Reaping responsibly

For many years the earth's botanical resources were treated as a free-for-all, bringing benefits to mankind but none to the local populations. Now a more responsible attitude towards the forests has been adopted.

The rosy periwinkle, Catharanthus roseus, is a common plant on the East African island of Madagascar. But today, because of destruction of the forest, it is less common than it was in the 1950s when biochemists homed in on two of the 70 alkaloids produced by the plant. From them, pharmaceutical company Eli Lilly developed Vincristine, which led to an 80% improvement in the survival rate for children with leukemia, and Vinblastine, vital in the treatment of Hodgkin's disease. These brought effective treatment to multitudes of patients and comfortable profits for the company.

Halfway across the world in 1967, Dr Thomas Brock discovered microscopic organisms known as Archaea living in a hot spring in Yellowstone National Park, US. He named one species Thermus aquaticus Yellowstone Type-1, or Taq YT-1, and lodged a type specimen in the American Type Culture Collection. Some time during the 1980s a researcher working for the Cetus Corporation was looking for an effective, cheap method of reproducing DNA to improve DNA fingerprinting methods. He hit upon the type specimen of Taq YT-1 and found it ideal for his purposes in developing the Polymerase Chain Reaction (PCR). The PCR patent today earns around US$500m/yr (€571m) for its owner, Hoffman-La Roche.

These two discoveries had several things in common: they were based on species that were collected in natural habitats;

In those days, it was felt that the natural environment should be a freely available common heritage of mankind, with no restrictions on scientific research. As time went by, some people began to question that presumption. Increasing pressure of population growth, combined with a growing thirst for natural resources, placed huge and often conflicting pressures on natural environments. The world was polarising, with a strong increase in the prosperity of the so-called 'first world', which was not being matched by improvements in the so-called 'third world'. Yet the 'third world', by nature of its under-development, retained a disproportionate share of pristine natural environments, including the vast majority of tropical rainforests, with the greatest concentration of biodiversity.

During the 1980s there was a rush by chemical and pharmaceutical companies, usually working through academic researchers, to collect the knowledge of traditional healers. Researchers would interview shamans, herbalists, witchdoctors and medicine men to identify the plants and animals they used to treat particular symptoms and diseases. Ethno-botany became the hot property of fundamental pharmaceutical research. The industry tried to position itself as the saviour of this valuable knowledge, which was being lost as the art and practice of traditional healing was dying away with the older generation, leaving the younger people increasingly dependent on pharmaceuticals.

There was more than an element of truth in this claim, but when the traditional communities grew to understand the motives of their questioners, they rebelled. Faced with a representative of a huge, wealthy multinational corporation who was keen to make use of the knowledge that had been passed down through generations, they understandably asked 'What's in it for us?' A lecture about the Good of Mankind was likely to fall on deaf ears, and did.

sovereign rights

This was also a period of rapid growth for Non-Governmental Organisations (NGOs). Pressure groups like Friends of the Earth, Greenpeace and Survival International had the ears of the media and campaigned relentlessly on behalf of deprived people and threatened environments in developing countries. To feed the sensationalist leanings of their publicists in the media, these organisations frequently attacked the corporations behind the research, tarring them all with a brush that was not universally deserved. The image of greedy capitalists ravaging ancestral knowledge has stuck, making companies sensitive about their activities in developing countries. Governments too responded with a rash of legislation controlling access to research materials.

If it had been handled fairly and reasonably, this could have been a win-win situation; instead it was lose-lose. It is true that the valuable cultural knowledge of medicinal properties of plants is being lost as the old practitioners die and their children lose interest. It is equally true that those who co-operated with the researchers have rarely seen any benefit to themselves, their communities or their environment.

By the early 1990s, the concept of nature as a common heritage was falling away. The 1992 Convention on Biological Diversity, signed by most countries at the United Nations Earth Summit in Rio de Janeiro, Brazil, acknowledged that states have sovereign rights over their own biological resources. In the nature of such international agreements, the Convention is wordy, often non-specific and full of provisos and let-out clauses, but it did signal a fundamental shift in the economic status of the constituent parts of a country's biodiversity. It suddenly made sense that those profiting from discoveries arising from materials collected in the wild should share the benefits with the owners of the original wild environment.

Following the 1992 Convention, it became possible for researchers to enter into binding legal agreements to gain access to natural environments. Such contracts are often based on the tenets of the Convention, and include a mix of provisions. There is usually an up-front payment for access to samples, together with provisions for payment of royalties on any products arising from the samples. There is also usually some transfer of technology, in the form of education of local academics and researchers, training, provision of scientific equipment and access to non-sensitive research carried out on the samples. Many companies also become involved in local research initiatives of no direct benefit to themselves.

Such agreements usually rely on a local partner. One of the best established is in Costa Rica, where Merck & Co has for many years had an agreement with the National Biodiversity Institute (INBio). Other companies using INBio agreements to access Costa Rican ecosystems include Bristol-Myers Squibb and fragrances and aromas company Givaudan Roure.

needle in a haystack

Another collaborator is Diversa, based in San Diego. Established in 1994, Diversa is one of the leading companies in high throughput screening for DNA. Its main objective is to identify DNA fragments that provide the gene coding for commercially useful enzymes and other biologically active compounds. Although so far only three products have reached the market, there is a long pipeline of 51 products in various stages of development. Diversa's commercial collaborators include an impressive array of the market leaders, such as GlaxoSmithKline, Syngenta, Aventis and The Dow Chemical Company.

Diversa believes strongly in the importance of its base raw materials. "Genome diversity is as vast as it is precious," says president and ceo Jay Short, "Nature's evolutionary power has generated a rich, unexplored repository of novel genes."

Diversa uses a process known as directed evolution to shuffle genetic sequences extracted from the materials it collects in the natural environment, producing an enormous array of synthesised DNA fragments. The company has developed proprietary technology that reassembles genes from various sources that are not necessarily related in any way. Using the company's GigaMatrix high throughput screening system, which incorporates 3.3 x 5in plates, each with an unprecedented 100,000 wells, Diversa scientists are able to find the proverbial needle in the haystack of gene fragments that has the desired profile of activity.

High throughput screening companies are also growing up in some of the more advanced developing countries. In Brazil, Extracta Moleculas Naturais was set up to increase the local capacity for research on domestic biodiversity, in line with the Biodiversity Convention. It is creating its own library of plant extracts, fractions and pure compounds, all collected within Brazil, mainly in the increasingly threatened remnants of Atlantic Rainforest. This unique ecosystem has been reduced to a mere 5% of its original extent, but the small fragments of forest that survive have proved to be hotspots of biodiversity. Who knows what bio-treasures were lost during the destruction of the other 95%? Although Extracta's 96-well assays cannot compete with Diversa, this is nonetheless an important move to build local capacity.

In the NGO sector, there is a new breed of entrepreneurial non-profit organisation whose objective is to facilitate the establishment and organisation of contracts between international corporations, governments, local communities and local scientific institutes for the mutual benefit of all parties. Foremost among these is Paris-based Pro-Natura International. Originating in Brazil, the organisation became international when ex-ICI director Guy Reinaud took over as president. He has expanded the organisation until it now has projects in 20 countries.

'Our remit is to protect biodiversity by working with local communities,' he says. 'We help them to establish more productive agricultural systems based on the local ecology. This reduces threats to the natural environment, especially in areas where there are subsistence farmers on the borders of protected areas of high natural biodiversity. Governments in developing countries often don't have the resources to police their reserves effectively, so the best way to protect these areas is by establishing a buffer zone where stable local communities feel they have an interest in looking after their environment.'

effective mechanisms

Wherever possible Pro-Natura works with local counterpart organisations, using their contact with local people as a two-way conduit. Initially they assess the most appropriate way in which to work in the particular region. Once this has been done, Pro-Natura provides two precious commodities: money and scientifically based technical support.

Bioprospecting agreements have proved a very useful means of achieving its objectives. It has developed a standard contract under its Biodivalor programme, which is again based on the Biodiversity Convention. Its contract with Hoechst Marion Roussel (now part of Aventis) established a relationship between the company, Pro-Natura International and the countries providing access to the natural environment. In some cases Pro-Natura and its local collaborating NGO actually collect the samples; in others the participating companies prefer to send their own scientists.

In Gabon, Pro-Natura used an imaginative system to access the upper reaches of the rainforest. Professor Francis Halle of Montpellier University had a theory that the highest incidence of biodiversity in rainforests was likely to occur in the tops of canopy trees. He hypothesised that because plant and animal organisms there are subject to the greatest environmental stresses – high levels of exposure to variations in heat, moisture, wind, sunlight, insect and animal predation – they were likely to have developed a greater range of active compounds to protect themselves. It is also where growing conditions are most favourable, so it was likely to be the location of greatest diversity in micro-flora and fauna.

In association with adventurous French architect Gilles Ebersolt, Pro-Natura developed a device known as the Canopy Raft. It uses inflated tubes to form a framework that is flexible enough to follow the contours of the forest canopy, while rigid enough to support a tough net from which up to five scientists can work. It is placed in position by a giant hot-air dirigible airship, which is manoeuvrable enough to do the job but does not cause the level of disruption to the local microenvironment which would occur using a helicopter.

A smaller, similarly constructed device, the Canopy Sledge, is used to trawl over the tops of the canopy, allowing collection from a much wider range of trees. It supports three scientists, and can cover several kilometres in a two-hour flight, again using the airship to transport it.

Several international companies made use of the Gabon expedition to collect samples, including Hoechst and Givaudan Roure. Each company was bound by the terms of the Biodivalor profit-sharing agreement, and Pro-Natura had a counterpart contract with the government of Gabon to cover the application of the income generated.

Up to 75% of pharmaceutical products can be traced back to original substances found in natural environments, while 25% are derived from compounds originally found in tropical forests. It is becoming even more vital to preserve the raw materials of future breakthrough discoveries.

Responsible bioprospecting is an equitable and effective mechanism for rewarding the owners of biodiverse natural environments for protecting them, and encouraging further conservation for the future.

In the interests of the future of all biochemical based industries, it is essential that companies use their best efforts to ensure that everything possible is done to ensure that this almost limitless palette of raw materials is not squandered, to the detriment of future generations.