Milind Watve’s book Doves, Diplomats and Diabetes challenges the current understanding of diabetes and prods researchers to test his alternative model. Here, Watve chats with us on the origins of his book and of the ideas presented in there.
When did the ideas presented in this book originate and how are they tied in to your research?
The origin of the idea lies in the katta system that we used to run in Garware College for a long time. Katta started in 1993, it is an informal gathering of anyone interested in discussing science; unlike a journal club where someone presents a paper, katta is an informal chat. And we talk about a large number of things related to the development of the logic of science, biology in particular.
A renowned diabetologist in Pune, Dr. Yajnik, was a regular contributor to katta for quite some time and we got talking about what was happening in the field of diabetes. I found that there were so many interesting things there and I suggested to him that we should apply the logic being nurtured at katta to the area of diabetes. Within a few months of working on this, we had begun to see results different from what is described in text books or what the medical field has accepted for years. We published one of our first papers on this work in 2007 and a series of papers in the next few years. By 2010 it became clear that I need to compile our literature analysis and the proposed model for addressing diabetes through a book.
In this book, you question the existing understanding of type 2 diabetes by saying that we are beating around the wrong bush. Why do you think diabetes research needs a new paradigm?
Our literature analysis and research on diabetes suggested that type 2 diabetes is not what the text books have been saying, it is not what people have believed and it is not what today’s treatment is based on.
Type 2 diabetes is characterized by high blood sugar levels. The traditional theory of diabetes believes that obesity makes cells resistant to insulin, a hormone that would otherwise help cells take up glucose thereby helping the body regulate blood glucose levels. Over the years, as molecular tools to manipulate the insulin gene and receptor have become available, evidence has been accumulating against the insulin resistance based theory.
For example, when people knocked down insulin receptor in muscle, the expectation was that insulin levels in the body would go up and if not, sugar levels should go up; but neither of these was seen. In another set of experiments in animals as well as humans suppression of insulin production in an insulin resistant state was expected to increase blood sugar. But , after suppressing insulin production, the ability of cells to respond to insulin increased rapidly and blood sugar levels remained normal.
Therefore the belief that insulin resistance and the inability to meet the rising insulin demand cause type 2 diabetes is now seriously under question. The myth of obesity and diabetes being related at a genetic level is also exposed in the same way. Much of the beliefs are breaking down now, that is why we need an alternative thinking. The book compiles the results of all the experiments which make a strong case against the current beliefs about the origins of type 2 diabetes.
What is your alternative interpretation of type 2 diabetes, what do you think causes the disorder?
I think the role of behavior in diabetes research has not been addressed well in the past and this is where we need to focus our efforts to be able to contain this and, possibly, other metabolic disorders.
People knew for a long time that behavior has something to do with metabolism but the link was mostly through an ill-defined term called stress and anything that could not be explained was generally put under the category of stress. So the real understanding of how and why behavior is linked to metabolism or to immunity was not coming forth. I could see that the hawk and dove model, with roots in game theory, can throw light on it. Hawk and dove are two behavioral strategies and they are such that they can coexist in a population. Some individuals are aggressive (hawks) and other individuals are aggression avoiders (doves). And they coexist in a dynamic way in a society so that none of them have any all time advantage. Some people choose to behave in a specific way, as a response, other people choose a different strategy which is complementary or contrasting this, in such a way that this imparts different kinds of advantages to different people. This is how different personalities develop over evolutionary time. Personality is not just about decisions taken by the brain, personality is about the endocrine system, immune system, muscle, the way the gut behaves; personality is about the entire body.. Primate and other animal data have shown a robust pattern that a “Hawk” is characterized by high levels of sex hormones, low cholesterol, low cortisol, low insulin and are insulin sensitive. A “dove” on the other hand has high cholesterol, cortisol, insulin, low testosterone and is insulin resistant. This is independent of calorie intake or body fat.
There are complex interactions between the different organs of the body, the cognitive as well as the non-cognitive part of the brain. All of this is in a network. Today, people are talking more and more about networks at a sub-cellular level, at systems level, protein-protein interactions level, transcriptional level, but what is missing here is behavior as a component of these networks. Once you bring in behavior, the entire body’s system begins to look different. The reason why the networks have evolved this way, for eg, why a single molecule has so many functions is because these functions are behaviorally related to each other.
Each behavior, or a behavioral syndrome, is related to several neuroendocrine pathways and metabolic pathways. You cannot keep behavior out and try to understand metabolism. That is not possible. Behavior is an integral part of the metabolic pathways in the body and therefore a number of things are behavior driven. If behavior is a part of the network, we could have behavioral deficiencies, in a similar manner as dietary deficiencies. This is a concept that is highlighted in this book. In short type 2 diabetes and a number of other disorders are behavioral deficiency disorders. The deficiency of concern here is that of physically aggressive or “hawk” behavior.
Can you explain more on how you think behavior could be a factor in causing diabetes?
The concept is that we have evolved a set of behaviors which were adaptive for a hunter-gatherer life. Today’s lifestyle is far removed from this. When practicing agriculture we still had links to the hunter-gatherer lifestyle; acts like driving away wild animals, digging, cutting wood for fire, and these operations are like the hunter gatherer operations. All the behaviors that were evolved for hunter-gatherer lifestyle are missing now. The entire society is undergoing severe behavioral deficiencies. Each behavior is linked to a certain metabolic pathway, neurocrine pathways, and when you give up one behavior for decades together, the pathways could get affected too! For example, I have not taken up fights with anyone. Since I left school, I have not had a physical fight with anyone. There is a deficiency for forty years now. Fighting is related to testosterone and several other molecules in the body, EGF, NGF, CCK, serotonin, dopamine etc. When I have given up fighting for four decades there is a change in these pathways. In a network, any change in any part of the network affects the whole network.
Today we have developed more than half-a-dozen behavioral deficiencies. You see metabolic effects of these behavioral deficiencies in terms of a variety of complex disorders, which include diabetes, hypertension, osteopenia, and osteoporosis or PCOS. Some of the psychiatric disorders such as the chronic fatigue syndrome can be triggered by behavioral deficiency. If this is true, the message is simple: Just like you supplement dietary deficiencies with pills, there could be behavioral pills, they would come in the form of specific games or sports and specifically designed exercises.
You need to identify what is deficient and play a sport which supplies that. For example, physical aggression is one of the deficiencies, adventure is another deficiency, by adventure I mean a voluntary behavior which predicts injuries or takes risk, but an enjoyable risk. This was extremely common in a hunter gatherer life. Now we are missing that sort of physical adventure. We don’t even have an ant-bite in years. As a result of our understanding of networks, we now know the pathways through which these deficiencies work. For eg, deficiency of injury causes cumulative deficiency of a number of factors required in wound healing, which are growth factors such as EGF, PGDF etc. The same growth factors are involved in beta cell regeneration as well. So, if we do not have injury, the wound healing factors go down, as a result, beta cell regeneration is also affected. This is just one example of how behavioral deficiencies are related to other pathways.
In proposing an alternative understanding of diabetes, you are suggesting one can now explore alternative ways of combating the disorder…
Yes, the main argument is if the origin of the disorder is behavior, pharmaceutical treatment is not going to work. Current diabetes treatment does include exercise such as walking or walking on the treadmill, but these have no behavioral component. These are suited only for burning calories. A behavioral component is important in this treatment. People have shown that small bout of very intense/rapid cycling is more effective than several minutes of moderate cycling. Studies show that boxers are much more insulin sensitive than swimmers. The former is an aggressive exercise and the latter is a relatively non-aggressive exercise.
There is a difference between walking and stalking. There is a difference between running and chasing. You have to cycle as if you are chasing someone!! We need to design different kinds of adventure sports for different age groups. They should also be simple enough so that even a partly debilitated person will be able to do. That should be the main goal.
Behavioral supplementation as a treatment for type-2 diabetes is one of many testable predictions that you made in the book.
Yes, if the prediction is correct, behavioral supplementation should reverse most of the complex disorders provided you have the right kind of intervention and it is followed up with the right marker. We are doing some preliminary experiments, the sample size is small now, but we can see that the type of exercise matters more than the duration for which the exercise is performed or the total calories required. There are several other specific predictions related to action of hormones have been mentioned in the book. The main prediction is that behavioral intervention should alter the metabolic state substantially.
What do you think will be the response of the medical community; do you think the community is well placed to test your predictions?
I have been talking about this concept in various platforms in and outside India. There is a good deal of interest shown in the alternative hypothesis. Interestingly, I have not come across any counter argument. I would like it if the predictions made in the book get tested, I’m not worried about criticism. A number of principles in science suffer from this fate of ignorance, not from criticism. Take the example of vitamin C. With a neat set of experiments, James Lind had predicted in the middle of the 18th century that scurvy is a deficiency disorder and something in citrus fruits can help treat the disorder. For nearly two centuries, no one took him seriously and people continued to suffer from scurvy. In 1900’s vitamin C biochemistry was worked out and then people understood the significance.
I do get a sense that diabetes researchers are on the look-out for a better model of treatment. I was at an R&D unit of a pharmaceutical company recently to present this concept to a diabetes focus group. I told them that my talk will be in two parts. In my first part, I would discuss reasons why I think the foundation of current research on diabetes is wrong. And if they were convinced of these arguments, I can move on to my second part of my talk. At the end of the first part, the surprising reaction I got from them is that this is not entirely new to us, we know that the current understanding has some serious issues. But this is the first time someone has compiled this evidence and is presenting a case for a change in the basic approach. The audience was so keen on understanding the alternative model that the second part of my talk went on for three hours followed by further rounds of discussions!
So far, in medicine, India’s contribution has been little. We have good doctors and good hospitals, but we have to think about what new drug has come from India and what new therapy has originated in India. I see this new paradigm in diabetes as an opportunity for India to make a series of important contributions. We need people across many fields—researchers from molecular biology, cell signaling, physiology, and biochemistry; clinicians; pharmaceutical companies—to come together and make an organized effort.
-As told in a chat with Shanti Kalipatnapu