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“From then on, it was daggers drawn…”: Michael Morgan on a decade of the human genome

24 Jun, 2010
Michael Morgan

Dr Michael Morgan

On June 26 2000, Bill Clinton stood in the White House and, with Tony Blair on a screen via videolink behind him, he announced that the working draft of the human genome sequence had been completed. This day was the culmination of many years of scientific and political effort, discussions and disagreements.

Ten years on, I caught up with Dr Michael Morgan, a former Programme Director at the Trust and former Chief Executive of the Wellcome Trust Genome Campus.

Dr Morgan played a major role in developing the Trust’s involvement in genetics in the 1980s, 90s and beyond. He told me of his memories of the sequencing effort, the birth of the Sanger Centre, and falling out with Craig Venter.

When did genetics become a significant part of your work?

Sometime in the late 1980s it was becoming apparent that, one way or another, genetics was infiltrating all areas of research that the Trust supported. We didn’t have any mechanism to ensure that grant applications containing a significant genetic component were properly appraised. We decided against setting up a genetics funding panel, as genetics was a tool rather than a discipline. Instead we set up a genetics advisory group with representatives from other funding panels on it. Looking back, we had a number of genetics luminaries, including James Watson and Peter Goodfellow.

Around this time, the genetics field was making a move from sequencing DNA manually to using machines. I remember a lot of scepticism about whether machines would be as good as humans at sequencing – it’s amazing to recall.

How did the Trust’s involvement in genetics grow?

John Sulston [who would become the first Director of the Sanger Institute] was leading the Drosophila [fruit fly] sequencing programme at the MRC Laboratory of Molecular Biology (LMB), Cambridge. He’d been approached to set up a human genome project in the private sector in the United States. To try and keep John in the UK, the Trust entered into a partnership with the MRC, with a view to setting up a joint project at a joint institute. The big question then was where to set it up.

How was a location for the facility chosen?

We essentially toured the countryside. One site that sticks in my mind is a chicken farm, where John and I discussed putting sequencers in the coops! Eventually John found an abandoned scientific site at Hinxton Hall. The idea was to build a temporary facility, as no one at that time thought this was going to be a big deal. John submitted a grant application to set up a sequencing facility on the site, and subsequently, in 1992, the Trust made its biggest grant up to that point, of £46.5 million. The Sanger Centre was born.

How did the Centre develop?

Originally we took out a two-year lease on the facility from the owners, but it soon became clear that we weren’t going to sequence the human genome in two years. A case was put to the Wellcome Trust’s Governors to purchase the site. What’s important to remember is that the Trust had never owned a research institute to that point – the initial plans were to get the sequencing facility housed by a university. However, it became very obvious to me that to get it up and running in a short period of time, then the Trust had to buy the site.

It’s hard to get into the mindset now of the early days, when there were sincere discussions about whether sequencing the entire human genome was actually feasible. People were looking for reasons it would fail. I remember one dinner for Wellcome Trust Governors and senior managers where I was interrogated about whether they were building a white elephant at Hinxton. Going ahead was, for me, the bravest decision the Governors had ever made.

How did the European Bioinformatics Institute become part of it?

Around the same time as the Sanger Centre was being founded, there were discussions in Europe about setting up a biological computing facility. Hinxton was put forward as a potential location for this, and, in 1992, it was chosen to house the European Bioinformatics Institute. In 1994, the MRC transferred its Human Genome Mapping Project Resource Centre from Northwick Park to the site. The rest is history.

The Wellcome Trust Genome Campus, as it became, was very viable, very early on. If you go to Hinxton now, you would assume it’s something that was planned. In essence, it was serendipity – grasping something that happened to all fit together.

What happened next?

Once the facilities were established, John [Sulston]’s focus fell on how we were actually going to tackle the human genome. We planned to get everyone together and see what we could hatch – that was the first Bermuda meeting in 1996. The ground rules were set out, including what I think is one of the most unexpected outcomes of the human genome project, the data release policy.

I was a biochemist by training and my favourite organism was E. coli. When I first came to the Trust and started working with the human genome community I found it astonishing how reluctant the community was to share information – and many still are. It wasn’t obvious to a number of people who would be working on the sequencing activities that it should be open access.

How did people respond to the call for data sharing?

John [Sulston] and Bob [Waterston] had the most experience in large-scale sequencing at the time and were held in such high esteem that the resistance to data sharing at the first Bermuda meeting was easy – well, not exactly easy – but possible to overcome. The project wouldn’t have been the same without that.

There were some fights at the meeting though. Craig Venter was there and totally against the data sharing, but he did agree eventually. We tape recorded that meeting, but no one knows where the tapes are!

How did you find out about Craig Venter founding Celera Genomics?

In 1998, the Trust was going through a planning application to extend the Genome Campus and I was often in a taxi going between the Trust’s HQ and the barristers’ chambers. One day I got a phone call from Jim [James] Watson alerting me that Craig was up to something. On the following Monday, a press release was issued, detailing the formation of Celera Genomics.

The timing of this was interesting, as John Sulston – keen to have the funds to sequence a third of the human genome outside of the USA – had submitted an application to the Trust. So, coincidentally, as Craig Venter was calling for the public sequencing effort to abandon the human sequence and stick to the mouse, the Trust had been reviewing John’s application, which they agreed to fund.

John and I flew to the genome meeting underway at Cold Spring Harbor Laboratory, and when we arrived everyone was in turmoil. I read a statement that we’d prepared, which announced the increased funding to Sanger. It also said that while we were aware of developments in the private sector, we felt that the human sequence had to be in the public domain. If our colleagues were unable to do that then we’d take on the burden to do it ourselves. The reaction was great and the whole mood turned around. From then on, it was daggers drawn! The situation with Celera became extremely interesting over the next few years.

What was it about Celera’s formation that was so divisive?

The funny thing was that there were a number of other companies that were sequencing human DNA then, but a key difference between them and Venter’s company was that they weren’t undermining the public programme. There was no problem as such in him setting up the company, but he set out to rubbish the public effort, which no one really enjoyed. It can’t be denied though that the pressure from Celera pushed everybody and was a major incentive to get the job done.

Were any attempts to work with Celera made after that?

There were a number of abortive negotiations between the pubic programme and Celera. However, Celera’s insistence on keeping the data private always led to the talks breaking down. In the end I was banned from the negotiating team as Craig Venter refused to sit opposite me. Why? I suppose I was too belligerent and absolute; neither John nor I were prepared to shift on the data sharing issue.

Were you always convinced of the value of the sequencing the human genome?

Yes, although I wasn’t always convinced that the cost justified it. There were moments of doubt, but John [Sulston] was a tremendous advocate. People like him, Bob Waterston, Eric Lander, Maynard Olson and Francis Collins were true visionaries and could really see how important this was.

How does it feel 10 years on from the announcement?

There’s been a whole revolution in new sequencing technologies since, which are changing the face of the science. Working on the sequence seemed very, very important at the time, but this revolution does put it into perspective somewhat. That’s not to take anything away from the project: it was groundbreaking and one of the most exciting times of my life. What felt momentous was getting the genome sequenced. You can only produce the first sequence once, and it will be there forever.

Image credit: Michael Morgan
3 Comments leave one →
  1. Nadiye Morgan permalink
    12 Jul, 2010 8:35 pm

    Well done Dad! xx

Trackbacks

  1. Happy Birthday human genome (sequence) « Wellcome Trust Blog
  2. 75th stories: Sir John Sulston and the Human Genome Project « Wellcome Trust Blog

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