One complains the other is ruthless and avaricious; the other accuses its rival of bureaucracy and inefficiency. Like two warring siblings, in some ways they rely on each other, in others, well, they just get in each other’s way.
The mapping of the human genome is the perfect illustration of this conflict.
The idea of mapping the human genome was born in the US, in the mid 1980s. It was an ambitious proposal, to sequence the entire 3 billion DNA bases that make up the human genome and find all the genes contained therein. In fact, some thought it was impossible.
But imagine the possible benefits, advocates argued. What good could be done if we knew in detail the structure, organization and function of the genome?
How could it be done? Why, the same way you’d eat an elephant. A little bit at a time.
Using little bits of chopped-up DNA and using littler genomes. What if they started with sequencing a yeast genome, and a worm’s. That would be excellent practice for the greater task.
As the seed of the idea grew, funding was sought. In the U.S, the National Institutes of Health and the Department of Energy lent their support. James Watson, a founding father of the new genomic landscape, came on board and gave the wacky idea significant credibility.
The project had big ideas; it welcomed collaborators from all over the world. After all, it wasn’t simply the ‘American’ genome that would be sequenced; the human genome belonged to us all.
Shouldn’t we all strive to understand our shared molecular heritage? The UK was next to come on board, with the Medical Research Council pledging £11 million to the cause. Other countries followed suit; Japan, China, France and Germany joined the US and the UK in forming the initial HGP team (known as the International Human Genome Sequencing Consortium). 1
The work was divided up between 20 institutions in these countries and a total of $3 billion of public funds was poured into the project.
The Human Genome Project (HGP) officially launched in 1990 with the aim of completing the work within 15 years. One of its express principles was that of publishing the sequencing information entirely freely within 24 hours of its completion.
This would mean that scientists from whatever background – whether in academia or in industry, could benefit rapidly from their findings.
Such lofty goals; such a beautiful example of cross-cultural co-operation. The HGP was like the Benetton advert of science.
The Consortium’s public sector harmony, however, did not go down well with everyone.
Opposition came in 1998, in the form of Craig Venter, scientist and founder of what was to become Celera Genomics. He was unimpressed by the work of the HGP.
Why was it taking so long, he asked? Why was it using so much public money?
He could do the same job quicker and cheaper. And he planned to patent up to 6000 genes before releasing their sequences. Venter’s aims and values were, let’s say “different”, to those of the HGP.
The best part? Venter proposed to sequence and assemble the entire human genome in just three years, finishing in 2001.
However, the HGP was already considering accelerating its work, and with increased funding, they were able to. The race was on.
But how was Venter able to be so confident that he could yield results so quickly? It was all down to his approach. The HGP used a technique called ‘hierarchical shotgun sequencing.’
This involved breaking DNA down into overlapping fragments of around 150,000 base pairs. Each fragment was inserted inside a bacterial artificial chromosome (BAC) and cloned.
It was then possible to see where the fragments overlapped without knowing the actual sequence. The overlapping sections were then used as a guide to create a contiguous map.
This process alone took six years. After that, Sanger sequencing was used to sequence each cloned fragment.
This approach, though rigorous and time-consuming, minimized the chances of misassembly, which was a real risk as the human genome has so many repetitive sections.
Venter, on the other hand, planned to use a strategy called ‘whole genome shotgun sequencing.’ This effectively skipped the mapping and cloning phase entirely.
Instead, the DNA was broken into fragments of varying sizes and sequenced directly. The assembly was done by finding regions of overlap between the sequenced fragments.
From the moment Celera was a contender, both groups worked furiously, sequencing and assembling all over the world. Initial hopes for a collaboration between the two groups quickly faded as Celera insisted that data would have to be locked away for five years.
Talks were abandoned. There was a fair amount of public mudslinging. One cried ‘vanity,’ the other, ‘red tape.’ Public versus private. You know how it goes.
However, in 2000, the Consortium faced governmental pressure to resolve their conflict with Venter. Some suggested that the upcoming US presidential election encouraged the calls for a happy resolution.
After all, it was becoming embarrassing: what should have been celebrated as one of humankind’s greatest achievements was descending into a huge row.
Eventually, on 26 June 2000 at a White House Gala, it was announced that both sides had completed their own working draft of the human genome sequence and would work together to publish soon. The race would be a three-legged one for the final leg. Détente was declared.
In February 2001, both groups published their findings simultaneously. Working drafts of over 90% of the human genome were now available. The HGP had delivered its major aim four years ahead of schedule.
The race had ended in a tie.
Did the competition change the outcome, or would the HGP have been on track to finish early anyway? Was it the collaborative approach itself that accelerated the pace of research, rather than any private sector interference? It’s impossible to know.
What is clear, however, is that the HGP laid the groundwork for many important discoveries; the identification of disease-causing genes as well as advances in sequencing technologies. As Francis Collins, the director of National Human Genome Research Institute noted in 2001, the genome can be thought of as a book with multiple uses: “It’s a history book - a narrative of the journey of our species through time. It’s a shop manual, with an incredibly detailed blueprint for building every human cell.
And it’s a transformative textbook of medicine, with insights that will give health care providers immense new powers to treat, prevent and cure disease.”2
Nonetheless, one thing seems certain. While the Consortium’s collaborative, data-sharing approach was unusual and inspiring, the human drive to compete is with us to stay. And those arguing siblings, Private and Public will probably never willingly embrace - unless Mother tells them to.
Source:- Futurelearn.com
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