Sunday, October 25, 2015

Can fasting prevent Alzheimer's disease ? And how to answer such questions

Women of Rennell Islands: Were they spared from Alzheimer's disease due to famine experienced in childhood ? 

Humans love to think of themselves as gods, as bright dazzling balls in the sky, radiating ideas and exchanging pointers on how their ideas can solve all the problems in the world. Nowhere is this conceit more apparent than people blathering on the internet. Mea culpa. But the other day, this conceit has been broken for me, when all of a sudden I woke up with a stiff back. Years of lounging on a work desk have taken their toll on my back muscles and they decided to apply for an early retirement package. Of course, I am not willing to grant them that. But their message has been heard, their point has been taken. As if to reinforce the point, which might be lost in subtlety and in the humdrum of life, the changing seasons also gave me a sore throat and a cold. I am reminded that I am a bag of sticks which is held together by fibers, wires and valves, any of which can be twisted out of shape. I used these sick days of staying at home for reading through a set of books that I purchased recently. As it happens, they have to say nary a bit about this physical condition of human existence.

Humans are pipe-shaped animals, with the biggest pipe - the intestinal pipe going from the mouth to the anus. 
This is how Giulia Enders colorfully puts it in her book "Gut: The inside story of our body's most underrated organ".  This book was a good starting point to learn how viscerally our brains are connected to our viscera. But I finished reading another book, that made an exhaustive deconstruction of the notion that we humans live in a Platonic sphere of abstraction and ideas. That is the book "Village Effect" by Susan Pinker, which forcefully reminds us how our brains are tied to our bodies. I think every computer engineer needs to read this book. I recommend this book especially to my friends in the Silicon Valley, plotting their next big social apps or cyber addictions on the unsuspecting masses. As I mentioned, people are not dazzling gods made of ideas, but inherently tied to their physical bodies., which are like bags of sticks. In fact, human bodies are even more rickety than that analogy suggests.

Firstly, our bodies have their genetic makeup of the DNA code, which we have not deciphered yet, but which predisposes us to certain physical and mental states. Beyond the DNA, our bodies have digital switches triggered by the environment, that turn on or off large sections of genetic code. This is known as epigenetics, a phenomenon that can even be transmitted from parents to children. Beyond this digital circuitry at the cellular level, our bodies have a layer of complicated organic chemistry, known as the endocrine system. Various chemicals secreted into our body at different glands make our hearts beat faster, activate our immune systems or shut them down, make us feel comfortable or cranky, and dramatically color our emotional states. Chemicals such as serotonin, epinephrin and oxytocin dictate how we behave as humans. This is why people get addicted to drugs, and why they can be saved by pharmaceuticals. At a layer higher than chemistry, our body is a network of neurons - not just in the brain but significantly also in the gut. The thoughts that we think, the experiences that we have, and the foods that we digest will all influence which chemicals get secreted into our bodies and which digital switches (epigenetics) get turned on so that our DNA can be expressed. Digital technologies pretend that we are simply a software of consciousness running on the hardware of our brains. But this is far from the truth. Designing a good user interface means taking care of all the layers of being human: including the chemical and genetic layers. Needless to say, addressing this level of complexity has not been attempted by anybody yet, and what we have today are awful user interfaces - both for digital systems and for social systems.

This brings me to another book I purchased "The human use of human beings" by Norbert Wiener.  This book is a classic from 1950s and Wiener is one of the founders of computer science, specifically the theory of cybernetic control that addresses the interface between the human and the machine. I have not got to reading this book yet, but Wiener was a visionary not only for computer theory, but also for the monumental blunders that will be done by digital technologies to humankind. According to Wiener, digital technologies are pretty similar to socio-economic and legal systems: both encode a protocol of communication with humans for making them do what is expected of them. The sad thing is that we were tremendously wrong on designing both socio-economic systems as well as digital technologies, simply because we misunderstood humans to be Platonic agents of ideal action, and not as rickety bags of DNA and chemicals.

Getting back to the "Village Effect" by Susan Pinker, the book is a revelation on many fronts: People with strong social circles, as in a small tightly-knit village, lead long and healthy lives. People without strong social bonds suffer not only from loneliness but also from an early death due to a severe lack of immunity to diseases. Face-to-face conversations and pats on the back boost the oxytocin in our bodies which revitalizes the immune system, something which does not happen with virtual messages. Mobile devices and screens have documented negative effects on the cognitive growth of babies and adolescents. Adolescents using digital media and online social networks are at a greater risk of bullying and social conditioning.  The  thing that stuck me is how unanimous the psychologists are. These are fairly new findings in psychology, but they are not controversial. Like the tobacco industry, the computer industry has been simply ignoring these findings. It considers these as "somebody else's problem", nothing to do about it. After reading the book, I was stuck by the mental image of an Indonesian baby that was recently on the news, who was addicted to cigarettes and sniffing out tobacco smoke like a chimney. This disaster in Indonesia is in no small measure due to the advertising of tobacco companies that saw a remarkable growth of sales in the rising populations of Asia (even as the dangers of tobacco got apparent in the USA). The future generations of humanity will probably judge us as badly, letting the young and vulnerable people get addicted to the charms of social networks and digital pornography.

However, there is a fundamental problem that prevents us from connecting cause and effect in complex fields like psychology.  As mentioned earlier, our bodies are like Rube-Goldberg machines, composed of complex systems of chemicals and DNA, each of which is triggered by non-linear switches. The effects of any cause will become apparent only much later, and can only be gauged in a probabilistic sense. Like my stiff back that resulted from my sedentary lifestyle of several years of  lounging on the chair, the effects of modern living on my mind will be apparent only much later. Typically, such effects will be reduced cognitive skills, reduced social empathy, and reduced immunity to diseases. These effects will probably show up clearly only in my old age, when I will be the most vulnerable.

It is said that scientists working in most fields suffer from a physics envy, eager to condense the topic of their study to a pithy set of equations. Unfortunately, this approach to doing science is not valid for complex subjects that have many variables and non-linearities. Nevertheless, scientists in fields as diverse as biology and sociology have the urge to reduce their subjects to crude one-dimensional models, sometimes with tragic consequences. A similar envy exists in medical fields, though I believe it is less known. I term this the Penicillin envy: every pharmacologist and medical practitioner wants to find a wonder drug that can cure the disease of their study. In fact, this is a very modern jealousy, stemming from the remarkable success of the antibiotic drug Penicillin. It just works, as long as the infection is bacterial and the bacteria are not resistant to this drug (which was typically the case when the drug was first tested). This wonder drug inspired the search for many similar drugs that can take effect on the body just as quickly. However,  this search has often been a fool's errand. Our bodies are not pristine laboratories for physics experiments. As I said, they are like Rube-Goldberg machines, complex and remarkable when they work, but threatened by collapse and failure at multiple levels. The complex multi-layered metabolism of our bodies has its own way of healing; drugs and medical procedures can only facilitate this natural healing procedure. Despite great advances in medical science, the workings of our body remain mostly a mystery, and this is especially true for psychological ailments.

In fact, digital technologies are not unique in  creating a set of rich world diseases. People living in traditional hunting-gathering societies have very little problems with diabetes, coronary heart disease, or indeed, back pain.  Our modern sugar-rich diets and sedentary lifestyles are exerting hidden pressures on our internal organs, our immune systems, and our brains. These problems are systemic - stemming from how our society is organized, and not from individual personal choices. For example, the fact that the majority of drinks in the super-market contain massive loads of sugar predisposes us to making that choice for a sugary drink. The fact that the majority of our friends are on Facebook predisposes us to post on Facebook.

Perhaps, the most tragic of the modern diseases is Alzheimer's disease, where the brain shrinks as it becomes clogged by protein. This is a disease closely connected to diabetes (sometimes called type-3 diabetes). With Alzheimer's, the brain suffers a gradual loss in long-term memory, as well as in its capacity to form new memories. Sometimes, people experience mental hallucinations and delusions. In the intermediary stages, they may gradually lose their vocabulary. As the disease advances, people may suffer complete loss of speech and become unable to even perform simple tasks independently. This is a slow and painful way to die. I came across two remarkable essays  on how Alzheimer's disease affects the patients and their caregivers. You may read them at your leisure.

Even after a hundred years of intense study, there is no cure in sight for Alzheimer's. People still dream of a miracle cure, similar to Penicillin. But it is more likely that this disease will be similar to cancer, presenting many fronts on the battle. One interesting piece of information I learnt from Susan Pinker's book is that starvation in mice seems to have a protective effect against Alzheimer's disease as the mice get old. Several scientists speculate that this could be true for humans as well. Pinker also wonders if the elderly people she studied in Sardinia, who live exceptionally long lives, had a protective benefit against Alzheimer's due to starvation they suffered during the second world war. Why should starvation protect against a late onset disease like Alzheimer's ?

This got me thinking about evolutionary reasons, where people who suffered starvation during childhood may have an additional impetus to live older lives, and to keep their memory from deteriorating. I got reminded of Jared Diamond's book "The world until yesterday", where he recounts a singular case from Rennell Islands. In a different online essay, he  relates the same experience.
In 1976, I visited Rennell Island, one of the Solomon Islands, lying in the southwestern Pacific’s cyclone belt. When I asked about wild fruits and seeds that birds ate, my Rennellese informants named dozens of plant species by Rennell language names, named for each plant species all the bird and bat species that eat its fruit, and said whether the fruit is edible for people. They ranked fruits in three categories: those that people never eat; those that people regularly eat; and those that people eat only in famine times, such as after--and here I kept hearing a Rennell term initially unfamiliar to me-- the hungi kengi.  

Those words proved to be the Rennell name for the most destructive cyclone to have hit the island in living memory--apparently around 1910, based on people’s references to datable events of the European colonial administration. The hungi kengi blew down most of Rennell’s forest, destroyed gardens, and drove people to the brink of starvation. Islanders survived by eating fruits of wild plant species that were normally not eaten. But doing so required detailed knowledge about which plants are poisonous, which are not poisonous, and whether and how the poison can be removed by some technique of food preparation.  

When I began pestering my middle-aged Rennellese informants with questions about fruit edibility, I was brought into a hut. There, once my eyes had become accustomed to the dim light, I saw the inevitable frail old woman. She was the last living person with direct experience of which plants were found safe and nutritious to eat after the hungi kengi, until people’s gardens began producing again. The old woman explained that she had been a child not quite of marriageable age at the time of the hungi kengi. Since my visit to Rennell was in 1976, and since the cyclone had struck 66 years before, the woman was probably in her early eighties. Her survival after the 1910 cyclone had depended on information remembered by aged survivors of the last big cyclone before the hungi kengi. Now her people’s ability to survive another cyclone would depend on her own memories, which were fortunately very detailed.  

It seems likely that starvation in childhood may activate an epigenetic pathway that prompts the body to live a longer life and to be mentally agile in old age, in order to guide younger kin to stave off hunger and danger when the need arises. This is justified from an evolutionary point of view, whether such a thing exists in the physiology of the human body is an open question. If it does, it is very likely that we can fool our bodies into activating this pathway, by fasting at the right period of our lives.

There are two problems for testing such a hypothesis. Firstly, providing a systematic review of the causes and outcomes will take a very long time : especially if human tests need to be performed, as opposed to using other mammals as proxies. Secondly, there is no money to be made by such a discovery. No pharmaceutical company will become rich by suggesting that people fast. This is the tragedy of our economy. Our society is structured in such a way that important medical advances are being stunted.

I posed this question on fasting and Alzheimer's disease only as an illustrative example. The medical field is replete with such questions. More specifically, serious questions in psychology cannot be answered easily by simple experiments. Due to the very nature of the human body and its multi-layered physiology, we need to conduct experiments on a very large scale and across large timelines. We simply do not have the scientific apparatus today to do those experiments.

Things get even more depressing when you consider economics. If medicine is concerned with the physiology of a single human body, economics ought to be concerned with the health of whole societies (and whole eco-systems). These are, by definition, even more complex systems. But the trend in economics is to argue for simple theories. Very often, these theories are not even tested. Economists suffer very much from tribal affiliations - with opposing camps refusing to engage in a common dialogue and in a common framework for scientific enquiry. In any case, posing open questions that require long-term inspection is not encouraged in this era of high-frequency trading. So what we have in economics today is a pseudo-science, disguised in a plethora of numbers.

In 1949, the Nobel prize in medicine is awarded for a surgical procedure known as "lobotomy", where the neural connections are cut between the pre-frontal cortex (dealing with rational thinking and cognitive complexity) and the central areas dealing with emotions. This was professed as a cure for mental ailments such as Schizophrenia, but later understood to be a tragic disaster. Before this understanding dawned, many patients were lobotomized and turned into vegetables. The Nobel committee realized this fiasco fairly soon, but I wonder how long it will take them to realize such blunders with the Nobel prize in economics, where entire societies have been lobotomized.

The one hope that I have for the future is that it will be possible to model large complex systems directly from the data, using advanced machine learning. These models will ultimately replace the simplistic models in medicine, psychology, human-machine interaction and economics - with more accurate predictive models. This will take time, but ultimately we will realize the follies of the current age.

1 comment:

Ray Lightning said...

Excellent TED talk by Siddhartha Mukherjee on how to look at the human body as a complex regenerative system: