Doves, Diplomats, and Diabetes: A Darwinian Interpretation of Type 2 Diabetes and Related Disorders

385 Pages·2013·6.517 MB·English

by  Milind Watve (auth.)

Doves, Diplomats, and Diabetes
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Milind Watve
Doves, Diplomats,
and Diabetes
A Darwinian Interpretation of Type 2
Diabetes and Related Disorders
Milind Watve
Indian Institute of Science Education
and Research Pune (IISER-P), India
ISBN 978-1-4614-4408-4 ISBN 978-1-4614-4409-1 (eBook)
DOI 10.1007/978-1-4614-4409-1
Springer New York Heidelberg Dordrecht London
Library of Congress Control Number: 2012943959
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Prologue: Advantage Ignorance
A physicist, a chemist, and a biologist decided to collaborate for an ambitious
experiment that needed expertise from all the three disciplines. Painstakingly
they put all the experimental set up together. They performed the experiment
and it appeared to work. They got some results in hand. Now they thought
they wanted to prove the reproducibility of the results and so they did it again.
Everything worked fi ne and they had the fi nal readings again, just that it was
somewhat different than the earlier one. To see which of the two results was
correct; they performed it again and got a still different result. Pretty soon
they realized that although they could draw some roundabout conclusions,
the experiment was not quite precisely reproducible. Everyone started won-
dering what could be wrong. The physicist said that the experimental systems
were perhaps not very stable. He started checking all the circuits, instruments
and their errors, sensitivity to voltage fl uctuations, temperature variations,
etc. The chemist believed that they needed greater care and more precision in
performing the experiment and thought they would achieve it by doing it
again and again and he would be happy when they get three consecutive iden-
tical readings. The biologist appeared least worried and said “well, there is
bound to be some intrinsic variation. Let us take an average!!” Leaving aside
the naivety of the story, it illustrates how people trained in different disci-
plines of science think in different ways, although they might be addressing
the same problem. It is dif fi cult to predict whose approach would ultimately
turn out to be fruitful. What is important is to try more than one way of think-
ing and that increases the chances of fi nding a solution. Until you have the
solution you need to keep your mind open to all the different possible
approaches. At times the solution comes from the most unexpected approach
and perhaps the least authoritative person.
So many times in the history of science, a person crossing over the borders
of disciplines has contributed novel concepts to science. This is natural as a
person trained in one way of thinking crosses borders and goes to a different
fi eld of science he carries a different line of thinking to that fi eld. Perhaps
people trained in that fi eld were trained to see things with a speci fi c and lim-
ited viewpoint and therefore failed to see some important angle. A fresher
might just happen to see those things owing entirely to his freshness. This is
extremely important in today’s science, particularly in the fi eld of medicine
where professional specialization is making the vision deeper but simultane-
ously narrower so that one seldom talks about his concepts, ideas, and visions
v
vi Prologue: Advantage Ignorance
to people from very different fi elds. Such talks would often be chaotic and
fruitless but once in a while may give unexpected rewards. The ideas behind
this book have arisen in precisely the same manner.
It is tempting to relate another story that I happened to hear sometime in my
school days. A war broke out on the border of a country and it was urgent and
desperate to move soldier s, arms, and ammunition to the front. Trucks loaded
with ammunition were being transported through a village that had an ancient
historical arc across the road. The fi rst truck got stuck there since its height
was just half an inch more than what the arch allowed. Looking at the urgency
and desperation a quick solution was most imperative. Troop leaders and vil-
lage elders came together and debated on the alternatives, whether to make an
alternative road, whether to demolish the arch, or whether to dig up the road to
reduce its level. Ultimately, a simpler and ef fi cient solution came from a small
illiterate village kid who suggested “why not de fl ate the tyres a little bit.” This
will reduce the height of the truck by an inch or so which could be enough to
solve the problem. We were told this story in school to emphasize that wisdom
can come from anyone and we need to keep our minds open for it.
My viewpoint to this book is that of this young boy who could see things
differently. Wisdom lies in the ability to keep our minds open to a suggestion
that can come from one of the most unauthoritative and unexpected persons.
My writing a book on diabetes was a surprise to most of my friends who must
have wondered how someone who never had any training in medicine or
physiology can write a book on diabetes. People have spent their entire lives
researching on some specialized aspects of diabetes adding inch by inch to
the understanding of the complex disorder. Is it possible that some new and
revealing light comes from someone completely naïve to the fi eld?
The story narrated above is the only possible answer to the question. I claim
no authority by knowledge. But when the emperor has no clothes only a child
has the authority to expose him. I can certainly write with this authority. I did
happen to see things differently and therefore in the true spirit of science it
might be worth taking this point of view seriously.
I have one major advantage with which I can dare to write such a book.
That is an advantage of ignorance. In today’s science, and particularly in the
fi eld of medicine and biomedical research, expertise is highly valued, quite
rightly so. But there is a negative side of expertise too. It builds castles of
comfort zones around a person. A researcher is comfortable in his/her own
area of research and generally avoids talking about things beyond this com-
fort zone. With increasing depth of research the comfort zones are becoming
increasingly narrower. As a result there is no one left to take a wider perspec-
tive. Having a wider perspective is important in order to understand any com-
plex system. But when a system is big and complex and the visions of insiders
are narrow, an outsider is more likely to do a job complementing the insiders’
work so that a coherent picture emerges.
Making a map of a large territory involves many compromises and trade-
offs. The bigger the area the more dif fi cult it is to fi ll in details. Too many
details ultimately defeat the purpose of making a map. A map is always an
oversimpli fi ed version of the territory. But every map has a purpose and how
much one should simplify depends upon whether the purpose is being served.
Prologue: Advantage Ignorance vii
When available data are very large and still growing exponentially, taking a
birds’ eye-view involves an inevitable trade-off with details. This is what I
have to do and it is a dif fi cult choice. I have tried to go into only as much
depth as is needed for the expression of the central argument of the book but
have avoided unnecessary details.
Besides both these limitations, that of my expertise and that of the inevi-
table trade-off between width and depth, as far as I know this is the fi rst time
that type 2 diabetes is being depicted on such a wide canvas. When the canvas
becomes wide, the entire picture looks very different and it is this difference
that I want to convey through this book.
Most books are written by experts in a fi eld and are meant for general
readers, students of the fi eld, and other experts too. This is a book written by
a general reader for experts, students in that fi eld, and other general readers.
I am an undergraduate teacher by profession and until recently I did not hold
a job that expected me to do research. I am not writing this book as a researcher.
As a teacher one has to face unexpected and provoking questions from stu-
dents. It is the students’ questions that have driven all my science so far and
this book is no exception. Being a teacher solved many of my problems. I did
not know how to write a scholarly book. I just did it as if I am talking to a
group of students. Therefore this book is not to be treated as an authoritative
piece of work. It is intended to raise questions and suggest alternative view-
points in order to fi nd solutions. I would be happy even if experts in this fi eld
do not agree with me on my solutions. They still need to answer the questions
I have raised and that would inevitably lead to some good science.
Recently I happened to attend a talk by the 1989 Noble laureate Mike
Bishop addressed to an audience of young scientists settling into research
careers. Although no more young, I found his advice extremely useful for
being able to write this book. “Dare to be wrong,” he said “and follow your
nose.” A number of times I stopped and asked myself a troubling question. If
what I see is very different from what everyone else says and believes, is it
possible that there is something wrong in my vision itself? But I followed my
nose and that helped me complete this book. I am open to the possibility that
my thinking is completely wrong. But if the questions I raised are getting
answered while proving me wrong, I would say it was worth being wrong
after all.
The book is arranged in the following sequence. Most students of medi-
cine and physiology are not really familiar with evolutionary theory beyond
knowing that it is something about “survival of the fi ttest.” Real insights into
the subtleties of evolutionary theory started coming since 1960s. It is hard to
give an adequate account of modern evolutionary theory in a small chapter,
but I have attempted to do so in Chap. 1 restricting to the concepts that are
used later in this book. As a counterpart, for readers who have not studied
medicine or physiology Chap. 2 is devoted to an introduction to textbook
picture of type 2 diabetes. The real stuff in the book begins at Chap. 3 , which
raises a number of questions and exposes a number of paradoxes in the clas-
sical theory of diabetes. This would sound like harsh criticism, which is
quite against my nature, but it is only meant to raise questions and expose
paradoxes only on the background of which the following chapters can be
viii Prologue: Advantage Ignorance
appreciated. Chapter 4 takes a quick review of the earlier attempts to explain
evolutionary origins of obesity and diabetes. Here we also lay out a set of
expectations from an evolutionary theory of diabetes. At the end of the book
we need to return and see how much of it the new theory meets. Chapter 5
makes a fresh beginning by looking at some behavioral aspects of life in the
wilderness that are relevant to physiology. The foundation of an alternative
theory of insulin resistance is laid in this chapter itself, but not in the human
context. Things are different in the human context and that difference is
made clear in Chap. 6 . Here the central argument of the new theory is stated,
but it is still super fi cial, the details of which start fl owing through the next
several chapters. From Chaps. 7 – 1 3 all the complex pathophysiological
mechanisms of diabetes are elaborated at some depth in the light of the new
way of thinking. As we progressively build the arguments based on evi-
dence, logic, and a little bit of mathematics, the existing theory of diabetes
appears increasingly inadequate and perhaps completely wrong. Chapter 12
suggests a rather startling possibility that insulin resistance and relative insu-
lin de fi ciency are not the cause of diabetic hyperglycemia. The alternative
cause suggested appears more logical and evidence based. Chapter 1 3 leads
to another fundamental deviation from classical thinking that insulin resis-
tance is unlikely to be central to the pathophysiology of type 2 diabetes and
that hyperglycemia may not be the root cause of diabetic complications. The
reader needs to go stepwise to appreciate these possibilities. The chapters
are arranged in a logical sequence to build the series of arguments. There are
alternative pathways for the pathophysiology of diabetic complications.
Chapter 1 4 broadens the theme and suggests how the same line of thinking
may be useful in understanding a variety of other modern diseases. Chapter
15 takes a brief review as well as a critical look of the entire synthesis and
suggests possible lines of research for the future.
I would request readers to begin reading with a fresh and open mind and a
skeptical but unprejudiced viewpoint.
Acknowledgments
A number of people have been instrumental in persuading me to write this
book. My interest in diabetes was triggered by Dr. Chittaranjan Yajnik and
his research group at KEM hospital, Pune, about a decade ago. We wrote a
couple of papers together. I would have liked him to coauthor this book since
we developed some of the basic ideas together. But looking at his busy sched-
ule, I suspect, making him coauthor would have perhaps delayed the book by
at least another 10 years.
As the ideas were being developed, discussions with a number of students
and coworkers were extremely crucial. I need to mention particularly Maithili
Jog, Anagha Kale, Pramod Patil, Samit Watve, and Prajakta Belasare among
several others. We had a weekly forum called “Science Katta” where free and
random branching discussions on anything in science took place. That was
the fi rst outlet for these ideas and the fi rst platform to debate on them. These
heated debates in which mainly undergraduates participate have been the
most important chaperones for my thinking. After having published over half
a dozen papers, I found myself increasingly unhappy with research papers as
a medium to express this set of new ideas. This was because a wide perspec-
tive was developing and it was necessary to paint that on a suf fi ciently wide
canvas. Only a small part could be painted in one research paper at a time
which was unlikely to give readers any idea about the broader picture.
Coincidently, I happened to meet Janet Slobodien, the editor for Ecology and
Evolution titles of Springer in August 2010 who convinced me that a book
would be the right canvas.
While the book was not even half way, I had the opportunity to organize a
meeting funded jointly by the Royal Society, London, and the Department of
Science and Technology, India. Participants in the meeting were experts in
widely different areas including epidemiologists, physiologists, psychiatrists,
clinical diabetologists, neurobiologists, cell biologists, geneticists, epigeneti-
cists, population ecologists, primatologists, ethologists, psychologists, and
philosophers of science. This was just the right kind of audience to give an
exposure to and debate on the upcoming ideas. This was an extremely enlight-
ening experience for me. I was encouraged by observing that although not
everyone agreed with my way of thinking; they thought it was worth taking
seriously, debating, and putting it to test. During and following this meeting,
detailed discussions with many participants were useful. They include
Jonathan Wells, Jason Gill, Raj Bhopal, Daryl Shanley, Chittaranjan yajnik,
ix
x Acknowledgments
Giriraj Chandak, Neeta Deshpande, Nishikant Subhedar, Vidya Bhate, Palok
Aich, Pranay Goel, Sanjeev Galande, Saroj Ghaskadbi, Sutirth Dey, Vidita
Vaidya, Mili Bandopadhyay, Asmita Phadke, Ullas Kolthur, K.P. Mohannan,
Kalpana Joshi, and Leena Phadke. A large number of questions and objec-
tions were raised that put me back on the thinking track. The critical thinking
and dialogue that was initiated in this meeting helped me re fi ne the upcoming
hypotheses and put things in a better perspective. A few new proposals were
generated and some new lines of research were also planned during the
meeting.
The synthesis in this book is a reinterpretation of existing information that
is based on a large body of research particularly over the last two decades.
Therefore although I might be tempted to call it m y hypothesis or my theory ,
I presume it is only a natural culmination of the rapid accumulation of new
data throwing new light on old things. I am sure if I did not come up with a
new interpretation, someone else would have, sooner or later. I view it as a
natural culmination of research efforts by a large community of researchers.
In preparation of the book I was helped mainly by my current and former
students including Maithili Jog, Anagh Purandare, Manawa Diwekar, Gauri
Tendulkar, Sakshi Sharda, Anamika Chatterjee, Neelesh Dahanukar, Ulfat
Baig, Uttara Lele, and Ashwini Keskar. When I was only expecting some
information inputs, Pramod Patil wrote almost half of Chap. 2 and the tables
thereof. Organizational help in research from Vinay Kolte, Charu Kumbhar,
Prajakta Belsare, Archana Watve, and Mukta Watve was helpful. Selected
chapters or the full text at a draft stage were read and commented by Jonathan
Wells, Palok Aich, Sutirth Dey, Bill Sheehan, K.P. Mohanan, Chaitali Anand,
Uttara Lele, and Pritee Oswal and their detailed comments were useful in
shaping the book. Salil Lachke, a former student of mine who is an Assistant
Professor at University of Delaware now, commented through a series of car-
toons, most of which I have included in the book since they convey a meaning
beyond words. The credits for other fi gures and illustrations go mainly to
Neelesh Dahanukar, Manawa Diwekar, Anamika Chatterjee, Sakshi Sharda,
Rama Hardeekar, and Ajey Hardeekar.
The research leading to this book did not have any project-speci fi c fund-
ing, but institutional support by IISER, Pune; particularly the extraordinary
academic freedom in this institute needs a special mention. Two Indian com-
panies, LabIndia and Anujeeva Biosciences Pvt. Ltd., extended crucial
fi nancial support earlier during my dif fi cult times without which the develop-
ment of the concept would have been dif fi cult.