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The banker and the biologist

E.coli bacterium
E.coli bacterium found in an egg sandwich

A POINT OF VIEW

E.coli can have a bad reputation. But a hippy scientist and an unemployed banker harnessed the benefits of this bacterium - and launched the biotechnology revolution, says Harold Evans.

We have to change the adage - man's best friend may not have four legs and bark. In fact, the creature I have in mind is only a ten-thousandth of an inch long and answers to the name E.coli.

If you're one of the zillions of hypochondriacs on our planet, you will know that this is not Mr Edward Coli of Twickenham, but the bacterium Escherichia coli - E.coli for short - a version of a single cell microscopic bug.

Food poisoning
E.coli can do us good - or ill

You may not be on speaking terms with E.coli if you've encountered it on your travels. Like all families, it has uncouth members. If certain strains of E.coli get together in big numbers in your gut, you will know about it. The sickness they produce as a gang can be nasty, so ordinary mortals prudently avoid contact, walk the other side of the street as it were; when we get caught by the gang we call it food poisoning.

Ugh. But stay with me. The good thing about E.coli - the very good thing - is that it has qualities a brilliant scientist exploited to bless mankind with a variety of life-saving medicines - medicines so valuable in combating cancer and age-related blindness, for instance, they are now at the heart of a raging takeover battle for control of the wonderfully successful company founded on his original work with E.coli.

His name is Herbert Boyer. I'll come to him and his young friend Robert Swanson shortly.

Hostile takeover

The company they founded on the campus of the University of California, San Francisco, with $500 dollars apiece is Genentech, and its scientists are furious that the Swiss-based pharmaceutical giant Hoffman La Roche is making a hostile bid for the 44% of Genentech shares it doesn't have.

Harold Evans

Robert Swanson, an unemployed banker, had an idea that molecular biology had progressed to the point where it could become a business

Billions of dollars are at stake, but at heart it's not really about money. It's as much a confrontation of cultures, the free-spirited microbiologists of south San Francisco v what they see as the uptight bureaucrats from Basel.

Hoffman La Roche's medicines are chemical compounds, Genentech's are derived from genetic engineering - in the stock market tables they're listed as DNA, controversial for some - but in my view there's nothing scary about what they do. It is a very natural process.

Hoffman La Roche is one of the leading companies in what's known as Big Pharmaceuticals - Big Pharm. Big Pharm generally has been having a dry run for the past few years, while the genetic engineers have scored success after success. Genentech has had its 15 major medicines investigated without one coming up negative.

The Wall Street Journal has been following the takeover struggle, but don't go near its website unless you're clad in flame-proof clothing. It's ablaze with many scores of comments from both sides of the fight. "Roche," says one, "you are an opportunistic sleazebag trying to take advantage of the US economy." To which a Roche defender says: "Genentech has a campus full of educated idiots."

Opposites attract

It is a long way from the science meets business dialogue that took place on Friday, 17 January, 1976, on the campus of the University of California, San Francisco.

Robert Swanson, described as a "short, chunky, chipmunk-cheeked" 28-year-old unemployed banker, dropped in on the university lab of Herbert Boyer, just 10 years his senior. Swanson had an idea that molecular biology had progressed to the point where it could become a business.

One Genentech scientist remembers, "We were standing out in the hallway laughing at this guy in a three-piece suit. We didn't get people like that visiting us." But Swanson's 10-minute pitch was persuasive enough for biologist and banker to walk out for a beer at Churchill's, a local hangout for molecular biologists.

By chance, Swanson had stuck his pin on the right name. Boyer was a working class boy from a small mining community in Pennsylvania. He was a star football player, but a perceptive coach, who also taught chemistry and biology, advised him to direct his energies into science.

James Watson, right, and Francis Crick, with DNA model
Watson and Crick's DNA discovery inspired many

Francis Crick and James Watson helped, too. As Boyer graduated to a small liberal arts college, the famous Anglo-American duo shook the world with their double-helix, the model of the genetic blueprint of life, DNA.

Boyer was hooked. He named his Siamese cats Watson and Crick and when he arrived at the University of California as a 36-year-old assistant professor in 1966, he really considered himself a member of a new profession - molecular geneticist.

He was a 60s rebel. Marching through the streets shouting anti-war and civil rights slogans, he did not look the sort who would be a caring father, given his tumbled mop of hair, his flamboyant moustache, his open-necked shirt, his faded jeans, his unbuttoned leather vest.

But he was. He fretted that his son might be on the small side. A paediatrician told him it was possible he could be treated with a human growth hormone. Boyer had never heard of it. But he had the glimmerings of an idea that something might be done with E.coli, the bacterium first discovered by the German paediatrician and biologist Theodore Escherich in 1885.

Gut bacteria dividing and reproducing
Divide and conquer

One bacterium brushing against another may pick up a gene floating on the surface of the other in a tiny, closed loop called the plasmid. This is the way bugs learn how to resist a bug killer - one bug which has learnt how to beat the bug killer passing on the immunity to another bug through the plasmid.

Boyer reasoned that if E.coli plasmids were so ready to receive and transfer new genetic information from their peers, perhaps they could be induced to combine with a gene from a higher organism.

Such a recombination of DNA would offer amazing prospects of exploiting the normally malevolent capacity of a bacterium to make millions of copies of itself in day. The hybrid plasmid, infiltrated with the appropriate gene, could in theory convert the bacterium into a pharmaceutical factory.

Peanuts

This was a very distant prospect that kept Boyer and Swanson talking for two hours. Boyer didn't have the $500 Swanson suggested they put up to create a company. He had to borrow it. They were ambitious, but modest young men.

At work in the Genentech lab
At work in the Genentech lab

Swanson suggested they call the company Boyer and Swanson, then rejected Swanson and Boyer, and they both recoiled from Her-bob. So they named their putative company Genentech, derived from Genetic Engineering Technology.

While Boyer got on with his research, Swanson kept looking for a job. He wound up drawing unemployment money for six months, living on peanut butter sandwiches, then finally decided to devote himself fulltime to a heartbreaking search for money for Genentech.

Meanwhile, in the lab it was a mammoth task for Boyer, working with fluids no bigger than a teardrop, with disappointments all long the way, but with co-operation from other scientists.

He heard of a researcher called Stanley Cohen who'd found a way to remove plasmids from E.coli and package them in test tubes.

Over corned beef sandwiches late one night at a delicatessen across from Waikiki Beach, Hawaii, the ebullient Boyer and the quiet Cohen made an agreement. Cohen would supply the plasmids. Boyer would chop up the appropriate DNA with an enzyme - think of that as scissors - and try to infiltrate an alien gene in the plasmid for the E.coli to manufacture. Boyer and Cohen published their work in November 1973: they'd cloned a gene.

Nurse checks blood sugar of a diabetic
Diabetics have much to be thankful for

In this way, Boyer went on to induce bacteria to make human growth hormone, and insulin. The triumph was very hard won and there were many more conundrums - but the way was open for the foundation of the whole biotech industry.

Genentech stock went on sale in 1980, the first public offering for a biotech company and one of the most spectacular in the history of Wall Street. It made rich men of them both, though Boyer suffered much from the jealousies of other academics.

There are now 1,500 biotech companies in the United States, and the Food and Drug Administration has approved 120 biotech medicines. More than 350 biotech drugs and vaccines are in human clinical trials, aimed, among other things, at treating various cancers, diabetes, multiple sclerosis, Aids and obesity.

In 2001, Genentech broke ground in California on the largest biotechnology research facility in the world. It is pleasing to see in the quadrangle a life-size metal sculpture of two men sitting at a table, each with a beer, one in a suit leaning forward in his enthusiasm, the other in a denim vest and bell-bottom pants, "sceptical but intrigued".

A pity that harmony between business and biology has not been sustained.


Here is a selection of your comments.

I would disagree that "harmony between business and biology" as there are lots of good scientists who go from academic research institutions into business R&D and vice versa. In more recent decades, other innovations like monoclonal antibodies have come down the pipeline. The big problem with "Big Pharma" right now is that it's focusing on lifestyle drugs for minor ailments - most of which are small molecules rather than the more high-tech protein or nucleic acid (DNA or RNA) drugs. They are also ignoring life-saving treatments for infectious diseases because poor people can't pay much. Yet I believe that companies that target these diseases could still make reasonable profits from sheer volume, as long as their CEOs don't want astronomical salaries.
Shi-Hsia Hwa, Madison, WI/Penang, Malaysia

The next time you hear anyone spouting off about how useless some obscure branch of science is (say, historical linguistics as an example, or whatever), just ask him or her how far biology got in the years 1860 - 1865. The answer is: nowhere. Gregor Mendel published a ground-breaking paper during those years, and, as Jacob Bronowski once put it, achieved instant oblivion. Read his paper - it is available online - and wonder at the obtuseness of people. Today's crazy idea is what saves the world tomorrow.
D Fear, Heidelberg, Germany

If the human race is to survive, harmony between business and biology will have to be sustained. "Green" technologies will have to be the goal of all business and only research in biology will be able to forewarn us of calamities which global warming may bring. Forewarned is forearmed for the top of the food-chain - us.
Marion Monahan, Bristol UK

I am 15 and when I was 11 I caught E.coli. So far it has destroyed my life so yes, maybe it can cure cancer, but I can't believe that this evil bacteria has a good side.
Matthew, Swarthmoor, Ulverston

E.coli does much more good than harm. It is generally a commensal bacteria that colonises all of us and thus helps prevent the establishment of many other pathogenic bacteria. Pathogenic strains of E.coli are comparatively rare. This is an example of the media grabbing hold of a story and tainting the public's view. We have more bacteria living on and inside us than we have human cells.
Ian, Halifax, NS, Canada

I worked as a microbiologist in a hospital path lab and came across E.coli in many guises - causing urine infections, D and V in children as well as adults. I had not heard of the gene work that is being done as I have not worked for a little while. Thanks for bringing this to my notice.
Viv Addey, Leicester, UK

I'm a UCSF alumni and while I was there, we had actually sued Genentech over the growth hormone, if I'm not mistaken, and that money was used towards the building of our new campus and other things. Nevertheless, Genentech is a great company and I wish I had bought stock in it in 1980.
Caleb, Irvine, CA

I have followed the Genentech stock since before their IPO in 1980 and wish I had hung on to it. Their first success was synthetic interferon - the first anti-viral drug ever developed.
Santiago Matamoros, Singapore

It sounds like they sold too many shares of their company. They should have kept a majority (controlling) interest in their own company. But they did it to get rich and they got rich so you can't feel sorry for them.
Thomas, Clemson, US

E.coli - by far the best understood organism at the molecular level. It is the organism of choice for literally decades for fundamental biochemical research.
Pyers Symon, Worcester

Another example of answers in life being right in front of us... they are two creative artists able to join minds and think in a new language.
Bonnie Newman, Orlando, FL, US

This story sounds so familiar. Was it the one that inspired a few chapters in Michael Crichton's terrific novel Prey? A must read for every one interested in this subject and its consequences. Or was it in his other novel Next, which delves on this topic perhaps even more so.
Ginaveda, Bendigo, Victioria, Australia

"He did not look the sort who would be a caring father, given his tumbled mop of hair..." What appalling prejudice. And it doesn't even have anything to do with the story. What's that all about?
John Sawyer, Swansea



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