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Sanger Institute

By Kim - Posted on 18 October 2010

We arrived at ‘The Red Lion’ at Hinxton at 12:10. This was the rendezvous for the various parties to meet, there being a car sharing plan in place. Most had lunch here. It was a little pricy, but the quality was good.

We left the pub at 13:35 and drove to the Sanger Institute in convoy. We later learned that originally we could have walked down the road to the site of the Institute in a couple of minutes. But a Victorian lord had diverted the road to create a private deer park. Today the Institute stands in that park.

We arrived in drizzle at 13:40 and after regrouping we went into reception where Mike made us known. We were ticked off against the security list. They then wanted us to move the cars from the visitor’s car park to the main car park. We quickly worked out that only the drivers needed to go out in the rain for this. In the meantime the two reception staff were asking Mike about Humanism and I slipped a BHA leaflet to both of them.

Our host for the visit was Dr Don Powell, who had given up research to concentrate on public relations. He introduced himself and took us over to another building, which contained a canteen and a lecture room. He gave us a PowerPoint presentation on the institute.

The Sanger Institute employs 900 people. They have 40 principle researchers and have 180 staff with PhDs or are MDs. The Institute is of course named after Fred Sanger, the father of the science of genetics, who celebrated his 92nd birthday this very week. The institute was founded by the Welcome Trust, who continue to finance it. The Trust was once an agency of the Welcome drugs company, but it is now independent, with investments of 15 to 16 billion.

The project to map the Human Genome took 13 years. It was a collaborative effort involving centres in several countries. The Sanger Institute was the leading centre, mapping 30% of the genome. Since the project ended in 2003, techniques have become much faster. They can now map a genome in 13 hours!

There are several projects in process at the moment. One is the cancer genome project. Cancer is a disease of the DNA. The project aims to understand the mutations which lead to cancer and to find drugs to interfere with the process. We were told that there were drugs currently in field trails as a result of the work so far. Another is the fight against malaria. Some human societies have a natural resistance to malaria. If the reason for this can be found it could lead to new drugs to cure or prevent the disease.

Members of the group were asking too many questions and time was pressing. So Don handed over to Dr Chris Tyler-Smith, who had the interesting job title of Human Evolutionary Geneticist. Chris appeared as a slight eccentric with long hair, beard, and flip-flops.

Chris’ presentation was fascinating, looking at the development of humanity and its migration across the planet. “Humans are unusual great apes”, he said, putting up a family tree of the great apes, of which the hominids, the family from which we are descended, formed one branch. Specifically there are 2 species of Orang-utan in the world today, 3 species of gorilla (some zoologists claim 4), 4 species of chimpanzees and bonobos, and one species of human being.

There are stark differences between humans and the other great apes. The apes tend to live in isolated pockets, all of which lie in the tropics. Human beings occupy the whole planet. The maximum population of any of the other great apes is naturally around 100,000 individuals. Human beings number 6 billion.

Interestingly, humans have the lowest genetic variation, that is to say the degree by which the genetic code of one individual can differ for another. For example, peas have a genetic variation of 1.3%, flies 1.2%, fish 0.5%, orang-utans 0.4%, gorillas 0.15% and humans 0.1%. This implies that human beings are a very young species.

Going back to the hominids. The earliest fossils which have been identified are 6 to 7 million years old. This is the time at which the chimp / hominid split occurred and they are our earliest direct ancestors.

From that time to the present day some dozen hominid species have evolved and died out. This was not a linear process, often more than one hominid species lived at the same time. Until 2 million years ago, all of the hominids lived in Africa. All the evidence, genetic, archaeological and fossil, all agrees on this African origin. We are all Africans therefore.

Homo Sapiens, us, are a mere 0.2 million years old. In fact, the earliest evidence of our ancestors, in Ethiopia, dates from 195,000 years ago.

The earliest archaeological evidence of modern human behaviour is 100,000 old. Behaviour is not reflected in the genes; this has to be archaeological evidence.

By examining the genomes of native populations their genetic diversity can be found. This project is still going on, with the eventual aim of mapping the genomes of 2,500 native peoples from across the world.

Initial results already allow us to map our spread out of Africa. Genetic diversity decreases according to distance from East Africa, indicating fewer individuals being the founders of the native populations the further from Africa one travels.

The migration of modern humans began from 50,000 to 60,000 years ago. We reached Australia 50,000 years ago, Europe 40,000 years ago, and Central Asia 39,000 years ago. America was not reached until a recent 25,000 to 15,000 years ago. America was reached by the land bridge that existed over what is now the Bering Strait.

Going back to hominids generally. There were three waves of migration from Africa, of which modern humans were the last. Neanderthals evolved from one hominid species which moved out of Africa. Neanderthals did not themselves come from Africa, and they are only found in Europe and Western Asia. Some DNA has been recovered from Neanderthal remains. This has been enough to determine that there was no interbreeding between Neanderthals and modern humans. So whatever else may have happened to them, they did not merge with us.

One other stark difference between modern humans and the great apes is the use of language. There are already clues as to what might be the genetic mutation that lead to speech. It seems that once that mutation was made, it became positively selected for by evolution. Male pattern baldness is another such trait that has apparently conferred evolutionary advantage, but nobody asked for details and we left scratching our (in some cases bald) heads about that one.

Chris ended his presentation with a photo of his team. Somebody observed that he seemed to be wearing the very same flip flops in the photo! He confessed that he had been in the habit of buying his flip flops from Woolworths in Saffron Walden. “I bought six pairs just before they closed”.

There was now a coffee break. Tea, coffee, Kitkats. We were introduced to Steve Scott, who would show us the sequencing machines. A rain shower and the need to change buildings delayed us a little. We stopped by one of the computer rooms on the way.

The institute has three computer rooms in use and one as a spare for future use. Three rooms give resilience. The amount of data being generated is immense. They need storage, not processing power, so there are no supercomputers here. Instead they use racks of ‘blade servers’, stripped down but powerful PCs mounted in dense arrays, 120 or so to a rack. Their storage is measured in petabytes. A petabyte is 10 to the fifteenth power, or one thousand million million characters.

In addition to storing the data being generated by the automated sequencing machines, there are websites to maintain. The Institute is not a company operating for profit. All of their findings are made available on their websites for researchers worldwide to make use of and the public to view.

In one of the sequencing buildings we passed a printout of part of the human X chromosome hanging in the lobby. Genes are represented by the letters A, C, G and T. A genome consists of these letters, one after another. There are 13 billion letters required to represent a human being. The small X chromosome needs 1.3 million letters to describe it. The printout we were looking at, the text smaller than in this newsletter, was 1 metre wide by 7 metres high. It would take 115 such sheets to print the whole X chromosome. The entire human genome would require 2,226 such sheets.

Finally we were issued with laboratory coats and taken into one of the sequencing rooms. Here rows and rows of machines were working, 24 hours a day, to sequence DNA. They don’t do it once, they do it over 100 times now to be sure they have it right. We were shown the ‘old’ machines, then the ‘new’ machines, which are many times faster, scanning glass slides containing the biological material. Each slide contains a grid, each square of which has to be checked. They did not go into details, too complex for our short visit, but the next generation of machines was already on the way, able to scan a complete slide (both sides) rather than having to work cell by cell.

Charles had smuggled his camera in and we asked if we could have a picture of us in our coats. Don said yes. In fact ,we were free to take any pictures we liked. I kicked myself. I was so sure that photos that would not be allowed that I had left my camera in the car and not even bothered to ask!

That was that. It was just a case of being taken back to reception, thanking our hosts and getting ready to depart. We took a group photo outside the complex, although some had already slipped away by then. A fascinating afternoon. A big thank you to the Sanger Institute for hosting us and for making such senior staff available to speak to us.

I’m now researching what I need to do to become a human evolutionary geneticist. I don’t think the flip-flops are compulsory.

(Written by Kim Northwood)



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