Green biotechnology and European competitiveness

TRENDS in Biotechnology Vol.19 No.4 April 2001

http://tibtech.trends.com 0167-7799/01/$ – see front matter © 2001 Elsevier Science Ltd. All rights reserved. PII: S0167-7799(00)01572-9

135Opinion

The ability to understand and reprogram life formsis going to become one of the key drivers of the globaleconomy. Some of the world’s largest companies havecompletely restructured themselves to become lifescience companies1–3. For example, DuPont, sold offits oil subsidiary, Conoco, to fund an aggressive lifescience expansion. The same is happening tocompanies involved in farm inputs, pharmaceuticals,food processing, energy, mining, cosmetics and eveninformation technology. IBM’s largest computerproject, Blue Gene, is an attempt to build a machinethat can process the enormous amount of newgenomics information. As these businesses grow, orwither, they will change the competitive positions ofcountries. Europe is in ever-greater danger of fallingfar behind in this massive industrial restructuring.

Europe birthed large parts of the biotechnologyrevolution. Many examples of leadership come to mindincluding Mendel’s peas, Crick and Watson’s DNAand the Roslyn Institute clone (Dolly). During the raceto sequence the human genome, the Sanger Centreserved as a global example and motor; the UKgovernment was among the first to advocate the useof embryonic stem cells. But despite cutting-edge

research science, Europe is finding it hard to translatebiotechnology discoveries into the thousands of newcompanies and vast wealth that has accrued in theUSA in Cambridge MA, San Diego, Maryland andSilicon Valley. Furthermore, current debates andpolicies might further isolate the continent, with severerepercussions for employment and overall wealth.

Euroskepticism

There are many reasons why Europeans arejustifiably skeptical of a biotechnology panacea,including health concerns, regulatory efficiency,budget implications and potential environmentalimpacts. Over the past decade, various Europeancountries have suffered a series of food crises. Manywere caused by the introduction of ever larger andmore complex agro-industrial processes. Bovinespongiform encephalitis (BSE) started because of‘improvements’ in cow feed4. Fear of processed foodsincreased after revelations of dioxin in farm animals,contaminated Coca-Cola and lax Salmonellaregulation. During 2000, a US subsidiary of a Frenchcompany Aventis, released Starlink corn into thehuman food chain with global consequences.

Each of these incidents undermined the alreadyshaky credibility of European regulatory authoritiesand politicians. When Europeans were asked whoseopinions they trust to tell the truth on biotechnology,the results were: consumer organizations 26%,medical professionals 24%, environmentalorganizations 14%, international institutions 4%, andnational government 3% (Ref. 5). Most believe thatregulators focus too much on the needs of farmers andcompanies instead of protecting consumers. Eurocratsand politicians reacted by becoming ever more wary ofnew technologies. Low credibility, fear, and lack ofscientific literacy makes it ever harder to usescience-based arguments to promote biotechnology,particularly after the first attempted impeachment ofthe whole of the European Commission for theirhandling of the BSE crisis; precaution often trumpsinnovation in the Europe of today.

Budget deficits have also instilled a fear ofbiotechnology. Europe leads the world in attemptingto erase borders and reconcile multiple regulatoryframeworks, as well as discussing common security

Green biotechnology

and European

competitiveness

Juan Enriquez

Europe has led many aspects of gene research and yet it has been unable to

translate these discoveries into a globally dominant industrial sector. There

are valid societal, political and financial reasons for its reluctance to deploy

agricultural biotechnology but this reluctance might have unintended

consequences. It will be hard to de-commoditize agriculture and improve

farmer’s lives. Research in medical biotechnology and the global

environment might suffer. Europe could damage its overall economy and

its global competitive standing.

Juan Enriquez

DRCLAS. HarvardUniversity, 61 Kirkland St,Cambridge, MA 02138,USA. e-mail: [email protected]

23 Sham, Y.Y. et al. (1997) Consistent calculationsof pKas of ionizable residues in proteins:semi-microscopic and microscopic approaches.J. Phys. Chem. 101, 4458–4472

24 Hendsch, Z.S. et al. (1998) Parameter dependencein continuum electrostatic calculations: A studyusing protein salt bridges. J. Phys. Chem.102, 4404–4410

25 Oliveberg, M. et al. (1995) pKA values of carboxylgroups in the native and denatured states ofbarnase: the pKA values of the denatured stateare on average 0.4 units lower than those of modelcompounds. Biochemistry 34, 9424–9433

26 Swint-Kruse, L. and Robertson, A.D. (1995)Hydrogen bonds and the pH dependence ofovomucoid third domain stability. Biochemistry34, 4724–4732

27 Kuhlman, B. et al. (1999) pKa values and the pHdependent stability of the N-terminal domain ofL9 as probes of electrostatic interactions in thedenatured state. Differentiation between local andnonlocal interactions. Biochemistry 38, 4896–4903

28 Whitten, S.T. and Garcia-Moreno, E.B. (2000) pHdependence of stability of staphylococcal nuclease:evidence of substantial electrostatic interactions inthe denatured state. Biochemistry 39, 14292–14304

29 Elcock, A.H. (1999) Realistic modeling of the denatured states of proteins allows accurate calculations of the pH dependence of protein stability. J. Mol. Biol.294, 1051–1062

30 Frankenberg, N. et al. (1999) Does the eliminationof ion pairs affect the thermal stability of coldshock protein from the hyperthermophilicbacterium Thermotoga maritima? FEBS Lett.454, 299–302

31 Strop, P. and Mayo, S.L. (2000) Contribution ofsurface salt bridges to protein stability.Biochemistry 39, 1251–1255

and tax structures. But integration has not beencheap. European budgetary debates are ever tougherbecause the amounts involved are significant, andsome countries are net contributors whereas othersare net beneficiaries of European Union (EU) funds.Ireland, for example, has received the equivalent of3% of its GNP in transfers from the community. Thereis increasing pressure within the taxpayer base of thecountries that provide the most funds, particularlyGermany and the UK, to reduce the amountsprovided to the EU.

But the EU bureaucracy cannot achieve austerity ifagricultural subsidies remain sacred. These subsidiesrepresent close to one half of the entire EU budget; theagricultural sector received US$ 50.5 billion in 1999,which was 16% above previously stated target spendinglevels6. Cultivating smaller farms, maintaining a rurallifestyle and avoiding a showdown with farmers getsmore expensive every year. Europe pays a lot toproduce, or not produce, food it does not need. Withinthe EU, the price of the average farm product is almosttwo-thirds more than the world price. During 1999,wheat imports paid a duty equivalent to 93% of theworld market price (see http://www.fas.usda.gov/grain/highlights/1999/99%2D06/ft6%2D15.htm).Maintaining this system requires combining hightariffs, effective barriers to entry and large internalsubsidies. This scheme becomes even more difficultto balance as the EU expands.

By 2000 the EU had accepted membershipapplications from ten Central and Eastern Europeancountries. Potentially, this could lead to the inclusion ofmore than eight million agricultural workers andmillions of acres of crops. More applications, includingthat from Turkey, are pending. Few farmers withinthese prospective EU members sold their produce atEU subsidized levels. In November 1998, Polandwas selling rye 28% below EU intervention prices andHungary sold its wheat ~40% below the EU price. Atwo-tier price structure, for old members and newmembers would be hard to legitimate and police withinthe context of open borders, but the cost of maintainingand broadening the current agricultural system couldbecome overwhelming. However, attempts to reformthis system, such as Agenda 2000, have foundered.They were gutted after farmer protests. Even if theEU achieved its objective and cut grain subsidies by15%, rapid productivity gains without priceadjustments could upset an already strained system7.

New technologies are often unpopular because manyEuropean policy makers believe that each additionalkilo of agricultural produce leads to demands for newsubsidies rather than to a decrease in the EU budget asa result of productivity gains. As green biotechnologythreatens to overwhelm budgets and regulations,many European governments have turned to safetyrestrictions in an attempt to protect their farmers.Battles over beef exports have raged between the EUand the USA because hormone-treated cattle growfaster and more efficiently. This could be a preview of

even more bitter confrontations as biotechnologyproducts continue to reduce the cost of staple crops.

Finally, there are good reasons to debate andworry about the environmental and health impactsof the gene revolution. As with any new technologythere will be serious mistakes and accidents. Itwould have been difficult to imagine World War Iwithout technologies such as electricity and steel, or the Cold War without nuclear weapons.Scientific revolutions create great wealth but alsocreate potential for misuse. Some of the technologiesthat help grow crops or create new medicines mightalso be used to design weapons.

However valid these concerns might be, Europe’sattempt to ignore or slow down progress inagricultural life science could end up being extremelycostly. Instead of just focusing on the potentialproblems of this revolution, the EU should alsoexamine the consequences of falling far behind in akey technological revolution.

Rapid change, but not in Europe

The agriculture–biotechnology revolution is in itsfirst and highly experimental stage; the firstcommercial genetically modified (GM) crops weregrown in China in 1992 and large-scale adoption inthe USA only began in 1996; changes can, andshould, occur very rapidly. Agricultural productivityincreases will grow and compound. Within the USAthe speed of GM crop adoption was spectacular. ByJune 2000, 61% of cotton, 54% of soybeans and 25% of corn were grown from GM seeds8. Globally,however, this is still a highly localized phenomenon.In 1999, the USA planted 69% of the world’s GM crops,Argentina 14%, Canada 10% and China 3%.

Companies that established a leadership positionin green biotechnology research soon dominated theproduction of key export crops. Chemical andpharmaceutical conglomerates bought most largeseed companies and by 1999 Monsanto and DuPont controlled more than four-fifths of USAcorn seed and over half of its soybeans9. The entitiesbuying, distributing and processing food and fiberalso consolidated.

As a few countries embraced new technologies,Europe was busily building a moat around its ruralenvironment. In the short term, Europe’s decision torestrict green biotechnology has hurt a few Europeancompanies but it has not been a disaster. There is stillconsiderable debate over the relative productivity andprofitability of GM and non-GM crops. A recent EUreport concluded, ‘studies do not provide conclusiveevidence on the effective profitability of GM crops’10.Although this position might be arguable today, itcould soon be overwhelmed by a mass of new bio-tools,patents, brain drains and marketing strategies.

Consequences of selling commodities

In a commodity system, those who can produce andsell ever cheaper, high quality goods create


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136 Opinion

enormous pressures on inefficient producers.Sometimes it is hard to recall just how relentlesslytechnology lowers prices; in 1897 a pair of scissorscost the equivalent of US$ 67, a phone US$ 1202and a bicycle US$ 2222. Over the past few centuries,growth in food production and efficiency hasexceeded the increase in human population by asignificant margin. In 1919 it took the average USworker 2 hours and 37 minutes to earn enough tobuy a chicken; by 1997 it took 14 minutes11. Today,there is more than enough grain available to feedeveryone on the planet (although this is far fromequally distributed). Even famine-prone countries,such as India, are now producing grain surpluses.China imported corn as late as 1995, but by 1998 itwas a net exporting country. Billions of people cannow occasionally eat what were previously consideredluxury foods, such as meat, because there is enoughgrain to feed some cattle, which have a veryinefficient feed–meat conversion ratio.

In real terms, the price of the average commodityis about one-fifth of what it was in 1845 (Ref. 12).World wheat prices are expected to decrease by 43%between 1988 and 2010 and corn could drop by 22%(Ref. 13). This creates a relentless tendency towardsconsolidation wherever economic efficiency is the keydriver of bulk agricultural production. In 1989, largefarms produced half of USA agricultural output; adecade later they sold close to three-quarters of USAagricultural output. Scale brought efficiency, andby 1998, the USA was producing 45% of the world’ssoybeans, 40% of all corn, and 10% of wheat14.

Over the past 50 years, most productivity gainshave come from seed improvement, and the enormoussums invested in seed genetic research over the pastdecade will probably accentuate these gains. If cropyields increase faster outside Europe, it will becomeharder for an EU farmer to export his produce and thesubsidy required to keep foreign produce out willgrow year by year. Because agriculture representssuch a large portion of the overall EU budget, theshort-term consequences could be significant. Iffarmers in the Americas and Asia continue to useGM seeds and increase overall productivity 2% peryear faster than Europe, the EU might have to dedicateup to 1% more of its total budget each year tomaintain farmer’s current living standards.

Labeling and decommoditizing

In an attempt to exclude foreign GM produce, Europehas vociferously called for detailed labeling but thistoo might have unintended consequences. Theargument that the public has a right to know is toughto counter, and adopting widespread labeling could,in the short term, harm GM food producers,particularly those in the USA, Argentina, Canadaand China who grew 99% of the world’s GM crops in2000 (see http://www.issaaa.org/briefs/Brief21.htm).Thus, at least initially, labeling could serve as aneffective trade barrier and limit imports. Those who

use GM organisms (GMOs) and label theircommodities, fear becoming the target of boycotts.

Even with no direct attacks, GMO producerscould suffer because most benefits fromagricultural–biotechnology, so far, accrue mostly to themanufacturer and to the farmer, not to the consumer.A customer walking into a supermarket today cannotdetermine by look, taste or feel the difference betweenGM produce and ‘all-natural’ produce. If two identicallooking piles of corn were labeled ‘all-natural’ orproduced with GM seeds, most people would purchasethe all-natural corn as long as the price premium wasnot very high. Because there is little consumer pull,companies face increasingly hostile retailers as theytry to push their products; many Europeansupermarkets, restaurants and fast food outletsalready advertise that they sell GM-free produce.

Furthermore, the labeling of GMO producerequires a major and costly change in the agriculturalcommodity system. Farmers would have to separateseeds and plots, and harvest the crops separately.Processing, sales and distribution would also requirea separate and parallel set of channels. A bulkcommodity system would gradually become a seriesof discrete business units, something that makeslittle economic sense unless the end product can besold at a premium. This is by no means the case withmost GM products today.

In the short term, farmers and companies sellingGM crops in Europe are at a disadvantage. This hasled to the implosion of many business venturesparticularly those launched together withpharmaceutical companies. Monsanto and Searledivided with the pharma component becoming part ofPharmacia & Upjohn; Novartis and AstraZeneca alsospun off and merged their agribusiness units(Syngenta). American Home Products is selling itsagricultural component to BASF. Rhône Poulenc spunoff and merged its agribusiness with Agrevo (Aventis).

However, as the spread of genomic informationincreases, the types of traits that can be engineeredinto plants and animals should create significanteconomic advantages15. A/F Protein Company hasgenetically engineered salmon to grow twice as largeand four times as fast as ‘natural’ salmon. GM cottonplants require a lower frequency of pesticideapplications and are more resistant to the toxicity ofthe pesticides than non-GM plants. The consumptionof ‘golden rice’ helps to reduce vitamin A deficiency, andsoon GM sugar beet will produce far more sugar thannon-GM varieties. Crops that are tolerant to drought,frost, pests and salt will help to reduce a farmer’s keyrisks. Customers might be willing to pay a premium forhealthier peanuts, seedless vegetables and non-allergenicfoods. Many chemical products, such as textiles,detergents, lubricants, cosmetics, plasticizers, inks anddyes, are now grown instead of manufactured.

Food can be engineered to have medicinal benefits.Fruits and vegetables can be genetically engineeredto produce vaccines and to help fight cancer. As



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medicine and nutrition blend together, manyproducts can be sold as neutraceuticals. In the future,a customer walking into a supermarket would facenot two but various types of corn that could, forexample, help prevent osteoporosis or conception orprovide extra vitamins.

If European farmers and processors declare thecontinent a GM-free zone and do not invest in theequipment and systems needed to isolate GMOs fromwild-type organisms throughout the system, from thefield through to the shopping cart, they could end upremaining bulk product suppliers for key crops.Remaining only a commodity system makes itimpossible to sell products at a premium. Within theUSA, one-quarter of the grain elevators are alreadysegregating GM corn and one-fifth are segregatingsoybeans16. This could have significant consequencesin overall wealth creation if GM crops begincommanding a price premium.

Resistance to green biotechnology could impact red

biotechnology

Green biotechnology products reach consumers longbefore red biotechnology products do. The firstskirmishes and broad societal changes caused bybiotechnology are occurring within agriculture,precisely the field in which there is the greatestresistance to GM technology within Europe.However, many Europeans who do not want to eatGM foods have little objection to GMO-producedmedicines. European policy makers seem to believe that they can deal with this dichotomy bylimiting some forms of gene research and stillremain competitive in a science in whichinformation is accumulating at twice the speed ofthe computer revolution.

In shutting down most plant and animal GMproduct research, while attempting to promotehuman research, Europe risks its competitiveadvantage. Gene expression pathways in plants andanimals provide important clues for theidentification and treatment of disease in humansbecause once evolution finds a useful way to fulfil a specific task in a living organism it oftenrepeats it. As a result, the basic instructions orcodes that regulate life’s processes repeat andoverlap across many species.

The genes contained in the simplest bacteria areoften replicated and duplicated several times inthose bacteria that have larger genomes. Forinstance, a small genome, such as that ofMycoplasma genitalium, has few cell transporters totake material from outside the cell and transport it tothe inside17. Mycoplasma pneumoniae has developedfar more sophisticated and abundant transportersbut it also contains almost the entire M. genitaliumgenome18. These overlaps often recur even within themost complex organisms; the number of humangenes that have no counterpart in mice isestimated to be less than 5% and ~2% in orangutans

(http://www.ornl.gov/hgmis/faq/compgen.html).Various companies and research institutes, includingCelera, Incyte and TIGR, are looking at parallel geneexpression networks across bacterial, plant, animaland human genomes.

Getting a bioengineered agricultural product tomarket is far harder within Europe than within theUSA or most of Latin America. Final approval in theUSA takes nine months on average whereas in theEU it takes two to three times as long, if approval isforthcoming19. As companies and scientists involvedin green biotechnology find it increasingly difficult towork in Europe, they leave or close down. Novartis, aleading Swiss pharmaceutical company, initiallyinvested billions of dollars in building its agriculturallife science capability and became one of the world’slargest GM seed and agrichemical producers. But asprotests grew, it had to stop using food grown withNovartis seeds for its baby food division. Then itbowed to public pressure and declining agriculturalmargins and announced that it would spin off mostagricultural life science assets. By August 2000, ithad stopped using any agricultural GMOs in any ofits food products. Novartis’ story is similar to that ofmany other European conglomerates; there is littlesupport for agricultural genetic research withinGermany or France.

European companies are ever less likely to fundbasic research, development and production ofgenetically engineered products. As the Europeanpublic becomes ever more wary of GM produce, somehave started to question red biotechnology. Swisspharmaceuticals waged an aggressive and expensivecampaign to overcome a public referendum thatwould have prohibited most gene research. Thenotion that you can attack green biotechnologyresearch, and have little effect on red biotechnologyresearch is proving false.

When European gene research does continue it isoften offshored. Rather than face protests at home,many companies are moving their labs, sometimeswithin Europe, sometimes to the USA or Asia.Pharming moved from the Netherlands to Belgium tocarry out its research. Ironically, after its drugproved successful, it was imported back into TheNetherlands. Increasingly, European companies aresimply shifting their research to a few regions withinthe USA; after the UK’s two leading pharmaceuticalcompanies (SmithKline and Glaxo Wellcome)merged, they immediately shifted most of theiroperations to the USA. Commercial biotechnologyresearch and start-ups are far more common in theUSA than they are in Europe.

Saving the environment?

Europe’s reluctance to accept GMOs might beunderstandable politically, and there are potential, ifunproven, environmental and health risks. However,attempts to ban GMO adoption worldwide could havesevere consequences for the environment.



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Global food needs are increasing; by 2020 theworld will probably consume 80% more meat and 60%more cereals than in 1990. Close to 85% of the land inthe UK that could conceivably be used for agriculturalpurposes is already under cultivation. To increasefood production and meet additional global needs,either existing farms throughout the world have tobecome more productive or an area the size of theAmazon rainforest has to come under tillage.

Agriculture remains the single most destructiveactivity vis-à-vis biodiversity and natural landscapes.A key objective should be to reduce its footprint andimpact on land that remains virgin. This is onlyfeasible if small-plot farmers can grow goods thatproduce greater value (i.e. high quality neutraceuticalsor materials) and if commodity food production can beincreased substantially on existing large farms.

Europe’s attack on biotechnology is slowing theadoption of technologies that could reduce the use ofpesticides and the destruction of rainforests. Mostnotably, Brazil has been very reluctant to usebiotechnology despite enormous pressures on theAmazon forest. Its agricultural border continues toexpand instead of emphasizing more productive farms.Most Africans continue practising organic agriculture;they have little choice. The net result is that free rangecattle and slash-burn planting have destroyed much ofthe forest and fauna without increasing overall wealthand well being. These outcomes are particularly ironicgiven that the most vocal opponents of biotechnologyhave been green parties and NGOs.

Precaution might not be good enoughMany recent technological revolutions have roots inEurope; the development and adoption of a commonGSM mobile telephone standard birthed greatcompanies such as Nokia and Vodafone, but thereare also many examples of leadership lost. Bringingtogether monitor and phone, using one’s home as abase for many services and transactions, wiring acountry coast to coast, all occurred throughout

France in the early 1980s, years before the Internetbecame popular. However, there were few incentives,or openings, to compete against the phone monopolyand so the Minitel did not breed a large new economyor attract thousands of young global entrepreneurs.Meanwhile in the USA, a myriad of start-upssurrounded research centers such as Xerox Parkand Bell Labs. They developed technologies thecorporate behemoths ignored and, in some cases,became larger that the conglomerate that ignoredwhat seemed like a tangential technology.

Investing and supporting emerging gene companiescould be a crucial component of future competitiveness.From 1999 to 2000 the number of genomics patentsgranted within the USA increased by 25%; they nowexceed those granted for computing and Internetapplications. While Europe debates the future of itscountryside and tries to convince the world not to adoptGMOs, the USA has built a gene-based economy thathas a market capitalization greater than everythingArgentina produces during the course of a year.

Fueling public fears and blocking biotechnologyresearch might solve some immediate political andfinancial concerns but, in the long run, falling behindin the biotechnology revolution could be very costly.The new economy does not require a generation,large factories and thousands of workers to generategreat wealth20. Information and data fuel wealth inthe knowledge economy; those who produce and usethis resource are highly mobile.

Many of Europe’s best minds are already in theUSA. If one looks at Europeans who are awardedPhDs in science and engineering from a USuniversity 60% of those from the UK and 42% ofGermans do not return to their home countries21. Inlife sciences, the incentives to carry out research orlaunch new companies within the EU are decreasingas the public backlash increases. If Europe cannotattract and develop people and companies that areworld competitive in life sciences, it risks significantlydamaging its overall economy and competitive future.



139Opinion

References

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Acknowledgements

I thank Profs RayGoldberg, Otto Solbrigand Robert Paarlberg, aswell as Rodrigo Martinezfor their help and ideas.

Documents

Green biotechnology and European competitiveness