In Search of Techne

Ch 3.5: Applied Biology and Biotechnology

(c) Roy Johnston 1999

(comments to rjtechne@iol.ie)

February 19 1970

International collaboration in scientific work, with co-ordination of effort and common standards, has in recent decades become...fashionable. There is currently on foot an international collaboration in biology, known as the International Biological Programme (IBP), for which the central national corresponding body is the National Committee for Biology of the Royal Irish Academy. A sub-committee, under Pat O'Donnell of an Foras Taluntais, co-ordinates the national effort.

An annual grant of 15,000 has been made available through the Department of Education to the RIA for this purpose. This was by no means automatic; it had to be lobbied for. The existence of the National Science Council, which advises the Minister, is generally regarded as having been helpful in this respect.

The work involves no less than eleven centres, so that the grant is spread rather thinly. However it is to be welcomed that a multi-centred collaborative effort within Ireland has been stimulated in this way.

The centres include the Zoology and Botany Departments of TCD and the corresponding departments in UCD, together with the Departments of Chemistry, Microbiology and Industrial Microbiology. From AFT are involved the Soil Physics section at Kinsealy and the Glemamoy centre in Mayo. The Gowla research station of the Department of Lands is also involved, as well as the Engineering Department of University College Cork. The whole effort is backed up with technical support from the Meteorological Service. There are a total of 30 researchers involved.

The unifying factor in this, at first sight curious, assembly is a well-known national resource: peat.

There is no participation by either Bord na Mona or the Sugar Company, despite the substantial interests of both bodies in peat research. The reason for this is that the primary concern of these bodies is in the uses of peat, rather than the mechanisms of its formation, with which the collaboration is primarily concerned. Also the type of bog selected for the collaboration (at Glenamoy) is not in the mainstream of the economic resource development programme.

It is a pity however that the opportunity has been missed, on the part of Bord na Mona, of getting the academics involved in looking at the cutaway bog utilisation problem; this might have followed had they been in on the planning. There appears to be a cultural gap between the peat technologists and the peat scientists.

There is needed a group in applied peat research which would have the respect of the development technologists, and would also be sufficiently aware of what the scientists were doing to be able to talk to them, and perhaps influence the planning of the experiments so as to get information of eventual relevance to peat technology.

...Government science policy needs to foster the existence of bridge-groups such as this, by tax-concessions or subsidies. The lack of such bridge-groups is the single most effective factor in keeping the results of research in the academic journals. This pattern also exists in Britain; we have historically been influenced to copy it(1), to the detriment of the vitality of both science and technology in Ireland.

***

One of the central long-term problems in feeding the world is how to replace the nitrogen, used in all living things as a key body-building component, which is taken up by the plants from the soil.

Leguminous plants (peas, clover etc), by a process involving micro-organisms living in the roots, enrich the soil with nitrogen fixed from the air.

This subtle process has declined in relative importance since the discovery of the Haber process for ammonia production, at the end of the last centruy. This process involves extremes of temperature and pressure, and high-intensity electrical discharges; obviously a brute-force method for doing what the micro-organisms do by cunning.

It is now being realised that this short-cut has its drawbacks. Not only does the continued use of chemical fertiliser tend to degrade the soil structure.....but also run-off of soluble nitrogen compounds into the rivers and lakes has so enriched the latter that in warm weather one gets explosive growth of blue-green algae on the surface. Algal blooms have been reported on Lough Neagh in recent years....

It is therefore timely that attention is being given by an Foras Taluntais to the unravelling of the natural process.....

The complexity of this problem is illustrated that in a sense the nitrogen-fixing organism in the clover is a 'disease' that the plant is trying to get rid of. Bumper crops of legumes can be obtained if it is eradicated by chemical tampering. This is fine for animal feed, but bad for nitrogen fixation.

April 7 1971

The Dublin section of the Society of Chemistry in Industry is holding a symposium on the industrial applications of enzymes on April 15-16... This is of importance for industries dependent on natural products.

Anyone reading Dr W Fogarty's article in the March Technology Ireland, and who realises as a result that his process depends basically on the working of these subtle biochemical catalysts should take time off to go.....

Those little fellows in the TV ads who gobble up the stains in the washing really exist; they would count as enzymes of the proteolytic variety. It is questionable whether they are active at the temperature of the average wash; a warm soak is better. They are voracious enough to attack human skin, and there is a tendency for manufacturers on the US market to withdraw them. Consumers in Ireland are, alas, not well-enough organised and influential to raise these matters sharply.

The real pay-off in enzyme chemistry, I suggest, lies in the solution of the problem of retaining the fresh quality of food under storage conditions(2)....

April 21 1971

The biological sciences, and especially biochemistry, are currently enjoying a bonanza, something like the physicists did in the decade after the second world war.

The reasons for this are partly technological and partly socio-economic in origin. The technological reason is the increasing availability of techniques imported from physics; this is healthy. It is in the same tradition as the century-old borrowing between physics and electrical engineering, with the added dimension that it is 'lateral' (ie across the specialities) rather than 'vertical' (ie along the 'fundamental-applied' axis).

The socio-economic reason is not so basically healthy. Insofar as the market is dominated by the demand among the rich in the rich countries, knowhow tends to be pulled into the production of biologically-derived products to cater for ailments caused by over-indulgence in food, and lack of excercise due to over-indulgence in mechanised transport. This is the same principle as the Roman vomitorium.

Also, as medical science progresses, there are found increasingly rare conditions which depend on some sort of enzyme deficiency. Addition of the appropriate enzyme to the diet constitutes a cure, in the sense that insulin is a cure for diabetes.

The funding of this kind of research comes mainly from the pharmaceutical industry, which can be quite unscrupulous about generating wants, as distinct from satisfying needs, and from bodies such as the Wellcome Foundation.

Professor Fottrell, in UCG, has been funded by Wellcome for work on intestinal mucous enzymes relating to coeliac disease. This condition involves the damaging of the intestine by protein contained in wheat, with serious results. If the missing enzyme (ie that responsible in normal digestive systems for taking care of the offending protein) can be identified, isolated and replaced, another cause of human suffering will have become amenable to management, at a cost which can be reduced as production techniques improve.

Professor Fottrell was one of the speakers at a seminar at the April 15-16 seminar......

Professor Spencer of TCD gave an introductory address outlining the present and possible future applications of enzymes in the Irish economy. Dr Gray, of London University, outlined some techniques for isolating and extracting enzymes on the industrial scale. Professor Fox, of UCC, outlined applications in the food industry. Dr Letters, of Guinness's, described current brewing enzyme knowledge......Mr A E Lawrence, from a British tanning firm, spoke of the role of enzymes in his industry, and Mr C Culligan spoke of some of the problems of enzyme production on a commercial scale in Ireland.

There was evident to me a considerable gulf between the thinking of the academics and the industrial biochemists. This may be illustrated by noting the preoccupation of the former with the isolation and preparation of pure substances, in contrast to the brewers and the tanners who were content to let the enzymes work away in the mash or the bate(3), more or less as the good Lord intended. Enzyme know-how is useful for control purposes, but isolated pure enzymes are more or less irrelevant.

This gulf in thinking is illustrated by the relative sizes of the Irish market (200,000) and the world market (50M) for enzymes. By concentrating on this chickenfeed the academics appear to be overlooking the value to the Irish market of goods of which the quality depends decisively on enzyme-controlled processes; this exceeds by a large factor the total world market for purified enzymes.

Thus the way forward is to get to understand and control the enzyme-dependent processes in the food industry; this is where the mass of the academic effort should go. Professor Fox, to judge from his paper, is aware of this....

I do not want to dismiss entirely the pharmaceutical end of the business. There is a large supply of gland material in our abattoirs currently going to waste; this could be a good source of purified enzyme material; so could fish offal. The latter produces partucularly potent enzymes which can work at low temperature.....

Mr Culligan, of Chemical Export Co, Shannon, developed a few useful ideas for a synergetic approach between food and pharmaceuticals. Dr Gray, of London, had previously outlined the process engineering techniques involved in enzyme extraction. Mr Culligan pointed out that the unit-processes involved were substantially the same as those involved in milk processing, and that the creameries could perhaps go over to enzyme production in the off-season(4)......

The further purification of enzymes is basically a laboratory-type operation. Dr Nichol declared the intention of developing this capability in the IIRS.

Mr Culligan had a criticism to make of the so-called export tax incentives. Because he is based in Shannon, his suppliers of offal get an export tax rebate. If he were, technically, an Irish manufacturer instead of an 'export-market', his suppliers would be taxed. Thus the tax system works to penalise vertically-integrated Irisn industry based on local raw materials.

There emerged in discussion a similar and more serious lunacy, which partly underlies the present crisis in the shoe industry. Hides are exported, thus gaining tax rebate. Irish tanneries import hides for tanning, then they export the leather, gaining tax rebate. Finally the unfortunate shoe manufacturer has to import leather, some of which is local Irish raw material which has crosses the Irish Sea four times.

Thus it seems that there are means to hand of increasing the wealth of the nation without spending anything on exotic knowledge!

***

I received recently some ideas from MJ Clancy, of AFT Oakpark, which fill the gap between what I can label as the 'traditional natural product' people (brewers, tanners) and the 'ultras' who are interested in pure pharmaceutical enzymes. They would benefit from interaction with the type of thinking in Dr Gray's paper (above). I'm not sure if I am entitled to label it the 'Clancy process' as it owes much to Professor Joslynn of Berkeley(2) who is currently at Oakpark.

Basically the process consists in the use of yeast for the production of high-quality protein from wheat, supplemented by urea as a cheap nitrogen-source.

The core of the process is the use of a low-protein flour suspended in a urea solution as a substrate for growing yeast. This can be done continuously on an industrial scale. The yeast is then processed to extract the nucleic acid, which can be used to synthesise a high-grade marketable vegetable protein which is meat-like in texture. There is growth potential in this market. The residues go for animal feed.

A yeast is a much more efficient protein concentrator than an animal.

But how does one get this process to the production stage, even experimentally? Pilot-plant work should be factory-based, not laboratory based. In the former case one has some hope of estimating the costs.

The natural place for such a plant would be near its largest raw-material source, in other words, a flour mill. The laboratory people who had invented the process would need to live with the scale-up for a period. Someone would have to pay for this development, and someone would have to own the resulting process. There are many structural snags here, which perhaps illustrates why science in Ireland tends to remain academic!

May 5 1971

I have to hand it to the UCD engineers and medicals; they have apparently been practising what I have been preaching with success. When I listened to Dr JJ Kelly's paper on the theoretical basis of blood-clotting on foreign surfaces on November 27 last, I was inclined to dismiss it as another piece of academic paper for the weighing-scales, rather than anything to do with chemical engineering, on which ground it nominally existed.

But when on April 14 there was unveiled a blood-clotting instrument, as developed and patented in UCD and manufactured by MSE ltd, I was moved to take off my hat. This proves it can be done: a practical example of how applied, patentable, revenue-earning research can be combined with a spin-off of reputable academic material, publishable in such a way that no-one would suspect what else was involved.

The actual device, as reported by the Medical Correspondent on April 14, is the joint work of Dr Noel Clarke, Tom Moriarty and B P Woods, who are respectively pathologist, engineer and biochemist. This will give a good start to the newly founded Biomedical Engineering Society(5).....

December 1 1971

...A contract for the transfer of ergot technology was announced on November 5 between the IIRS and Lilmar ltd. The system involves classical agricultural techniques, bacteriological-type techniques to prepare an inoculum, novel agricultural techniques to inoculate the rye-crop, industrial techniques to separate the ergot from the rye grains at harvest-time, followed by the techniques of biohemical engineering to extract the alkaloid and prepare it for medicinal use.

(Failure to control ergot infection of rye in the middle ages led occasionally to a communal disease known as 'ergotism', brought about by eating infected rye bread. There was an outbreak in France during the 50s of this century.)

The type of organised multi-disciplinary know-how involved in this project is perhaps typical of what has come to be known as an 'operational research' approach to problems.....

March 28 1973

On March 16 I attended the inaugural meeting of the UCD Biological Society. The main speaker was Dr Wullstein of the University of Utah, where he holds the Chair of Environmental Studies; the subject was a review of the present position on nitrogen fixation by biological processes.

This topic is of key long-term importance. Dr Tom WalshV(6), who spoke to the paper, attempted to bring this out, but failed evidently to break through to the student audience, which spent its time whispering and tittering. I attribute this type of student facetiousness, this lack of a serious-minded approach to serious topics, to the retardation on mental growth caused by the repressive environment in some of 'our' secondary schools. I put 'our' in quotes because we, the taxpayers, pay for them, yet they are not our property and we have, apparently, little or no say in what goes on in them. My sympathy goes out to the dedicated minority who are prepared to serve on committees of student scientific societies and squirm while audiences like this insult distinguished guest speakers.....

Professor Wullstein quantified the 'information explosion': 25 papers from 1906 to 1925, 12 per annum from 1928 to 1958, 1200 papers since 1958.

He outlined the classic 19th century controversy in which Liebig, one of the founding fathers of industrial chemistry, ridiculed the idea that free nitrogen could be removed from the air by biological processes.

As early as 1858 it was discovered that the nodules on the roots of legumes contained bacterial (Rhyzobium) which were able to remove free nitrogen from the air and make it available to the host-plant. These bacteria, however, if free in the soil, were unable to do the job, while others, such as azotobacter, were able. But 'free fixers', as they are called, are no good in agriculture; conditions in the soil are too harsh.

The details of the mechanism are starting to emerge. The metals molybdenum and iron play a key role, being bound in large protein molecules. The key chemical step is the formation of a complex nitride of iron and molybdenum, the nitrogen subsequently being reduced to ammonia. Haemoglobin is involved; its role is to remove the oxygen from the environment, allowing the nitrogen fixation to take place under anaerobic conditions.

All this occurs in the nodule on the root of the clover, supplied with photosynthetic energy by the leaves of the plant: an elegant symbiotic system which succeeds by cunning in doing what the chemical industry requires high-pressure, high-temperature reactions to do, at the expense of substantial consumption of irreplaceable fossil fuel.

This elegant process supplies, at present, the bulk of the world's nitrogen, and has done so for many millions of years. On the other hand, 'brute force' nitrogen applied in agriculture, as well as running off the land into the rivers, stimulates the plants to deplete the reserves of natural fertility in the soil. This in the long-term is ecological suicide.

When the price of fossil fuel goes up with scarcity, perhaps clover will come back into its own. In the meantime, according to Professor Wullstein, the art of fixing nitrogen is becoming understood to the extent that it is now possible to persuade bacteria to do so by fiddling with their genetic structures: 'genetic engineering'. If this can be transferred to higher plants, we could, perhaps, get grass which supplied its own nitrogen needs from the air.

Dr Tom Walsh, commenting on this, pointed out that our national consumption of nitrogenous fertiliser in successive decades was 10, 25, 65 thousand tonnes and that by 1980 this figure would be 400 thousand tonnes if the livestock targets were to be achieved.

Despite this, there were no measures of available nitrogen for plants. There were less than five people engaged in basic research in this direction in the country. Here was an area of basic research which was academically at the frontiers of knowledge, and at the same time was closely linked to our main economic activity. (These considerations, which are, I suggest, important, the student audience found to be either a bore or a joke.)

Dr Wullstein is working at Johnstown Castle(7), on sabbatical leave. This is the main centre where work in this important basic-applied field is going on; I have referred previously to the work of Masterson and others(8).

It is likely that some cross-links between the Universities and an Foras Taluntais will develop as a result of his stay. The UCD Biological Society deserves credit for having taken the initiative in this respect.

April 25 1973

The Federation of European Biochemical Societies, which met in Dublin last week, received good news coverage from David Nowlan(9), who picked out a handful of the 114 papers which were of public interest and treated them in some depth.

It remains for me to give an over-view of the event, to assess its significant features....... Having been involved last year in the international conference of the Federation of Operations Research Societies....I find the FEBS event interesting, as an element in the experimental material available to the student of conference-ology.

Whether a conference is a success or not for its participants depends on how its parallel sessions are organised. They can be structured so as to give maximum frustration to the maximum number, in which case the conference is judged by consensus to have been a failure.

An ideal structure would give the participant what he or she wanted in the way of specialist information, while enabling people to browse a bit, to peep over the boundaries.

I met one participant who dismissed it as a waste of time, while another praised it as an opportunity to 'get back into the swim'. Both had read papers, both were in non-academic applied biochemistry, and both must have felt that in the Irish environment they were out of 'the swim'. This suggests a gulf between academic and applied biochemistry in Ireland. But to judge from the content of the conference, this is a world phenomenon. Where is 'the swim'? Does one define it in terms of topics which the academic establishment think are important?

I suggest that a person's feeling for where the mainstream is depends on the degree of personal fulfilment in current work, and the extent to which it is appreciated and accepted. A conference like this is a success for someone if, when the work is explained, people 'buy' it and ask for reprints.

It is instructive to do some analysis to display the trends in fashion. The 'symposia' are invited papers giving reviews of the current situation. The 'free communications' provide a channel for people to break through and become recognised. The ratio of the latter to the former is a measure of the rate of increase or decreas on interest in a field.

     Topic            Symposia            Free Communications
                   other    Irish       other          Irish

     Enzyme
       production    3         0           6             2
       purification  2         1          17             4
       application   2         1          13             5

     Fermentation
       Brewery       3         0           9             1
       Other         3         0          19             0

     New Protein
     Sources         3         0           6             1

     Industrial
     Effluents       3         0           4             2

     Bio-deter-
     ioration        3         0          10             1

     Biodegrad-
     ation           3         0          10             1

     Antibiotics     3         0           9             1

     Other Drugs     3         0           7             1

     Drug
     Metabolism      3         0           6             1

     Carbohydrates   3         0           4             4

     Lipids          3         0           4             4

     Analytical
     Techniques      3         0           6             5

     Miscellaneous   0         0           7             5


The two Irish invited papers were by Dr P O Carra of UCG on affinity chromatography, and by Professor PF Fox of UCC on the use of enzymes in food-processing.

The O Carra paper is interesting becasue it described a mathematical technique for strengthening the 'signal' relative to the backgound 'noise' of irrelevant background biochemical reactions which occur when one attempts to isolate and purify enzymes by the affinity chromatography technique......good front-line stuff....invented as recently as 1968.

In the 'free communications' category, one can look at (a) the general run of fashionability, and (b) the extent to which the Irish participate in the fashion rat-race.

Clearly, enzyme work in all its forms is the current high fashion, and the Irish, proportionately, are well up in the forefront of it. The effort is concentrated in UCG (Professor O h-Eocha's department) with four papers; there were two from UCC (Professor Fox's department) two from Guinness's brewery and one from UCD. The basic long-term strategy in all this work is the improvement of our understanding of what goes on in food; in Galway there is also an interest in enzymes of marine origin. The one exception is the UCD paper which is concerned with uricase therapy in gout.

Industrial effluent work seems to be a not 'high fashion' internationally, the Irish effort however being relatively high; it consists of an evaluation of the Pfizer effluent at Ringaskiddy and some UCD work on activated sludge. The other work was from Britain and from Belgium.

The Irish work on carbohydrates and lipids also is relatively high, against a general background which is low. This work is from Moorepark, Dunsinea, UCD and the Sugar Company. It is consistently directed at problems connected with the quality of milk, meat and processed vegetables. In this area the Irish contribution is comparable to the total of all the others. We need not worry about being 'out of the mainstream' here; the mainstream, ultimately, will come to us(10).

The analytical techniques section also includes a strong Irish effort. The Moorepark work on milk protein testing (McGann and O'Connell) achieved some impact(11). Other work came from the IIRS (Findlater and Orsi), TCD (Winder and Campbell, who have been using radioactive tracer techniques) and from Guinness (Egan, O'Connor and MacMurrough.

The 'Miscellaneous' section can be a dustbin or a hothouse for new growths. The Irish contributions consisted of contributions from Donnelly and Delaney (Moorepark) on concentration of whey protein, Spencer and Burnham (TCD) on penicillin assay (could this not have been classed as 'techniques?), Coughlan and Johnson (UCG) on immobilised xanthric oxidase, also Johnson and Thornton on the immobilisation of lacto peroxidase.

The UCG work is clearly testing out the implications of the affinity chromatography technique; I forsee that next time round this will have assumed 'high fashion' status.....

If I were dictating strategy, I would pay more attention to new protein sources. Bailey, in TCD, is a lone wolf in this field in Ireland, as far as FEBS participation is concerned. He is working on an old protein source, wheat. Whatever happened to the work of Clancy in Oakpark, who some years ago was concentrating protein from wheat by fermentation? This is a development area of long-term significance. David Nowlan gave good coverage on this topic, correctly reporting the clash in philosophies between the hydrocarbon people and the others. It is, of course, nonsense to be using fossil fuel as a protein source; this work, if successful, can only hasten the day of ultimate scarcity when the fossil fuels are gone. On the other hand, wheat is still the cheapest source of protein of all; it does constitute a 'new' source in that people have to be re-educated as to its value. Work in this field covers areas like microalgae, metabolic take-up of synthetics etc.

To conclude: we as a nation need never again feel that we are a backwater, at least in this sector of scientific effort. We have let the world know that we are a good base for a 'know-how-intensive' industry. We have the competence to start this ourselves; we do not have to wait until someone leads us by the hand. The obstacles are not among Irish scientists and technologists, but in the economic and administrative environment.

The Minister for Labour, Mr Michael O'Leary, is, however, still at the stage of calling for foreign firms to do their R and D here. He and his colleagues have more than their voices; they have tax policy and grant policy at their disposal. They can start listening to, and underwriting with IDA support, the various 'offensive' proposals coming from the IIRS(12), and the various indications of entrepreneurship emanating from AFT.

January 16 1974

I attended a 'Genetics Operations Research Workshop' in TCD on January 3-4; this was an international event, attended by people from Britain, France, Germany, Switzerland, Holland, Scandinavia and elsewhere.

It was organised by Dr E P Cunningham of AFT, who has established an international reputation as an exponent of statistical techniques for assessing the cost-effectiveness of animal-breeding programmes......

Dr Cunningham is also on the staff of the TCD Department of Genetics; this was founded by Professor George Dawson with a grant from the Sugar Company. When the Sugar Company plant-breeding interests were taken over by an Foras Taluntais, the TCD Genetics Department became closely associated with all AFT plant and animal breeding work.

Undergraduates now receive a balanced course in basic and molecular genetics, and in those aspects of applied genetics which are important to the Irish economy.

Supervision of research students by AFT staff encourages the integration of the Department's work into the national objectives: a model university-industry linkage, in which students are introduced to important applied work by those engaged in it. The latter also have the stimulus of being members of a university department with a wide-ranging research programme, where their capabilities as supervisors are in demand; thus the industry gains the advantage of direct contact with the rising generation of younger scientists, some of whom it may wish to attract to permanent posts.....

As well as Dr Cunningham's work on farm animals (for which the pay-off of a 1% improvement in an economic trait is measurable in millions of pounds.....) there is Dr David McConnell's work on molecular genetics, supported by the NSC. At present a bacterial virus system is being studied, which involves techniques to be developed which are expected to be applicable to cancer viruses; the group is beginning to turn its attention to the latter..... Dr Shaha Thompson (who is Iranian by origin; she is married to Dr Archie Thompson the DIAS physicist) has been developing a service for screening food and drugs for cancer-inducing agents.....

How should this work be financed? It is clearly a waste of time for people with these skills to have to go around with a begging bowl. This is a field where the value of the goods delivered is beyond question. It may, however, be necessary to do some packaging and salesmanship before the market (in this case the farmers, horse and dog breeders, health services, food manufacturers) becomes aware of it and learns to pay up regularly and willingly, on a steady flow basis, by a levy.

The trouble is that most business people place financing academic research at the end of the queue, among the miscellaneous charities. Fortunately in some areas the academics are beginning to recognise the importance of the market, and to do some hard selling. In genetics the product is eminently saleable....

To return to the 'Genetic OR Workshop': the best papers were by Alister Pease ('Investment Strategies in Complex Breeding Programmes') amd Maurice Bichard ('Optimising Multiplication Pyramids with respect to Profit'). The former started in a steel-works as an OR analyst, the latter was an academic geneticist. Both are now teamed up and are heading a European-scale pig-production system, with breeding, multiplication and production vertically integrated. They have a 2.5 year lag between breeding a new trait and introducing it, compared to the usual seven years. They have a contract to introduce their procedures into the Bulgarian state farm system.

Clearly there is money in genetics, and we are lucky to have in Dublin a research centre capable of pulling a conference like this. Incidentally this was a first-ever attempt to bring together the people who work in cost-effectiveness of breeding programmes and to interact them with the operations research people.

February 27 1974

The Irish Dental Association on February 18 launched a fund to finance a team of specialist dental health educators. The theory is that if oral hygiene is taught in the schools, some impact may be made on the national backlog of untreated dental ill-health, estimated at 15M pounds, as well as reducing the loss of working days due to dental disease, estimated at 1M per annum.

The target for the fund-raising campaign is 15,000 in the first year. The first cheque was presented to the Fund by Michael Foy on behalf of the Sugar Company(13).

Dr Seamus O'Hickey, joint chairman of the Dental Association's education committee, paid tribute to the Department of Health, which is '...to make a contribution towards a national dental education programme'.

In this kind of anticipatory tribute to a contribution which had visibly not yet been given I detect a note of desperation. Indeed, this whole excercise should not be necessary if the Departments of Health and Education were doing the jobs for which we pay them. By taking on projects like this the Dental Association is 'letting the State off the hook', and substituting a scheme of which the success is by no means guaranteed.

I suggest that some organised political pressure by dentists, who could spread the word through their patients by issuing each one with a list of points to be raised in letters to TDs, could pull much more than 15,000 out of the Minister for Finance.

There is a mass of scientific work to be done (I include in the the behavioural sciences) in order to find out what goes wrong with teeth, and how an effective system of prevention and treatment can be organised. It is basically a 'systems research' problem, which can only be approached effectively with a co-ordinated interdisciplinary team, under good research management.

It is the policy of the NSC(14) to bring about a situation where all State services automatically provide a flow of funds of the order of 1-2% of their budgets to research. This should include a continuous evaluation of the cost-effectiveness of their present systems, as well as a search for improved systems, methods and devices.

Presumably it is one of the functions of the Department of Public Services to monitor the State departmental system quasi-externally. From the angle of the DPS, the Dental Association's fund-raising scheme should be interpreted as a strong indication that existing oral hygiene education is pitifully inadequate, and should be improved immediately by appropriate measures jointly between the Departments of Health and Education.

Anyone with any experience of private fund-raising schemes will be aware that they tend to eat up in administrative costs rather a large fraction of the funds that they raise. I suggest that the cost of the various schemes which fill the many gaps in the State health services ...be included in any cost-effectiveness study....

September 4 1974

The July/August issue of Technology Ireland contains two articles of biotechnological interest....

There is a project led by Micheal Mac Giobun, of Comharchumann Chorca Dhuibhne, at Baile an Fhirteirigh. For an investment of 10,000 in equipment, of which 3,000 is cultivation machinery, the Co-op has brought 33 acres of land into cultivation growing belladonna, hyoscyamus, chamomile and peppermint. All these are herbs which, if picked at the right time and dried, are valuable raw materials for the pharmaceutical industry.

They have also put down parsley and sage for culinary use; these are relatively easy to grow and bring in a steady profit of the order of 250 per acre. The other herbs are more risky, but highly profitable when successful, bringing in over 1000 pounds per acre. As yet however the frequency distributions of the yields under Kerry conditions are not known.

This type of entrepreneurship is badly needed; it can if successful generate a healthy local industry.... The type of work involved requires a high degree of training in the technicianship and technology associated with the fine-chemicals industry; it could usefully employ science graduates.

As regards the risk-element: there are techniques available whereby using the computer one can evaluate the probable financial returns over a series of randomly-chosen ten-year periods; given some crude information about the relative yields of the risky crops, one can develop a strategy for minimising the risk of failure, while at the same time benefiting from the high profitability of the risky crops.

The IIRS in fact has done some work(15) in a rather similar field some years ago, in relation to growing ergot (a fungus infestation of rye) as a pharmaceutical crop....

The principal scientific input in this case has come from Dr CS O'Connor, head of the Phamacognosy Department of the College of Pharmacy(16) in Dublin.....

Dr AC O'Sullivan, of Moorepark, has an article on 'Ireland's Potential as a Bio-industrial Base', which develops in a more traditional manner the above theme.

In it he re-iterates an old position, on the need for vertical integration with agriculture and the food-processing industry, the staple products being milk and meat.....he exposes the basically wasteful use of food fit for human consumption....as animal-feed; the EEC uses 75% of its skim powder as animal-feed, while 99.4% of US skim powder goes for human consumption.....

He calls also for the development of a high-grade bio-industry, involving sophisticated extraction techniques, fermentations etc applied to by-products.

However it is not enough to list the things which are technically possible and then to wonder why people don't start doing them. It is necessary to do the techno-economic analysis, to develop a financial model of the projected investment, using all that is known about the technical coefficients of the processes, the supply characteristics of the raw materials and the specifications and prices expected in the market.

The basic weakness of Tony O'Sullivan's position is that in this article he repeats uncritically the mythology about quadrupling meat production and doubling milk production by 1983 which has been characteristic of recent Irish Farmers' Association publications. He seems to think that if there is all this production, the overflow of finance into processing will be automatic.

The trouble is that you cannot predict expansion in the livestock industry simply by projecting trends.. You have to understand the dynamics of a livestock population system, with particular reference to the lagged responses and the positive feedback loops in the system which make it fundamentally unstable. The only way to stabilise a system like this is with a very precise feed-forward control, as any engineer will tell you.

A system which allows the price of a basic by-product (and raw material for a related sector), calves, to vary from over 60 in 1973 to less than 5 in 1974 is clearly pathological, requiring close dynamic analysis, with a view to developing effective forecasting and control(17).

Nor can you expect a high-grade bio-industry to establish itself unless it can ensure continuity of supply, and uniformity of quality of its raw materials..

The techno-economic analysis of the seasonality of supply of milk to the milk processors, calves to the beef producers and finished animals to the meat factories, viewing the whole as a vertically and horizontally integrated system on a national basis, is well within the current state of the art.

The output of such an analysis would be a prediction of the cash flow pattern and overall profitability of the type of high-grade industry which Tony O'Sullivan has in mind, as a function of the number of farmers who can be enticed, by suitable contractual arrangements, to become specialist in the management of October-calving herds(4).

Without this analysis, the wild fluctuations induced by the EEC bonanza will continue, and those unfortunate farmers in the West, whose income depends primarily on the sale of calves and young stores, will be bankrupted.

March 30 1976

I was impressed by the BBC 'Horizon' programme on March 8, which showed how what used to be laboratory biochemistry has become scaled up and industrialised, with the aid of some generous and far-sighted finance by the Science Research Council, starting in the 60s.

At that time, the bulk of science research money was still going to 'big physics', which was living on the prestige of having delivered the key weapon systems of world war 2. It took a decisive break with that tradition a decade ago for money to begin to go to enzyme chemistry in significant amounts. Britain is now beginning to reap the harvest, as it holds most of the key patents, and is able to licence out industrial processes which are now serving the US market with mass-produced products.

One of the billion-dollar products is corn syrup. This is 1.5 times as sweet as sugar, and already has a substantial share of the US market for sweeteners. It is produced by enzyme action on corn starch. The enzyme is retained on a fixed substrate, while the starch solution passes through it, as through a filter-bed, converting to sugar without significant expenditure of energy. This is a beautiful process, hopefully a prototype of other similar processes still to come, which in the end will replace many of the 'brute force' processes of the chemical engineering tradition.

The process will work equally well with potato starch. It should therefore be possible technically for the Irish Sugar Company to switch over from sugar beet to potatoes as their main raw material. Whether this is economic or not will depend on the EEC price structure as between sugar and starch.

A key link in the chain between laboratory and full-scale process is the pilot-plant. One of the first major investments of the SRC, in the early days of diversion of funds from 'big physics', was some pilot-scale equipment for the biochemists of University College, London.

A similar investment has been made by the NSC and the IIRS into some industrial-scale equipment which is now set up on the campus of UCG, in close association with the Biochemistry Department. This plant is already generating revenue on the world market for fixed enzymes.

There are other areas where enzyme chemistry is going to transform traditional industry. One of these is the process of making paper from wood.. By breaking down the lignin with an enzyme, all the cellulose can be extracted. In the traditional alkali extraction process, half of the cellulose is lost to the effluent. Now not only do you avoid polluting the lakes, but you get twice the paper per tree. For good measure, you can grow a fungus on the residual lignin, which not only produces the enzyme that you need, but also can be used as animal-feed, replacing fishmeal, and releasing fish for human consumption. This work is being done in Sweden.

The final piece of enzyme wizardry is the replacement of the 'slipped disc' operation by a procedure whereby a proteolytic enzyme is injected (of necessity with some accuracy) into the offending piece of carthilage, dissolving it away. The same enzyme is used to tenderise meat.

One of the snags about this field is that it tends to be secretive. It is difficult to patent what is basically a natural process. Now that it is becoming a big industry, the situation is becoming more acute. The tension between university-based work and industrial needs will probably be resolved in a direction away from free publication and towards direct control by industry, with the university research groups being taken over by business interests. As long as the products of industry are socially useful, this does not present an ethical problem for those concerned with academic freedom. The trouble is that for as long as the sole determinant is the market, the social utility of the product is a matter of chance. Currently, the enzyme people are replacing high-energy inefficient processes by low-energy efficient ones. This is socially useful, and no academic need be afraid of being associated with the process.

Not unrelated tothe foregoing is the work of the UCD Department of Industrial Microbiology, which ran a seminar on February 25......

Dr WM Fogarty, of UCD, outlined the use of fermentations as sources of industrially useful enzymes...particularly beta-amylase, which is the enzyme referred to in the Horizon programme, on which the production of maltose from corn-starch depends.

Dr McKillop reviewed....the types of compounds at present produced in this way, and the range of compounds which could, in principle, be obtained.... Professor Geoghegan spoke on the production of blue-green algae....and Dr GG McEvoy on genetics.

There is scope for strengthening the links between these islands of scientific enterprise in the Irish research system, and the industrial scene in Ireland. The latter should not have to depend on BBC programmes for knowing the state of the art and what their competitors are up to, as I suspect is the case with many firms in the Irish food industry.

September 21 1976

On July 8 of last year I gave preliminary attention to Badgett Cooke Biochemicals, a firm which was at that time seeking a site in Ireland(18). One of the principals, Jeremy Cooke, is a TCD microbiology graduate.

This project has now taken the name Worne Biolytics (Europe) ltd, and is set up in Dun Laoire manufacturing a range of industrial micorbiological products.

The parent company in the US was built up by Dr Howard E Worne over the 30 years since world war 2. The origin of the know-how was the need to preserve military electronic from bacteriological and fungal attack in the tropics.. Dr Worne, while working against the active organisms, had the vision to build up a bank of bacterial and fungal strains with a view to future commercial application. This formed the basis of a business which developed in the late 50s and 60s, whereby bacteriological war was waged against unwanted substances.

Freeze-dried bacteria are prepared in Dun Laoire in quantities of the order of 100,000 pounds weight per annum, and shipped in drums to industrial consumers all over the world (outside the US, where the parent company takes care of the market).

One rapidly growing market is provided by oil tankers operators, who as a result of envrironmentalist pressures now increasingly prefer to buy 'Petrobac' for cleaning out their oil tanks, rather than dump the oily washings in the sea. This useful organism thrives on oil wastes and reduces them to harmless water-soluble residues.

Another useful product is Phenobac, which thrives on cyanide wastes, phenols, insecticides, naphthalene etc. Worne Biolytics currently have a salesman in Italy negotiating with those in charge of cleaning up the aftermath of the Seveso disaster. The noxious chemical concerned is phenolic; Worne are optimistic that somewhere in their arsenal they can find an organism that will cut it into digestible bits and eat it raw.

The range of available biolytics includes Thermobac (which deals with cellulose, lignin etc in paper-mill effluents) and Lipobac which deals with fats and greases.

Agrigest is an animal waste digester and de-odoriser; Agribac is a non-symbiotic nitrogen fixer that can replace nitrogen fertiliser for cereal crops, providing 40-50 lb of nitrogen per acre fixed from the atmosphere at a cost currently claimed to be competitive with chemical nitrogen. The organism is claimed to be active at soil temperatures above 5 degrees C.

This is only a sample of the range of biolytic products which are available. The concept is sound and deserves to succeed, replacing as it does brute-force physical processes with biological cunning. The feasibility of breeding bacterial strains with enhanced specialised activity has been clearly demonstrated in practice.....

NOTES

1. See Chapter 2.1 (Irish Background) for a development of this argument.

2. See also Chapter 4.5 (Agriculture) on 17/9/70.

3. There is a virgin field for someone in the analysis of industrial jargons. The tanners' 'bate' used to be an enzyme-rich concoction of dog and hen excrement. Now it is composed of minced pancreas; the residue after the insulin has been extracted will do. Brewers' 'wort' and 'trub' sound equally exotic. The fact that they are 'four-letter words' testify, perhaps, to their earthy origins. Industrial jargons constitute a barrier to the academically-trained scientist finding his or her feet in industry, and should be given the respect of the study that they deserve.

4. This idea, which at first sight looks technically plausible, would be likely to run foul of the quality standards. For remarks on the quality-seasonality problem, in milk, see Chapter 4.4 (Agriculture) on 25/3/75. I conjecture that the quality control problem for seasonal enzyme production would be substantially more exacting.

5. See 7/4/71 in Chapter 3.1 (Engineering and Manufacturing).

6. Director of an Foras Taluntais (AFT), the Agricultural Institute.

7. The Soils Division of AFT, near Wexford. See Chapter 4.4 (Agriculture) on 10/6/70.

8. See Chapter 4.4 on 18/6/70.

9. The Irish Times Medical Correspondent. If this column is weak in medical science and technology, it is because the writer tended to leave this field to Dr Nowlan.

10. This I think was bad judgment on the writer's part. Most of the Irish work in this field is a rearguard action attempting to defend the quality of Irish dairy produce against the adverse effects of seasonality of supply of the prime raw material.

11. For some remarks of the question of payment for protein rather than fat, see Chapter 4.4 (Agriculture), particularly 19/8/75. See also Chapter 4.5 (Food) on 31/10/73.

12. See Chapter 1.2 (Structures and Institutions) on 26/7/72.

13. Clearly the Sugar Co has a conscience about the role of its product, and the taste for it imposed on children by social pressure, in the genesis of dental decay.

14. This piece, being basically 'policy', should arguably have been in Chapter 1.1.

15. See Chapter (), (date).

16. Now part of the University of Dublin (Trinity College).

17. An approach to this has been developed by Raymond Crotty, who predicted the 1974 disaster in the autumn of 1973, but no-one believed him. He subsequently generalised his livestock population modelling approach to various systems in different parts of the globe, publishing the results in a book 'Cattle, Economics and Development' (Commonwealth Agricultural Bureau, 1980). He is currently with the Systems Development Programme, University of Dublin (Trinity College). The writer is indebted to him for useful insights into the dynamics of Irish agriculture.

18. See Chapter 3.3 (Innovation).

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