Sunday, February 16, 2014

Neanderthal Man by Svante Paabo - Book Review

With the completion of the full human genome sequence in 2003 and the rapid fall in DNA sequencing costs over the subsequent 10 years, we have been awaiting major advancements in many fields such as Healthcare, Agriculture, Drug Discovery and so on. However, the progress has been slow and the deluge of genome sequence data has been a tough problem to handle.

But, Svante Paabo in this fascinating book on the 'Neanderthal Man' shows how the new technologies have enabled him to sequence the genomes of our extinct relatives - the Neanderthals and the Denisovans. The data proves how our ancestors moved out of Africa about 50,000 years back and interbred to a small extent (2 to 7% of our genes come from them) with the Neanderthals and Denisovans and maybe drove them to extinction. Many interesting facts come out of these studies such as, (a) that gene flow seems to have been from the Neanderthals to us (and not the other way), (b) the founding population of the Neanderthals also seems to have pretty small like in the case of the humans (c) we split from the Neanderthals about 500,000 years back (d) the Denisovans split about 1 million years back (e) the Denisovans seem to be closer to the Neanderthals than to humans, and much more...

The book is not only fun to read, but Paabo detective mode of story telling will also keep the reader focused. By mixing his personal stories with scientific research, Paabo provides a refreshing frankness to the narrative. We get a direct view of the challenges in scientific research and how the role of institutional support and adequate funding can make research a success. Paabo's journey from Egyptian mummies to Mammoths, to Sloths and finally the Neanderthals and Denisovans is a great inspiration to all students of science. He shows how passion, perseverance, attention to detail, and collaboration can deliver results not only in Science but in all aspects of life.

Paabo explains the Science very clearly and the narrative shows us how he has become the world's expert in 'ancient DNA'. But in order to do that he often has to go into intricate details of lab work which some readers might find difficult to follow. Still it will not affect the story and if you are interested to learn how we became what we are, this is a book that you should not miss.

Tuesday, February 11, 2014

Healthcare - Dramatic Changes ahead!

(This has been published in Future Medicine Magazine -

The era of personalized medicine has arrived with the developments in genomics studies. But the studies have stumbled on obstacles like the amazing complexity of genomics data, slowing down its progress

With the full sequencing of the human genome in 2003 and the drastic fall of DNA sequencing costs in the last decade, there were great expectations in the scientific community as well as in the public’s mind that the heath care sector would see dramatic changes. The era of personalized medicine seemed to have arrived heralding individualized treatment regimes based on a person’s genome. However neither has this expectation been met nor has the practice of medicine changed significantly, yet.

What happened? Why did the Science fail to deliver?

The main reason for the seeming lack of progress has been the amazing complexity that the genomic data presented.  Every step forward seemed to open up more avenues than scientists could explore and it soon became clear that it would take decades of effort to understand what it took Nature millions of years to evolve. The first revelation was rather surprising – contrary to the initial expectation that the human genome would contain about 80 to 100,000 genes, there were only about 20,000 genes to do the job. Not only that, many plant genomes were bigger and more complex than the human genome and hence bigger did not mean better! More surprising revelations were on the way - decoding the gene sequences were shedding very little light on diseases or even traits. Even characteristics that looked genetically straightforward like ‘height’ could not be pinned down on specific genes. The non coding regions of the genome - what was considered once as ‘junk DNA’ – was playing an important part in regulating gene activity.  Other factors such as environment, food and even stress level were playing a major role.   Further, the importance of epigenetics (heritable, chemical modifications to the genome that would affect the function without changing the sequence) and the microbiome (the microbial cells in the human body that not only number about 10 times more than the human cells, but also play a significant role in digestion and immunity) was sufficient proof that the belief that the genomic data was the entire and only blueprint for the development of the organism was naïve at best.

At the same time, what we could understand of the genome offered tantalizing glimpses into our past, present and future health. The genomic data proved beyond doubt the origin of humans in Africa and we could now trace our migratory path over the rest of the earth in the last 60,000 years. During this migratory journey our species did breed to a minor extent with other homo species like Neanderthals and Denisovans (and maybe others as well), acquiring 5 to 8% of their genes.  As we split into different ethnicities in different regions, the climate, food and other environmental pressures led to different groups acquiring different genetics mutations leading to changes in appearance as well as different capabilities like lactose tolerance, disease immunity and so on.  We could now understand why many drugs create adverse reactions in some and why we react so differently to various disease causing pathogens. Genes causing over 6000  rare inherited diseases have now been identified.  We have been able to pinpoint specific genetic mutations that lead to cancer in about 35 to 40 % of the cases.  A number of drugs that can treat these cancers have been released and many more are on their way. Genes that play a major role in cardiovascular diseases, diabetes etc. have been identified and we are on the path to reaching the dream of predictive and personalized medicine.

What more should be done?

While there is no doubt that we are moving in the right direction, we still need a considerable amount of genomic studies across the world.  Surprisingly, it has been a recent realization that India is a treasure trove for genomics. Over the last 2000 years, unknowingly, India has been the home to the largest genomic experiment in human history. Due to religion, caste and geography, the Indian population has been split to over 4500 groups and till recently has been strictly breeding within the groups. This has created unique genetic mutations that when co-related with susceptibility to diseases can lead to major discoveries. India also suffers from a higher burden of inherited diseases due to inbreeding and consanguinity and thus a better understanding of the genome can lead to proper treatment and cure. Counseling and carrier testing of couples can significantly reduce the occurrence of many inherited diseases thus reducing the burden on the family as well as the society.

India is also home to traditional systems of medicine like Ayurveda which promoted ‘personalized’ medicine 3000 years ago. However, the science was very basic at that time and hence there was no clear understanding of why the herbal medicines or treatment practices worked. Now, if we can combine the genomic understanding with traditional practices and conduct extensive studies across our population, we would be able to make a difference in the healthcare sector by providing solutions in a cost effective manner.

Friday, February 7, 2014

Our Mathematical Universe by Max Tegmark - Book Review

Welcome to Nerd land - Our Universe is a Mathematical Structure!

 I have never been a great fan of Mathematics though I had been always been fascinated with Science. But I often had the foreboding that Mathematics is not only the foundation of everything but is also the only thing that is completely independent of us and our Universe. Now in this thrilling book, Max Tedmark tries to prove that our Universe is just a mathematical structure (though we do not know the equation) and that there will be as many Universes as there are viable Mathematic structures!

Going beyond parallel universes and multiverses, Max takes us through a fascinating journey to the Level 4 of the Mathematical Universe Hypothesis (MUH) in order to understand the ultimate reality of everything. In this journey you will learn a lot of cosmology, physics and maths and Max’s style of storytelling will keep you engrossed throughout. The book can be divided into three parts, with the first one addressing  “How big is everything” – from planets to galaxies and Level 1 multiverse to Level IV multiverse. The second part addresses “What is everything made of” – from elementary particles to mathematical structures. And then in the third part, Max brings us to his conclusion that the answers to the first two questions lead to mathematics as the basis of reality.

One good thing about the book is the summary at the end of each chapter which Max calls ‘Bottom Line’.  While going through such tough concepts as cosmological inflation, cosmic microwave background, galaxy clustering, dark matter, dark energy, the horizon problem, the flatness problem, level 1 to level IV of parallel universes (and the evidence for each), particle physics, why randomness is an illusion, decoherence,  and various aspects of reality, it is great to have a brief summary at the end of each chapter that highlights the important points.

Max’s writing style is very simple and conversational and his ability to mix his personal learning from childhood onwards and the occasional anecdotes makes the book a pleasure to read. But I found it difficult to buy into all the conclusions that the hypothesis leads Max to, especially the need for a parallel universe for every decision branch of every individual!  However since he starts from the basic principles and builds up his case explaining the assumptions made at each level and the counter points to his arguments, it is a great example of not only how science should be practiced but also how it should be taught.

The concluding chapter is a call to action. Instead of just remaining in the exalted pedestal of  a scientific researcher, Max takes the plunge of becoming an activist and bringing the learning to influence the path society should take. The analogy of Earth as a spaceship with limited resources and in a challenging environment (which can often turn hostile) is very apt. I found his suggestions of managing this spaceship and its inhabitants very positive and admirable and I hope this book will influence a large number of people.