Friday, September 22, 2006

Interview with Richard Jefferson

Today I am publishing an interview with Richard Jefferson, founder and CEO of CAMBIA, and advocate for the Biological Open Source Movement. This is number nine of The Basement Interviews.

The first part of the introduction is being published here on my blog. The interview itself, including the full introduction, is available as a downloadable PDF file (see below for details). The interview is being published under a Creative Commons licence.

The Basement Interviews
Biological Open Source

Richard Jefferson, founder and CEO of CAMBIA, and leading light of the Biological Open Source Movement, talks to Richard Poynder

Richard Jefferson was born in California in 1956, the son of music promoter and producer Carl Jefferson. His mother, Hermeline, was a stage actress turned librarian.

Jefferson's parents divorced before he was born, so he and his two siblings lived with their mother in a single-parent household. As they were "financially challenged", says Jefferson, all the children had to pull their weight, and there were few treats. "I worked as a 4 am to 8 am paperboy most of my childhood. We never even had a family holiday — not one — and almost all my clothes were from 'goodwill' or Salvation Army."

After a brief period in what he refers to as "a pretty feeble Catholic elementary school", Jefferson entered the public school system, where he was put into a programme for "mentally gifted minors"

Although good at biology at school, Jefferson was more excited by physics and physical chemistry. Physics, he explains, offered "an underlying method in which you can distil the fundamental principles of life." By contrast, biology was just "a lot of cool observational stuff."

The best undergraduate

Jefferson's attitude to biology changed in 1974, however, when he went to the University of California in Santa Barbara (UCSB), and was exposed to what he calls "hardcore molecular biology." Specifically, one of the first lectures he attended was given by molecular biologist John Carbon, who talked about the research he had been doing on recombinant DNA during a recent sabbatical at Stanford University.

As he listened, Jefferson realised that Carbon was describing the same kind of "core unifying logic" that had thrilled him in his school physics, but had until now been absent from biology. Increasingly excited at what he was hearing, Jefferson began firing questions at Carbon, and the lecture turned into a two-way conversation, with the other students gazing on with glazed eyes.

The incident was sufficiently singular that Carbon recalls it vividly. As he explained to me by email: "I remember I talked about recent developments in recombinant DNA research (this was when that field was in its infancy). Rick Jefferson — as he was then known — asked several questions during the lecture, and then afterwards came up to talk with me, and to ask more questions. He was very excited about the research I described."

Jefferson was so enthralled, in fact that he immediately embarked on a campaign to persuade Carbon to let him work in his lab — an unheard of privilege for an undergraduate.

Eventually, says Carbon, "I invited him to help out, even though I had never taken a first year student into the lab previously. At first he helped out post-doctorals and grad students, but eventually he became more independent; more like a grad student when he was a senior. And he worked there until he graduated."

This was at the dawn of molecular biology, and Carbon's lab was one of only three or four labs in the world then working in the field.

Determined to learn as much as possible about molecular biology, Jefferson then began pestering the University of Edinburgh, in Scotland, to let him spend a year of his undergraduate studies in the lab of Ken Murray. "I managed — by perseverance — to push my way into a lab in a culture where undergrads just don't do that," says Jefferson. "And I spent a wonderful and instructive undergraduate year there when research on recombinant DNA was just beginning in Europe."

After returning to Santa Barbara and completing his degree, Jefferson moved to Boulder, Colorado, to do a PhD in the lab of David Hirsh.

It wasn’t long before Jefferson made an important contribution to molecular biology himself, developing a gene reporter system called GUS. This was revolutionary because it allowed molecular biologists for the first time to monitor exactly what was going on when they were trying to implant foreign genes into an organism. As Jefferson explains, before he developed GUS "people were just chucking stuff into blenders without any idea of what was happening!" As we shall, see GUS was later to become a key tool in the armoury of molecular biology.

At Boulder, Jefferson acquired a reputation for being a talented but somewhat maverick scientist. As the then head of department Bill Wood told me by email, "Richard was a flamboyant and impressive grad student here, who also drove us crazy at times."

Jefferson's view is that his colleagues simply didn’t understand his obsession with methodology, and so didn't respect or appreciate what he was doing. "Everything in science is determined by the tools that fall into scientists' hands," he says. "And GUS is an example of really good methodology; it's a great tool."

In other words, scientists can be as brilliant as they like, but without the right tools they are limited in what they can achieve. Yet most researchers remain focused exclusively on the sexy business of pushing back the frontiers of knowledge, not on the quotidian task of creating the tools to enable cutting edge discoveries to be made. "Methodology has always been really dissed in science, and yet it is so important," complains Jefferson.

By the time he finished at Colorado, Jefferson had decided to shift the focus of his research: GUS had grown out of his work on worm embryonic development, but Jefferson had concluded that the genetic activity of plants is far more interesting. He began, therefore, to apply for funding to adapt GUS for plants.

To his anger and dismay, however, it took two years to get the necessary funding — a career hiccup, he later discovered, caused by the lukewarm references that David Hirsh had been writing for him.

Incidents like this were eventually to convince Jefferson that academia is not the meritocracy it claims to be, but an old boy's club. Too often, he complains, scientists' career prospects hang on decisions made in a non-transparent way, and on a "You scratch my back" basis.

However, in 1985 Jefferson eventually got funding from the National Institutes of Health to go to the Plant Breeding Institute in Cambridge, England.

Bench jockeys

For personal reasons, Jefferson's time at PBI was emotionally difficult. It was, however, a very productive period of his professional life. Discovering that adapting GUS was fairly straightforward, he turned his attention to other matters. And practically everything he touched, he says, "turned to gold".

Most notably, on June 1st 1987 Jefferson became the first person in the world to successfully plant a transgenic food crop. In doing so, he beat biotech giant Monsanto to the punch by one day!

At PBI Jefferson also found himself working alongside a great many scientists from developing countries — an experience that was to convince him that researchers from the West routinely exploit their colleagues from less wealthy nations, using them as "bench jockeys" for their own ends.

The greatest victims of the academic Old Boys' Club, he concluded, are scientists from poorer nations, since those in the West are all too happy to stand on their backs to further their own careers.

This means, says Jefferson, that even those able to get to the West to do some research can generally only aspire to "do some science, publish a paper, and then disappear back into Africa or China, or wherever." Once back home they lack the necessary tools, the funds, and the opportunity to carry on with their research.

In the context of biotech, Jefferson concluded, this meant that those countries that had most to gain from molecular biology were the least likely to benefit from it.

Worse, this inequity was being exacerbated by an undesirable new development in science, as its traditional openness was giving way to a culture of secrecy and greed.

When he started in Carbon's lab, explains Jefferson, everybody shared data and not a single patent had been filed in the field. As the potential of biotechnology became apparent, however, a patenting frenzy had gripped the scientific community, with individual scientists and biotech companies falling over each other to secure intellectual property rights — not only in the basic tools of molecular biology, but in the raw material too.

There is no better example of the way in which core technologies were being appropriated than the fate of the two principle means for transferring genes into plants. The gene gun developed at Cornell University had been patented, and the rights then sold on to DuPont — a transaction that earned for Cornell more money than the University had ever earned in royalties before.

Meanwhile, a technique utilising Agrobacterium tumefaciens was itself rapidly being encircled by a sea of patents — patents that were later to become the subject of intense litigation — as Syngenta, Monsanto and Dow all fought over the rights.

While the increasing enclosure of the biotech commons was a growing source of frustration for scientists in the West, Jefferson saw that the consequences for developing countries were potentially devastating — since the hefty licensing fees required simply to engage in transgenesis threatened to lock them out of the considerable benefits that biotechnology promised, not least the ability to develop new plant varieties able to provide food security for their people.

More controversially, as initiatives like the Human Genome Project gathered pace, it was becoming evident that Western scientists and biotech companies were now intent on appropriating the very building blocks of life itself — by, for instance, patenting gene sequences.

Shared with the world

By now Jefferson had become convinced of the importance of making the basic tools of biotechnology freely available to all. Increasingly appalled at the way biotech was developing, he concluded that, whatever other people might do, he at least could act differently. In short, he decided to share GUS with the world.

So in 1987 he prepared 10,000 tubes of DNA sequences for use with GUS, wrote a comprehensive manual explaining how to use it with plants, and distributed lab packs to 500 research institutions around the world.

The result was instructive: Within a short space of time GUS was the most widely used reporter gene in the field. "Because Richard shared GUS freely, and because it worked effectively, everybody started using it," explains Gary Toenneissen, director of food security at the Rockefeller Foundation. "This meant that even though other reporter genes had become available, GUS was the tool of choice for most scientists."

In short, although at the time not conscious of the parallel, Jefferson had independently come up with the same strategy as the Free Software Foundation (FSF), which was later to blossom into the Open Source Software Movement. GUS became first choice for molecular biologists for the same reason as the Open Source server Apache has become the most widely used web server software on the Internet: it was freely available, and it worked!

Jefferson also began to receive "bug reports" about GUS, enabling him to improve it. In doing so he demonstrated that Linus' Law — "given enough eyeballs, all bugs are shallow" — is as applicable in biological innovation it is in software development. All in all, says Toenniessen, GUS was "a good example of how the Open Source software model can work in biotechnology."

As a consequence, GUS was to prove instrumental in helping scientists around the world create more efficient varieties of maize, wheat, rice, soybean and cotton — not least Western-based biotech companies like Monsanto, which used GUS to develop the now hugely successful and ubiquitous Roundup Ready soybean.

Excited by this turn of events Jefferson began to a hatch plan for a much grander project. Wouldn’t it be great, he thought, if he could generalise what he had achieved with GUS throughout biotechnology?

By now Jefferson had also had first-hand experience of what he characterises as the "vicious, sophisticated but untidy, manipulative, staggeringly money-driven" process of biotech patenting. For when the University of Colorado had declined to patent GUS Jefferson had done so himself.

Explaining his decision to do so today, Jefferson says that at the time he was somewhat naïve about intellectual property (IP). At the back of his mind, he explains, was a vague thought that by patenting GUS he could use the royalties to fund the creation of new inventions.

Whatever the reason, the experience was to prove an important milestone in his IP education, since it led him to enter into what he now refers to as a "horrible Faustian Pact" with a highly-regarded US patent attorney called Leslie Misrock — a pact that was to lead to a great deal of pain, and eventually legal action.

But this was all the more reason to try and do something about things. And the best way of doing so, Jefferson concluded, would be to create an organisation focused on encouraging and supporting greater sharing of core technology. But how and where?

By the late 1980s Jefferson had become sufficiently disillusioned with the Old Boy's Club that he saw no opportunity of creating such an organisation within academia. What was needed, he concluded, was a more conducive environment. Consequently, he says, "I decided to leave the star maker machine: professorships and stuff. I had come to hate it with a passion."

After hitting an emotional low point in 1988, Jefferson was rescued by his friend Stephen Hughes, whom he had first met in Edinburgh, in Ken Murray's lab. Hughes, he says, "dragged me off to Southern Italy with my tail between my legs."

At that time director of biotech research for an Italian food conglomerate, Hughes organised a six-month visiting professorship for Jefferson, and helped him sketch out his plans for the future.

"It was a very important time for me because Steve is a very creative man and gave me a lot of help," says Jefferson. "Many of the good ideas I came up with came out of discussions with Steve in those early days, in Mozzarella land."

Feeling that the kind of organisation he had in mind would be most effective if it were able to operate under the aegis of an international development body like the United Nations, in 1989 Jefferson accepted a post as the first molecular biologist with the UN's Food and Agricultural Organisation (FAO).

Sadly, the FAO proved a false start. Within a short space of time it became apparent to Jefferson that the UN was just one more old boys' club — with member nations more focused on pursuing their own narrow interests than in helping the world's less wealthy nations feed themselves.

Disappointed by his inability to make headway, and disillusioned by the incestuous politics of the UN, in 1991 Jefferson left the UN, having determined that he would need to create a private initiative. Out of this disappointment and disillusionment would be born CAMBIA and the BiOS initiative …


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