Tip:
Highlight text to annotate it
X
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.