As recently as a decade ago, the legalities ofobtaining samples of plants, microbes, andanimals were straightforward. In manyinstances, a researcher could simply arrive ata field site, collect samples, and take themhome. There was no applicable law. Theresearcher might obtain informal permissionfrom a local community or landholder, asmuch for being on the land as for collecting.At most, the researcher might be required toobtain a permit similar to a fishing or hunt-ing license to collect from national lands.

Recent changes in the legal environmenthave made it much more complicated toobtain biological samples. In effect, access tonature’s greenhouse has become regulated. Inaddition to habitats and species being wipedout at an alarming rate, the new regulationshave compounded the difficulty of findingand identifying new biological materials.

Sources of the new rulesThe new rules for biodiversity prospectingand natural products research derive fromthree sources: international treaties, nationallaws, and professional self-regulation. The1993 Convention on Biological Diversity(CBD) established sovereign national rightsover biological resources and committedmember countries to conserve them, developthem sustainably, and share the benefitsresulting from their use. Sustainable use ofbiological resources means finding newdrugs, crops, and industrial products, whileconserving the resources for future studies.

The 1994 General Agreement on Tariffsand Trade (GATT) set minimum standardsfor protecting patents, trade secrets, trade-marks, and copyright. These standards will bein place for most countries by the year 2000,with the least developed countries, notablyAfrican countries, given five more years tocomply. The effect of the GATT Trade-Related Aspects of Intellectual PropertyRights (TRIPS) agreement is to increase dra-matically the international value of intellectu-al property. Some people view the sovereignrights created by the CBD as an ecologicalcounterpoint to the technological intellectualproperty rights that we in the US are familiar

with, which are expanding due to the GATT-TRIPS agreement. Thus, the combined influ-ence of TRIPS and the CBD is leading us to anew intellectual property regime.

Through national biodiversity-related lawsand regulations, countries have begun to exer-cise their sovereign rights over biologicalresources as established in the CBD. In effect,many of these laws create a new category ofpoaching, in which biological materials are col-lected or exported without obtaining permis-sion (informed consent) and without satisfyingcertain conditions such as benefit sharing.

Meanwhile, many institutions and profes-sional organizations have decided to imple-ment natural products research policies fortheir members, and these policies have quasi-legal or contractual status. Examples include

botanical gardens (Kew Gardens in Londonand the Missouri Botanical Gardens in St.Louis), biotechnology companies (Shaman, S.San Francisco, CA; Monsanto, St. Louis, MO),and professional groups (the Declaration ofBelém of the International Society ofEthnobiology, based in Athens, GA).

The basic bargain underlying passage ofthe CBD was that sovereign rights would betempered by providing access to geneticresources in exchange for a share of the bene-fits, including access to biotechnology. Tosatisfy the three goals of the CBD (conserva-tion, development, and benefit sharing), theprinciple of sovereign rights is best appliedthrough what has become known as Accessand Benefit Sharing Agreements (ABAs).

Under the CBD, prior informed consent isthe standard for ensuring a fair and equitableABA. The source country providing access togenetic resources must know in advance whatwill be done with the resource, and what ben-efits will be shared. Without such an under-standing between the collector and the sup-plier, there can be no fair agreement on bene-

NATURE BIOTECHNOLOGY VOL 17 SEPTEMBER 1999 http://biotech.nature.com 921

fit sharing. (Benefits may include support forresearch and conservation, contributions ofequipment and materials, assistance toindigenous and local communities, up-frontfees, milestone payments, and royalties.)

Consequences of breaking the rulesThere is a very simple reason for people whocollect biological samples to follow the newrules on informed consent and benefit shar-ing: the consequences of following the old“take-and-run” approach are extremely seri-ous. First, patents on natural product inven-tions are subject to attack unless all publicknowledge about the species in question andits use are fully disclosed. Organizations inthe bioresource-rich but economically poorcountries of the developing world havedemonstrated a willingness to attack naturalproduct patents on the basis of traditionalknowledge, motivated by principles of jus-tice rather than the economic forces usuallyunderlying patent disputes.

For example, a 1995 patent, “Use ofturmeric in wound healing,”1 was canceled in1998 after a reexamination proceeding insti-tuted by India’s Council of Scientific andIndustrial Research. The new evidence estab-lished that use of turmeric to promote woundhealing had been known for generations inIndia. Likewise, a 1986 plant patent2 claims anostensibly new, distinct variety ofBanisteriopsis caapi, known in the Amazon asayahuasca. However, new evidence establishesthat the claimed plant is actually the wilduncultivated type, and is neither new or dis-tinctive. COICA, an organization of indige-nous people, and the Amazon Coalition haverequested reexamination of the ayahuascapatent, seeking to eliminate what is perceivedas an immoral expropriation of their tradi-tional and biological heritage. More suchchallenges can be anticipated.

Where a plant sample is collected illegallyand then a new drug compound or valuablegene is isolated from the sample, patented,and commercialized, the patent could be heldunenforceable as the result of “taintedresearch.” The tainted research doctrine isillustrated in the case Regents of the Universityof California v. Eli Lilly & Co.3 In developingcDNA encoding human insulin, someresearchers violated NIH regulations thatembargoed the use of uncertified plasmids inmammalian recombinant DNA research.They then lied in their patent application,

RESOURCES

PATENTS

New rules for natural products researchDwindling natural resources have spurred tighter regulations for biodiversity prospecting.

Michael A. Gollin

Michael A. Gollin is a partner at Venable,Baetjer, Howard & Civiletti, LLP, 1201 NewYork Avenue, NW, Suite 1000, Washington,DC 20005 (magollin@venable.com).

The new rules for biodiversity prospecting and natural productsresearch derive from threesources: internationaltreaties, national laws, andprofessional self-regulation.

© 1999 Nature America Inc. • http://biotech.nature.com©

199

9 N

atu

re A

mer

ica

Inc.

• h

ttp

://b

iote

ch.n

atu

re.c

om

922 NATURE BIOTECHNOLOGY VOL 17 SEPTEMBER 1999 http://biotech.nature.com

RESOURCES

stating that they had used a certified plasmid.The lower court held the patent unenforce-able for fraud, the illegitimate fruit of a for-bidden tree. However, the appeals courtreversed, holding that it would not haveaffected examination of the patent if the truthhad been told. In other words, the misrepre-sentation in the patent was not “material.”

This case teaches that if an invention isbased on tainted research material, such as aplant sample smuggled out of a country in vio-lation of its laws, and the inventor lies about itin a patent, a case of fraud might be made.However, the inventor must have gained someadvantage by the misrepresentation, such asbeing the first to make the invention.

It is already common practice (if notrequired) for natural product patents toidentify the country from which biologicalmaterial was obtained. In 1997, theEuropean Parliament went further by adopt-ing a measure that would have required apatent applicant to indicate the geographicalplace of origin of biological material, and toprovide evidence that the material had beenused in accordance with access and exportrestrictions in force in the place of origin(e.g., entering an ABA). Ultimately, theEuropean Commission rejected that propos-al on the grounds that it exceeded therequirements of the CBD. However, if such aproposal were ever adopted in any country,then an absence of source country approvalwould doom a patent. Likewise, a misrepre-sentation would become considered materi-al, and would jeopardize the patent.

A second consequence of breaking therules is that if a researcher removes biologicalmaterial illegally from a source country, andthen profits from the material, the sourcecountry or affected person could recover all orsome of the profits, in a US court, based on atheory of misappropriation and related doc-trines. Thus, there is a real legal risk for some-one who fails to reach agreement on an ABAbefore taking a sample home. The conditionsa court might impose for a successful productcould be much more onerous than one thatcould be negotiated at the outset, when suc-cess is still a highly unlikely outcome. This riskis highest in a country that requires an ABA.

Third, clean title to biological materialnow means that it was obtained legitimately,and with prior informed consent fromwhomever had initial control over it. If thereis no clean title, the value of the material isseriously reduced. The collector of an illegit-imate sample will not be able to pass it on, inturn, to collaborators, partners, or third par-ties in the normal course of conduct forresearchers. Absent assurances that thematerial was collected in compliance with allapplicable laws and regulations includingbenefit sharing, a savvy recipient of biologi-cal material will not accept material.

Moreover, if the supplier certifies that a sam-ple was properly obtained, and it was not,then the recipient could assert a contractualclaim for damages back against the collector.

To assure a clean, cloud-free chain of titlefor materials collected since 1993 (the CBD’seffective date), compliance with the newrules needs to be established. Material col-lected before 1993 is “grandfathered” underthe CBD, such that sovereign rights and theobligation of prior informed consent do notapply. Nonetheless, claims to such pre-CBDmaterial are being asserted by source coun-tries, too, on political, if not legal grounds, soit could be advantageous to show that pre-CBD material was collected with priorinformed consent and benefit sharing. Thecenters of the Consultative Group onInternational Agriculture Research haveadopted a trust agreement whereby theirextensive pre-CBD collections are held intrust for the benefit of the world.

Fourth, as a practical matter, if a collectordoes not agree to provide an equitable shareof benefits, in advance, to the source of bio-logical samples, the collector may well bedenied access to the samples. Simply put, thepossibilities for fieldwork will dry up.

Fifth, someone who is branded as a “biopi-rate” will suffer from the bad reputation.Likewise, someone who gains a reputation forevading access restrictions, or for being hardto deal with, may find it increasingly difficultto find doors open for further research. Thereis an intense gossip-mill active on the Internet,and self-anointed watchdog groups like RuralAdvancement Foundation International andthe Center for Law in the Public Interest arequick to spread the names of companies andinstitutions they believe are violating the stan-dards for collection.

Corporations have recognized that adher-ence to principles of sustainable develop-ment, including the use of ABAs for naturalproduct research, brings significant benefitsto the company. Why are companies follow-ing the new rules? By doing so, they can (1)improve the reliability and quality of thematerial supplied to them; (2) benefit fromaccess to traditional knowledge about plantsand insects; (3) establish goodwill that canpay off in present or future markets for thetheir products; and (4) distinguish them-selves from less green competitors, thusobtaining a competitive advantage.

On the other hand, a company that isassociated with biopiracy may end up withweak patents, be exposed to equitable claimsfor profit sharing, lose sources of supply, andface the prospect of consumer and govern-ment boycotts, barriers to importation ofbiotechnology products, loss of market share,and financial penalties.

Finally, the ultimate legal sanction—criminal penalties, including jail—may

apply. It is not uncommon for hunters to bejailed for poaching or trespassing, and thereis at least one instance of a researcher whowas temporarily detained in Australia forunauthorized collecting of plant materials.Collection of biological materials without abenefit-sharing agreement is likely to find itsway into the list of criminal violations insome countries, so that biopiracy could resultin a jail sentence.

ConclusionsIn summary, given all these risks, manyorganizations have concluded that it is wiseto enter into an access and benefit-sharingagreement for every collection. Additionaltips for collectors and recipients of biologi-cal materials include these: Cultivate long-term relationships with suppliers; makefriends with local regulators and find outwhat the local rules are; find out what youcan offer (it may be worth more to theprovider than to you); allow plenty of timeto obtain permits; plan big, long-term pro-jects instead of small, one-time deals; beproactive and enter into an ABA even if nolaw is in place; try to obtain materials with-out restrictions; scrutinize the records ofintermediaries (botanical gardens, brokers,institutions) to be sure the material wasproperly obtained; and be sure to disclose allrelevant information to regulators, collabo-rators, and patent offices.

Just as it is becoming harder to obtainnatural materials, it is becoming easier toobtain synthetic samples from combinatorialchemistry and genomics. Research in naturalproduct supply, high-throughput screening,and new extraction methods must competewith genomics, biosynthesis, and combinato-rial chemistry. But will the demand for newnatural materials disappear? No. As E.O.Wilson points out, “Organisms are superbchemists. . .collectively better than all theworld’s chemists at synthesizing organic mol-ecules of practical use (p. 285).”4

The true risk to natural product research isnot that the greenhouse door will be shut, thusreducing supply, or that demand for naturalproducts will cease. It is that supply will dropbecause species are disappearing faster thanwe can study them. As Wilson says, “Usefulproducts cannot be harvested from extinctspecies (p. 282).”4 The most fundamental riskto natural products research is continued lossof biodiversity. If the new rules for biodiversityprospecting succeed in reducing biodiversityloss, while allowing research to continue, thenany inconvenience they bring will be justified.

1. US Patent No. 5,401,504.2. US Plant Patent No. 5,751.3. 39 USPQ2d 1225 (S.D.Ind. 1995), reversed in perti-

nent part, 119 F.3d 1559, 1570 (Fed. Cir. 1997).4. Wilson, E.O. The biodiversity of life. (Harvard

University Press, Cambridge, MA; 1992).

© 1999 Nature America Inc. • http://biotech.nature.com©

199

9 N

atu

re A

mer

ica

Inc.

• h

ttp

://b

iote

ch.n

atu

re.c

om