biology and medicine as a means to bring scientists from all
countries together and try to prevent what turned out to be
catastrophic war. And so there is a tradition here, and I
suppose through this prize to try to use the fraternity of scientists
as a hedge against the forces that divide people. I thought it was a nice sentiment. I mean, the truth is that you do science – at least I do science – and it’s mainly for those
moments where you know you see something in a way you didn’t see
before or learn something new. You have that experience all the time in
science. I would say certainly the discovery of leptin was quantitatively greater than that which I’ve
experienced in other instances, but if I ever stop experiencing that sense of
excitement about new results or new knowledge, I’d probably start thinking about doing something else.
I haven’t gotten to that point yet.

7 thoughts on “Jeffrey Friedman discusses research on leptin and obesity

  1. Incredible story about your discovery of leptin. I have measured several hundred leptin levels in my clinical practice that focuses on diseases from anorexia to obesity and metabolic syndrome. I have targeted leptin whether too low or too high in order to help promote metabolic and reproductive function in my patients. Obesity and overweight is clearly biological! thank you so much for your excellent work and the gift your discovery has and continues to give my patients and practice.

  2. Dr. Friedman

    You're a genius. We NEED scientists such as yourself. Please keep up the great work. The future lies in YOU or someone on your level ( not many) . 🙂

    Thanks for all of your work .

    Best Wishes,


  3. One more step towards your discovery of Leptin. There is a peptide discovered that can change, turn off and on, our genes. With that being said, we CAN improve our genetic make up …

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