Book Synnopsis: Neanderthal man, In Search of Lost Genome

As the technology proceeds at a very fast pace, full genome or DNA sequencing is becoming increasingly accessible, and in few decades, it will be a common thing for all individuals. Not only alive humans or animals, sequencing has become vital tool to analyze our genetic history and answering questions about evolution. Few decades ago, discovery of the fossils of Dinosaurs had generated huge interest worldwide. Am sure the question goes through many people's mind: Is it possible to sequence the DNA of dinosaurs, and hence possible to clone them in future in a lab at a future date?

In March, I went to a small party at my previous share house, and had a short discussion with Rick Bowen, who told me about an exciting news: 'Blood samples of dinosaurs have been discovered at a fossil site'. Though I didn't know much about these things, it seemed quite incredulous to me, as survival of blood samples for such a long time didn't look correct. Reading the news article, it did say that red blood cells from dinosaurs 75 million years old have been discovered.

Few days later, I went to Umeda Book store, as there was a sale going on for foreign language books. Accidentally, I saw the book: 'Neanderthal Man: In search of Lost Genome'. With part trepidation and part enthusiasm, I bought a copy of the book. Next week, I was traveling to India. Not only due to the long travel hours, but because of its fantastic writing style, the book became a memorable read for me. I will try to recollect my impressions from the book.

The Book
Written by Svante Paabo, a Palentologist and Group Director at the Max Planck Institute of Germany, the book presents a fascinating account of his research work of last 30 years. His journey in the field of ancient genomes started from his PhD days, where apart from his lab work, he started pursuing extracting the DNA materials from Egyptian Mummies as his hidden project! The mummy extracts were obtained from a museum curator in East Germany. He actually showed that DNA material can be obtained from the Mummy, and his work led to a single author publication in the prestigious journal Nature! This led him to being invited to give talks at the Cold Spring harbor seminars, and he moved to an American university for his post doctoral fellowship. Subsequently, he moved to East Germany after few years to start his independent lab.

Challenging aspects of Ancient DNA
Why is extracting the ancient DNA challenging? There are two major problems in this.

• The first problem is, DNA are long chained molecules which replicate, and acquire mutation or error in this process. But error correction mechanisms remove the error most of the time, but this process consumes energy. But after death, the cells of the body dont get any more energy supply, and start to decompose, leading to breakdown of the biomolecules. Thus, the cells, DNA, RNA, proteins all start to break into small components, and get fragmented. Presence of humidity aids this process. 
• The second problem is contamination with genetic material of other species. Suppose some ancient genetic material has been obtained. But the genetic material is so abundant in our environment, that the ancient samples may easily get contaminated with other materials, and may lead to erroneous conclusions, if sufficient attention is not paid to it.

The book talks about how the research group of Svante solved the above two problems, and established protocols for reliable extraction of ancient DNA. Svante discusses the following things in this context:

Obtaining Ancient DNA: If some genetic material, for example some cellular extracts, is located in a cavity, or an interior cave which protects it from humidity, then some extracts of identifiable genetic material can be found. Using identification and purification techniques of cloning, these extracts can be multiplied by many order of magnitudes, and can be used for sequencing. The author mentions that even with ideal conditions, ancients DNA cannot survive beyond 10 million years. He also mocked some results published in Science, which claimed to sequence the genetic material of about 75-80 million years old.

Preventing the contamination: Svante established two clean rooms in his lab, where one must wear full body gear to enter, and the work could be done only after first arrival in the lab, and not after lurking around other parts of the lab. He also established the protocol that before sequencing the DNA, first empty labels should be shown to be free of any contamination.

Based on the above two principles, his group has been able to discover a significant number of important results and insights. The major topics and results discussed in the book are the following:

• Sequencing the Neanderthal Mitochondrial DNA in 1997
• Sequencing the Neanderthal Genome: Full DNA Sequencing in 2008
• Sequencing the DNA of Ice-man, 20,000 years old
• Sequencing the DNA from finger remains of a new species: Denisovans, about 2010
• Comparing DNA sequence of neanderthals, humans and apes to analyze why humans gained superior ability

Starting his career, Svante was motivated by the question of sequencing the DNA of Neanderthal Man, and shed light on the evolutionary tale of humans. He devoted his energy towards this, and obtained DNA samples from museums, which allowed them samples of size 5x5 cms. In 1993, they started by focusing on the mitochondrial DNA, which is acquired through the maternal side and is mostly unchanged across generations. Using a sequence of length 300 nucleotide, they were able to identify the mitochondrial DNA of the Neanderthals, and they compared it with humans. The result was published in the journal Cell.

Their group kept on upgrading their methods, and around 2005, they found ways to purify and amplify DNA samples 20 times as compared to their methods in 1997. This led them to ambitiously try sequencing the full DNA sequence of the neanderthals, in which they were generously supported by an extraordinarily large grant from the Max Plank institute. With breakneck speed, they completed this work and let the world have a peek at the DNA sequence of our most close ancestors! The fossil remains were about 3-4 million years old.

Using their method, they did many few other interesting works, like sequencing the DNA of ice-man, who was found buried in ice for last 20,000 years. On the evolutionary scale, this is quite recent, and they found difference in just one place in a sequence length of about 40 if I remember it right. They also analyzed a sample of finger tips, and showed that instead of neanderthals, it belonged to another species, subsequently called the Denisovans. It was the first time that instead of fossils, DNA sequencing led to the discovery of a new species.

Difference between Apes and Humans, and why copying is not that bad!
Based on the differences between apes and humans, and comparing with other psychological studies, a partial answer to a very interesting question comes to light. Why did humans became so powerful, and which genetic mutation enabled them?

Some scientists analyzed the differences between apes and humans, by comparing the growth of their babies, and saw two differences. First, they saw that even if ape babies are put in human families, have access to language and spoken words, they cannot develop the ability of language beyond 3-4 elementary words. Another interesting difference they saw was, the development of ape and human babies is similar till about 1 year. But after that, human babies develop the habit of copying the actions of nearby people, which apes cannot do! This ability to copy others, and thus learn from others, is one of the foundations of learning, education, and hence civilization. Thus a mutation, which enabled us to copy others could be the reason for humans becoming so powerful!

One funny aspect of this book is the author keeps on criticizing the two journals, Nature and Science, calling them hungry for publicity and tending to publish work just to gather attention. At the same time, they keep on publishing in these two journals by scores!

On a personal note, the book is very honest and candid. The author talks about many personal aspects, like his lab meetings, heated discussions and freedom in group meetings, need of young scientists to publish in the competitive world of science, intense competition and rivalry between different labs and groups etc. He also accepts his affair with the wife of a colleague, where the lady was his old post doctoral friend, and they subsequently marry each other. The book was like a thriller and a provocative read.

Postscript: Even more powerful ways to extract ancient DNA
In May, I googled for new results from the Paabo group, and it took my breath away. The author with one of his students have taken ancient DNA extraction to another level, by purifying and extracting such DNAs from a handful of dust of the ancient caves. That is, they purify dirt and dust, and look for lingering pieces of very small amount of DNA in them. This would totally change the approach in paleontology, and should lead to remarkable and diverse discovery in the future.

So the casual discussion on dinosaur blood samples, and a serendipitous encounter in a book store led to an enthralling read, one of its kind. Grab a copy of it, if you have sufficient time and leisure!