Turning green into gold

July 28, 1995

Biotechnology and Biological Sciences. This week The THES summer series on research begins. As mainstream teaching ends for the summer vacation in much of higher education, academic staff and research students have more time and space for research and for the conference round of the academic world.

This summer, uncertainties stemming from the Government's decision to shift the Office of Science and Technology to the Department of Trade and Industry: and the approach of the next research assessments are sharpening anxieties in the research community. Will "basic" research suffer? Who will win and who will lose when the music stops next March and each university department tots up the achievements of its research active staff?

It is important also to celebrate the vitality of British research and draw attention to new directions and possibilities. The THES has therefore asked the heads of each of the research councils and the chairman of the Humanities Research Board to contribute a signed leader sketching out the growth areas in their subjects. THES reporters will be visiting some of the councils' star projects.

We begin this week with biology and biological sciences, with Tom Blundell (below) and with peas, important to biologists at least since Mendel (page 5)

During the 19th century Britain abandoned its traditional approach to wealth creation and built its economy on non-renewable energy and heavy engineering. Britain's industrial landscape became a triumph for physics and chemistry; indeed industry seemed to be inherently different from nature - Blake's satanic mills. At the same time Britain began to neglect its own agriculture and to import more food and other raw materials from the colonies. This was in strong contrast with earlier times when our rural economy had provided us not only with food but also with fuels, fibres, pharmaceuticals, construction and many other materials.

Now, with an increasing emphasis on sustainable development, biological processes are again looking more attractive. They are renewable and minimise pollution. Furthermore British industries that depend on biological systems pharmaceuticals, food, healthcare and agriculture are among the most productive and wealth creating. When other British industries are having much greater difficulties in competing in world markets, our future competitiveness will depend increasingly on the bio-industries. Can we use our strengths in research to turn green into gold?

It is, of course, a time of tremendous opportunity for the study of biological systems. Molecular genetics has given us the ability to sequence the DNA of genes, to modify and manipulate it and to transfer it across species barriers in a way that cannot be achieved by classical breeding. At the same time the anatomy of living organisms has been developed at the level of the cell and the macromolecule. Biological sciences have been transformed by these revolutionary changes.

Let us take one of my own areas of interest, how signals are communicated between organs in the body and then into specific cells which can be caused to multiply, differentiate or die. Most of the primary messengers - growth factors, hormones, neurotransmitters - are present in very tiny quantities, but they can now be expressed in large quantities for academic study and clinical use.

The receptors, enzymes and adaptors that link them in transducing the message inside the cell can also be characterised. The powerful techniques of nuclear magnetic resonance, electron microscopy and X-ray analysis can then be used to define the architecture of the individual gene products and more importantly the complex structural relationships in the cell.

For the pharmaceutical industry this has created wonderful new opportunities. New macromolecular targets can be identified for almost any disease process. They can be used to screen candidates for lead compounds in drug discovery. In this way a biological target will be used to select a few compounds from a library of several hundred thousand chemicals. Chemistry is also imitating biology in producing combinatorial libraries of related compounds that can be used for screening. Once a lead is found by screening natural compounds or combinatorial libraries, knowledge of the architecture of the macromolecular target can often be used to optimise the lead; this is structure-based design.

The systematic sequencing of genomes is also changing drug discovery. Some believe it is quicker to sequence the whole genome and then try to select interesting gene products. In many ways man is imitating nature! The emphasis is to produce a great variety combinatorial libraries, natural compounds, gene sequences and then selectfor function.

This is rather like nature's evolutionary process where diversity is created and the organism is selected for fitness. Thus, the emphasis in genome studies is moving towards selection for function and that in combinatorial chemistry towards affinity selection of the active ingredient from a mixture of thousands of compounds.

Rather than using the natural products and processes that we see in the world today, we can create new ones, using the tools of molecular biology.

At the molecular level we can use our knowledge of the structure and function of proteins to engineer specific changes that will give new properties. For example we can use designer enzymes that can distinguish between the right and left-handed forms of asymmetric molecules that are not found in nature. If organic chemists could have done the same years ago, the thalidomide tragedy might have been avoided.

Several microbial enzymes are already being used commercially to make valuable fine chemicals for industrial syntheses. Others are being explored with a view to their use in the industrial manufacture of anti-viral and anti-cancer agents. This strategy also lies behind bioremediation, where the accumulative and degradative skills of plants and micro-organisms are being harnessed to clean up environmental pollution.

The ability to transfer genes between species is also transforming life sciences and the industries that depend upon them. Gene transfer offers new approaches to therapy in human medicine. There are possibilities of replacing abnormal genes in genetic diseases like cystic fibrosis or providing antisense sequences that turn off genes, for example the oncogenes that cause cancer. These opportunities will undoubtedly transform medicine in the coming years and provide ways of regulating genes where the products are very difficult to target specifically using small molecules.

In a similar way genes can be transferred into plants. These can be used to slow down natural processes such as ripening so that fruit can be kept fresh for longer. Alternatively, natural genes can be introduced into crops from wild plants to confer disease or pest resistance. A further possibility is to change the specific chemistry of a seed oil or starch to a product that is in short supplyin industry.

Many products, for example biodegradable polymers, are made at present using microbiological fermentation, but such processes can be quite expensive as the microbes have to be fed on chemicals. By transferring the process to plants, which provide their own chemicals, the product might be made more cheaply. In this way green can be turned to gold!

Even though these are biological processes their study and their exploitation is truly multidisciplinary. Mathematical modelling, physical approaches to the determination of structure and chemical characterisation of genes and gene products are all enormously important. Of course, the processing of agricultural fermentation or other biological products poses new challenges for engineering.

One often hears the view that biological processes are merely an extension of physics and chemistry. In fact, biological processes are introducing new ways of thinking into many physical and chemical processes.

For example, a housefly can make most of the manoeuvres that might be desirable in industrial robots. Effort is being made to identify how circuits in the insect's brain cells process information received from the eyes, and to relate neural processing to the computations required to control locomotion. Eventually, it should be possible to use our biological knowledge to design more sensitive and responsive artificial visual systems, such as those needed in robots.

The cells of invertebrate brains are very similar to those of the human brain. Our greater brain power comes from the larger number of cells and their more complex patterns of networking. An understanding of how these connections work is not only shedding light on phenomena such as memory, but is also providing models for the design of decision-making, for example, to control manufacturing processes.

Understanding neuronal networks in living systems has in fact influenced the way that many learning processes are encoded in computers. In these algorithms inputs are linked by networks to certain outputs with weights that are varied in the learning process. Genetics are also having an influence. They are also changing ways in which computer algorithms explore opportunities for optimising processes: these are known as genetic algorithms.

A further example is the way in which engineers design fibres based on biological materials, for example with properties of flexibility and strength. Thus, understanding nature is also influencing the way we do things!

Many moral philosophers have expressed the view that modern biotechnology raises nointrinsically new or different ethical issues from those already with us from more conventional technologies.

However, there is clearly public interest, and in some quarters worries, about whether biotechnology is always natural, ethical, safe, socially desirable and economically advantageous. There are fears of its potential and of the dangers in "playing God".

Scientists must not remain aloof from this debate. It will be our responsibility to keep the public informed, to provide information and to evaluate the opportunities arising from biotechnology. Ultimately, it must be the public that makes decisions about the use of biotechnology on the basis of an evaluation of its social, legal, economic and other repercussions for the future.

Thus, we also need scientists who can understand more about society's needs and priorities. Most urgently we need a genuine debate with participation by practising scientists and the public: these issues are too important to be left solely to market forces or political exigencies.

For the first time in the United Kingdom, we recently organised a consensus conference to involve lay people in discussion of the complex issues. This gave ordinary people the opportunity to learn about the science, call witnesses from scientists, industrialists, environmentalists and those involved in ethnics, and to write a report on their views. This is being used by our research council and government in formulating new policy.

Biotechnologists must look carefully at the question of risk assessment. Although there are clear guidelines for contained organisms, there is much to be learnt about assessment of risk when they are released into the environment. We must carry out an ecological assessment and this will mean bringing molecular biologists and physiologists together with experts in ecology, comparative morphology and taxonomy.

As a practising scientist I am aware that the pleasure in pursuing my research should not blind me to the social consequences, and the genuine concerns of the public. Much of our knowledge is fragile and I am conscious of our ignorance of large areas of biological science.

Nevertheless, I remain optimistic about the contributions of new biotechnology. The opportunities from the biorevolution should be the basis for an efficient industry that provides food, fibres, fuels, pharmaceuticals and chemical feedstuffs. It has the real potential to be central to health, welfare and wealth creation in our communities in the future. For the UK it is a real opportunity for economic prosperity and improvement of the quality of our lives.

Tom Blundell

Professor Tom Blundell FRS is the chief executive of the Biotechnology and Biological Sciences Research Council. He is amolecular biologist and carries out researchas honorary director of the Imperial Cancer Research Fund Unit of Structural Molecular Biology at Birkbeck College, London University. He has recently been elected to theSir William Dunn Chair of Biochemistry inthe University of Cambridge, where he willmove in October 1996.

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