Life scientists and chemical engineers are different animals with different needs and activities with a chasm between them, a large seemingly impenetrable barrier to collaboration. Engineers are creative innovators and designers whilst life scientists are discoverers, and hypothesisers. Engineers solve problems and life scientists understand nature.

It has been estimated that only five per cent of academic life scientists are sufficiently interested in the problem solving, application directed research favoured by engineers to collaborate well with them. Once such people are found collaboration can be fruitful.

Disease and infirmity are problems of life - we wear out, get sick, our fundamental life processes go wrong and we as individuals see this as a problem which we would like to see solved. Increasingly the solutions to such problems are going to require a combination of skills and approaches, which will bring together different disciplines and different tools. Chemical engineers have skills, which can be of great value in this area. The major players will be surgeons and physicians, but they will need the skills of engineers.

The concepts of biotechnology have changed forever the way we look at biology. The ability to modify genetic structures gives us the ability to design new structures, add new capabilities to different organisms. We have always enhanced the process of natural selection through plant and animal breeding programmes. We have forced evolution on micro-organisms to increase the yields of penicillin for example. These processes were ones in which we induced random mutations and then through a screening process selected those organisms that had performed best. Now we are looking at engineers trying to use their methods of control of the environment to accelerate evolution by continuously modifying the selective pressures imposed on the organisms. Effectively we have created environments that will select for a particular property of an organism. These properties are particularly favoured in the artificial environment whereas other deficiencies may be forgiven by careful supply of nutrients.

There are now engineers who are looking to modify several different genes within an organism to give a multiple capability. This could be so that a whole metabolic pathway is introduced into an organism, combining pathways from different organisms. In modifying the organism in this way there are a number of considerations which need addressing; including concentrations, rates of synthesis, internal controls and physiology of the organism as a whole.

In order to contribute to the solution of these sorts of problems chemical engineers need to be well versed in the major tools of the discipline. These are modelling techniques, problem-solving, control of mass transfer, an understanding of chemical reactions, and the quantification of their progress. We have an understanding of the rate processes, both physical and chemical, which result in the changing of matter. We are able to bring together diverse factors in order to create new products, have the ability to pose questions correctly in order to use the answers to solve practical problems. An ability to focus on the main objective in solving a problem. We are skilled at solving and dealing with complex problems and are familiar with the difficulties introduced by temporal change.

In a sense the above skills are the chemical engineers tool kit which is carried around ready to be used to solve a problem.

Interdisciplinary research investigates phenomena using the techniques of different disciplines, or develops new products, or processes using tools, fabrication methods, measurements, or modelling procedures which have been characteristically introduced by one or other discipline. In modern science, there is a large range of powerful tools and techniques. These must be made available to all scientists irrespective of their discipline. It must be assumed that the ability to use a tool is not limited to those of a particular type of degree training. It is also true that the solution of some problems is facilitated by knowledge of different fields. Again people from different disciplinary backgrounds can acquire knowledge of other fields, and bring these tools back to their ‘home’ discipline.

I submit that we must move away from the thinking that our role is in scaling up existing biosciences developments. Innovation now moves quickly and we must not wait around to do the scale-up but be involved in the innovation.

Some areas which chemical engineers might work in are:

• therapeutic proteins using rDNA. All biochemical engineers are aware of this are of research. Most of the modern protein drugs are being produced by recombinant DNA organisms or modified cells. The development of solid chemical engineering input requires that we do these modifications within the chemical engineering laboratories. We must become skilled and learn the potential of the techniques. After all they are now routinely done in undergraduate biology laboratories. In carrying these modifications out we learn the difficulties which occur when there is incorrect glycosylation of the protein. What are the factors which influence glycosylation - can they be controlled.
• biomaterials - tissue engineering is thought to be the next big area, it includes skin - replacements (ulcers, burns), cartilage, vascular grafts as well as whole organs. The key role for chemical engineering is in getting the design parameters worked out
• drug delivery - this is an engineering problem, there is need to design to enter the human body in the right place, and not just the preparation of a chemical. Cytosine activity, say, depends on rates of synthesis over extended time scales and not just concentrations
• smart materials for recognition using peptides;
• the quantification of cellular biological processes
• genomics: the problem of development of high throughput screening using nanolitre volumes, and ligand/receptor models
• directed evolution and metabolic engineering offer possibilities for reactor network models to be used in cell physiology and microbial physiology.
• multiple gene manipulation.
• contribution to developmental biology

In order to understand our future roles we need to understand more about the nature of the new biotech businesses and the nature of the innovative enterprise in the market place. These general principles govern the way in which biotech industries develop. The role of engineers in these businesses is crucial but not traditional. There remain a role for bioprocess engineering and the traditional skills but there are other roles with which they must be combined.

Design of a useful product can be reverse engineered. The starting point is a customer's need, usually for a service, which may be perceived to be satisfied through the provision of a product. The product needs to be produced by a process, which needs some knowledge assembled or created to make it possible to achieve. The design starts with the product, then the process, then the research. In order to achieve rapid innovation all knowledge required to produce the product must be assembled or created in parallel. This way the engineering is brought straight back to the design of the research programme. Involvement of the engineer in the initial concepts, innovation and designs leads to being involved in designing and carrying out he research programme. An interdisciplinary knowledge is required as the research programme will involve collaboration between many disciplines. Engineers will use their talents at the laboratory scale and in modelling to accelerate the innovation process. Engineering will not have the time to optimise a process. Any process used will have to be feasible and reliable.

The greatest prize for the life sciences is a full understanding of the human body and especially the brain. Engineers can help in such an enterprise and may have as a target an immensely ambitious project to model mathematically the full set of processes in the human body. Such a model could then be used to simulate the effect of administering any given drug in any mode or formulation. How does the body work? Can we model it in sufficient detail to predict the fat of a drug administered at any point in the body? How do we build the information to connect the models to data and inter-relate sub-models? The body is a complex multi-site reaction/diffusion/convection system with built in and external control mechanisms that operate on both the short and long term, and on scales which vary from the sub-cellular organelle through cell, tissue, organ, circulation system and whole body. This task of building a comprehensive model dwarfs the human genome project. It builds on the latter but requires the full information on genome functionality and also on the factors, which lead to the expression of different genes.

The model which engineers would help build of the human body would be expected to help answer many questions. Rather like a flight simulator or chemical plant simulation model the human body model would simulate the action of drugs and other manipulations. In order to build the model much biological science, pharmacology and medical knowledge is required but the engineering skills lie in bringing it together.

What questions should we expect to have to answer? How do drugs act on the body? How does the point of administration affect passage though the body and its effects? Sub-cutaneous implantation, powder injection, aerosol inhalation, skin patches as well as the standard oral and anal routes need modelling. The formulation of a drug to control the rate of release is vitally important. We need to understand the relationship between concentration, rate of release and action on the body.

Can the body be induced to change its metabolism in order to synthesise active pharmaceutical ingredients locally? Can we use cell signalling with hormones, peptides, rare-earth metals to induce the synthesis of complex and active compounds by the bodies cells? How do multiple ingredients act together to change the bodies response? Even more important is the need to account for human individuality. The greatest difference between the physicist and the physician is that the physicist creates cosmic models meant to apply to all similar items in universal laws. The physician regards the data on one patient as being unique and only applicable with a great deal of caution to the response of another patient. Can genetic information be used to incorporate individuality into understanding of pharmaceutical response? Already some companies are marketing genetic tests to allow different heart disease treatments to be given depending on the patients genotype.

Obviously the grand goal of the body simulator will require a lot of development of models on the constituent parts of the body. These avenues for the use of chemical engineering knowledge are quite different from the traditional view of biochemical engineering. There are other possible roles for the engineer, which also differ from the traditional objectives of scaling up a process.

Traditionally bioprocess engineering has been concerned with the development and optimisation of hardware for carrying out the cultivation of cells - animal or microbial or plant, and the separation and purification of their products. The automation and use of biosensors etc have also been important. The traditional role has been important for the pharmaceutical industry producing relatively large quantities of product. Even now whilst the mass of active ingredients is usually smaller the concentrations tend to be lower and so fermentation volumes may be significant but no longer large. Antibiotics are beginning to lose their effectiveness and we may need to turn to new techniques to handle infectious diseases. Immunology and the control of the body's own immune systems may be the next breakthrough. The effects are likely to be achieved with small doses of perhaps multiple activity drugs. The problems of scale-up and design of large facilities will no longer be important. The nature of the involvement of the engineer will be completely different.

I believe that biochemical engineers need education at the post-graduate level in microbiology, molecular biology, advanced statistics, mathematical modelling, drug formulation and pharmacology as well as increasingly sophisticated knowledge of reactions, catalysis and transport not to mention thermodynamics. The integration of such knowledge is difficult and time consuming. It cannot be done easily within the conventional UK PhD programme with its three-year time horizon and limited advanced course structure. The need to learn to work in teams makes me believe that an approach to post graduate research will require a virtual education system using distance learning for some courses but local contact between students in different disciplines working together on the same project area. Funding for large group projects is not traditional and so putting together such teams across departmental boundaries will not be easy. On the other hand it should provide the greatest benefit to all members of the group where they are interested in producing value added and innovative products which is only of interest to a subset of biologists.

Students doing research in biochemical engineering should be expected to take courses in biochemistry, molecular and cell biology, cell physiology, microbiology, genetics and protein chemistry.

It is most likely that these approaches will be of more immediate value to the medical fraternity but they, whilst finding it easier to understand the motivation of engineers, find it harder to understand their true function. The soft contribution of engineers to design, and modelling is not as easy to understand as the hardware contributions to making hip-joints, MIR machines or wheel-chairs. There is an educational gap here that we need to bridge. If we do not do this we will always be seen as those who come in when all the exciting science has been done to build the big fermenters and perform scale-up and incremental process change.

We want to be concerned with the fast innovation, the sharp end and working in the industrial areas where the jobs and opportunities are growing not declining.

At MIT the Centre for Bioprocess engineering used to work on downstream processing and cell culture but now the emphasis has shifted to cellular processes and nucleic acid technology, protein design and production (protein engineering; gene expression). cell migration, neural and vascular tissue engineering. These fields represent a great deal of the current activity in biochemical engineering across the USA. Some other interesting current areas include Metabolic Engineering, Directed Biosynthesis, Signal transduction, Metabolic modelling, Drug design, Biological membranes, Bio-sensors, Biocatalysis

• "Whilst interactions between chemical engineers and molecular biologists allows application for NIH funding, it was not clear that research in this area had reduced funding available for biochemical engineering from NSF as yet".
• "Not enough people are being trained in the area of bioprocessing in USA which industry still requires."

A vast amount of biomedical engineering work is now being carried out in the USA. As far as Chemical Engineers are concerned the great interests are in tissue engineering, artificial organs, and drug delivery. These are carried out in collaboration with biologists and also medical scientists and physicians who were though to be more sympathetic to an engineering approach.

In order to develop the interdisciplinary research culture in the UK we need to start to recruit applied scientists - physicists, chemists and biologists into the chemical engineering departments so that we have an overall culture which automatically imports useful tools into chemical engineering from wherever they are currently being used. We need to become expert in their use. It is useful to look at how biochemical engineering has developed in the USA, and how chemical engineers there comment on the UK and European scene. During a visit to the USA by chemical engineering academics in 1998, many chemical engineering faculty in leading Departments across the USA were interviewed. They had views on the differences between their own activities and out chemical engineering departments.

• One U.S. department commented that "Everyone hired since 1982 is in the area of applied physics, chemistry, biology, i.e. engineering science. This is not what the UK does".
• There is greater interaction with other departments (e.g. biology, physics, chemistry and materials). This contrasts with Europe, where there is much less interaction between various disciplines. Through contacts with chemistry, new horizons are being opened up. One of the challenges for UK and US chemical engineers is to bridge the gaps between disciplines.
• Often we were told that that they [the US] considered their UK competitors to be in physics and chemistry departments, and that "Contacts with UK are rarely in chem eng."

To work in a field, which would be thought interdisciplinary at present, requires either a team of people with different backgrounds to work on the problem, or a set of versatile individuals. Individuals can acquire most of the specific knowledge necessary, and refer to expert consultants where support on background information is required. Substantial funds are required to support a team approach, so having a centre in which a number of people collaborate on a variety of different projects, facilitates team working without excessive expenditures on single projects. A single investigator who has developed the necessary skills can use the second approach. It would be helpful and efficient if encouragement is given to people willing to follow this course so that they can be encouraged to acquire additional expertise through working on an appropriate project.

In the US, we found both approaches being used; in the UK we have found both approaches were thought to be difficult. The IRCs have not tended to spread a wide interdisciplinary umbrella, and have not assembled very diverse teams. Individuals have reported extreme frustration in having grant proposal referees requesting that they set up collaborations which are really too cumbersome for the size of the projects proposed. In addition, the constraints of the RAE work against scientists collaborating with another discipline that they perceive to be publishing in "low impact factor" journals. In general chemical engineering journals have much much lower impact factors than the top biology journals.

Unless these structural difficulties can be overcome, it will be difficult for the UK researchers to make progress in the new areas at the interface between chemical engineering and biology and/or medicine. There are other difficulties too, which relate to a suspicion of those with a life sciences background wanting to join chemical engineering departments. The more traditional or conservative heads of departments do the discipline few favours if they insist on holding back the development of the profession into the new and expanding areas of industrial importance.

We need to learn how to teach students in an interdisciplinary environment. There is a model that places a student in one department with supervisors in two different departments. This is difficult for the student as it is never easy to serve two masters. How do individual faculty develop these interdisciplinary skills?

The UK is not unique in having these barriers; the US had the same problem, but overcame them about 15 years ago. They did it, by and large, by having exceptional individuals who learned the tools from other disciplines and imported them into chemical engineering. Perhaps the climate was easier, perhaps the individuals were exceptional, in any case the pioneers made the current highly interdisciplinary approach possible for the majority. It is probable that the inclusivity and diversity of their funding system made it easier for these exceptional individuals to find the gaps and get the funding process and learning processes underway.

A particular strength of many of the chemical engineering departments, which we visited, is the naturally multidisciplinary staff (physicists, chemists and biologists). However, encouragement of individuals is not the only mechanism in the US to promote multidisciplinary work. There are centres at many universities (and departments) for encouraging collaborative work. The centres themselves define project areas that require a multidisciplinary approach. But this is not the whole of the story, for we have seen evidence that even these approaches do not yield the highest levels of teamwork considered essential for some projects. The Department of Energy in particular will first look towards the national laboratories when commissioning a highly multidisciplinary project. The national labs in their natural structure and management are said to work best of all. A former director of a national lab attributed this to, amongst other things, the appraisal system that rewarded the team, group, or department, rather than individuals. An important philosophical note about centres is that the US now considers that… "

The funding available to the US biochemical engineers comes from many different sources which allows a greater diversity of approaches than if it is all channelled through a single committee as has happened in the UK. However enlightened the committee it cannot possibly pay equal attention to all the important issues in such a wide field. The US has the National Institutes of Health (21 separate bodies in terms of funding decisions), the Bioengineering and Environmental Systems Division and the Chemical and Transport Systems Design Division each separately fund biochemical engineering through their different programmes. It is an inclusive theory of funding not an exclusive one, which has to first determine the boundaries and woe betide anyone who tries to step across them.

Different disciplines have different cultures, and successful collaboration requires mutual learning. Many considered collaboration to be neither easy, nor natural. Often, pure scientists are concerned with a single area, with the aim to become a specialist. Chemical engineers will tackle anything, which they can contribute to, and often the important areas are related to a problem in industry. There is strong anecdotal evidence that the strategies and policies of the NSF have driven the chemical engineering community towards more collaborative ventures. This may have been via the push towards pure science at the boundaries of traditional subjects, where chemical engineers found that they had to collaborate in order to be successful. Another important factor for fruitful collaboration is for each party to contribute to learning the other’s field. Further collaboration is either cemented of generated by attending conferences. Chemical engineers brought their own approach to these joint problems and projects. For example, biologists want to understand the question, their experimental systems are set up to reveal knowledge, and they want clean data:

It is common to find many different ‘home’ disciplines in a chemical engineering department. Those staff with non chemical engineering backgrounds will naturally continue their research using the knowledge gathered when studying their earlier discipline(s). They may well also take on students with non-chemical engineering backgrounds. Typically such students would be located in the most relevant department, to avoid them having to take all the chemical engineering core courses, though they will inevitably be required to take some chemical engineering courses.

In the UK, our study showed that there is now a wide range of disciplinary backgrounds for staff chemical engineering departments. In the UK, about 25% had Ph.Ds from departments besides chemical engineering, compared to 34% in the USA. More significant was that those non-chemical engineers in UK departments had usually only switched from their first discipline on appointment as staff. Those in the USA tended to move around much earlier. In the USA a postdoc is now almost universal for new academics, and predominantly it will have been in a discipline different from the home one (to fill their ‘toolbox’ with new ideas and techniques). Whereas in the UK, many will do a postdoc, most often in the same type of department as their Ph.D, and in many cases in the same institution. The majority of new appointees in the US will have made an early switch of discipline. In fact, one department said that

The responses to the UK questionnaire indicated a difficulty in progressing research that incorporates new scientific knowledge into chemical engineering research. However, it is very encouraging that there are UK people who are trying to break into truly multidisciplinary areas.

Time and again we were told of the need for there to be intellectual excitement (not just challenge) to attract the best young people into chemical engineering. The US has interpreted this as needing to break into areas started by pure science, or to generate whole new areas of research themselves – both routes are naturally multidisciplinary. The new areas of the life sciences are exciting and there are great challenges. Learn as many new tools as you can , apply them to innovation and development of new products. There is also excitement in the environmental field examining techniques for bioremediation of ecosystems and soils. These again are complex problems requiring the marrying of mathematical and modelling skills with the ability to make measurements and use new synthetic tools to create new entities and products which will benefit society. Universities must once more be fun places to work.

Multiple reactions occur in a eucaryotic cell and the sites are distributed in the cell requiring transport mechanisms. If these cells are being used to manufacture a pharmaceutical how can we ensure that all the cells in a large reactor system behave the same way? Do we want to scale-up cell culture systems by calculating the average response or do we want to design such systems so that each cell receives the same or controllably different stimuli from their environment.

How can we control the growth of different types of cells together so as to make tissue? How do we control the flow of nutrients to a complex 3-dimensional cell structure. If we are culturing patients cell in tissue for future use as an auto transplant how do we control the apoptosis or programmed cell death?

Modifying the environment of a cell will modify its responses. The modification can be in the form of common physico-chemical variables such as pH and dissolved oxygen concentrations but also in the use of cell signalling molecules and complex nutrients and hormones which change the response of the cells. Cells may be developed from a stem cell with differentiation into different functions. In other cells the differentiation occurs because of the environmental situation as in the liver. Here different cells make fibronectin and bile acids and other compounds from the cells which detoxify alcohol for example. How is that differentiation achieved?

Recombinant techniques or other forms of gene manipulation may induce genetic modification of the cell. Developing good techniques to transfer genetic information into animal cells is needed to develop gene therapy from the current rather unsatisfactory situation to the practical use of the therapy. Using animal cells means that target proteins are easily expressed by the cell into the surrounding media and therefore more easily recovered than with some bacterially produced proteins. However for therapeutic use these proteins can be contaminated with retrovirus particles. This prospect is sufficiently problematic that the standards require less than 1 particle in 10¹² doses. The requirement makes it extra-ordinarily difficult to validate. It cannot be done by analysis and has to be done by using multiple separation steps each of which have had their clearance rate proved. The problem is not present for proteins to be used in analysis and so monoclonal antibodies for diagnostics are a major product of animal cells. Here standardised culture facilities are used to produce a wide range of similar products. New engineering is not required at the process level.

Sometimes multiple genes need inserting and the expressed genes produce enzymes which work together to have a fully functioning pathway. The modelling of the expression systems and the engineering of the pathway so that bottlenecks are avoided and the right amount of each gene is inserted into the cell is well handled by a good model. Engineers have the ability to take on such complex modelling tasks.

The presence of a cell signalling agent will modify the response of a cell. The quantity which will be present in the vicinity of a single cell will depend on local transport mechanisms. This is important to quantify properly. Controlling metabolism by these techniques and incorporating methods of influencing the natural control methods of the body will require new devices which are sensitive to the presence of small specific molecules and also provision of micro-manipulation techniques which can provide the correct corrective action when control is required. Getting this right when the cell has truly complex metabolic requirements is not straightforward. The interaction of the different control mechanisms needs modelling and quantifying.

Devices may be constructed such as controllers, tissue systems, metabolic manipulator pumps or drug delivery systems with intelligent membranes surrounding the drug and varying the release according to the local environment. The design of such devices is an engineers task.

It is now possible to purchase chips which will reveal the nature of the expressed genes in a microbial or other cell culture. If we investigate the relationship between environment and gene expression, and if we know the function of a given gene and how it operates quantitatively as well as qualitatively we can use the gene chip to investigate understand and ultimately control microbial physiology.

The processing of the information gathered by such chips which will become increasingly much cheaper is another gigantic task facing information technology. How do we process intelligently such a vast amount of information relating to functional genomics. Is the current technique of neural network modelling going to be sufficient to relate such information in the form of a useful model or will we need new mathematical approaches in order to make sense and add value to the data. The engineers' approach of always seeking to add value to information so that it becomes capable of exploitation for the good of mankind is necessary to involve in such exercises at an early stage. Pragmatism in interpretation will be required at least in the short term so that information acquired on different time and length scales can be integrated usefully.