Trends in Biotechnology, Vol. 2, No. 4, 1984 109

(cat). Downstream from the coding sequence, the 3' end of the Ti-plasmid nos gene was linked in, providing ter- mination and polyadenylation signals.

Following infection of tobacco plants with the Agrobacter ium, the resulting tumours were induced to produce leaf- like structures containing mature chloroplasts. Only in those cells con- taining mature chloroplasts was the cat

gene expressed. Further, if chloroplast- containing tissue was incubated in the dark, the expression of the cat gene was at a very low level. These results show that the expression of the bacterial cat

gene was under the control of the Ti promoter, and furthermore, the pre- sence of the ssu upstream regulatory sequence caused the cat gene to be con- trolled by light as if it was the normal ssu gene. This interpretation is confirmed by the finding that light- regulation of cat expression did not occur if the ssu regulatory sequence was replaced by the nos promoter.

Finally, in the natural situation, the light-regulation of the ssu gene is at the level of transcription 6. Light-induced

expression of the cat gene (as measured by enzyme activity) was shown to be correlated with a large increase in the amount of the corresponding mRNA, again indicating that the ssu regulatory sequences in the chimaeric gene were acting normally.

The experiments of the Ghent/ Rockefeller groups 5 provide the first published example of a foreign gene inserted into a plant cell being expres- sed at a high level using a specific regulatory signal. That is not to say that regulation of expression of foreign genes in plants can now become routine. Expression at high levels in green cells or tissues may be useful for some purposes, such as conferring resistance to leaf pathogens or modi- fying photosynthetic metabolism to operate under environmental stresses. But for other purposes, for example, modification of bulk storage protein or lipid for nutritional or industrial use, for example, expression at a particular developmental stage (such as embryo- genesis) is required. For these develop- mental switches, we are a long way

from identifying either the cellular signals or the DNA sequences on which the signals act. The experiments on light-regulation of foreign genes, exciting and significant as they are, are thus but one step along the road to con- trolled genetic manipulation of whole plants.

JOHN A. BRYANT

Department of Plant Science, University College, PO Box 78, CardiffCF1 1XL, UK.

R e f e r e n c e s 1 Herrera-Estrella, L., Depicker, A., Van

Montagu, M. and Schell, J. (1983) Nature 303, 209-213

2 Bevan, M. W., Flavell, R. B. and Chilton, M.-D. (1983) Nature 304, 184-187

3 News (1983) Bio/Technology 1, 461-462 4 Bedbrook, J. R., Smith, S. M. and Ellis,

R. J. (1980) Nature 287, 692-697 5 Herrera-Estrella, L., Van den Broeck, G.,

Maenhaut, R., Van Montagu, M., Schell, J., Timko, M, and Cashmore, A. (1984) Nature 310, 115-120

6 Gallagher, T. F. and Ellis, R. J. (1982) EMBO J. 1, 1493-1498

Insurance - an old safeguard for a new technology

Ken Davis

Biotechnology companies today experi- ence many exciting opportunities, but also face a number of unique risks. Consider for a moment the impact each of the following events might have on your company's finances and future prospects:

(a) Safety authorities carry out an examination of your laboratory and order its immediate closure. All work is brought to a standstill pending inves- tigation.

(b) Due to accidental cross infection, the culture bank is destroyed.

(c) A member of your staff leaves your employment taking details of your breakthrough in interferon production to a competitor.

(d) An accident occurs causing an escape of dangerous materials which

results in substantial claims for damages from your staffand the public.

Any of these sorts of events could be catastrophic for your company, but insuring yourself against such occu- pational risks provides a background of security against financial loss.

Insurance practices vary from country to country, and the likelihood and consequences of litigation are even more varied. Although this article is written with the British biotechnology and insurance scenes primarily in mind, its general themes are relevant to most other countries. In particular, the need for insurance in the USA is notably greater since that country has especially strict regulations and a record of massive financial compen- sations for damage.

So what risks do companies need to cover themselves against? The follow- ing case study shows how a fictitious biotech company, ABC Biotech Limited, approaches its insurance needs.

A ' m o d e l ' c o m p a n y ABC Bi0tech Limited is involved

in making and marketing finished products to food and drink manu- facturers and the pharmaceutical and veterinary industries. They " also undertake contract research and joint ventures in cell hybridization and recombinant DNA research. Their product range covers organic acids and enzymes for the food and drink industry, monoclonal antibodies and interferons for the pharmaceutical industries.

The company employs around 100 laboratory staff and 500 manufacturing staff, and runs two laboratories in the UK. Revenue comes mainly from UK manufacturing sales but with a growing contribution being made by exports to the USA and Europe. They also receive earnings from research fees and tech- nology licensing fees. The risks they need to cover include:

M a t e r i a l d a m a g e - to protect plant, buildings, stock and the culture

© 1984, Elsevier Science Publishers B.V.~ Amsterdam 0166 - 9430183/$02.00

110

bank. This includes the compulsory disposal &the culture bank because of accidental cross infection of the culture or mutations. The figure insured repre- sents the reseach and laboratory costs of restoring and reinstating many years of research investment.

B u s i n e s s i n t errupt ion - this covers (on All Risks basis) closure, including compulsory closure or seizure by Civil Authorities of work or laboratories because of infection of cultures or other accidents rendering the laboratory or work uninhabitable. This would include such instances as the escape of infected or polluting gases, liquids, organisms or other sub- stances and the consequential loss involved. This would result in con- siderable loss of research revenue and contracts together with a complete standstill in production if whole culture lines have to be destroyed.

E m p l o y e r s ' l iab i l i ty - In the UK, the Health and Safety at Work Act has gone a long way towards concentrating the minds of employers and employees on the risks in laboratory and process situations. However, the increase in work done by ABC Biotech in the field of monodonal antibodies, hormones, vaccines, antibiotics and many other materials has brought with it further risks of a yet unchartered nature.

The insurance policy offers protec- tion against legal liability to pay damages to an employee who is killed, injured, or contracts an illness, infection or disease as a result of their employment.

Additional cover is provided for legal defence costs arising out of actions under the Health and Safety at Work Act - claimant costs and expenses and the cost of legal representation. Reimbursement costs would also be covered to employees who have obtained judgments against a third party but are unable to secure payment.

ABC Biotech are also concerned with the problems of environmental impair- ment. They recognize that emissions at levels which are legally accepted at present may in the future give rise to claims from both public and employees

alike. This risk is also included in their policy.

Pub l i c l i ab i l i ty Liability for damages is not of course

restricted to staff alone - cover should include the following risks:

(a) Protection against legal liability to pay damages to members of the public who are killed or accidentally injured or contract any illness, disease or infection or where property is damaged as a result of business activ- ities.

(b) Claimants' costs and expenses, cost of legal representation, com- pensation for court attendances and legal defence costs.

P r o d u c t l i ab i l i ty In such a highly competitive

industry, where new discoveries and developments stand to make substan- tial profits if successful, no-one wiU need reminding that the converse can be true if a new product does not meet specifications. Many firms would not

b e able to take the financial strain that could conceivably arise should an action be brought against them. ABC should think about cover for faulty or defective products causing bodily injury or damage and for clinical trials. In addition ABC Biotech will be able to purchase cover for financial loss, where legal liability is proved against them even though no actual loss or injury is sustained, and product guarantee insurance to cover the situation which might arise if a product does not perform in accordance with its spe- cifications. In this latter case the insurers will provide an indemnity for the cost of removal, repair or replace- ment of the product.

P r o f e s s i o n a l i n d e m n i t y ABC Biotech are particularly keen to

cover themselves under this heading as they are aware of their vulnerability to the effect of innocent or fraudulent acts of their employees. They do a consid- erable amount of research work under contract for XYZ Limited, a major household name in the drugs industry. Should one of ABC's employees leave to join a competitor taking with them a vital breakthrough in interferon-

Trends in Biotechnology, Vol. 2, No. 4, 1984

producing bacteria which ultimately enables XYZ's nearest rival to launch a new product faster, problems would follow. XYZ would no doubt bring an action against ABC. In this respect ABC are covered.

P r e m i u m a s s e s s m e n t s The premium the company will be

asked to pay for this kind of comprehensive coverage will dearly depend on a number of factors. Many of the factors already discussed obviously apply as much to the 'old' biotechnologies as to the new. A major difference, however, is the lack of case history from an insurance point of view of products and processes which involve genetic engineering, mono- donal antibodies and the like. Thus the estimation of risks - and hence premiums - is extremely difficult. There are, however, a few fairly obvious factors that all insurers will take into account. They are:

(a) the number of employees involved in laboratory and process work.

(b) the age, state and design and layout of premises and maintenance of equipment.

(c) the range of work currently/pro- posed to be undertaken.

(d) the claims experience in the particular work being undertaken. Insurers keep abreast of all safety regu- lations, reported accidents, claims made, government reports issued etc.

(e) liabilities to third parties. This would be related to the work carried out and the categories of people who would be involved - i.e. the type and scale of clinical tests.

It is clear that a biotechnology company needs to acquire a comprehensive insurance package to cover the special risks it faces. Such packages are now becoming available and as the industry expands and new risks and hazards are identified, new insurance solutions will undoutedly be developed.

Ken Davis is at Reed Stenhouse UK Ltd, PO Box 214, Two South Place, London EC2P 2DX, UK.