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Medical Biotechnology Achievements, Prospects and Perceptions Medical biotechnology:Achievements, prospects andperceptions TOKYO u NEW YORK u PARIS 1 Introduction: Biotechnology, bio-industry and bio-economy . .
2 Medical and pharmaceutical biotechnology: Current achievements and innovation prospects . . . . . . . . . . . . . .
4 The economics of pharmaceutical biotechnology and bio- 6 Medical and pharmaceutical biotechnology in some developing 7 Social acceptance of medical and pharmaceutical biotechnology 8 The globalization of regulatory standards and ethical norms: Solidarity with developing nations . . . . . . . . . . . . . . . . .
Introduction: Biotechnology,bio-industry and bio-economy The word ‘‘biotechnology'' was coined in 1919 by Karl Ereky, a Hungar-ian engineer, to refer to methods and techniques that allow the produc-tion of substances from raw materials with the aid of living organisms. Astandard definition of biotechnology was reached in the Convention onBiological Diversity (1992) – ‘‘any technological application that uses bio-logical systems, living organisms or derivatives thereof, to make or mod-ify products and processes for specific use''. This definition was agreed by168 member nations, and also accepted by the Food and Agriculture Or-ganization of the United Nations (FAO) and the World Health Organiza-tion (WHO).
Biotechnologies therefore comprise a collection of techniques or pro- cesses using living organisms or their units to develop added-value prod-ucts and services. When applied on industrial and commercial scales,biotechnologies give rise to bio-industries. Conventional biotechnologiesinclude plant and animal breeding and the use of micro-organisms andenzymes in fermentations and the preparation and preservation of prod-ucts, as well as in the control of pests (e.g. integrated pest control). Moreadvanced biotechnologies mainly relate to the use of recombinant deoxy-ribonucleic acid (DNA) techniques (i.e. the identification, splicing andtransfer of genes from one organism to another), which are now sup-ported by research on genetic information (genomics). This distinction ismerely a convenience, because modern techniques are used to improveconventional methods; for example, recombinant enzymes and geneticmarkers are employed to improve fermentations and plant and animal MEDICAL BIOTECHNOLOGY breeding. It is, however, true that the wide range of biotechnologies,from the simplest to the most sophisticated, allows each country to selectthose that suit its needs and development priorities, and by doing so evenreach a level of excellence (for example, developing countries that haveused in vitro micro-propagation and plant-tissue cultures to becomeworld-leading exporters of flowers and commodities).
The potential of biotechnology to contribute to increasing agricultural, food and feed production, improving human and animal health, miti-gating pollution and protecting the environment was acknowledged inAgenda 21 – the work programme adopted by the 1992 United NationsConference on Environment and Development in Rio de Janeiro. In2001, the Human Development Report considered biotechnology to bethe means to tackle major health challenges in poor countries, such as in-fectious diseases (tuberculosis), malaria and HIV/AIDS, and an adequatetool to aid the development of the regions left behind by the ‘‘green rev-olution''; these are home to more than half the world's poorest popula-tions, who depend on agriculture, agroforestry and livestock husbandry.
New and more effective vaccines, drugs and diagnostic tools, as well asmore food and feed of high nutritional value, will be needed to meet theexpanding needs of the world's populations.
Biotechnology and bio-industry are becoming an integral part of the knowledge-based economy, because they are closely associated withprogress in the life sciences and in the applied sciences and technologieslinked to them. A new model of economic activity is being ushered in –the bio-economy – in which new types of enterprise are created and oldindustries are revitalized. The bio-economy is defined as including allindustries, economic activities and interests organized around living sys-tems. The bio-economy can be divided into two primary industry seg-ments: the bio-resource industries, which directly exploit biotic resources– crop production, horticulture, forestry, livestock and poultry, aquacul-ture and fisheries; and related industries that have large stakes as eithersuppliers to or customers of the bio-resource sector – agrochemicals andseeds, biotechnologies and bio-industry, energy, food and fibre process-ing and retailing, pharmaceuticals and health care, banking and insur-ance. All these industries are closely associated with the economic impactof human-induced change to biological systems (Graff and Newcomb,2003).
The potential of this bio-economy to spur economic growth and create wealth by enhancing industrial productivity is unprecedented. It is there-fore no surprise that high-income and technologically advanced countrieshave made huge investments in research and development (R&D) in thelife sciences, biotechnology and bio-industry. In 2001, bio-industries wereestimated to have generated US$34.8 billion in revenues worldwide and to employ about 190,000 people in publicly traded firms. These areimpressive results given that, in 1992, bio-industries were estimated tohave generated US$8.1 billion and employed fewer than 100,000 persons.
The main beneficiaries of the current ‘‘biotechnology revolution'' and the resulting bio-industries are largely the industrialized and technologi-cally advanced countries, i.e. those that enjoy a large investment oftheir domestic product in R&D and technological innovation. Thus, theUnited States, Canada and Europe account for about 97 per cent of theglobal biotechnology revenues, 96 per cent of persons employed in bio-technology ventures and 88 per cent of all biotechnology firms. Ensuringthat those who need biotechnology have access to it therefore remainsa major challenge. Similarly, creating an environment conducive to theacquisition, adaptation and diffusion of biotechnology in developingcountries is another great challenge. However, a number of developingcountries are increasingly using biotechnology and have created a suc-cessful bio-industry, at the same time increasing their investments inR&D in the life sciences.
According to the Frost & Sullivan Chemicals Group in the United Kingdom, some 4,300 biotechnology companies were active globally in2003: 1,850 (43 per cent) in North America; 1,875 (43 per cent) in Eu-rope; 380 (9 per cent) in Asia; and 200 (5 per cent) in Australia. Thesecompanies cover the gamut from pure R&D participants to integratedmanufacturers to contract manufacturing organizations (CMOs). TheUnited States has the largest number of registered biotechnology compa-nies in the world (318), followed by Europe (102). In 2002, the annualturnover of these companies was US$33.0 billion in the United Statesand only US$12.8 billion in Europe. Some US$20.5 billion was allocatedto research in the United States, compared with US$7.6 billion in Europe(Adhikari, 2004).
US biotechnology and bio-industry The consultancy firm Ernst & Young distinguishes between US compa-nies that produce medicines and the others. The former include pioneerssuch as Amgen, Inc., Genentech, Inc., Genzyme Corporation, ChironCorporation and Biogen, Inc. The annual turnover of these five compa-nies represents one-third of the sector's total (US$11.6 billion out ofUS$33.0 billion); in addition, their product portfolio enables them tocompete with the big pharmaceutical groups in terms of turnover andstock value. For instance, Amgen, with US$75 billion market capitaliza-tion, is more important than Eli Lilly & Co., and Genentech's marketcapitalization is twice that of Bayer AG (Mamou, 2004e).
MEDICAL BIOTECHNOLOGY In 2002, Amgen, had six products on the market producing global rev- enues of US$4,991 million. Genentech was in second place with 11 prod-ucts on the market and revenues worth US$2,164 million. The remainingplaces in the top five were filled by Serono SA (six products, US$1,423million), Biogen (two products, US$1,034 million) and Genzyme Corpo-ration (five products, US$858 million) (Adhikari, 2004).
Over the past decade, a clutch of companies has amassed signifi- cant profits from a relatively limited portfolio of drugs. There is, today,heightened recognition that lucrative opportunities await companies thatcan develop even a single life-saving biotechnology drug. For instance,Amgen's revenues increased by over 40 per cent between 2001 and 2002owing to the US$2 billion it made in 2002 from sales of Epogen and theUS$1.5 billion earned from sales of Neupogen. Over US$1 billion in salesof Rituxan – a monoclonal antibody against cancer – in 2002 helped Gen-entech record a 25 per cent growth over its 2001 performance (Adhikari,2004).
In California, there are two biotechnology ‘‘clusters'' of global impor- tance: one in San Diego–La Jolla, south of Los Angeles, and the other inthe Bay Area, near San Francisco. A cluster is defined as a group ofenterprises and institutions in a particular sector of knowledge that aregeographically close to each other and networked through all kinds oflinks, starting with those concerning clients and suppliers. In neither bio-technology cluster does it take more than 10 minutes to travel from onecompany to another. The San Diego cluster is supported in all aspects ofits functioning, including lobbying politicians and the various actors inthe bio-economy, by Biocom – a powerful association of 450 enterprises,including about 400 in biotechnology, in the San Diego region. The clus-ter relies on the density and frequency of exchanges between industrymanagers and university research centres. For instance, one of its objec-tives is to shorten the average time needed to set up a licensing contractbetween a university and a biotechnology company; it generally takes 10months to establish such a contract, which is considered too long, so thecluster association is bringing together all the stakeholders to discuss thismatter and come to a rapid conclusion (Mamou, 2004e).
The clusters have developed the proof of concept, to show that from an idea, a theory or a concept there could emerge a business modeland eventually a blockbuster drug. Such an endeavour between the re-searchers and bio-industry would lead to licensing agreements that re-warded the discovery work. A strategic alliance between politics, basicresearch and the pharmaceutical industry (whether biotechnological ornot) within the cluster would be meaningless without capital. In fact,bio-industries' success is above all associated with an efficient capitalmarket, according to David Pyott, chief executive officer of Allergan, the world leader in ophthalmic products and the unique owner of Botox –a product used in cosmetic surgery and the main source of the company'swealth. No cluster can exist without a dense network of investors, busi-ness angels, venture capitalists and bankers, ready to get involved in thesetting up of companies (Mamou, 2004e).
The two Californian clusters represented 25.6 per cent of US compa- nies in 2001. The corresponding figures for other states were as follows:Massachusetts, 8.6 per cent; Maryland, 7.7 per cent; New Jersey, 5.9 percent; North Carolina, 5.8 per cent; Pennsylvania, 4.6 per cent; Texas, 3.4per cent; Washington, 3.1 per cent; New York, 3.1 per cent; Wisconsin,2.5 per cent; the rest of the country accounted for the remaining 29.7per cent (data from the US Department of Commerce Technology Ad-ministration and Bureau of Industry and Security).
Europe's biotechnology and bio-industry The European bio-industry is less mature than its US counterpart. Ac-telion of Switzerland qualified as the world's fastest-growing drugs groupin sales terms following the launch of its first drug, Tracleer, but it did notachieve profitability until 2003. Similarly, hardly any European biotech-nology companies are earning money. Only Serono SA – the Swiss power-house of European biotechnology – has a market capitalization to rivalUS leaders (Firn, 2003). Serono SA grew out of a hormone extractionbusiness with a 50-year record of profitability and is the world leader inthe treatment of infertility; it is also well known in endocrinology andthe treatment of multiple sclerosis. In 2002, Serono SA made US$333million net profit from US$1,546 million of sales; 23 per cent of the reve-nue from these sales was devoted to its R&D division, which employs1,200 people. The Spanish subsidiary of Serono SA in Madrid is nowproducing recombinant human growth hormone for the whole world,whereas factories in the United States and Switzerland have ceased toproduce it. The Spanish subsidiary had to invest @36 million in order toincrease its production, as well as another @5 million to upgrade its instal-lations for the production of other recombinant pharmaceuticals to beexported worldwide.
In spite of a wealth of world-class science, the picture in much of Europe is of an industry that lacks the scale to compete and is facing thefinancial crunch, which may force many companies to seek mergers withstronger rivals (Firn, 2003).
Germany has overtaken the United Kingdom and France, and is cur-rently home to more biotechnology companies than any country except MEDICAL BIOTECHNOLOGY the United States. But, far from pushing the boundaries of biomedicalscience, many companies are putting cutting-edge research on hold andare selling valuable technology just to stay solvent. Until the mid-1990s,legislation on genetic engineering in effect ruled out the building of aGerman bio-industry. According to Ernst & Young, the more than 400companies set up in Germany since then needed to raise at least US$496million from venture capitalists over 2004 to refinance their hunt fornew medicines. Most were far from having profitable products and, withstock markets in effect closed to biotechnology companies following thebursting of the bubble in 2000, they were left to seek fourth or even fifthrounds of private financing (Firn, 2003).
The biggest German biotechnology companies, such as GPC Biotech and Medigene, were able to raise significant sums in initial public offer-ings at the peak of the Neuer Markt, Germany's market for growthstocks. But when the technology bubble burst in 2000, it became clear toGPC Biotech that investors put very little value on ‘‘blue-sky'' research.
‘‘They wanted to see proven drug candidates in clinical trials'', saidMirko Scherer, chief financial officer (cited in Firn, 2003). The only op-tion for companies such as GPC Biotech and Medigene was to buy drugsthat could be brought to market more quickly. GPC Biotech has used thecash it earned from setting up a research centre for Altana, the Germanchemicals and pharmaceutical group, to acquire the rights to satraplatin,a cancer treatment that was in the late stages of development. In October2003, regulators authorized the initiation of the final round of clinicaltrials (Firn, 2003). After a series of clinical setbacks, Medigene has moth-balled its early-stage research to cut costs and has licensed in late-stageproducts to make up for two of its own drugs that failed. The strategywill help the company eke out its cash; but cutting back on research willleave little in its pipeline (Firn, 2003).
Many of Germany's biotechnology companies have abandoned ambi- tious plans to develop their own products and chosen instead to licensetheir drug leads to big pharmaceutical companies in exchange for fundingthat will allow them to continue their research. This approach is sup-ported by the acute shortage of potential new medicines in developmentby the world's biggest pharmaceutical companies. But Germany's bio-industry has few experimental drugs to sell – about 15 compared withthe more than 150 in the United Kingdom's more established industry.
Moreover, most of Germany's experimental drugs are in the early stagesof development, when the probability of failure is as high as 90 per cent.
That reduces the price that pharmaceutical companies are willing to payfor them (Firn, 2003).
Companies also have to struggle with less flexible corporate rules than their rivals in the United Kingdom and the United States. Listed compa- nies complain that the Frankfurt stock exchange does not allow injectionsof private equity, which are common in US biotechnology. As a result,few of Germany's private companies state that they expect to float inFrankfurt. Most are looking to the United States, the United Kingdomor Switzerland, where investors are more comfortable with high-riskstocks. However, many German companies may not survive long enoughto make the choice (Firn, 2003).
Faced with this bleak outlook, many in the industry agree that the only solution is a wave of consolidation that will result in fewer, larger compa-nies with more diverse development pipelines. A number of investors inGermany's bio-industry are already pushing in this direction. TVM, theleading German venture capital group, had stakes in 14 German biotech-nology companies and was trying to merge most of them. TVM sold offall Cardion's drug leads after failing to find a merger partner for the arth-ritis and transplant medicine specialists. After raising US$14.1 million in2002, Cardion has become a shell company that may one day earn royal-ties if its discoveries make it to market. UK-based Apax Partners wassaid to have put almost its entire German portfolio up for sale. The fateof MetaGene Pharmaceuticals, one of Apax's companies, may awaitmany others. In October 2003, the company was bought by the BritishAstex, which planned to close the German operation after stripping outits best science and its US$15 million bank balance (Firn, 2003).
GPS Biotech's chief financial officer was critical of the investors who turned their backs on Germany and put 90 per cent of their funds in theUnited States, when a lot of European companies were very cheap. Andalthough Stephan Weselau, chief financial officer of Xantos, was frus-trated that venture capitalists saw little value in his young company'santi-cancer technology, he was adamant about the need for Germany'semerging biotechnology to consolidate if it was to compete against estab-lished companies in Boston and San Diego (Firn, 2003).
The United Kingdom The market for initial public offerings in the United Kingdom was all butclosed to biotechnology for the three-year period 2000–2002; it reopenedin the United States in 2003. City of London institutions, many of whichtook huge losses on biotechnology, were reluctant to back new issues andhave become more fussy about which quoted companies they are pre-pared to finance (Firn, 2003).
The United Kingdom is home to one-third of Europe's 1,500 biotech- nology companies and more than 40 per cent of its products in develop-ment. Although the United Kingdom had 38 marketed biotechnologyproducts and 7 more medicines awaiting approval by the end of 2003, MEDICAL BIOTECHNOLOGY analysts stated that there were too few genuine blockbusters with the sortof sales potential needed to attract investors' attention away from theUnited States. A dramatic case is that of PPL (Pharmaceutical ProteinsLtd) Therapeutics – the company set up to produce drugs in the milk ofa genetically engineered sheep (Polly). By mid-December 2003, the com-pany had raised a paltry US$295,000 when auctioneers put a mixed cata-logue of redundant farm machinery and laboratory equipment under thehammer. This proved that exciting research (Dolly and Polly sheep) doesnot always lead to commercial success (Firn, 2003).
The profitable British companies reported pre-tax profits of £145 mil- lion in 2003, less than 15 per cent of the US$1.9 billion pre-tax profits re-ported by Amgen. By mid-2003, the British biotechnology sector seemedto be coming of age. Investors could choose between three companiesthat had successfully launched several products and boasted market cap-italizations in excess of US$884 million. Since then they have seen Pow-derJect Pharmaceuticals plc acquired by Chiron Corp., the US vaccinesgroup, for a deal value of £542 million in May 2003; and General Electricswooped in with a £5.7 billion bid for Amersham, the diagnostics andbiotechnology company, in October 2003. Earlier, in July 2000, OxfordAsymmetry had been purchased by the German company Evotec Biosys-tems for £343 million, and, in September 2002, Rosemont Pharma wasacquired by the US firm Bio-Technology General for £64 million (Dyer,2004).
In May 2004, Union Chimique Belge (UCB) agreed to buy Celltech, the United Kingdom's biggest biotechnology company, for £1.53 billion(@2.26 billion). UCB decided Celltech could be its stepping stone intobiotechnology after entering an auction for the marketing rights to Cell-tech's new treatment for rheumatoid arthritis (CPD 870), touted as ablockbuster drug with forecast annual sales of more than US$1 billion.
After seeing trial data not revealed to the wider market, UCB decidedto buy the whole company. The surprise acquisition was accompanied bya licensing deal that gives UCB the rights to CPD 870, which accountedfor about half the company's valuation. Go¨ran Ando, the Celltech chiefexecutive who will become deputy chief executive of UCB, stated: ‘‘wewill immediately have the financial wherewithal, the global commercialreach and the R&D strength to take all our drugs to market.'' News ofthe deal, which will be funded with debt, sent Celltech shares 26 percent higher to £5.42, whereas UCB shares fell 4 per cent to @33.68 (Firnand Minder, 2004).
Celltech had been the grandfather of the British biotechnology sector since it was founded in 1980. With a mixture of seed funding from theThatcher government and the private sector, the company was set up tocommercialize the discovery of monoclonal antibodies that can become powerful medicines. Listed in 1993, the company made steady progress inits own research operations, but gained products and financial stabilityonly with the acquisitions of Chiroscience in 1999 and Medeva in 2000.
It also acquired Oxford GlycoSciences in May 2003 in a deal worth £140million. The great hopes Celltech has generated were based largely onCPD 870, the arthritis drug it planned to bring to market in 2007 thatcould be by far the best-selling product to come out of a British biotech-nology company. After the UCB–Celltech deal, the group ranked fifthamong the top five biopharmaceutical companies, behind Amgen, @6.6billion in revenue in 2003; Novo Nordisk, @3.6 billion; Schering, @3.5billion; and Genentech, @2.6 billion (Dyer, 2004; Firn and Minder, 2004).
Based on 2003 results, the combined market capitalization of UCBPharma and Celltech will be @7.14 billion; revenues, @2,121 million; earn-ings before interest, tax and amortization, @472 million; pharmaceuticalR&D budget, @397 million; number of employees, approximately 1,450(Firn and Minder, 2004).
Celltech is the biggest acquisition by UCB, which branched out from heavy chemicals only in the 1980s. Georges Jacob, its chief executivesince 1987, stated that when he joined UCB he found a company ‘‘de-voted to chemicals, dominated by engineers, pretty old-fashioned andvery much part of heavy industry''. UCB had been built entirely on in-ternal growth, and its only other sizeable acquisition was the specialitychemicals business of US-based Solutia in December 2002 for US$500million, a move that split the Belgian group's @3 billion revenues evenlybetween pharmaceuticals and chemicals. One constant was the continuedpresence of a powerful family shareholder, owning 40 per cent of UCB'sequity via a complicated holding structure (Firn and Minder, 2004).
UCB made its first foray into pharmaceuticals in the 1950s with the development of a molecule it sold to Pfizer, Inc. This became Atarax, ananti-histamine used to relieve anxiety. The relationship with Pfizer wasrevived in a more lucrative fashion for UCB following the 1987 launchof Zyrtec, a blockbuster allergy treatment that Pfizer helped to distributein the United States. Although UCB has a follow-up drug to Zyrtec, itfaces the loss of the US patent in 2007. UCB also had to fight patent chal-lenges to its other main drug, Keppra, an epilepsy treatment. With thetakeover of Celltech, UCB will gain a pipeline of antibody treatmentsfor cancer and inflammatory diseases to add to its allergy and epilepsymedicines. According to most analysts, the expansion in health-careactivities will lead the group to divest itself of its remaining chemicalbusiness (Firn and Minder, 2004).
After this takeover and following the earlier acquisition of PowderJect Pharmaceuticals and Amersham by US companies, there is not much leftin the United Kingdom's biotechnology sector except Acambis, another MEDICAL BIOTECHNOLOGY vaccine-maker, valued at about £325 million, and a string of companiesbelow the £200 million mark where liquidity can be a problem for in-vestors. The industry was therefore afraid it would be swamped by itsmuch larger rivals. Martyn Postle, director of Cambridge Healthcare andBiotech, a consultancy, stated that ‘‘we could end up with the UK per-forming the role of the research division of US multinationals'' (cited inDyer, 2004). According to the head of the Bioindustry Association(BIA), ‘‘it is clearly the fact that US companies are able to raise much,much more money than in the United Kingdom, which puts them ina much stronger position'' (cited in Dyer, 2004). The BIA called forchanges in the rules on ‘‘pre-emption rights'', which give existing share-holders priority in secondary equity offerings. Because Celltech was byfar the most liquid stock in the sector, there could be a broader impacton the way the financial sector treats biotechnology, including a reduc-tion in the number of specialist investors and analysts covering the sector(Dyer, 2004).
It is important for the United Kingdom to create an environment in which biotechnology can flourish. The industry has called for institutionalreform, including measures to make it easier for companies to raise newcapital. The British government must also ensure that its higher educa-tion system continues to produce world-class scientists. That reinforcesthe need for reforms to boost the funding of universities. The Celltechtakeover need not be seen as a national defeat for the United Kingdom.
The combined company may end up being listed in London. Even if itdoes not, Celltech's research base in the United Kingdom will expand.
Its investors have been rewarded for their faith and, if its CPD 870 drugis approved, UCB's shareholders will also benefit. But, for Celltech's ex-ecutives, the acquisition is a victory for Europe. The takeover creates aninnovative European biotechnology company that is big enough, and hassufficient financial resources, to compete globally. ‘‘The key was to haveviable European businesses that have a sustainable long-term presence,''stated Go¨ran Ando, who confirmed that UCB's research will be run fromCelltech's old base in Slough (cited in Dyer, 2004). A lot of hopes areriding on the success of UCB and Celltech, which would allow the fledg-ling bio-industry to thrive in Europe and prevent the life sciences frommigrating to the United States (Dyer, 2004).
In France in 2003, according to the France Biotech association, therewere 270 biotechnology companies focused on the life sciences and lessthan 25 years old. They employed 4,500 people – a number that couldbe multiplied four or five times if about @3 billion were to be invested in public research over three years. In 2003, France invested only @300 mil-lion of private funds and @100 million of public funds in biotechnology,far behind Germany and the United Kingdom, which each invested about@900 million per year. In 2003, France launched a five-year Biotech Planaimed at restoring the visibility and attractiveness of France in 2008–2010. Three areas – human health, agrifood and the environment – wereexpected to attract the funds as well as the efforts of universities, publicand private laboratories, hospitals, enterprises and investors (Kahn,2003b).
SangStat, a biotechnology company created in 1989 in the Silicon Val- ley by Philippe Pouletty (a French medical immunologist), is working onorgan transplants. It was established in California because, at the time ofits creation, venture capital in France was only just starting to supportsuch endeavours in biotechnology. Between FFr 600 million and FFr 2billion were needed to set up a biotechnology corporation to developone or perhaps two new drugs, and bankruptcy was very likely in France.
SangStat is now a world leader in the treatment of the rejection of organtransplants and intends to extend its expertise and know-how to thewhole area of transplantation. It is already marketing two drugs in theUnited States and three in Europe (Lorelle, 1999a).
A second corporation, DrugAbuse Sciences (DAS), was established by Pouletty in 1994, by which time venture capital was becoming a morecommon practice in Europe. Two companies were created at the sametime: DAS France and DAS US in San Francisco, both belonging to thesame group and having the same shareholders. Being established in Eur-ope and the United States, greater flexibility could be achieved from thefinancial viewpoint and better resilience to stock exchange fluctuations.
DAS was able to increase its capital by FFr 140 million (@21.3 million)in 1999 with the help of European investors (Lorelle, 1999a).
DAS specializes in drug abuse and alcoholism. Its original approach was to study neurological disorders in the patient so as to promote absti-nence, treat overdoses and prevent dependence through new therapies.
Pouletty had surveyed 1,300 existing biotechnology companies in 1994and found that hundreds were working on cancer and dozens on genetherapy, diabetes, etc., but not one was working on drug and alcohol ad-diction. Even the big pharmaceutical groups had no significant activity inthis area, although drug and alcohol addiction is considered the greatestproblem for public health in industrialized countries. For instance, 2.5 percent of the annual gross domestic product in France is spent on these ill-nesses, and some US$250 billion in the United States (Lorelle, 1999a).
A first product, Naltrel, improves on the current treatment of alcohol- ism by naltrexone. The latter, to be efficient, must be taken as pills everyday. But few alcoholics can strictly follow this kind of treatment. In order MEDICAL BIOTECHNOLOGY to free patients from this daily constraint, a monthly intramuscular injec-tion of a delayed-action micro-encapsulated product has been developed,which helps alcoholics and drug addicts to abstain from their drug. Themolecule developed inhibits the receptors in the brain that are stimulatedby opium-related substances.
Another successful product, COC-AB, has been developed for the emergency treatment of cocaine overdoses. This molecule recognizes co-caine in the bloodstream and traps it before it reaches the brain; it is thenexcreted through the kidneys in urine. Commercialization of the medi-cine was expected to help the 250,000 cocaine addicts who are admittedannually to the medical emergency services. In the long term, DAS in-tends to develop preventive compounds that can inhibit the penetrationof the drug into the brain (Lorelle, 1999a).
DAS was expected to become a world-leading pharmaceutical com- pany by 2005–2007 in the treatment of alcoholism and drug addictionor abuse. This forecast was based on the current figures of 30 millionchronic patients in the United States and Europe, comprising 22 millionalcoholics, 6 million cocaine addicts and 2 million heroin addicts (Lorelle,1999a).
Another success story is the French biotechnology company Eurofins, founded in Nantes in 1998 to exploit a patent filed by two researchersfrom the local faculty of sciences. Eurofins currently employs 2,000people worldwide and in four years increased its annual turnover 10-fold(to @162 million). Its portfolio contains more than 5,000 methods of ana-lysing biological substances. The company is located in Nantes, where130 people carry out research on the purity and origin of foodstuffs. De-spite the closure of some of Eurofins' 50 laboratories in order to improvethe company's financial position in the face of the slowdown in the econ-omy, Eurofins wants to continue to grow.
This success story has led the city of Nantes to think about creating a biotechnology city. It has also given a strong impetus to medicalbiotechnology at Nantes' hospital, where the number of biotechnologyresearchers soared from 70 to 675. In October 2003, the Institute of Gen-etics Nantes Atlantique initiated the analysis of human DNA for forensicpurposes. This institute, which received venture capital from two mainsources, was expected to employ 50 people within two years in order tomeet the demand generated by the extension of the national automateddatabase of genetic fingerprinting (Luneau, 2003).
Oryzon Genomics is a genomics company based in Madrid. It appliesgenomics to new cereal crops, grapevines and vegetables, as well as tothe production of new drugs (especially for Parkinson's and Alzheimer's diseases). It is a young enterprise, an offshoot of the University of Barce-lona and the Spanish Council for Scientific Research (CSIC), located inBarcelona's Science Park. With a staff of 22 scientists, the company is ex-periencing rapid growth and is developing an ambitious programme offunctional genomics. It was the first genomics enterprise to have accessto special funding from the NEOTEC Programme, in addition to finan-cial support from the Ministry of Science and the Generalitat of Catalo-nia. Moreover, the National Innovation Enterprise (ENISA), which ispart of the General Policy Directorate for Medium and Small SizedEnterprises of the Ministry of the Economy, has invested @400,000 in Ory-zon Genomics – this was ENISA's first investment in the biotechnologysector. At the end of 2002, Najeti Capital, a venture capital firm special-izing in investments in technology, acquired 28 per cent of OryzonGenomics in order to support the young corporation. In 2003, OryzonGenomics' turnover was estimated at @500,000, and its clients comprisedseveral agrifood and pharmaceutical companies as well as public researchcentres.
Japan's biotechnology and bio-industry Japan is well advanced in plant genetics and has made breakthroughsin rice genomics, but it is lagging behind the United States in humangenetics. Its contribution to the sequencing of the human genome (byteams of researchers from the Physics and Chemistry Research Instituteof the Science and Technology Agency, as well as from Keio UniversityMedical Department) was about 7 per cent. In order to reduce the gapwith the United States, the Japanese government has invested significantfunds in the Millennium Project, launched in April 2000. The projectcovers three areas: the rice genome, the human genome and regenerativemedicine. The 2000 budget included ¥347 billion for the life sciences. Thegenomics budget, amounting to ¥64 billion, was twice that of the neuro-sciences. Within the framework of the Millennium Project, the Ministryof Health aimed to promote the study of genes linked with such diseasesas cancer, dementia, diabetes and hypertension; results for each of thesediseases were expected by 2004 (Pons, 2000).
The Ministry of International Trade and Industry (MITI) set up a Centre for Analysis of Information Relating to Biological Resources.
This had a very strong DNA-sequencing capacity – equivalent to thatof Washington University in the United States (sequencing of over 30million nucleotide pairs per annum) – and will analyse the genome ofmicro-organisms used in fermentation and provide this information tothe industrial sector. In addition, following the project launched in 1999by Hitachi Ltd, Takeda Chemical Industries and Jutendo Medical Faculty MEDICAL BIOTECHNOLOGY aimed at identifying the genetic polymorphisms associated with allergicdiseases, a similar project devoted to single-nucleotide polymorphisms(SNPs) was initiated in April 2000 under the aegis of Tokyo Universityand the Japanese Foundation for Science. The research work is beingcarried out in a DNA-sequencing centre to which 16 private companiessend researchers with a view to contributing to the development of med-icines tailored to individuals' genetic make-up. This work is similar tothat undertaken by a US–European consortium (Pons, 2000).
On 30 October 2000, the pharmaceutical group Daiichi Pharmaceutical and the giant electronics company Fujitsu announced an alliance in ge-nomics. Daiichi and Celestar Lexico Science (Fujitsu's biotechnology di-vision) were pooling their research efforts over the five-year period2000–2005 to study the genes involved in cancer, ageing, infectious dis-eases and hypertension. Daiichi devoted about US$100 million to this re-search in 2001–2002, and about 60 scientists were involved in this work offunctional genomics (Pons, 2000).
On 31 January 2003, the Japan Bioindustry Association (JBA) an- nounced that, as of December 2002, the number of ‘‘bioventures'' inJapan totalled 334 firms. This announcement was based on a survey –the first of its kind – conducted by the JBA in 2002 to have a betterunderstanding of the nation's bio-industry. A ‘‘bioventure'' was definedas a firm that employs, or develops for, biotechnology applications; thatcomplies with the definition of a small or medium-sized business as pre-scribed by Japanese law; that was created 20 years ago; and that doesnot deal primarily in sales or imports/exports. The 334 bioventures had atotal of 6,757 employees (including 2,871 R&D staff), sales amounting to¥105 billion and R&D costs estimated at ¥51 billion (Japan BioindustryAssociation, 2003). The average figures per bioventure were: 20 em-ployees (including 8.6 R&D staff), sales worth ¥314 million and R&Dcosts of ¥153 million.
The three regions with the highest concentrations of bioventures were Kanto (191, or 57 per cent of the national total), Kinki/Kansai (55, or 16per cent) and Hokkaido (32, or 10 per cent). One-third of all ventures(112) were located in Tokyo (within the Kanto region). The most com-mon field of bioventure operations was pharmaceuticals and diagnosticproduct development (94 bioventures), followed by customized produc-tion of DNA, proteins, etc. (78 bioventures), bioinformatics (41 ventures),and reagents and consumables development (38 bioventures).
Australia's biotechnology and bio-industry In its 2003 global biotechnology census, the consultancy firm Ernst &Young ranked Australia's A$12 billion biotechnology and bio-industry as number one in the Asia-Pacific region and sixth worldwide. Australiaaccounts for 67 per cent of public biotechnology revenues for the Asia-Pacific region.
The Australian government gave a boost to the bio-industry by provid- ing nearly A$1 billion in public biotechnology expenditure in 2002–2003.
There were around 370 companies in Australia in 2002 whose core busi-ness was biotechnology – an increase from 190 in 2001. Human therapeu-tics made up 43 per cent, agricultural biotechnology 16 per cent and diag-nostics companies 15 per cent. Over 40 biotechnology companies werelisted on the Australian stock exchange (ASX) and a study released bythe Australian Graduate School of Management reported that aninvestment of A$1,000 in each of the 24 biotech companies listed onthe ASX between 1998 and 2002 would have been worth more thanA$61,000 in 2003 – an impressive 150 per cent return. During the sameperiod, shares in listed Australian biotechs significantly outperformedthose of US biotechs, and the overall performance of listed Australianbiotech companies was higher than that of the Australian stock marketas a whole.
Over A$500 million was raised by listed Australian life science compa- nies in 2003, and the ASX health-care and biotechnology sector had amarket capitalization of A$23.4 billion in 2003, up 18 per cent on 2002.
There has been a maturing of the Australian biotechnology sector, withgreater attention paid to sustainable business models and the identifica-tion of unique opportunities that appeal to investors and partners. Theindustry is supported by skilled personnel – Australia is considered tohave a greater availability of scientists and engineers than the UnitedKingdom, Singapore or Germany.
Australia is ranked in the top five countries (with a population of 20 million or more) for the number of R&D personnel. In terms of publicexpenditure on R&D as a percentage of GDP, it outranks major OECDcountries, including the United States, Japan, Germany and the UnitedKingdom (Australian Bureau of Statistics, 2003). For biomedical R&D,Australia is ranked the second most effective country – ahead of theUnited States, the United Kingdom and Germany – particularly withrespect to labour, salaries, utilities and income tax. Australia is rankedthird after the Netherlands and Canada for the cost competitiveness ofconducting clinical trials.
Australian researchers indeed have a strong record of discovery and development in therapeutics. Recent world firsts include the discoverythat Helicobacter pylori causes gastric ulcers, and the purification andcloning of three of the major regulators of blood cell transformation –granulocyte colony-stimulating factor (GCSF), granulocyte macrophagecolony-stimulating factor (GMCSF) and leukaemia inhibiting factor(LIF). Australia is cementing its place at the forefront of stem cell re- MEDICAL BIOTECHNOLOGY search with a transparent regulatory system and the establishment of thevisionary National Stem Cell Centre (NSCC). An initiative of the Austra-lian government, this centre draws together expertise and infrastructure;in 2003 it entered into a licensing agreement with the US companyLifeCell.
Strong opportunities exist in areas such as immunology, reproductive medicine, neurosciences, infectious diseases and cancer. There are alsoopportunities for bioprospecting given that Australia is home to almost10 per cent of global plant diversity, with around 80 per cent of plantsand microbes in Australia found nowhere else in the world. Although 25per cent of modern medicines come from natural products, it is estimatedthat only 1 per cent of plants in Australia have been screened for naturalcompounds.
Australia is the most resilient economy in the world, has the lowest risk of political instability in the world and possesses the most multiculturaland multilingual workforce in the Asia-Pacific region. Its geographicallocation has not been a deterrent to the establishment of partnerships.
According to Ernst & Young's 2003 ‘‘Beyond Borders'' global biotech-nology report, Australia had 21 cross-border alliances in 2002 – morethan France and Switzerland, and 18 more than its nearest Asia-Pacificcompetitor. All the major pharmaceutical companies have a presencein Australia and pharmaceuticals are the third-highest manufactures ex-port for Australia, generating over US$1.5 billion. The largest drug-exploration partnership in Australian history, between Merck & Co., Inc.
and Melbourne-based Amrad to develop drugs against asthma, otherrespiratory diseases and cancer, was valued at up to US$112 million(plus royalties) in 2003. It is therefore no wonder that the pharmaceuticalindustry in Australia, which has annual revenues of US$9.2 billion, isincreasingly viewed by the main global players as a valuable source ofinnovative R&D and technology.
6 United Nations University, 2005 The views expressed in this publication are those of the author and do not neces-sarily reflect the views of the United Nations University.
United Nations University PressUnited Nations University, 53-70, Jingumae 5-chome,Shibuya-ku, Tokyo, 150-8925, JapanTel: þ81-3-3499-281 Fax: þ81-3-3406-7345 United Nations University Office at the United Nations, New York2 United Nations Plaza, Room DC2-2062, New York, NY 10017, USATel: +1-212-963-6387 Fax: +1-212-371-9454 United Nations University Press is the publishing division of the United NationsUniversity.
Cover design by Rebecca S. Neimark, Twenty-Six Letters Printed in Hong Kong ISBN 92-808-1114-2 Library of Congress Cataloging-in-Publication Data Sasson, Albert.
Medical biotechnology : achievements, prospects and perceptions / Albert Includes bibliographical references and index.
ISBN 9280811142 (pbk.)1. Biotechnology. 2. Biotechnology industries. 3. Pharmaceutical biotechnology. [DNLM: 1. Biotechnology. 2. Technology, Pharmaceutical.
QV 778 S252m 2005] I. Title.
TP248.2.S273 Medical Biotechnology: Achievements, Prospects and Perceptions
Albert Sasson
For many people, biotechnology means genetically modifi ed organisms, alien species, toxic weapons or hormone-treated beef. Yet it is also a tool to control plant and animal pests, preserve species, utilize genetic resources for health and nutrition and protect the environment. Society's ability to manage, share and regulate advanced biotechnology offers many opportunities and raises many challenges and risks.
This book explores the issues of advanced biotechnology and examines the progress made in recent years. It looks at the drivers of medical and pharmaceutical biotechnology development in the United States, the European Union and Japan. It describes the biotechnology tools to fi ght major global health concerns such as Ebola fever, the human immunodefi ciency virus, the SARS virus and the Avian fl u virus, as well as regulatory concerns and public perceptions.
Professor Sasson also provides a state of the art analysis of the progress of selected developing countries in fostering their own bio- industries. He examines some of the most controversial areas of medical biotechnology, including issues such as stem cell research and gene therapy and some of the ethical issues they raise.
"The fi ndings of this book are a valuable contribution to the state of our
knowledge about modern biotechnology, to UNU-IAS efforts to raise
awareness among policy makers and stakeholders, and to educating
the public at large about the greater implications and prospects
concerning the advances of this rapidly growing new technology."
From the Foreword by A. H. Zakri, Director of the United Nations
University Institute of Advanced Studies
Albert Sasson is a Senior Visiting Professor at the United Nations
University Institute of Advanced Studies. He has had a distinguished
career as a scientist and scientifi c advisor and he was Assistant
Director-General of UNESCO from 1993 to 1996. His work and
research have culminated in over 200 publications. Professor Sasson is
an Associate Member of the Club of Rome and holds a number of
honorary appointments and degrees, including an appointment by the
King of Morocco as a Member of the Human Rights Consultative
Council.
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