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Creative fever

Co-operation among universities, companies and the government makes discovery and the development of drugs in England easier

Carlos Fioravanti Rowers on the Thames in Oxford: building team spiritCarlos Fioravanti

From Oxford – This report is part of the study “New Perspectives on Drug Development in Developing Countries: a Case Study of the Brazilian Compound P-MAPA”, conducted in 2007 as part of a study program sponsored by the Reuters Institute for the Study of Journalism at Oxford University, England.

Penicillin is not just one of the most widely used drugs in the world, it is also the result of a pioneering approach, described by Robert Bud, director of research at the Science Museum in London, in his book, Penicillin – Triumph and Tragedy, published last year by the Oxford University Press. The transformation from a fungal extract discovered in a modest London hospital into a powder that began to be used during World War II, and that has since saved millions of lives, was the first collective drug development work in the world.

The link among scientific, economic and political powers is common in England today, but was not so common back then. The cogs and wheels of research and drug development have been adjusted little by little, and are now reasonably well connected, linking universities, companies, the government and funding agencies. Research into new drugs is taking place in 62 hospital or university laboratories and in a substantial number of the UK’s almost 500 pharmaceutical companies. As a result, 15 of the 75 best-selling drugs in the world were created and developed in the UK, including Viagra. Only the US, with their more profit-driven companies, have achieved more.

The British government has created an environment favorable to pharmaceutical innovation by encouraging the training of researchers, the teaming up of universities and companies, and the marketing of academic research. Scientists still have to make sacrifices and occasionally wear something more formal than their daily, almost white lab coats, besides spending a few hours talking to businessmen. At least twice a year Isis Innovation, a technology transfer company at Oxford University, holds dinners where there is no shortage of full-bodied French wines to feed the hopes of transforming ideas created in a lab into commercial products.

Both researchers and institutions get excellent government aid. Investment in public research may have reached almost US$ 4 billion a year in 2005/2006, though most of these funds are earmarked for basic science, clinical research being still relatively ill-served. Those who do not want government funds may resort to one of the 25 independent foundations, charities. Welcome Trust, the largest of them, created an extra fund – of up to £ 700 million (£ 1 equals about R$ 4) per project for three years – to encourage biomedical innovation until it reaches the point at which it can be supported by the usual financing mechanisms. Nich Dunster, from Welcome Trust Technology Transfer, presented this fund at BioTrinity, a  2 day trade fair in Oxford that brought together companies that research, produce or help entrepreneurs prepare business plans, find partners, license technologies, get financing or become better known in the UK, Europe or the USA. Many directors of small and medium companies that attended BioTrinity said that they intended to complete the initial clinical trials of the potential drugs they were working on and then set up a partnership agreement with large pharmaceutical companies, as they lacked the money to produce and sell their new products themselves.

Government officials who attended a British Chamber seminar held in November in São Paulo showed interest in encouraging the development of an environment friendly to pharmaceutical innovation in Brazil as well, in order to overcome a long-standing lack of cooperation among universities, firms and the government. One of the new forces is BNDES, Brazil’s National Economic and Social Development Bank, which released R$ 1 billion to firms of all sizes to invest in the production of active ingredients and in innovation. “Without innovation, we assume we will continue to be a fringe player forever,” commented Pedro Lins Palmeira Filho, head of BNDES’s industrial area. History shows this can be difficult. Two decades ago, Codetec, the Technological Development Company, planned to encourage the synthesis of pharmaceuticals, with government aid, thus reducing our external dependence, but lost steam due to lack of investment.

At Oxford, this fluid link started to be developed in 1997, when Tim Cook joined Isis after seven years as administrative director of technological companies and another seven as a private investor. According to him, the movement of creating companies and raising other sources of financing appeared because the university decided not only to become useful  by educating entrepreneurs and politicians, but also to look useful and become an economic power. It seems to have worked: the financial return was ten times greater than the investment. Cook and his team progressed as they encouraged communication and trustworthy relations between researchers and businessmen and saw the social and economic value of the scientists. “All we do here is applied sociology,” he said.

Fleming MuseumAnonymous heroines: penicillin girls looking after production at the University. Above, the Petri dish with the fungus that led to the world’s most widely used drugFleming Museum

Any one of the four thousand researchers of the university can resort to ISIS to prepare a business plan, get financing and manage a company.

For Graham Richards, director of the Oxford University chemistry department, an outstanding aspect of this model is that researchers need not leave the laboratory: as new firms normally have their own managers, and they are not the scientists that founded them, almost nothing changes in the latter’s academic life. It is not enough, however, to change academic culture: “We need champions as well,” he commented. “Two or three people make all the difference.” Besides Cook, Richards makes a difference. In addition to the firms that he aided or helped to create, he negotiated construction of a new chemistry laboratory worth £ 64 million with no financial aid from the university.

The chemistry department boasts a record of 18 spin-offs, which brought in £ 80 million for the university. Some 60 firms came out of the entire university, especially after 1987, when a new law granted universities the right to exploit intellectual property. The person behind this change was Margaret Thatcher, then prime minister, who was annoyed by a story about a monoclonal antibody developed at Cambridge that was not patented and that later generated a great deal of money for the company.

Almost 50 companies, including many of the largest in the USA, Europe and Japan, coordinate the clinical trials of some 500 potential drugs in the UK, carried out mainly in the NHS (National Health Service), the UK government’s healthcare system. The drugs approved in the trials are then reevaluated by the regulation authority (Emea, the European Agency for the Evaluation of Medicinal Products), which provides a single license for sale across all EU member countries.

This model has brought about a different end to the penicillin story.  “Fleming stayed here, along with three other doctors, smoking 60 cigarettes a day,”  a very thin and talkative woman in her sixties tells us, as she shows a small wooden table covered with jars, pots and a microscope, on the second floor of building in London’s St. Mary Hospital. It was in this room that, in September 1928, Dr. Alexander Fleming, a Scotsman, found a bacteria-exterminating fungus on a Petri dish upon returning from his vacation.

At first, Fleming worked enthusiastically. In 1929, he published an article in the British Journal of Experimental Pathology, but lost interest in the subject a few months later, as neither he nor his team managed to purify penicillin. Moreover, his immediate boss, Sir Almroth Wright, disliked biochemists who might have managed to solve the challenge, and did not want them around.

One of the British Journal editors, Australian pathologist Howard Florey, who years later would play a crucial role in the development of penicillin, must have seen Fleming’s work, but not the drug that might be born out of it. Nine years later, it was biochemist Ernst Chain, a Jewish refugee from Nazi Germany, who opened Florey’s eyes, when he found Fleming’s study in an Oxford University library and suspected that therein lay something precious. An Oxford University professor, Florey began transforming Fleming’s extract into medication. His team worked concurrently on animal trials, purification and penicillin production – at first in chamber-pots – in sufficient amounts for human trials.

Although he showed that penicillin placated bacterial infections in mice, Florey was unable to get British pharmaceutical industries interested, as they were more concerned about surviving World War II. But he crossed the ocean and managed to get help from the US government. US pharmaceutical companies came together and prioritized the production of penicillin, whereas the British ones were slow to reach a common ground. Later, England had to buy the patent on penicillin production methods from the USA. Fleming, Florey and Chain shared the Nobel Prize for Medicine in 1945.

Today, Florey would not have had to turn to the USA to complete penicillin’s development. He could have opened a firm, deposited a patent, obtained financing, completed his research and made a lot of money from royalties paid by the multinationals that would produce penicillin and sell it globally. When he got to Emea, however, he would find less favorable winds blowing. Contrary to the forties, when there were virtually no drug registration regulations, under the current regulation system Emea’s technical staff would not approve penicillin because it carries an allergy risk of 3% or more. Nothing personal, of course: many other drugs would be vetoed now.

Europeans are more wary also because, as shown at the exhibition at the Science Museum that maintained Robert Bud’s book title, penicillin was a story of victory over infections, but its uncontrolled use left in its wake an open path for the dissemination of bacteria and viruses. Currently, one of Britons’ chief fears is superbacteria, such as those that cause hospital infections or tuberculosis and are resistant to all available drugs.