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UNEP/CBD/SBSTTA/2/15 24 July 1996
SUBSIDIARY BODY ON SCIENTIFIC, TECHNICAL AND
Montreal, 2 to 6 September 1996
BIOPROSPECTING OF GENETIC RESOURCES OF THE
Note by the Secretariat
1. In recent years, there has been a steady increase in
public awareness worldwide of the economic, social, environmental, cultural,
recreational and other critical benefits derived from marine and coastal
biological diversity, including its components. As evidence of the priority
now being assigned by governments to this area, at its first meeting the
Conference of the Parties to the Convention on Biological Diversity (COP)
selected marine and coastal biological diversity as the first major ecosystem
"theme" to be addressed systematically under the Convention process,
as part of the COP's medium-term programme of work.
2. The Secretariat's report on access to genetic resources
prepared for the second meeting of the COP (document UNEP/CBD/COP/2/13)
noted, inter alia, that, as Article 15 of the Convention (which
provides the basis for the Convention's approach to controlling the use
of genetic resources) did not apply to areas outside national jurisdiction
and, given that it is unclear whether, or how, UNCLOS, or the common heritage
principle, applies to the genetic resources of the deep sea-bed, there
needs to be an in-depth study on how to best address the use of these resources.
3. The second meeting of the COP, in paragraph 10 of decision
II/10, requested the Executive Secretary, in consultation with the United Nations
Office for Ocean Affairs and the Law of the Sea, to undertake a study of
the relationship between the Convention on Biological Diversity and the
United Nations Convention on the Law of the Sea with regard to the
conservation and sustainable use of genetic resources on the deep sea-bed,
with a view to enabling the SBSTTA to address at future meetings, as appropriate,
the scientific, technical and technological issues relating to the bio-prospecting
of genetic resources on the deep sea-bed.
4. This Note presents a brief survey of the issues raised
on the bioprospecting of genetic resources on the deep sea-bed in light
of the provisions of the Convention and UNCLOS. Its purpose is to enable
the SBSTTA to make a preliminary assessment of the areas that it feels
it can make an effective contribution to the relationship between the Convention
and UNCLOS and to consider how it might make that contribution in a timely
fashion. It must be stressed, however, that the consideration of the relevant
principles of international law have not been reviewed by either the United Nations
Office for Ocean Affairs and the Law or the United Nations Office for Legal
5. The Note has been presented to the United Nations
Office for Ocean Affairs and the Law of the Sea by way of a preliminary
investigation of the nature of the relationship between the Convention
and UNCLOS with regard to the bio-prospecting of genetic resources on the
deep sea-bed. In this sense it represents no more than a preparatory step
for the study requested by the second meeting of the COP.
2. THE INTERNATIONAL LEGAL REGIMES GOVERNING THE USE
OF DEEP SEA-BED MARINE GENETIC RESOURCES
6. Marine genetic resources are subject to a set of legal
principles that essentially derive from UNCLOS, customary international
law and the CBD. These principles basically apply three different regimes
to marine genetic resources depending upon their location.
7. Marine genetic resources that are located within the
"national jurisdiction" (which effectively means the EEZ), are
under Article 22.2 of the CBD and subject to its principles to the extent
that this treatment does not conflict with the "law of the sea".
UNCLOS, which embodies the "law of the sea", attributes sovereign
rights to the coastal State for the purposes of exploring and exploiting
natural resources throughout the EEZ. In relation to the exploitation of
mineral resources on the continental shelf, however, the coastal State
is obliged to make payments or contributions in kind to the Parties to
UNCLOS through the International Sea-bed Authority ("ISA"), if
any are developed beyond the 200-mile limit. With respect to marine living
resources within the EEZ, the coastal State has certain conservation and
management obligations, including the obligation, in principle, to share
under-utilised resources with other States. For sedentary species, the
continental shelf legal regime is distinct from the living resources conservation
provisions of the EEZ found in Article 68. In both cases, however, the
general intent of the obligation is to control over-exploitation. As the
use of genetic resources is of a non-consumptive nature, these general
obligations have little impact or relevance. Consequently, most of the
obligations and rights affecting use of these type of marine genetic resources
derive from the CBD.
8. Beyond national jurisdiction, the CBD only applies
to "processes and activities", and the principal instrument is
UNCLOS. Matters not regulated by UNCLOS continue to be governed by general
principles of international law. UNCLOS imposes different regimes for the
water column and the sea floor. For the water column, UNCLOS maintains
that fishing and scientific research are freedoms of the high seas. The
freedom to fish is limited by the rights, duties and interests of coastal
states, the duty to take measures with respect to a State's own nationals
to conserve high seas living resources and to cooperate to conserve and
manage high seas living resources. These duties are being increasingly
clarified and being developed from broad guiding principles to binding
legal obligations. For example, the UN Agreement on High Seas and Straddling
Stocks considerably clarifies many of these freedoms and duties. Despite
the increasingly normative nature of the legal regime, as with the regime
for the EEZ, most of these obligations and duties are generally intended
to deal with the over-exploitation of fish stocks and have little relevance
to the use of genetic resources. Consequently, the genetic resources of
the water column are essentially unregulated.
9. UNCLOS designates the sea-bed, ocean floor and subsoil
thereof located beyond the limits of national jurisdiction as "the
Area" and designates the Area and its resources as the common heritage
of humankind. A special legal regime and institutional structure is established
by UNCLOS to control prospecting, exploitation and exploration of the Area's
mineral resources. The special regime does not extend to the non-mineral
resources of the Area or the water column immediately above the Area.
10. All rights in the mineral resources of the Area are
vested in humankind as a whole. In effect, the Area's mineral resources
have become international property to be exploited for the benefit of humankind.
Neither a State nor a private entity can exercise sovereignty or dominion
over any part of the Area or its mineral resources. Title to minerals passes
only upon their recovery in accordance with UNCLOS. The International Sea-bed
Authority is established to ensure that there is fair and equitable utilisation
of the Area's mineral resources.
11. The regime for the Area makes no reference to genetic
resources. As a result, it is not clear how UNCLOS may apply to the Area's
genetic resources. The most plausible interpretation is that, as with all
resources of the high seas other than mineral resources, they are freely
accessible, open- access resources, appropriable by anyone who collects
them. These types of resources are governed by a number of broad principles
included under the rubric of the freedom to fish.
12. Article 22.2 of the CBD has the effect that, despite
the apparent conflict between UNCLOS's approach of internationalising the
Area based on the concept of the common heritage of humankind and the CBD's
general approach of conferring sovereignty or nationalising genetic resources,
the UNCLOS approach prevails, and marine genetic resources found outside
national jurisdiction can therefore effectively be considered as unregulated
resources. This situation has arisen, however, by accident rather than
design. The potential value of marine genetic resources and their importance
in the benefit sharing rubric were not anticipated in the UNCLOS negotiations.
Consequently, as these genetic resources appear to promise considerable
economic value, the situation begs the question of whether this approach
is correct for these resources both with regard to their sensible exploitation
and in the wider sense of the precedent that they provide for other contexts.
13. Marine genetic resources outside national jurisdictions,
and especially those in the Area, provide both an opportunity and a challenge.
If properly developed, utilisation of these resources could provide an
opportunity to implement Article 15 and be an example to countries that
a fair and equitable sharing of benefits is possible. There are significant
parallels with the current circumstances surrounding the use of these resources
and those surrounding the development of the legal regime in Antarctica.
The experience in Antarctica suggests that there is a genuine possibility
that a regime could be established relatively quickly by international
standards. Factors such as an absence of vested economic interest, the
absence of dominion by private or public entities, and the fact that the
Area comes under the jurisdiction of two newly established regimes are
important and propitious in being able to successfully develop an international
regime. However, they are factors that will not persist for very long.
On the other hand, there is a danger that attempts to develop such a regime
will follow a similar path to deep sea-bed mineral resources, which might
not only inhibit equitable use of these resources but could also have serious
ramifications for the Convention generally.
14. There are a numerous ways that control over the bioprospecting
of these resources could be developed. Foreseeable scenarios include:
(a) leaving marine genetic resources unregulated and freely available to those who spend the resources to collect them;
(b) bringing them within the regime governing the Area and the ISA's authority;
(c) bringing them within the CBD regime; and
(d) establishing an entirely new regime to deal with these
special and new resources.
15. Each of these options has advantages and disadvantages.
The first option, for example, represent a pragmatic approach on the basis
that it may well be premature to even consider controlling the exploitation
of these genetic resources. Most private entities considering investigating
the potential of these genetic resources would take this view. Parallels
with the enormous waste of effort involved in controlling exploitation
of the Area's mineral resources come to mind. Similar parallels could be
drawn with CRAMRA and the mineral wealth of Antarctica. Certainly, leaving
exploitation of these resources unregulated has the attraction of providing
the most encouragement to opening up the wealth of these resources. Due
to the expense of developing these resources, it does, however, effectively
bequeath them to large multinational companies or well-resourced government
programmes; in other words, to developed countries. Establishing some form
of international control prior to the emergence of commercial pressures
for the exploitation of these resources would also mean that such a regime
could be more easily developed to reflect what is fair and equitable rather
than waiting until the resource is being exploited, when the regime would
be more likely to reflect existing interests, regardless of whether this
was fair or equitable. It would also avoid the problems of equity associated
with allowing unregulated exploitation. It may, however, create a bureaucratic
weight that industry cannot support, resulting in a situation where the
resources are not developed. This, of itself, may be a desirable outcome
on the basis that these resources should be protected as common heritage
until all can participate effectively and equally in their exploitation.
16. Arguments for an entirely new regime include the fundamentally
different requirements and pressures of utilising genetic resources, arising
from the fact that it is a non-consumptive process that is quite distinct
from the more conventional and consumptive use of marine resources, such
as fishing or mining. These distinctions question the applicability of
the UNCLOS rubric at all. Furthermore, given that the minerals have been
treated separately under UNCLOS, why not do the same with genetic resources?
Finally, the fact that the regime originally envisaged by the 1982 UNCLOS
was never accepted or applied in practice provides an ominous precedent
with regard to genetic resources.
17. On the other hand, the difficulty of establishing
a new international authority, along with the unacceptable equitable consequences
of leaving the resources in a state of open access and the sensibility
of drawing as much as possible on existing structures and regimes, supports
an approach that organically develops a regime out of the CBD or UNCLOS.
On this basis, even developing a new regime would be best done within the
existing structures provided by the FAO, UNCLOS or the CBD. A pragmatic
or organic approach would mean concentrating on controlling current and
foreseeable uses and not being overly concerned with future uses, which
may not eventuate. For the moment, marine genetic resources are largely
being used for research purposes. UNCLOS contains a number of provisions
dealing with marine research which cover the use of genetic resources of
the seas. The organic approach would therefore build upon this existing
regime, developing controls and implementing equitable benefit-sharing
within UNCLOS. Equitable sharing is ensured under UNCLOS by its requirement
that all research be for the "benefit of mankind". How this might
be applied in practice has not yet been elaborated, but it is likely to
build upon the technology transfer, information exchange and research and
training provisions of UNCLOS, which are similar to the CBD provisions
and in any event override the CBD's to the extent that they conflict. These
provisions do not, however, properly deal with the results of marine research;
neither do they touch upon how the benefits of commercialisation of marine
genetic resources should be shared equitably.
18. Regardless of which approach is adopted, there are
a number of common and familiar legal issues that would need to be addressed
in order to ensure that the regime that does emerge governs the use of
marine genetic resources in line with the principles of the CBD. Issues
such as retaining access for scientific research, avoiding unnecessary
obstacles to commercial exploitation whilst at the same time being able
to control unreasonable ones, avoiding the political problems that arose
with developing the legal regime governing the use of the mineral resources
of the Area, and identifying the beneficiaries all need to be resolved
before an effective regime that ensures the equitable sharing of benefits
can be implemented.
19. At the moment any consideration of these long-term
considerations is hampered by a lack of information and knowledge surrounding
the use of genetic resources from the deep sea-bed. Without this basic
knowledge, decisions about the type of control that is to be preferred,
possible or even practical cannot be made. The rest of this report will
briefly review existing information on these activities in order to give
some guidance to the SBSTTA as to what further studies might be necessary
in order to undertake a study of the relationship between the Convention
and UNCLOS on this matter.
3. MARINE GENETIC RESOURCES
20. Marine biological diversity is well-known for its
extraordinary diversity at the phylum level, or the basic body plan of
organisms. Of the 33 known phyla, 32 of these are found in the sea--15
exclusively so, while another five are comprised of species more than 95%
of which are marine (Ray 1988). Estimates of species diversity in the sea
are growing, and one recent deep-ocean study put this number as high as
10 million, roughly comparable to that of terrestrial species diversity
(Grassle 1992). Evidence is growing for high chemical diversity in the
sea as well.
21. Molecular diversity from genetic resources is enormous.
No reliable estimates exist for the number of marine genetic resources
screened to date. Marine invertebrates, usually sessile and/or soft-bodied,
have intrigued marine natural products chemists for decades. Scientists
have followed a so-called "bio-rational" approach to screening,
arguing that, with such seemingly vulnerable body plans, these invertebrates
must have evolved effective chemical defenses as a survival strategy (Scheuer
1990). In fact, marine natural products, toxins in particular, are noteworthy
for exhibiting highly complex chemical structures.
22. While the potential molecular diversity among marine
organisms is high, the potential molecular diversity among microbes, both
terrestrial and marine, is probably higher still, perhaps by orders of
magnitude (Paleroni 1994). Many microbes, including dinoflagellates, can
be cultured directly from the water column. There is also a growing panel
of techniques available for culturing symbiotic or commensalist microbes
such as bacteria, cyanobacteria and algae from the tissues of fish and
23. Substantial circumstantial evidence now exists that
chemically interesting natural products previously thought to be produced
by marine invertebrates are actually produced by microflora closely associated
with host species. For example, a group associated with researchers at
the Scripps Institute of Oceanography recently identified novel antibiotics
produced by a marine Streptomyces species (Trischman 1994). The bacterium
was originally isolated from a jellyfish.
24. As the technology for culturing marine microbes develops,
it is likely that interesting organisms will be discovered in a wide range
of marine hosts. Thus, conventional predictions about which marine species
will yield economically valuable chemicals are probably no longer valid.
If it is true that most if not all marine species provide critical microhabitats
for microorganisms producing potentially valuable compounds, this would
imply a high biodiversity value for all marine organisms, compounding the
value of highly diverse ecosystems such as coral reefs.
3.1 Genetic Resources Found in International Waters
25. The bottom of the deep ocean, dark and hence devoid
of photosynthetic activity, has been likened to a desert in terms of species
diversity. With no source of energy and carbon other than a thin drizzle
of debris from above, the ocean floor as an ecosystem exhibits essentially
zero primary production (Norse 1993). Two exceptions to this general rule
are known, both of which are benthic ecosystems characterized by energy
sources other than light.
26. Hydrothermal vents are mineral-rich regions in the
ocean floor defined by the borders between continental plates. Deep sea
vents are present at depths of 1800 to 3700 meters and are characterized
by the ejection of superheated water that is saturated with minerals by
the presence of underlying magma. These minerals include hydrogen sulfide,
an energy source. An unusual ecosystem has evolved to exploit this energy
source, known as the hydrothermal vent community, dependent upon specialized
chemolithotrophic bacteria and bacteria-like organisms of the kingdom Archaea
for primary production. Archaea represent an extremely old kingdom of life,
probably descendants of the original cells to evolve on Earth (Woese et
al 1990). Today they are found only in highly specialized niches, such
as hydrothermal vent communities that exist as narrow skeins of life strung
out along the ocean floor.
27. The only other known exception to the poverty of benthic
biodiversity is the as yet poorly characterized communities of bacteria
and archaea existing in deep-ocean sediments associated with petroleum
seeps (Rueter et al 1994). Research expeditions drilling to 5000
meters have discovered the presence of chemolithotrophic microorganisms,
apparently living off of the carbon and energy sources provided by the
petroleum. These microbes living within deep-ocean sediments may well prove
cosmopolitan, though further research is needed.
28. While both of these benthic ecosystems are good examples
of the high ecosystem diversity of the sea, neither is particularly rich
in species diversity as compared with coastal ecosystems. Hydrothermal
vent communities contain bacterial "mats" engaged in autotrophic
primary production, as well as a limited number of heterotrophic species
including zooplankton such as crustaceans and siphonophores, grazers such
as shrimp, and filter feeders such as mussels and tube worms (Jannasch
3.2 Coastal Genetic Resources
29. Higher marine species diversity is found in coastal
ecosystems, and by far the greatest diversity is in the tropics, particularly
southeast Asia and the South Pacific, the Indian Ocean, and the Caribbean
Sea, making the waters surrounding tropical developing countries the richest
marine source in the world for molecular diversity (Norse 1993). Examples
of coastal ecosystems include coral reefs (with the highest species diversity),
seagrass beds, oyster reefs, mangroves, salt marshes, and the continental
30. Preferred coastal marine organisms for genetic resources
research and development are usually sessile and/or soft-bodied invertebrates
such as coelenterates (corals), tunicates, soft-bodied mollusks such as
sea hares and nudibranchs, bryozoans, sponges, and echinoderms (sea cucumbers
and starfish). These organisms are likely to employ chemical defenses as
a survival strategy due to the highly selective pressure of predation existing
in coastal ecosystems. Additionally, recent work on culturing microorganisms
isolated from the water column, shallow water marine sediments including
oil seeps such as those observed in the deep ocean, or from marine animal
hosts has yielded a promising array of new chemicals (Fenical 1993). Although
known for their prominence in benthic hydrothermal vent communities, microbes
of the kingdom Archaea have been discovered in cold water at shallow depths
of 100 to 500 meters (DeLong 1992). These microbes may also yield interesting
new chemicals as techniques are developed for culturing them.
4. THE BIOPROSPECTING OF MARINE GENETIC RESOURCES
31. Genetic resources research and development, also known
as "biodiversity prospecting" or "bioprospecting,"
can be defined as the process of gathering information from the biosphere
on the molecular composition of genetic resources for the development of
new commercial products. Genetic resources, also known as natural products,
comprise biological diversity measured at the smallest scale (larger scales
being species and ecosystems). Genetic resources can yield either small
organic molecules called secondary metabolites, gene-encoding proteins
such as enzymes, or metabolic pathways linking enzymatic reactions in a
process known as microbial fermentation. Though why organisms produce secondary
metabolites is still debated, that these chemicals can have useful properties
is well known. These properties have been exploited by humans for millenia
as medicines, pesticides, cosmetics, and more.
32. Marine genetic resources are well-known for yielding
chemicals exhibiting unusual or highly complex structural diversity (Scheuer
1994). Coral reefs harbour the greatest marine species diversity and, presumably,
the greatest chemical diversity as well (Norse 1993). Additionally, harsh
marine environments such as deep-ocean hydrothermal vents and the polar
oceans are likely to yield valuable "extremophile" microorganisms
adapted to living under extreme physiological conditions of heat, cold,
pressure, pH, or salt concentration.
33. The use of naturally occurring genes by biotechnology
industries has the potential to offer a number of benefits to developing
countries. Biodiversity prospecting for genetic resources offers these
countries an opportunity to derive income from the process of natural products
research and development, creating economic incentives for biodiversity
conservation. This process involves extracting economically valuable information
(in the form of chemical structures, gene sequences, information on biological
activity such as catalytic properties, or fermentation processes in the
case of microbial isolates) from naturally occurring genetic resources.
The potential economic worth of these processes to developing countries
is considered in more detail in the Secretariat's paper on the economic
valuation of biological diversity prepared for this meeting of the SBSTTA
(see document UNEP/CBD/SBSTTA/2/15).
34. Genetic resources can also be traded for non-monetary
benefits, such as biotechnology useful for economic development. Given
that monetary compensation for genetic resources is usually modest, trading
for technology may be the more potentially rewarding strategy. Because
future uses of genetic resources information cannot be known beforehand,
what economists call the "option value" of this information is
probably high. Option value relates to the amount one is willing to pay
to conserve a resource for possible future use. Trading genetic resources
for biotechnology may augment, in particular, research on tropical infectious
disease, an area consistently underfunded worldwide despite some 600 million
sufferers in developing countries (World Health Organization 1992).
4. BENEFITS FROM THE BIOTECHNOLOGICAL USE OF GENETIC
4.1 The Value of Collaborative Genetic Resources Research
35. Genetic resources research and development can be
conveniently divided into a series of value-adding processes, beginning
with a biological inventory requiring accurate taxonomic identification.
Such information-gathering in itself adds value to genetic resources. The
taxonomic inventory of marine organisms differs from that of terrestrial
organisms in that collection expeditions are costlier and samples must
be frozen immediately, with the exception of marine microorganisms that
are often cultured. Following inventory, the chemicals or genes are extracted
from the genetic resource, and the extracts are tested to detect the desired
biological activity. Often these tests for bioactivity involve measuring
the manner in which the sample affects living systems such as animals,
or individual cells derived from these living systems, or even biomolecules
isolated from these cells.
36. For those biotechnology applications requiring the
isolation of a pure chemical compound, or enzyme, or microbial strain,
these biological assays or "bioassays" are used to guide the
purification process. The genetic resources sample is fractionated into
several components, each component is tested again for the presence of
the biological activity, and the active component is further fractionated
until a pure, biologically active principle is isolated. The further development
of a biologically active principle into a commercial product is usually
the most expensive and time-consuming process. Commercial development often
involves extensive animal and/or human testing of a product, especially
if it is intended for human consumption.
37. Because genetic resources research and development
entails substantial financial risk to private companies seeking to develop
commercial products, many firms seek out research collaborations as a risk-reducing
strategy to maximize their ability to discover promising new chemicals
or genes. Two strategies, outsourcing and in-licensing, are employed here.
38. Outsourcing entails contracting with private firms
to supply certain value-adding services, such as sample collection, extraction,
bioassay, etc. A sizeable industry has evolved to supply the outsourcing
needs of large companies engaged in genetic resources research and development,
involving suppliers such as natural products libraries or brokers and middlemen,
and specialized companies offering bioassay or chemical purification services.
These companies have evolved a market niche to profit from the process
of research and development. Many of the highly publicized biodiversity
prospecting contracts negotiated in recent years between private firms
and research institutes or NGOs in biodiversity-rich developing countries
are examples of outsourcing by large research and development firms. Companies
that outsource discrete research and development tasks expect to pay the
full cost of the research service being provided.
39. By contrast, in-licensing entails acquiring the rights
to valuable chemicals, genes or microbes that have been previously identified
independently by another research group. Large research and development
companies may in-license promising research material from other firms,
or, increasingly, from non-profit research institutes, including universities.
This is particularly common in the United States and the European Community
in the marine genetic resources field, as the cost of collecting expeditions
can be high. In these countries, marine collecting expeditions are usually
financed by government research grants, as is subsequent basic research
on the molecular properties of the marine organisms brought back to the
laboratory. However, private firms sometimes finance a portion of basic
research costs (but not the costs of marine collecting expeditions) in
return for rights to promising research material.
40. The results of a study performed in the United States
in 1991 by the University of Maryland Biotechnology Institute showed that
greater than 95% of the funding for marine biotechnology research at academic
institutions came not from the private sector but from government (Zilinskas
et al 1995). Nevertheless, 52% of academic respondents indicated that they
had some form of collaboration with private industry.
41. By contrast, in Japan there is an unusually high degree
of cooperation, including financial cooperation, between companies and
government and academia. It is not uncommon for private companies to pool
their resources with those of the government in financing collecting expeditions
and basic research (Sochaczewski 1995, Zilinskas 1995). Up to 80% of marine
biotechnology research in Japan is funded by the private sector.
42. Compensation for value-added research material provided
to private research and development companies usually includes a balance
of up-front compensation and market share (royalties offered as a percentage
of sales on commercialized products). Like up-front compensation, market
share increases with increasing value added by the provider. Note that,
particularly in the United States and the European Community, it is rare
for companies that in-license promising new research material from nonprofit
research institutes to pay the full cost of the research that led to the
discovery. In essence then, it is the governments of developed countries
that subsidize the research and development costs of their own biotechnology
industries by providing research grants to nonprofit research institutes,
including universities, which in turn can generate promising research material
for commercial development by industry.
4.2 Collection and Gathering of Marine Genetic Resources
43. Obviously, access to marine genetic resources, especially
from the deep sea-bed poses some significant problems that have limited
the use of these resources by biotechnology. Currently, there is little
reliable information on the collection of these resources, and what does
exist is largely unsubstantiated.
44. Both benthic and sedimentary ecosystems of the deep
sea-bed are extremely costly to sample. Taxonomic inventories of hydrothermal
vent communities must be conducted by scientists encased within deep diving
submersibles, of which there are perhaps five worldwide capable of reaching
these ecosystems (Walsh 1990). However, some researchers are beginning
to experiment now with the use of remote submersibles (Norman Wainwright,
personal communication). Typical deep-ocean scientific expeditions can
cost up to $30,000 per day, and usually last from one to two weeks. Many
benthic microorganisms recovered in this way can be cultured in the laboratory,
often at atmospheric pressure (Jannasch et al 1995). Microbes sampled from
especially deep locales are sometimes brought to the surface in pressure
cells and maintained at high pressure for laboratory study (Jannasch et
al 1996). As mentioned previously, governments of industrialized nations
heavily subsidize deep ocean collecting expeditions through grants for
basic marine science. For example, the European Community funds benthic
genetic resources research and development through its Extremophile Biotechnology
45. A number of private pharmaceutical and biotechnology
companies in Japan cooperate closely with the government in funding international
marine collecting expeditions. In the United States and the European Community,
private companies are more likely to pay for the isolation and culturing
of microorganisms collected previously by expeditions funded by government
research grants. In some cases, collaborating companies have signed formal
agreements with marine biology research institutes, providing money to
cover the costs of culturing marine microbes or of isolating useful enzymes,
but not to cover the much higher costs of collecting them. Market-share
agreements are also usually part of these contracts (F-D-C Reports 1995).
The high financial risk of developing new biotechnology products, especially
pharmaceuticals, deters private companies from financing their own deep
ocean collecting expeditions.
46. Coastal genetic resources are far more accessible
than benthic genetic resources, and are generally collected by scuba diving
at depths of less than 100 meters or by dredging at depths of between to
500 and 1000 meters on the continental shelf (D'Auria et al. 1993). Sampling
methods are relatively cheap, and, combined with the higher species diversity
of coastal ecosystems, the result is that there are far more collectors
engaged in coastal biodiversity prospecting. Virtually all of the governments
of industrialized countries finance coastal genetic resources collecting,
whether through academic research grants or by contracting with oceanographic
research institutes to collect for government research programs. As well,
it has been economical for private companies to employ divers as collectors,
either utilizing in-house marine biology expertise or by outsourcing to
47. Of all the industrialized countries, Japan leads the
world in its investment in marine biotechnology. In 1992, Japan's total
marine science and technology budget was $457 million, with approximately
80% of this money coming from Japanese industry (Zilinskas et al 1995).
In Japan, government-private sector partnerships fund international marine
genetic resources collecting expeditions by Japanese research institutes
(Sochaczewski 1995). By comparison, the United States government spent
some $45 million on marine biotechnology in 1992 (Zilinskas et al 1995).
The U.S. National Cancer Institute employs a private marine research institute
to collect marine genetic resources, also from the tropics. The European
Community also funds international marine genetic resources research.
48. The list of molecules derived from coastal genetic
resources that exhibit interesting pharmaceutical properties, some of which
are already in human clinical trials, is too long to chronical here. Examples
include anticancer compounds (didemnin, halichondrin B, halomon, dolastatin
10, ecteinascidin 743, and bryostatin 1; see Flam 1994 for a review), antivirals
(macrolactins), antibiotics (istamycins A and B, mimosamycin), antifungals
(swinholide A), anti-inflammatory agents (manoalide), and hormonal modulators
(Sternberg 1994). Coastal genetic resources have yielded industrial enzymes
such as proteases and collagenases from several marine Vibrio species (Deane
et al. 1987) and are also studied for clues for the development of new
agrochemicals (Cardellina 1986). Coastal genetic resources are also the
source of all marine biomaterials studied thus far, and the source of extremely
potent toxins, some of which may have applications as anticancer drugs
or as diagnostic and research tools (tetrodotoxin, palytoxin, ciguatoxin,
saxitoxin; Swift and Swift 1993). Coastal marine genetic resources are
also of interest to the cosmetics industry, and may one day yield new sunscreens
and other skin-care products. For example, an anti-inflammatory agent derived
from a tropical coral is under development as a skin-care product by a
major cosmetics firm (Jacob 1996). Finally, even higher marine animals
have yielded promising new pharmaceutical leads. One example is squalamine,
an antibiotic isolated from cartilage of the dogfish shark Squalus acanthias
(Moore et al. 1993).
4.3 Biotechnology Use of Marine Genetic Resources
49. The uses of marine genetic resources in the biotechnology
industry are many and varied. Although there has been no comprehensive
survey of the extent to which industry uses marine genetic resources to
develop new products, surveys of other aspects of this use give some indication
as to the market size and potential. Further details about the overall
contribution of naturally occurring genetic resources to these industries
are provided in the Secretariat's paper on the economic valuation of biological
diversity prepared for this meeting of the SBSTTA (see document UNEP/CBD/SBSTTA/
1. Industrial Enzymes:
50. Besides investigating small chemical compounds, biotechnology
companies also study complex proteins, known as enzymes, which catalyse
chemical reactions. The goal of industrial enzyme research and development
is to identify enzymes with commercially-valuable properties. Worldwide
sales of industrial enzymes exceeds $1 billion (Kelly 1996).
51. Industrial enzymes are used by a plethora of industries
as cost-effective and environmentally sensitive substitutes for chemical
processing. Examples include those used in detergent formulations, in food
processing, for the production of pharmaceuticals, for processing textiles,
wood pulp and paper, and for the production of fine and specialty chemicals.
For example, proteases, which are enzymes that degrade proteins, are particularly
useful in commercial laundry detergents for removing stains containing
protein (Deane 1987). The textile industry uses enzymes called cellulases
to break down cotton fibers for such processes as "stonewashing",
surface polishing, and softening.
52. Industrial enzymes must be stable to extremes of temperature,
pH, and salt concentration. For this reason, the isolation and characterization
of enzymes from a special class of microorganisms known as "extremophiles"
may yield useful new products for this industry. The deep sea-bed provides
many example of these extremophiles and consequently may be of interest
to companies involved in developing enzymes for this sector.
2. Biotechnology Enzymes:
53. A related application of industrial enzymes is their
use as research tools in biotechnology. The goal of biotechnology enzymes
research and development is to identify enzymes that are capable of carrying
out very specific molecular tasks, usually related to the modification
of DNA or RNA, for the creation of genetically modified organisms or for
diagnostic procedures. These enzymes go by a variety of names, including
restriction endonucleases, RNA and DNA polymerases, alkaline phosphatases,
kinases, reverse transcriptases, ligases, and so on. The market for these
enzymes has been estimated to be at least $600 million (New York Times
54. The isolation of enzymes from "extremophiles",
bacteria or bacteria-like microbes from the kingdom Archaea that are adapted
to living in markedly hot, cold, acidic, basic, pressurized, saline or
mineral-rich environments, is of particular interest to biotechnology companies
seeking to market new research tools. For example, a ubiquitous and powerful
biotechnology process known as the "polymerase chain reaction"
(PCR) depends upon an unusually thermostable enzyme known as Taq DNA polymerase
to replicate DNA in a test tube. The enzyme must be able to withstand the
alternating cycles of heating and cooling inherent to the PCR process.
55. Taq DNA polymerase is derived from a species of thermophilic
bacteria, Thermus aquaticus, originally isolated from a hot spring in the
western United States. In 1991 Hoffman-Laroche, a Swiss pharmaceutical
company, paid more than $300 million to Cetus Corporation, an innovative
biotechnology company that invented PCR and the novel use for Taq DNA polymerase,
for exclusive world rights to the process. Sales of Taq DNA polymerase
in Europe alone reached $26 million in 1991 (Roberts 1992). Worldwide sales
of PCR enzymes are in the range of $50-100 million, and the market for
biotechnology enzymes derived from extremophiles is forecast to grow at
15-20% per year (Frank Robb, personal communication, and New England Biolabs,
Inc., Beverly, Massachusetts, USA).
56. Harsh marine environments, such as deep-ocean hydrothermal
vents, polar oceans, and extremely saline bodies of water, have also yielded
valuable extremophile microorganisms for this and other biotechnology processes.
The identification of new "hyperthermophiles" from deep-ocean
hydrothermal vents has generated a modicum of press coverage recently (see
for example New York Times 1993, Financial Times 1995, Nikkei Weekly 1995).
Due to the high water pressures at the depth at which hydrothermal vents
are found, water temperatures can exceed that of the boiling point at sea
level. This environment has given rise to some of the most unusual microorganisms
on the planet, able to grow at temperatures exceeding 100 degrees Celsius.
Enzymes isolated from hyperthermophiles show a corresponding tolerance
for high temperatures (Jannasch 1995).
57. There is also a need for extremely heat-sensitive
enzymes as biotechnology research tools. Running biotechnology reactions
with heat-sensitive enzymes allows for better control over the reaction
process, since reactions can be terminated by heating to destroy the enzyme.
Since heating a reaction mixture can also affect the products of the reaction,
use of heat-sensitive enzymes allows scientists to stop the reactions at
lower temperatures. Heat-sensitive enzymes are derived from cryophiles,
organisms living in cold environments. At least one heat-sensitive product,
Shrimp Alkaline Phosphatase, is derived from a species of Antarctic shrimp
found in extremely cold polar waters (Olsen 1991).
58. Biodiversity prospecting for biotechnology enzymes
begins not with proteins, but with cellular DNA. DNA is extracted from
the organisms of interest, usually cultured microbes (sometimes it is merely
isolated as "environmental DNA" from seawater samples containing
recalcitrant organisms not easily cultured), and amplified by PCR to make
more copies of the DNA. The purified DNA is next transcribed to RNA and
expressed as protein. The proteins are then bioassayed for the presence
of the desired activity, for example the ability to polymerize DNA, or
to cleave it in a site-specific manner.
59. Along with the industrial enzymes described in the
previous section, scientists are studying the structure/function relationships
that govern the catalytic properties of enzymes, hoping to understand and
to one day actually design particular properties into these enzymes (Borges
et al. 1996). By isolating and identifying enzymes derived from organisms
living in a variety of environments, scientists are also trying to develop
panels of enzymes for industrial applications, each with a different temperature/activity
3. Industrial Microbes:
60. The goal of industrial microbial research and development
is to identify microorganisms possessing valuable metabolic processes that
can be exploited for industrial use, usually involving biological degradation.
Extremophilic microbes are also useful to this industry, as some have been
found living on unusual carbon and energy sources, including petroleum.
The industrial uses of microbes include industrial wastewater treatment,
municipal wastewater treatment, bioremediation of contaminated soils, bioleaching
of mineral-rich ores, food processing, and institutional services such
as janitorial services. Worldwide sales of industrial microbes have been
estimated at approximately $680 million (Perez 1995).
61. Environmental biotechnology requires microbes capable
of degrading or sequestering synthetic compounds or heavy metals for the
bioremediation of contaminated soils, or petroleum for the bioremediation
of oil spills (Leahy and Colwell 1990). A related application is the bioleaching
of copper, uranium and gold-bearing ores, in which microbes are used to
solubilize metal ions present in mined rock (Rawlings and Silver 1995).
62. The goal of pharmaceutical research and development
is to identify small chemical compounds that are non-toxic to the patient
yet effective against disease. Of all the markets for genetic resources-derived
commercial products, the world pharmaceuticals market is the largest, with
1994 sales of $256.2 billion (Scrip 1996). Some have estimated that as
much as 40% of prescription drugs are derived from natural sources, though
it is clear that the majority of these come from microbial sources, rather
than botanical or marine organisms. For example, terrestrial actinomycetes,
a class of gram-positive bacteria, have yielded the majority of antibiotics
discovered in the last half-century (Okami 1988). Fermentation broths,
prepared by culturing the microbes under diverse conditions to induce them
to produce unusual secondary metabolites, are the key starting material
for antibiotic drug discovery. There is growing evidence that substantial
actinomycetes diversity exists in marine environments as well (Takizawa
1993). Another area of commercial use of marine genetic resources is the
application of well-known toxins, derived from marine genetic resources,
to potential pharmaceutical applications (Zilinskas, et al 1995).
63. Other markets for marine natural products include
marine industrial or biotechnology products based on such marine polymers
such as chitin, carrageenan, or other polysaccharides (Harvey 1988, Abu
1992, Singleton 1988). Marine natural products may also offer clues to
the "bioengineering" of surfaces to reduce or prevent biofouling
of ship hulls and other submerged structures by sessile marine organisms
64. For the moment it appears that the commercial potential
of coastal genetic resources is much greater than the commercial potential
of benthic and polar genetic resources. In addition, benthic and polar
genetic resources are far costlier to sample, further increasing the risk
involved in their commercial development. Without heavy government subsidy,
it is unlikely that there would be any private-sector development of these
genetic resources. By contrast, the financing of coastal genetic resources
research and development is within the acceptable risk limits for private-sector
65. Research on extreme ecosystems has yielded valuable
new extremophiles capable of living at a variety of temperatures, pressures,
and on a number of carbon and energy sources. The extent to which new,
commercially useful extremophiles may come from the deep sea-bed is not
known. Consequently, the economic value of this market is entirely speculative
and, to date, unrealised.
66. Although public scrutiny has highlighted the contribution
of benthic and polar genetic resources to this field, extremophiles are
also derived from both coastal and terrestrial ecosystems. Developing countries
in particular are blessed with a number of unusual and extreme habitats,
including regions of high vulcanism characterized by high temperature,
extremes of pH and salinity, anaerobic conditions, or saturated mineral
solutions. Other unusual habitats include subsurface petroleum reserves,
which may contain hydrocarbon-metabolizing microbes, or cold alpine environments
likely to harbour cryophilic organisms. Extremophile research is still
in its infancy. Scientists from developing countries are in a position
to learn a great deal from their counterparts in developed countries. Indeed,
the equitable sharing of this benefit may be the only profit that can realistically
be expected from the genetic resources of the deep sea-bed for many years
67. What is clear from the survey is that the collection,
use and control of the genetic resources of the deep sea-bed is quite different
to that of genetic resources found within the national jurisdictions of
states. The lessons of other regimes, such as the regime governing Antarctica,
point to the benefits of considering these types of issues before strong
commercial interests are developed and of considering them on the basis
of best-available knowledge. On the other hand, developing complex international
regimes for governing the use of potentially "valuable" resources
has rarely proven to be a successful strategy for their equitable use or
a valuable use of international resources. Furthermore, the knowledge base
on which to make informed and appropriate decisions about how this area
might be controlled is almost non-existent. Such a situation points to
the clear need for more research from all relevant parties. The SBSTTA,
as the only scientific, technical and technological authority under the
Convention to provide advice to the Conference of the Parties, obviously
has an important role in developing the necessary understanding of the
area to make the appropriate decisions.
Abu, GO. 1992. Marine biotechnology: a viable and feasible
bioindustry for Nigeria and other developing countries. MTS Journal 26(3):20-25.
Borges, AlKM, SR Brummet, A Bogert, MC Davis, KM Hujer,
ST Domke, J Szasz, J Ravel, J DiRuggiero, C Fuller, JW Chase & FT Robb.
1996. A survey of the genome of the hyperthermophilic archaeon, Pyrococcus
furiosus. Genome Sci. & Tech. 1(2):37-46.
Cardellina, JH. 1986. Marine natural products as leads
to new pharmaceutical and agrochemical agents. Pure and Appl. Chem. 58:365-374.
Curtin, ME. 1985. Trying to solve the biofouling problem.
D'Auria, MV, LG Paloma, L Minale, R Riccio, A Zampella
& C Debitus. 1993. Metabolites of the New Caledonian sponge Cladocroce
incurvata. J Natural Products 56(3):418-423.
Deane, SM, FT Robb & DR Woods. 1987. Production and
activation of an SDS-resistant alkaline serine protease of Vibrio alginolyticus.
J Gen Microbiol. 133:391-398.
DeLong, EF. 1992. Archaea in coastal marine environments.
Proc. Natl. Acad. Sci. 89:5685-5689.
Farnsworth, N.R. & R.W. Morris. 1976. Am. J. Pharm.
F-D-C Reports. 1995. August 28 issue, page 15.
Fenical, W. 1993. Chemical studies of marine bacteria:
developing a new resource. Chemical Reviews 93(5):1673-1683.
Financial Times. 1995. The nature of things: a use for
the freaks. by Clive Cookson (20 May).
Grassle, JF & NJ Maciolek. 1992. Deep-sea species
richness: Regional and local diversity estimates from quantitative bottom
samples. American Naturalist 139(2):313-41.
Harvey, W. 1988. Cracking open marine algae's biological
treasure chest. Bio/Technology 6:486-92.
Jacob, M. 1996. Marine organisms yield new cytotoxic agents,
nutrients. Genetic Engineering News 16(3):1-9.
Jannasch, HW. 1995. Deep-sea hot vents as sources of biotechnologically
relevant microorganisms. J Mar Biotechnol 3:5-8.
Jannasch, HW, CO Wirsen & KM Doherty. 1996. A pressurized
chemostat for the study of marine barophilic and oligotrophic bacteria.
Appl. Environ. Microbiol. 62:1593-1596.
Jannasch, HW, CO Wirsen & T Hoaki. 1995. Isolation
and cultivation of heterotrophic hyperthermophiles from deep-sea hydrothermal
vents. In: Archaea: A Laboratory Manual. Themophiles, pp. 9-13, FT Robb,
K Sowerd, AR Place, HJ Schreier, SD Sarma & E Fleischman, eds (Cold
Spring Harbor Press, Cold Spring Harbor, New York, USA).
Kelly, EB. 1996. Biotechnology Scientists Modify Enzymes
for Cost-Effective Industrial Applications. Genetic Engineering News16(5):1.
Leahy, JG & RR Colwell. 1990. Microbial degradation
of hydrocarbons in the environment. Microbiological Rev. 54:305-315.
Moore, KS, S Wehrli, H Roder, M Rogers, JN Forrest, D
McCrimmon & M Zasloff. 1993. Squalamine: an aminosterol antibiotic
from the shark. Proc. Natl. Acad. Sci. 90:1354-1358.
New York Times. 1993. Strange oases in sea depths offer
map to riches. by William J. Broad (16 November).
Nikkei Weekly. 1995. Tapping bacterial pioneer spirit:
Microbes' ability to live in extreme conditions has wide implications.
by Shigehiko Nakajima (11 December).
Norse, EA, ed. 1993. Global Marine Biological Diversity,
A Strategy for Building Conservation into Decision Making ( Island Press,
Washington, DC, USA).
Okami, Y & K Hotta. 1988. Search and discovery of new antibiotics. In: Actinomycetes in biotechnology, pp. 33-67, Goodfellow, M, Williams, ST & M Mordarski, eds (Academic press, San
Olsen, RL. 1991. Alkaline phosphatase from the hepatopancreas
of shrimp (Pandalus borealis): a dimeric enzyme with catalytically active
subunits. Comparative Biochemical Physiology 99B:755-761.
Paleroni, NJ. 1994. ASM News 60(10):537-540.
Perez, P. 1995. Environmental Biotechnology--Business
Opportunities for the Next Five Years. Ninth International Biotechnology
Meeting and Exhibition (Biotechnology Industry Organization, San Francisco,
Rawlings, DE & S Silver. 1995. Mining with microbes.
Ray, GC. 1988. Ecological Diversity in Coastal Zones and
Oceans. In: Biodiversity, pp. 36-50, E.O.Wilson, ed. ( National Academy
Press, Washington, DC).
Roberts, L. 1992. Roche Gets Tough on Illicit Sales of
PCR Reagent. Science 258:1572-3.
Rueter, P, R Rabus, H Wilkes, F Aekersberg, F Rainey,
HW Jannasch & F Widdel. 1994. Anaerobic oxidation of hydrocarbons from
crude oil by new types of sulfate-reducing bacteria. Nature 372:455-458.
Scheuer, PJ. 1990. Some marine ecological phenomena: chemical
basis and biomedical potential. Science 248:173-7.
Scheuer, PJ. 1994. Marine natural products research: a
look into the dive bag. International Congress on Natural Products Research.
Annual meeting of the American Society of Pharmacognosy. World Trade and
Convention Centre, Halifax.
Scrip magazine, January 1996, p. 37
Singleton, FL & JG Kramer. 1988. Biotechnology of
marine algae: opportunities for developing countries. Genetic Engineering
and Biotechnology Monitor 25:84-90.
Sochaczewski, PS. 1995. Marine biodiversity: who benefits,
who pays? Global Biodiversity 5(1):2-5.
Sternberg, S. 1994. The emerging fungal threat. Science
Swift, AEB & TR Swift. 1993. Ciguatera. J. Toxicol.
- Clin. Toxicol. 31:1-29.
Takizawa, M, Colwell, RR & RT Hill. 1993. Isolation
and diversity of actinomycetes in the Chesapeake Bay. Applied and Environmental
Trischman, J, DM Tapiolas, PR Jensen, R Dwight, W Fenical,
TC McKee, CM Ireland, TJ Stout & J Clardy. 1994. Salinamides A and
B: Anti-inflammatory depsipeptides from a marine Streptomycete. Journal
of the American Chemical Society 116:757-758.
Walsh, D. 1990. Thirty thousand feet and thirty years
later: some thoughts on the Deepest Presence concept. Marine Tech. Society
Woese, CR, O Kandler & ML Wheelis. 1990. Towards a
natural system of organisms: Proposal for the domains Archaea, Bacteria,
and Eucarya. Proc. Nat. Acad. Sci. 87:4576-4579.
World Health Organization. 1992. Global health situation
and projections, estimates 1992. WHO, Geneva.
Wright, AE & PJ McCarthy. 1994. Drugs from the sea
at Harbor Branch. Sea Technology 35(8):10-18.
Zilinskas, RA, RR Colwell, DW Lipton & RT Hill. The
Global Challenge of Marine Biotechnology: A Status Report on the United
States, Japan, Australia and Norway (Maryland Sea Grant Publication, College
Park, Wright, AE & PJ McCarthy. 1994. Drugs from the sea at Harbor
Branch. Sea Technology 35 (8): 10-18.
Zilinskas, RA, RR Colwell, DW Lipton & RT Hill. The
Global Challenge of Marine Biotechnology: A Status Report on the United
States, Japan, Australia and Norway (Maryland Sea Grant Publication, College
Park, Maryland, USA, 1995).