HEALTH FROM THE HEART OF THE HEBRIDES

by Graeme Robertson, Director, Habitat Scotland

What have fish oil and heart disease, bog myrtle and midges, micro-algae and a superquarry all got to do with Scottish islands? The short answer is Scotia Holdings, an international pharmaceutical operation whose subsidiary company, Callanish Ltd, is based on the Isle of Lewis, Scotland’s most northern Hebridean island.

From this remote location, Callanish, named after the nearby community which contains the famous ancient standing stones, distribute a wide range of products based on fish and plant oils. They are used as diet supplements and in the treatment of heart disease, arthritis, skin disorders and premenstrual syndrome. Under the banner “Health from the Heart of the Hebrides” they are sold throughout Britain, across Europe and to the Middle East.

The company is seen as a good example of a business well suited to the Western Isles, producing low-bulk high value and easily transported goods based on natural resources and creating good quality jobs.

Callanish was set up in 1986 in a former fish drying factory at Breasclete. The company started with just four workers but soon had 35 employees. In 1992 their operations were stepped up following a £620,000 expansion of its laboratory facilities. In April 1994 they announced a £4.5 million investment programme to increase production and double the workforce to 70 over 18 months.

The driving force behind Callanish is Dr David Horrobin, one time Professor of Medicine at the University of Montreal, and founder of Efamol Ltd. Efamol started life in the late 1970s in Kentville, Nova Scotia, specialising in the production of evening primrose oil. This is used mainly for the relief of premenstrual syndrome, but recent medical studies have pointed to its use for atopic eczema, diabetic neuropathy and rheumatoid arthritis. It has also been shown to have an effect on the restoration of cognitive, perception and memory functions of alcoholics, and speeds up the rate of repair to liver damage.

In its initial years Callanish developed what appeared to be the best commercial process in the world for purifying the main active ingredients from a range of oils, the most important ones being eicosapentaenoic acid (EPA) from marine fish oil and gammalinolenic acid (GLA) from evening primrose oil.

Research has shown that EPA can play an important role in protecting the body’s vital functions. EPA is a type of Essential Fatty Acid and is used by the body to make prostaglandins. Low incidence of heart disease amongst Eskimos led to a study by a team of Danish scientists, and they discovered that the Eskimo blood was rich in EPA derived from their staple fish diet. In Japan, where fish consumption is also high, the incidence of coronary disease is very low.

EPA is obtained only from fish such as herring or mackerel and the more expensive salmon or halibut. Ideally our diet should include fresh fish several times per week. An alternative is to supplement the diet with fish oil. GLA production can be below normal in people with skin problems and in young and middle-aged women. The modern diet, rich in hard saturated fats, may also diminish production of GLA.

With this background in mind, Callanish started to introduce a range of nutritional supplements. Presented in easy to swallow oil capsules that are taste free, these included Marine 18 and Marine 25 (numbers refer to the % EPA) and the Omega Combination rich in both EPA and GLA. The company has since manufactured new products to capture a larger share of the home and overseas market. These developments have been based on highly purified forms of EPA and GLA and include Marine 50, a more concentrated successor to Marine 25, and a selection of multi-vitamins including garlic oil, ginseng, betacarotene and vitamins A, D and E.

The company has also introduced under its own label, The Callanish Collection, a range of skin care and toiletry products, some of which incorporate evening primrose oil and vitamin E. These products were originally developed for prestigious hotels but are now available in the retail sector.

In November 1994 Scotia Holdings launched the first of the over-the-counter products mentioned in its prospectus when it was successfully floated on the Stock Exchange in October 1993. The company’s OTC division, Efamol, have introduced a new patented, natural product designed to help women in the fight against the potentially crippling effects of osteoporosis.

Its Efacal nutritional supplement, a balanced combination of evening primrose oil, fish oil and calcium, will be made available at independent chemists throughout the country. Studies at the universities of Glasgow, Wales and Pretoria have shown that Efacal increases calcium absorption, reduces calcium excretion, increases calcium deposition in the bone and increases the formation of bone matrix on which calcium is deposited. The new supplement is also said greatly to increase the efficient utilisation of calcium already present in the diet.

Scotia currently have six products which have reached phase three of clinical trials, after which they have at least a 50 per cent chance of going commercial. They include drugs to cope with diabetic complications, rheumatoid arthritis, cancers of the pancreas, cancers of the head and neck, the side-effects of radiation treatment and blocked arteries.

Callanish have been directly involved with all these medical breakthroughs. They have developed a “magic bullet” which can seek and destroy cancer cells without harming normal cells. The first experimental formulations of the tumour killing agent lithium gammalinolenate, known as EF13, have shown encouraging results in patients with late stage pancreatic and breast cancers - patients for whom all other possible treatments have been exhausted. Present indications are that survival times are approximately doubled in these individuals.

A team at the medical college of St Bartholomew’s Hospital in London have also been in-vitro testing EF13 on HIV-infected human cells. The drug not only kills HIV-infected white blood cells, but leaves normal blood cells unharmed. In addition, normal cells exposed to EF13 become resistant to infection by HIV. Subsequent early stage trials in humans are now ongoing.

In conjunction with researchers at Oxford’s Churchill Hospital, Callanish have developed a new drug - EF27, made up of two compounds - which might substantially reduce the adverse effects of radiation used for around half of cancer patients. Radiotherapy can damage normal tissue particularly the skin, gastro-intestinal tract, the brain and the spinal cord, leading to distress for patients and limiting the dosage which can safely be given. Crucially, however, EF27 does not protect the cancer cell. Its two components have been shown to kill cancer cells without harming normal cells. The drug is therefore likely to enhance the effect of the radiotherapy on the cancer while reducing the damaging side-effects.

Unlike EF13 and EF27, the third new product has not been manufactured in Callanish. But the analytical work on EF9’s properties has been carried out at the Lewis factory. It is a new porphyrin compound which in combination with a laser can selectively destroy cancerous tissue. Safety levels are high and there is a low risk of toxicity. EF9 is a photodynamic drug which in itself is almost inert but which accumulates in cancer cells after intravenous injection. When light of an appropriate wavelength is shone on the tissue, the drug is activated to release toxic free radicals which kill the cancer cells.

What makes the EF9 compound important is that previous similar drugs have not been very effective and have caused harm to normal tissues. However, Scotia claim: “Recent clinical experience in patients with diffuse malignant mesothelioma (asbestos tumour), with colorectal tumours and with head and neck tumours has confirmed that use of the new EF9 compound ensured tumour damage through the full depth of the cancer with little or no damage to surrounding normal tissue, muscle, nerve or blood vessels. Nor has regrowth been seen at the treated sites in any of the patients.”

The Callanish workforce is also manufacturing EF5 which is a drug for the treatment of rheumatoid arthritis with few adverse side effects and EF12 for the prevention of restenosis after angioplasty. Angioplasty is the procedure whereby blocked arteries can be opened up by inserting a fine catheter and blowing up a balloon inside the vessel. The procedure is very successful initially but over the following year 40-60% of the arteries are likely to close again, a process known as restenosis.

Finally, Scotia will soon be applying for a product licence to sell EF4, a treatment which reverses the nerve damage suffered by diabetics. The drug has completed its crucial phase three trials and will help some of the 12 million sufferers of diabetes worldwide avoid amputation of limbs arising from complications. Scotia has signed a marketing deal with the large drug group Pharmacia for EF4 in Europe. The company is also looking for partners to market the product in Japan and the US. A competitor’s drug to treat diabetic neuropathy went on sale last year in Japan and it has already established a $400 million (£253 million) market.

Over the past few years, researchers at the Scottish Agricultural College at Ayr have reported what they describe as remarkable results from experiments using essential oils extracted from the thyme plant.

Working with universities in Hungary and Italy, they have shown that when elderly rats are fed the oils, the ageing process slows dramatically. Dr Ray Noble, head of the college’s biochemical sciences department, said the results should translate to humans.

At the end 1994 Efamol signed a commercial agreement with the college to allow the product to be manufactured and sold under licence. The two organisations will also collaborate on work aimed at establishing the benefit of natural products in promoting healthy development of babies.

Thyme oil and the other natural products under investigation all contain antioxidants which are known to play a major role in the maintenance of good health, particularly in relation to ageing and to foetal development. They prevent or reduce damaging oxidation by mopping up dangerous free radicals and stopping polyunsaturated fatty acids from breaking down in the normal way. As people age, the levels of key fatty acids fall, producing common degenerative diseases like Alzheimer’s.

A number of high-quality jobs could soon be created on the neighbouring Isle of Skye and the dreaded biting midge kept at bay in one fell swoop - thanks to a common marsh plant and a £50,000 research programme begun in 1994 by Efamol. Work involves test planting and harvesting the bog myrtle, which grows extensively on Skye, to see if the oil can be extracted commercially and developed as a cash crop to boost the income of local crofters.

Efamol began its research into the properties of bog myrtle oil in 1991 in conjunction with Angus Stuart, a retired professor of pathology now living on the island. Locally cropped leaves were analysed by Professor Stuart in his laboratory and the oil tested as an insect repellent in an ad hoc way by local people.

Scotia chief executive Dr David Horrobin said that initial research had shown the oil was as effective as other products on the market, but was also non-toxic. Tests have shown that the oil may also be effective in controlling house dust mites, a major contributory factor in asthma. The oil can also protect plants from aphids and fungus as well as crops from potato blight.

Dr Iain Cloughley, who is heading the project for Efamol, said: “Ultimately we hope it can be cultivated in plantations and the leaf cropped several times during the annual growing season, just like tea.”

Scotia, in association with a French company, are trying to find another source for two compounds currently extracted from fish oil, a raw material which is likely to become scarce the world over within five to 10 years. They have discovered that the compounds originate in tiny organisms called micro-algae which enter the fish food chain when eaten by plankton.

It is their intention to set up a pilot project on the adjoining island of Harris to farm the micro-algae in onshore containers. All that will be needed for the organisms to grow will be light and unlimited quantities of pristine seawater. Such a plant might employ 12 people and then, if all goes to plan, a permanent facility could be set up with around 50 workers by the year 2002.

Such an operation could be placed in jeopardy with Redland Aggregrate Ltd proposing to extract 600 million tonnes of anorthosite over a 60-year period from a £70 million coastal superquarry at Lingerabay in South Harris. Dr Horrobin, in his evidence to an ongoing public inquiry, said if Redland secure planning consent then the development would endanger the “exceptional asset” of a completely unpolluted environment. He was particularly concerned about ballast water discharge from bulk carriers servicing the superquarry and cannot foresee making a major investment in an area where there is even a tiny risk of such contamination.

The Callanish achievements in so short a time have astounded many people in the pharmaceutical industry, particularly those in the long-established companies. But sales director Ian Kennedy is not surprised. “We are sited in one of the most pollution free areas in Europe and this has obvious advantages for a business manufacturing products aimed at improving health care. We also have a very reliable workforce and benefit from being linked to an advanced telecommunications network. Together, they make a formidable combination.”