‘The wondrous map’: how unlocking human DNA changed the course of science
Twenty years ago this week, an international group of scientists announced it had put together the first genetic blueprint of a human being. After 10 years of effort, the team – made up of thousands of scientists working on both sides of the Atlantic – revealed it had pinpointed all 3bn units of DNA that make up the human genome.
The result was “the most wondrous map ever created by humankind”, US President Bill Clinton told a special White House ceremony to mark the event. A parallel event, hosted by Tony Blair in Downing Street, also featured glittering praise for the effort.
The $2.7bn (£2.2bn) Human Genome Project remains one of science’s greatest feats of investigation. It was described, at the time, as biology’s answer to the Apollo space programme. It took researchers on a very different journey – not of outward exploration, but an inward voyage: a mission to unravel the molecular essence of humanity.
Armed with the resulting “wondrous map”, scientists would soon, it was assumed, isolate the genes for height, eye colour, intelligence and myriad other human attributes. However, this simple goal has been confounded by the fact that a great many individual human attributes are determined by dozens, if not hundreds of genes. We are too complex for reductionism.
Nevertheless, the biological revolution let loose on 25 June 2000 has had remarkable results. The draft genome published that day was later followed up with more and more accurate “maps” of our DNA until the project was officially closed in 2003 with publication of a final, full human genome. Ever since, gene sequence studies set up in the project’s wake have been involved in growing numbers of remarkable discoveries.
For example, DNA studies have shown our species once mated with Neanderthals while other projects have pinpointed mutated genes that cause cancers and melanomas. Others have helped to develop new drugs for conditions ranging from cystic fibrosis to asthma.
These successes have been achieved because gene sequencing, over the decades, has become a highly automated and incredibly cheap process. “It took a decade of intense effort to create that first rough draft of a human genome,” said Cordelia Langford, of the Wellcome Sanger Institute, near Cambridge, where UK scientists played a prime role in Britain’s involvement in the Human Genome Project. “Today, we sequence around 3,000 full genomes a week. It has become a simple, straightforward process.”
Not all these genomes belong to humans. Some belong to other animals and others to our mortal enemies – such as the organisms responsible for malaria and cholera, a list of foes that has now been expanded to include Sars-Cov-2, the virus that causes Covid-19. Sequencing its tiny genome is now providing doctors and public authorities with critically important information about the disease.
“We are sequencing samples of SarsCov-2 from different sources to see if the virus is mutating significantly,” said Dominic Kwiatkowski, director of the Centre for Genomics and Global Health at Oxford university. “The jury is still out on that. However, we are also using sequencing technology to highlight tiny variations in samples from different places, and that should help us pinpoint the locations of new outbreaks.”
A very different use of sequencing technology is being pursued by Sarah Teichmann, leader of the Human Cell Atlas project. “Devices are now so sensitive that we can analyse DNA from a single cell and at the same time compare our findings with DNA from millions of other comparable cells,” she said.
That data tells researchers what the cells in our bodies are doing at a very high resolution and at a specific time, information that has led to the discovery of many new types of cells, many in the immune system and others in the body’s various tissues.
“This work has triggered a major revolution in understanding our bodies’ cells and their organisation in tissue and organs,” said Teichmann, who is also based at the Wellcome Sanger Institute. “By comparing healthy tissue with diseased tissue in this way, we are getting incredible new insights into the mechanisms of those diseases. This is a very powerful technique.”
Such insights have included pinpointing cells involved in the development of cystic fibrosis, asthma and certain human tumours. The discoveries have opened up the prospect of developing therapies for these conditions.
The Human Genome Project is clearly having a big impact on medicine and research, but its progress was not without controversy during the course of its work, which began in 1990. “We were in a race. It was as simple as that,” said Langford, who is now the Sanger’s director of science operation but who worked as a research assistant during the project’s early days. “We were out to stop people from putting patents on human DNA that was being sequenced elsewhere.”
At the time, a rival outfit to the Human Genome Project – known as Celera – had been set up with the maverick researcher Craig Venter as its head. “They wanted to put patents on the DNA they were uncovering. We wanted to make sure everyone could use the data and were putting every sequence we found into the public domain to block any attempt to privatise the genome. And in the end we succeeded.”
DNA studies have helped to develop new drugs for conditions ranging from cystic fibrosis to asthma