THE COLLABORATIVE INNOVATION OF

COMMERCIALLY VIABLE

MARINE-BASED NUTRACEUTICALS

Jayaram (Jay) K. Sankaran Associate Professor, Dept. of Information Systems & Operations Management

The University of Auckland, Private Bag 92019, Auckland, New Zealand. Telephone No: 64 9 373 7599, x87357. Facsimile No: 64 9 373 7430

Email: j.sankaran@auckland.ac.nz

January 07. Acknowledgment: This research has been funded by Contract # U0AX0303 entitled ‘Determinants of innovation and growth in the seafood sector,’ between the University of Auckland and the Foundation of Research, Science, & Technology of New Zealand (NZ). The General Manager of MacLab NZ’s marine farming operations is gratefully thanked for his time for interviews and a site-visit. The Managing Director of McFarlane Pty. Limited and the Managing Director and the Production Manager of Pharmalink Marketing Australia Pty. Limited are also sincerely acknowledged for giving generously of their time in interviews and making supplementary information readily available for the research. The assistance of J. Sibthorpe in literature search is also gratefully acknowledged. Thanks are also due to Richard Daniell and Extract Solutions Ltd. for hosting a plant visit for the author. The informative discussions that were held with one of the scientists, who were associated with the innovations, and one of his colleagues are also warmly appreciated.

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THE COLLABORATIVE INNOVATION OF

COMMERCIALLY VIABLE

MARINE-BASED NUTRACEUTICALS

Abstract Biotechnology is turning a traditionally low-tech industry (food) into a high-tech industry

(functional food/nutraceuticals). There is a real need to enhance managerial understanding by

clarifying the nature of innovation processes in the functional food industry, including the

role of R&D and collaboration.

The present investigation focuses on a particular segment of the functional food industry,

viz. marine-based nutraceuticals. We find that various hurdles thwart the fullest realization

of the business potential of marine bio-actives in the pharmaceutical space. However, the

innovation of commercially viable marine-based nutraceuticals/ cosmeceuticals is yet

possible if the extraction route for supply is a feasible fallback option, should industrial-scale

synthesis prove elusive.

Effectiveness in innovation is facilitated by the collaboration of various disciplines

including epidemiology, traditional/folkloric medicine, aquaculture/ fermentation, natural

products chemistry, and relevant strands of medical, pharmacological, and clinical research.

In this regard, the inter-disciplinary field of ethno-pharmacology rises to prominence.

Universities and government research institutes may be well-positioned to drive such

collaboration and reap the benefits from problem definition in addition to problem solving.

Towards this end, the findings from the present study are integrated into a phased approach

towards the innovation of commercially viable marine-based nutraceuticals that is targeted at

entrepreneurs in this field.

Keywords: nutraceuticals; marine biotechnology; collaboration; functional foods; natural

products; aquaculture.

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INTRODUCTION The food industry has been traditionally characterized as having a low intensity of R&D, as a

result of which it tends to be a downstream, consumer-oriented ‘carrier’ of new technologies

that are developed in upstream, high-tech industries such as electronics (Grunert, Harmsen,

Meulenberg, Kuiper et al. 1997, p. 7; Morgan et al. 2003, p. 335). A reflection of the low

research intensity of the industry is the comparatively small investment in R&D. In the UK,

the R&D expenditure of the food-processing sector has been estimated as 0.3% of sales

intensity compared with an average intensity of 2.1% in manufacturing as a whole (Morgan

et al. 2003, p. 335). In turn, the low intensity of R&D has been touted as a possible reason

for the relative paucity of research into innovation in the food industry (Harmsen, 1996, as

cited in Harmsen et al., 2000).

However, the research landscape is changing very rapidly: biotechnology is turning a

traditionally low-tech industry (food) into a high-tech industry (functional food) (Brännback

and Wiklund 2001, p. 197). While no commonly accepted definitions of the terms

‘functional food’ and ‘nutraceutical’ exist (Hobbs 2002, p. 559; Ovesen 1999, p. 809), it

suffices for the present purpose to adopt the definition furnished by the 2002 Merriam-

Webster Medical Dictionary: “any foodstuff enhanced by additives and marketed as

beneficial to health and longevity; also called nutraceutical (a foodstuff [as a fortified food or

a dietary supplement] that is held to provide health or medical benefits in addition to its basic

nutritional value).”i (In particular, we do not distinguish between the two terms strongly, as

the distinction between them is becoming blurred [Hobbs 2002, p. 560].)

Given the requirement of science-based research, the functional food ‘revolution’

(Heasman and Mellentin, 2001) is being accompanied by a sea change in the level of R&D

expenditure: 10-20% of revenues (Brännback and Wiklund 2001, p. 203). The differential

level of R&D manifests in an order-of-magnitude increase in the rate of new product

development. Although functional foods represent a market share of less than 1% of the total

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food and drinks market in Germany (and in the whole of Europe as well), they accounted for

19% of all innovations in that market in Germany in 1999-2000 (Menrad 2003, p. 182).

Thus, after adjusting for market share, the rate of innovation in the functional food segment

would appear to be nearly twenty times that of the overall food industry.

Such a heightened pace of change is ushering in a new ‘dominant logic’ (Brännback and

Wiklund, 2001) in the food industry of Finland, which has been described as “a kind of

Silicon Valley” of functional foods (Darrington 2003, p. 9), and elsewhere in the world. The

term ‘dominant logic’ is attributed to Prahlad and Bettis (1986). It refers to how managers

perceive what happens in the external business environment and bring that perception to bear

upon possible changes in the knowledge base of the company, which in turn enables the

company to innovate products and services for its key markets (Brännback and Wiklund

2001, p. 203).

In their study of the Finnish food industry, Brännback and Wiklund (2001) concluded that

the changes in the industry, since 2000, pertained to the emergence of functional foods.

Brännback and Wiklund (2001, pp. 203-204) tabulated these changes in terms of market

dynamics, production processes, R&D, pricing, market communication, and competitive

scope. They concluded that the Finnish food industry had moved from low knowledge

complexity to high complexity. Through interviews with 11 managers from four small-and-

medium-sized food companies, they found that the closer fit between the functional foods and

the pharmaceutical industries as compared with the traditional food industry compounded

managerial uncertainty (p. 205). Most managers were experiencing great frustration that the

industry, of which they used to be masters and had a sound understanding, was undergoing

dramatic changes. Knowledge collaboration (e.g. partnering with a biotech firm that provided

a nutraceutical ingredient that the food company then commercialised) appeared to be the

only viable route to business success (Brännback and Wiklund 2001, p. 203, p. 205).

The findings of Brännback and Wiklund (2001) highlight the need to enhance managerial

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understanding by clarifying the differential nature of innovation processes and activities in

the functional food industry, including the role of R&D and collaboration. That being said, it

is also important to note that thus far, the distribution of innovations in the functional food

industry has been skewed towards the soft drinks, confectionery, dairy, bakery, and baby

food market-segments. For instance, these segments together accounted for over 90% of

innovations of functional foods in the food and drinks market in Germany during 1999-2000

(Menrad 2003, p. 182). During that period in Germany, the other segments accounted for

38% of all innovations in the food and drinks market but only 8% of functional food

innovations in the same market.

As a result, the extrapolation of the insights received from sectors such as dairy would

have to be tempered by the contexts of individual sectors, such as seafood, which are

presently under-represented in the functional food landscape. The imperative of speaking

explicitly to the sectoral context of seafood arises in the present study, which has been

conducted under the aegis of an ongoing four-year project entitled ‘Determinants of

innovation and growth in the seafood sector.’ The project was in turn sponsored by the New

Zealand (NZ) Foundation for Research Science & Technology (FRST) expressly towards the

goal of stimulating innovation-led growth in the NZ seafood sector.

Nutraceuticals and functional foods that are derived from marine life-forms constitute an

emergent industry with considerable potential for knowledge creation and value-added

growth in the NZ seafood sector. In a keynote address given at a recent conference of the NZ

Seafood Industry Council jointly by the Chairman and the CEO of Crop & Food Research, a

NZ Crown Research Institute, the two executives acclaimed the potential of aquaculture in

producing unique bio-actives for the production of pharmaceuticals and nutraceuticals

(Bentley and Tocker 2004, p. 4).

Against the above backcloth to the present investigation, we frame our research questions

as follows: What are the salient features of innovation processes for commercially viable

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functional foods/nutraceuticals with specific reference to the seafood sector? In particular,

what is the role of collaboration? How can such collaboration be managed?

Our operational definition of ‘innovation’ follows OECD guidelines: innovation is the

introduction of a new or significantly improved product or service to the market, or the

introduction of a new or significantly improved process to a business. In the manner of

Harmsen et al. (2000, p. 152), who reported case study research on food companies, and in

keeping with the 1980 Frascati Manual (OECD, 1981), we treat R&D (Research &

Development) as being mainly the scientific steps associated with the innovation process.

This process also consists of those technical, commercial, and financial steps that are needed

for the successful development and marketing of new or improved products and the

commercial use of new or improved processes.

The manuscript is laid out as follows. We first review the relevant literature on

innovation processes in the traditional food-processing industry as well as the functional food

industry. We also briefly discuss the field of marine biotechnology in a manner that befits

the objectives of the present research. Then we present the methodology for the case study

research into the innovation of marine-based nutraceuticals. Following the case descriptions,

we draw various implications for the innovation of such products and the management and

organization thereof. In particular, we have developed a phased approach for the innovation

of commercially viable marine-based nutraceuticals that should be of value to prospective

entrepreneurs in this arena.

LITERATURE REVIEW

Innovation in Food As noted earlier, research into innovation in the food industry is rather scant. Under the aegis

of the UK Government’s Foresight Programme, Morgan and Blake (1999) and Morgan et al.

(2003) undertook case study research into the UK food and drink industry to reveal the

manifold ways in which firms have been innovative in their use of technology. The aim of

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Morgan et al. (2003)’s research was “to highlight innovation in the food chain and to

disseminate the lessons from the processes and outcomes of this innovation to the broader

sector,” (p. 335). Their analysis was at the level of specific innovations within the food chain

and they profiled eight cases of product and/or process innovation.

In the 1990s, as part of a research project entitled ‘Structural change in the European food

industries,’ an international group of researchers conducted collective case studies of the

product development function in food-processing companies that were dispersed across six

European countries (Traill and Grunert, 1997). The resulting insights were documented first

by Grunert, Harmsen, Meulenberg and Traill (1997) and then by Harmsen et al. (2000) and

Traill and Meulenberg (2002). A summary finding of these studies was that a food-

processing firm will be mainly driven by one of three orientations (product, process, and

market), which would also influence and direct the acquisition of the remaining

supplementary competencies (Harmsen et al. 2000, p. 159; Traill and Meulenberg 2002, p. 6).

None of the cases examined by Morgan and Blake (1999) and Morgan et al. (2003)

featured functional foods. On the other hand, the anthology of Traill and Grunert (1997) did

feature a case study (Göransson and Kuiper, 1997) of Skånemejerier (Skåne Dairies), a co-

operatively owned Swedish dairy company in the south of Sweden (Skåne) that has been very

active in the development of functional foods. (Skånemejerier had accordingly been deemed

to have a ‘product’ orientation [Traill and Meulenberg 2002, p. 3].)

Functional foods were the explicit focus of Mark-Herbert (2002, 2004), who examined

the process of their innovation through four longitudinal case studies situated in Sweden, one

of which featured Skånemejerier. All four cases involved probiotics (these are “live

microbial feed supplements which beneficially affect the host animal by improving its

intestinal microbial balance” [www.dictionary.com]). A summary finding of Mark-Herbert

(2004, p. 714) was that the successful innovation of functional foods requires creative

management that encompasses both entrepreneurial and strategic planning perspectives.

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Skånemejerier had been studied by Mark-Herbert (2002, 2004) in the context of ProViva,

a probiotic fruit drink that the dairy co-operative produces and markets. ProViva is based on

a Lactobacillus strain, Lp299v, which had been discovered earlier by Probi AB, a research

firm that specializes in probiotics. In fact, Proviva eventuated through a partnership between

Probi and Skånemejerier. (The discovery and development of Lp299v and ProViva has been

narrated variously by Göransson and Kuiper [1997, 169-170], Mark-Herbert [2002, Chapter

5], Lagnevik et al. [2003, Chapter 6], and Langlais, Janasik and Bruun [2004].)

The in-house R&D-activities at Skånemejerier have been characterized as “r&D,” (Mark-

Herbert 2002, p. 67): the relatively small r at Skånemejerier symbolizes the firm’s links with

Probi AB (besides universities) while the large D symbolizes the vast knowledge, skills and

technology within Skånemejerier that is related to handling raw materials, production,

packaging, marketing, distribution, and sales. In a similar vein, Traill and Meulenberg (2002,

p. 16) observed that the R&D activities at Skånemejerier are focused on development issues

whilst more fundamental research is contracted to external research groups. Partnerships

between entrepreneurial scientists, input suppliers, food processors, and/or medicinal

supplement firms, have been necessitated in the value-chain for functional

foods/nutraceuticals by the rapid growth of the sector (Hobbs 2002, p. 559).

The relationship between Probi and Skånemejerier has also been cast in the perspective of

knowledge networking by Langlais, Janasik and Bruun (2004). In the analysis of Langlais et

al. (2004), the identification of the Lp299v bacterium entailed ‘pioneer’ networking, wherein

temporary bridges were built between distinct knowledge frameworks by using ‘boundary’

objects such as charts, simulations, pictures, concepts, etc. On the other hand, the

commercialization of Lp299v (e.g. through probiotic foods such as ProViva) and the search

for other similar bacilli with interesting properties entailed a measure of ‘modular’

networking wherein a central coordinator integrated/synthesized knowledge that other

members produced independently. A third mode of networking is translational. Here, the

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members of the network communicate directly with each other by using a shared language or

some other mediating structure.

Distributed innovation, wherein companies carry out innovations through collaboration

with outside partners, is possible only in those fields that lend themselves to the

decomposition of innovation-related tasks (Valentin and Jensen 2003, p. 277). Complex

problems that manifest interdependencies between their constituent components cannot be

decomposed. A corollary of decomposability is specialization and collaboration: firms such

as Skånemejerier realize innovations such as ProViva by pursuing research collaboration with

outside partners, e.g. Probi AB, and compensating by building stronger capabilities in

manufacturing and marketing (Valentin and Jensen 2003, pp. 277-278).

The identification of Lp299v and the subsequent development of ProViva belong to that

realm of food science and technology which utilizes lactic acid bacteria (LAB). Valentin and

Jensen (2003) investigated the nature of distributed innovation in this field, using primarily

the 180 biotech-related LAB patents that had been claimed until the year 2000. They

proposed that problem processing could be split into problem definition/identification and

problem solving, each of which may have differing degrees of decomposability in innovation

processes. From their data, they concluded that LAB biotech R&D manifested highly

decomposable problem solving but low decomposability of problem identification. Thus,

firms with strong R&D integration capabilities are “advantaged by being positioned in the

point of confluence (emphasis not authors’) of critical flows of opportunities that allows them

repeated extractions of valuable problem definitions… once defined, these problems lend

themselves to partition-friendly solution,” (Valentin and Jensen 2003, p. 280).

In most of the 180 LAB patents that Valentin and Jensen (2003) examined, the patent was

assigned to only one of the R&D partners. This reflected the assignee’s playing “a leading

role in orchestrating (emphasis not authors’) the R&D producing the patent and in

identifying the problems and the benefits that motivate the R&D project,” (p. 292).

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In contrast with the pharmaceutical-related biotech discovery chain that prevails in the

US, dedicated biotech firms were present only marginally in LAB biotech and their role

emphasized problem solving over problem definition (Valentin and Jensen 2003, p. 292).

While universities contributed almost half of all the inventor organizations that underlay the

180 patents, their share of patent assignments was only six percent. (However, in

pharmaceutical-related applications of LAB biotech, where “information on opportunities and

targets flow in decomposed forms in the public domain,” universities could play an

increasing role in problem definition [Valentin and Jensen 2003, p. 296].) Unilever, Nestle,

and Chr. Hansen accounted for 38% of all patent assignments (Valentin and Jensen 2003, pp.

290-291). The authors thereby concluded that only a few of the actors in LAB biotechnology

were positioned at points of confluence.

With reference to Chr. Hansen, which is a world leader in cheese ingredients, Valentin

and Jensen (2003, p. 294) described an example of low problem decomposability in the

deployment of LAB biotechnology for reducing cheese maturation time. Through their deep

understanding of the cheese maturation process, Chr. Hansen knew precisely those leverage

points in the process where the most return on investment in biotechnology could be realized.

Marine Biotechnology Marine organisms, such as microalgae and invertebrates, have been acclaimed by marine

biotechnologists as being a largely untapped reservoir of novel and biologically active

compounds (Luiten et al. 2003, p. 429). For example, polyunsaturated fatty acids and novel

lipids can be produced by marine organisms for subsequent use in nutraceuticals.

Notwithstanding this potential, prior to 2003, not a single marine natural product

compound had been approved as a drug (Mendola 2003, p. 441). In the course of a review of

marine pharmacology and from the perspective of bioprospecting, Faulkner (2000) discussed

some difficulties that are encountered during the development of anti-cancer and anti-

inflammatory agents from marine bioactives. Figure 1 depicts these difficulties as well as

10

other challenges that are induced from Faulkner’s review of various bioactive marine natural

products. An additional reason that has been cited for the dearth in the development of

marine compounds as therapeutic agents is “the lack of an analogous ethno-medical history

as compared with terrestrial habitats,” (Amador et al. 2003, p. 1607).

Place Figure 1 about here. It should be noted that whilst a compound may have not yet been developed into a drug, it

can still have commercial value. A case in point is pseudopterosins, which are a group of

bioactive natural products extracted from the gorgonian (sea whip) Pseudopterogorgia

elisabethae, which is found in the Caribbean. As of the time of Faulkner’s review,

pseudopterosins had not been developed as anti-inflammatory drugs. However, a partially

purified extract of the sea whip was being used as a ‘cosmeceutical,’ specif. an additive in

cosmetic products made by Estee Lauder. The “supply problem” (Faulkner 2000, p. 141) is

at play here: demand for the extract is estimated at five times the current supply. Although

the gorgonians occur between 45 and 75 ft depth, diving is limited to about 60ft to allow the

deep-water specimens to furnish a reservoir of breeding stock.

Research initiatives that use cloning techniques are underway, whereby the genes

responsible for manufacturing a cancer-fighting chemical produced by, say, seasquirts, are

placed in an easy-to-culture bacterium, such as E. coli, which then produces the chemical

(Australian Institute of Marine Science, 2005). Such ploys circumvent the supply problem

because they require only a small sample of the source organism (e.g. seasquirts).

The paucity of success stories in large-scale production and product marketing has meant

that “the processing industry - the food industry and dominant players in the pharmaceutical

industry - are not eager to invest in marine biotechnology,” (Luiten et al. 2003, p. 432).

Luiten et al. (2003, p. 434) suggested that since it is “most often too hard to interest [the

vested industrial firms in food and pharmacy] directly, pioneers [in marine biotechnology]

need to co-operate with other small, knowledge-intensive firms,” whilst making “smart”

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choices. For instance, the product needs to fit with the portfolio of medicines/foods and/or

manufacturing processes of the target food/ pharmaceutical company (Luiten et al. 2003, p.

434).

METHODOLOGY The genesis for the present study lay in an endeavour to showcase successful instances of

value-chain innovation in the NZ seafood sector within the ambit of the FRST project noted

earlier. Knowledgeable observers in the seafood industry had cited a certain farmer and

processor of green-lipped mussels (GLMs) (of the species Perna Canaliculus, which is a

mollusc native to NZ) as being a prime example of value-addition in an otherwise

commodity-orientated sector of aquaculture. In contrast with the legion of GLM farmers who

constantly had to find and develop new markets for mussel, this firm, MacLab NZ

(henceforth, MLNZ), was growing/procuring mussels precisely to meet the demand for

value-added products and in particular, a nutraceutical called Lyprinol®. Subsequent

investigation revealed that the value-chain for Lyprinol® appeared to create a market value of

more than 100% over relatively unprocessed GLMs. Through public-domain information,

the size of the global market for Lyprinol® was estimated to be some/several tens of million

NZ dollars, which is substantive when viewed in relation to the total volume of sales of the

NZ Greenshell™ mussel ($204 million in 2005ii).

Lyprinol® is a patented and stabilised natural marine lipid extract that comprises a rare

combination of lipid groups and unique Omega-3 polyunsaturated fatty acids.iii The value-

chain for Lyprinol® is very complex. MLNZ farms mussels at various locations around NZ;

to meet the growing demand, it also buys GLMs from other farmers. The GLMs are then

brought to a processing plant in Nelson, NZ, wherein they are first de-shelled through a high-

pressure pneumatic machine. The mussel flesh is then minced before a stabilizing agent (an

organic acid) is added to it. The resulting slurry is freeze-dried and then milled to yield a

powder extract. The powder is freighted to one of two locations in NZ and Germany for the

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extraction of marine lipids. (Stabilized mussel powder extract is also directly supplied by the

MacLab group, under an exclusive contract, to a large multinational pet food and veterinary

products company, which uses the powder as a nutraceutical ingredient.) The bulk lipids are

then shipped to various locations worldwide where they are encapsulated.

Through both secondary data (e.g. www.lyprinol.com) and fieldwork conducted in two

phases and across three locations in Australia and NZ, we developed a case study of

innovation and value-chain management of Lyprinol®. The analysis proceeded at two levels.

The first (higher) level spoke to the ‘breakthrough’ (or radical, revolutionary, game-

changing) innovation (Veryzer 1998, p. 306) of Lyprinol® while the second (lower) level

spoke to other improvements and developments in the value-chain for Lyprinol® that were

relatively incremental in nature.

The full case description is beyond the scope of the present paper. Below, we present an

abridged account of the innovation process with a view towards specifying the nature of

knowledge networking and collaboration that is entailed in the innovation of nutraceuticals

such as Lyprinol®. We also report an auxiliary case-let of a dermaceutical called Isolutrol®.

THE INNOVATION OF LYPRINOL® The name ‘MacLab’ derives from Stuart McFarlane, who helped pioneer mussel farming in

NZ in the late 1960s. Alerted by interest from the US in GLM extracts for their cytotoxic

properties, McFarlane found that although the cancer treatment was not successful, patients

were reporting relief from arthritic pain as a welcome side-effect.iv This accorded with NZ

folklore that coastal dwelling Maoris who regularly consumed the mussel as part of their diet

suffered far less from arthritis than their inland dwelling relatives.v In 1974, McFarlane

launched a freeze-dried, concentrated mussel powder obtained from GLMs as an anti-arthritic

product marketed as Seatone™.

In the early 1970s, two Australian businessmen who were brothers, Jim and Bill

Broadbent, acquired a financial interest in certain mussel farming operations of McFarlane.

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They became interested in mussel extracts because of their reported anti-inflammatory

properties and subsequently established a new company in Australia for distributing the

extract and for registering the "Seatone" trademark worldwide.

In the early 1980s, the Broadbent brothers became major shareholders in Stuart

McFarlane’s company, McFarlane Laboratories. Owing to their conviction that “there was

something in the mussel which deserved investigation,” McFarlane Laboratories started

researching the reported health properties of Seatone (Clark, 2000). In 1982, they purchased

a mussel powder factory in New Zealand and established a research project at the Natural

Products Chemistry Division of the Royal Melbourne Institute of Technology University in

Australia (“RMIT”).vi The company initially sought hard scientific evidence that a naturally

occurring anti-inflammatory compound (a unique “marker” secondary metabolitevii) existed

in the mussel. Such proof would supersede the hitherto inconclusive empirical evidence and

help settle the medical controversy concerning the potency of mussel extracts.

In hindsight, the RMIT project was “on the wrong track” in the initial 1-2 years, being

directed towards the search for aqueous (water-based) fractions instead of non-polar fractions

(which Lyprinol® is comprised of). In 1983-4, a cohort of scientists that joined the Natural

Products Chemistry Division of RMIT was convinced the activity of the GLM was located in

lipid (non-polar) fractions. They called for a “whole new raft of funding” from McFarlane

Pty. Ltd. (part of the MacLab group) to continue searching for the marker. Despite the use of

a leading technology of the time, viz. high performance liquid chromatography (HPLC), the

RMIT scientists were unable to isolate the active lipid fractions from GLM extract powder –

one of the many challenges depicted in Figure 1.

In 1983, on a visit to Japan, Jim Broadbent met Professor Takuo Kosuge, a Professor of

Pharmacology at the Shizuoka University in Japan, who specialized in natural products

chemistry and had become aware of the GLM extract through a friend. Professor Kosuge

offered the collaboration of his research group with the scientists at RMIT. He ran his own

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series of tests but also failed to isolate the active fractions.

Professor Kosuge concluded the failure to isolate the fractions owed to the oxidation of

the active components: the freeze-dried mussel powder extract was unstable and with a

limited shelf life and therefore needed to be stabilized in the first instance if it was to retain

its potency. Indeed, oxidation has been deemed to be “one fundamental quality issue that

must be considered and controlled” in the extraction of marine oils; techniques of harvesting,

processing and storage impact on the oxidative stability and shelf-life of the oil product

(McLean 2002, pp. 18-19; Shahidi and Kim 2002, pp. 80-81).

By developing a pharmacological screen to check the activity levels of different batches

of mussel powder, Professor Kosuge himself confirmed that moisture and heat greatly

impacted on the level of bioactivity. After unsuccessfully experimenting with all the

recognized anti-oxidants as stabilizers, he turned to research work that he had conducted

some twenty years earlier that had identified the ancient technique used by traditional

Japanese fishermen to store fish in a special solution, which preserved the fish for years.

Professor Kosuge then tested a variation of this solution on the mussel flesh and found that

the oxidation was arrested. Thus, in keeping with the second stage of the developmental

period in the innovation model of Van de Ven et al. (1999), the development of the stabilizer

stemmed from the earlier setback encountered by the RMIT team in the isolation of active

lipid fractions from GLM extract powder.

Subsequently, Jim Broadbent, on behalf of the present-day MacLab group, and Yoshiki

Kosuge patented the above stabilization process. The MacLab group was then able to produce

a stabilized mussel extract product, after also making other major changes to the production

process.

Now that the mussel extract was stabilized, the RMIT scientific group were able to

successfully extract selected lipids that they believed held the beneficial activity. The

MacLab group’s plan was to establish a new, more effective product under a different brand

15

name to differentiate itself from the “Seatone” product in those markets where it no longer

owned the trademark.

To confirm the beneficial effects of the lipids isolated by the RMIT scientists, in 1992 the

MacLab group enlisted the services of Dr. Henry Betts, Principal Scientist at the

Rheumatology Research Laboratory, The Queen Elizabeth Hospital, in Adelaide, Australia.

Dr. Betts had earlier established an in-vitro method of testing anti-inflammatory compounds.

He then proceeded to test the fractions that the RMIT scientists had extracted.

While Dr. Betts found that two of these fractions were the most active compounds he had

ever examined in his testing system, he was unable to identify them because they were not

pure. He continued his work for 18 months during which time he tested the progressively

purified fractions developed by the RMIT scientists. (It turns out that Lyprinol® contains a

variety of active ingredients over and above the fatty acids that have been identified thus far

[Halpern and Edmonds 2001, p. 26].)

At the suggestion of Dr Betts, the MacLab group approached Dr Michael Whitehouse,

who specialized in testing compounds for anti-inflammatory activity in laboratory animals,

for an in-vivo test of the fractions. Dr Whitehouse commenced laboratory animal studies in

1994, which confirmed the activity that Dr Betts had found in his in-vitro testing.

Lyprinol® has since been found to be much more potent than the GLM powder extracts

that are prevalent in the market. Further, its use for treating asthma, besides arthritis, has also

been established, which is not the case with powder extracts.

It took a further two years of intensive testing to develop the protocols for the

supercritical fluid extraction process, which were then patented by the MacLab group. The

group continued the original search for a ‘marker’ metabolite from among the various

fractions and fatty acids that are latent in Lyprinol®. Such a ‘marker’ could pave the way for

chemical synthesis and subsequent development of an anti-inflammatory drug.

The Broadbent brothers have invested a total of AU$ four-five million in research into

16

Lyprinol®. Jim Broadbent is convinced that Lyprinol® would not have eventuated had he

and his company not relentlessly backed their “belief in what we were doing by putting some

funding into [the research]:” in some years during the innovation of Lyprinol®, Jim

Broadbent and his Australian concern were spending nearly half their income on the

investment in R&D.

Hobbs (2002, p. 562) observed that innovators are often unable to undertake value-chain

activities (e.g. production, marketing, and long-lasting clinical trials, such as expensive,

intervention studies with high numbers of patients) beyond technology transfer given their

limited access to equity capital. Thus, strategic alliances or joint ventures arise with

downstream players who have the financial and human capital resources to commercialize an

innovation.

In the late 1990s, the Broadbent brothers transferred their patents (except the patent for

the stabilising agent) to a new holding company, Pharmalink International Limited (PIL),

whilst becoming shareholders in PIL. This released capital for the MacLab group for

investment in GLM farms in NZ to meet the growing demand for Lyprinol®. PIL has

contracted its marketing, distribution, and production oversight functions to an affiliate,

Pharmalink Marketing Australia Pty. Ltd. (PMA). Through public-domain information, the

worldwide volume of sales of Lyprinol® may be estimated to be some/several tens of million

dollars p.a. Figure 2 traces the innovation and commercialization of Lyprinol® with

reference to the knowledge-networking perspective proposed by Langlais et al. (2004)

Place Figure 2 about here. Some years after the commercialization of Lyprinol, the Broadbent brothers concluded

that Lyprinol® did not contain a unique ‘marker’ that would explain its anti-inflammatory

potency; rather, the various fractions and fatty acids seemed to act in a synergetic manner.

Furthermore, Lyprinol® cannot be synthesized since the fractions are not completely pure.

At the time of fieldwork, PMA was investigating how Lyprinol® could be progressively

17

registered as a drug, notwithstanding the absence of a unique marker metabolite (and

prospects for synthesis) and the variation in chemical composition that is inherent in natural

extracts.

THE CASE OF ISOLUTROL® The collaboration between Jim Broadbent, Prof Takuo Kosuge, and the RMIT group also

underlay the commercial development of a dermaceutical, sodium scymnol sulphate, which

has been marketed by McFarlane Pty. Ltd. as Isolutrol®. The compound had originally been

discovered by Prof Kosuge in the 1980s; he had been led to this discovery after hearing about

fishermen off the Japanese coast who rubbed extracts of shark’s liver on to their face to

acquire clear, smooth skin.viii Research has also suggested properties in the compound that

might help with some types of liver toxicity (Barclay, 2001).

Prof Kosuge awarded Jim Broadbent the rights to market the compound worldwide

outside of Japan. Over a five-year period beginning 1987, the RMIT team, in collaboration

with Prof Kosuge, developed a method of extracting the compound from shark bile to 99.9%

purity. Tests have confirmed Isolutrol®’s efficacy in curing oily skin as well as its lack of

obvious toxicological or allergenic effects.

Isolutrol® is available as a spray lotion. It is the only compound yet developed that

reduces the oiliness of skin when applied topicallyix – a reflection of the low rate of

rediscovery of secondary metabolites that are derived from marine life-forms (Olaizola 2003,

p. 460).

The global market for acne treatments has been estimated to be AU$ 2 billion p.a.x

However, given that sharks are under threat in the wild, the extraction route (from shark bile)

for the manufacture of Isolutrol® is not scalable. At the time of fieldwork, synthesis on a

truly large scale continued to prove elusive. Nevertheless, the presence of a confirmed

marker in shark bile (i.e. sodium scymnol sulphate) leaves the door open for Jim Broadbent,

who holds the rights to the chemical structure of the compound, for achieving successful

18

industrial-scale synthesis at a later stage.

IMPLICATIONS OF THE CASE STUDIES Below we discuss the ramifications of the case studies with regard to: (i) the innovation

processes of marine-based nutraceuticals; (ii) the role and nature of the requisite collaboration

in such innovation; (iii) the prominence of the emerging field of ethno-pharmacology in such

collaboration; and (iv) a phased approach towards the innovation of commercially viable

marine-based nutraceuticals.

Innovation Processes of Marine-based Nutraceuticals The innovation of Lyprinol® involved, among other scientists: a pharmacologist, who

specialized in natural products chemistry (Prof Kosuge); natural product chemists with

expertise in HPLC (the RMIT group); a rheumatologist, who specialized in in vitro testing

(Dr Betts); and an inflammo-pharmacologist with expertise in in vivo animal testing (Dr

Whitehouse). Prof Kosuge’s ability to bridge disciplines such as natural products chemistry

and pharmacology suggests that a translational mode of knowledge networking played a

pivotal, if not indispensable, part in the innovation process.

As with the cases of Mark-Herbert (2002, 2004), the initial phase was divergent, allowing

for learning by discovery (Van de Ven et al. [1999, p. 16, pp. 203-204], as cited by Mark-

Herbert [2002, p. 20]). Thus, the first change of direction arose when the RMIT group

decided that the activity of GLMs lay in non-polar fractions. The second change of tack was

prompted by the failure of both the RMIT scientists and Prof Kosuge to extract fractions, and

in turn triggered Prof Kosuge’s development of a pharmacological screen, which confirmed

the need to stabilize GLM flesh prior to the extraction of fractions. In turn, this beckoned the

development of a stabilizing agent that was subsequently patented.

Once the RMIT scientists were able to extract fractions from stabilized mussel powder

extract, the innovation process became progressively convergent. Given that the MacLab

19

group was seeking hard evidence of the anti-inflammatory properties of GLMs, it was logical

for them to contact a rheumatologist (Dr Betts) for assistance. The trial-and-error iterations

between Dr Henry Betts and the RMIT research group vis-à-vis the extraction and in vitro

testing of active fractions, as also the development of protocols for the super-critical fluid

extraction process, speak to convergence in the innovation process.

With regard to functional foods, Menrad (2003) cited the limited participation of small

and medium-sized food companies (SMEs), which “mostly produce functional products for

market niches or offer ‘me-too’ products following the pioneering products of the

multinational companies,” (p. 184). Asserting that “often these products can ‘survive’ only

for a rather short time period (e.g. up to two years),” he attributed the low profile of SMEs to

their lack of know-how and resources for intensive R&D activities as well as their inability to

spend high sums of money on, for instance, long-lasting clinical trials (p. 184).

However, the putative advantages of organizational size (Menrad 2003, p. 184) may not

hold as strongly in relation to marine extracts. To begin with, the difference in the scale of

R&D between the dairy segment of the functional food market, which accounted for a fifth of

all functional food innovations in Germany in 1999-2000 (Menrad 2003, p. 182), and that of

marine-based nutraceuticals, such as Lyprinol®, spans at least an order of magnitude. For

instance, the cost for product development and market introduction of Nestle’s LC1 yoghurt

was estimated to exceed US$ 50 million. The requirement of science-based research is

compounded in the innovation of functional foods by the need to ensure the bio-availability

and efficacy of the nutraceutical ingredient when it is delivered in a certain functional food

(Howe 2000, p. S108). On the other hand, Lyprinol® is an extract and does not contain

additives.

Moreover, the numerous hurdles that can prevent marine bio-actives from realizing their

fullest potential (e.g. as approved drugs that reach the pharmaceutical marketplace) are

exemplified by the cases of Lyprinol® and Isolutrol®. The absence of a unique ‘marker’ in

20

Lyprinol® curtails the product’s business potential by thwarting the synthesis and subsequent

development of a drug that could otherwise have been manufactured and marketed as anti-

inflammatory medication by a pharmaceutical company under license. Unlike the case of

GLMs and Lyprinol®, the ‘marker’ metabolite in shark liver bile has been isolated and had

its structure elucidated (as Isolutrol®, by Prof Kosuge). However, the complicated nature of

synthesis and the lack of viability of the extraction route have constrained the revenue-

streams from Isolutrol® for the MacLab group and its business affiliates.

That being said, from the perspective of the MacLab group and its business affiliates (PIL

and PMA), if not that of a pharmaceutical giant, Lyprinol® is still commercially viable by

offering “a competitive alternative to products or compounds that are already on the market

[e.g. unstabilized GLM powder extracts],” (Luiten et al. 2003, p. 434). (In the context of

plant extracts, Etkin (2001, p. 181) similarly speculated that “some of the former interest [of

pharmaceutical companies] in natural products would be transposed to the development of

botanical complementary and alternative medicines.”) Subsequent institutional innovation

(e.g. legislation for functional foods/nutraceuticals [Kalaitzandonakes, 2000]) should work in

favour of Lyprinol® by enabling it to better differentiate itself in the marketplace from other

nutraceuticals, such as GLM extracts, on the basis of its superior clinical evidence.

In this manner, possibilities for the limited commercialization of novel marine natural

products are yet suggested by Figure 1, all of which will likely serve niche markets in the

nutraceutical/cosmeceutical space – perhaps in lieu of the pharmaceutical arena. Thus, while

“the commercial source of choice for the pharmaceutical industry is synthesis, which allows

the company to control all aspects of production,” (Faulkner 2000, p. 142) the extraction

route remains a potential alternative for the supply of nutraceuticals, provided the source

organism can be viably harvested through aquaculture/fermentation. Besides Lyprinol®, the

cosmeceutical that is derived from the sea whip (Faulkner 2000, p. 138) is a case in point.

21

The Role and Nature of Collaboration In both Lyprinol® and Isolutrol®, the seed for discovery was epidemiological/folkloric

evidence, namely, the differential prevalence of arthritis in coastal vs. inland Maori and

Japanese fishermen’s use of shark liver extracts to acquire clear, smooth skin, respectively.

This parallels the commercial development of health foods, such as those from the micro-

alga, Chlorella spirulina, which can be traced back to the centuries-old history of the

utilization of spirulina by natural populations in Africa and Mexico (Olaizola 2003, p. 459).

The two cases suggest that the innovation of commercially viable marine nutraceuticals/

cosmeceuticals entails collaboration across a multitude of disciplines. These include: natural

products chemistry; fisheries/aquaculture; epidemiology and/or folkloric medicine; and

relevant strands of medical, pharmacological, and clinical research that could be governed in

part by prior epidemiological evidence and/or folkloric medicine (e.g. dermatology in the

case of Isolutrol®). In particular, the need for effective linkage between fisheries/aquaculture

and natural products chemistry arises from the imperative of balancing considerations of

yield factors for the secondary metabolite(s) with those of the cost-effective, reliable, and

scalable farming and/or sustainable harvesting of the source organism(s).

The resulting “confluence of diverse critical flows of information” (Valentin and Jensen

2003, p. 280) will enable gainful problem definition: e.g. what fraction(s) in the GLM explain

its efficacy as a treatment for arthritis, as revealed by epidemiological and/or folkloric

evidence regarding coastal vs. inland Maori? As the case of Lyprinol® reveals, such

definition is fruitful of business opportunity by seeking to leverage epidemiological evidence

towards the discovery and development of a nutraceutical that serves a sufficiently large

market and is derived from a species that can be viably farmed through

aquaculture/fermentation.

Although the need to understand folk dialects is a complication (Alino et al., 1990),

public-domain literature on the use of marine organisms in folk medicine is available (e.g. of

22

fishermen based at the Tocantins River in Brazil [Begossi and de Souza Braga, 1992] or of

coastal people in central Philippines [Alino et al., 1990]). However, attempts to leverage this

knowledge towards commercially viable marine natural products are not common.

Moreover, such data as are available may not be useful for discovering marine bioactives,

being cast in relation to epistemologies that obtain in particular knowledge frameworks, e.g.

cultural ecology. A case in point is Begossi and de Souza Braga (1992), who investigated

food taboos in relation to both the use of fish for folk medicine and the piscivorous habits of

fish. The authors’ research objective was to compare and contrast the fishermen’s

explanations for food choices with materialistic and ideological theories of cultural ecology.

Therefore, their field data might not be in a form that is usable by marine pharmacologists,

which exemplifies the challenge of harmonizing objectives and integrating methodologies in

trans-disciplinary research (Etkin and Elisabetsky 2005, p. 23).

The presence of distinct knowledge frameworks would necessitate translational

knowledge networking (Langlais et al., 2004). Universities and government research

institutes could be well-positioned to achieve the needed confluence of diverse disciplines, as

well as translational networking, in the search for meaningful problem definitions and targets.

Further, it may not be really viable or even desirable to direct the innovation effort

primarily towards generating interest and capital from food and industrial firms (Luiten et al.,

2003), especially given that industrial synthesis may be elusive, for whatever reason. Venture

capital from pioneering entrepreneurs in marine biotechnology, such as the Broadbent

brothers, may be easier to attract given the management of risk through collaborative

innovation as well as the lack of dependence on industrial firms for subsequent scale-up.

The Salience of Ethno-Pharmacology The congruence of disciplines outlined above is spoken to by the research field of ethno-

pharmacology, a term that defies easy definition, being introduced only in 1967 (Heinrich

and Gibbons 2001, p. 425). As cited by Berlin & Berlin (2005, p. 425), Bruhn and Holmstedt

23

(1981: p. 406) defined ethno-pharmacology as the “interdisciplinary scientific exploration of

biologically active agents traditionally employed or observed by man . . . [based on] the

observation, identification, description, and experimental investigation of the ingredients and

the effects of such indigenous drugs.” (The variety of perspectives of the term is clear from

the definition furnished by http://www.biology-online.org/dictionary: ethnopharmacology is

“the study of differences in response to drugs based on varied ethnicity.”xi)

Etymologically, the term suggests the conjunction of medical ethnography and the

biology of therapeutic action (Etkin, 1996). Notwithstanding this notion, even journals that

are dedicated to the field (such as the Journal of Ethnopharmacology) feature only 4-6% of

articles that bestride disciplines (Etkin and Elisabetsky 2005, p. 24). In the context of the

majority of published studies that are ‘stand-alone,’ Etkin and Elisabetsky (2005, p. 24) cited

the tendency of laboratories to confine their attention to the therapeutic potentials of various

groups of plants against biological targets; there was little synthesis beyond such foundational

data. As described by Etkin (2001, p. 181), “… one is left with the sense of discrete bits of

research emerging from various laboratories with nowhere to go and no one to pull them

together. By all appearances, no one seems to reflect much on what the larger picture might

be.”

Furthermore, the ethnographic component of most published ethno-pharmacology has

been deemed to be weak, if not non-existent (Etkin and Elisabetsky 2005, p. 24).

Nevertheless, ethnographic evaluations of indigenous therapies, which “not only look at

empirical aspects of indigenous and popular … use [of natural products], but also at the

cognitive foundations of this use” (Heinrich and Gibbons 2001, p. 430), could be entailed in

the innovation of commercially viable nutraceuticals. Besides clarifying, for example, the

requisite dosage schedules, such evaluation also unravels the symbolism underlying ritual

therapies. Heinrich and Gibbons (2001, p. 430) cited an example from their ethno-

pharmacological research wherein the consumption of a certain yellow petal at the end of a

24

treatment arose not from any pharmacological effect (at that dosage) but from the petal’s

symbolization of the bread of the Last Supper according to Christian mythology.

Folkloric therapies represent intellectual property of the concerned indigenous peoples,

and their use and commercial exploitation are increasingly being safeguarded following the

1992 Rio Convention on Biological Diversity (Etkin and Elisabetsky, 2005; Heinrich and

Gibbons, 2001). With increasing methodological and theoretical exchange across the

disciplines that intersect with ethno-pharmacology (Etkin and Elisabetsky 2005, p. 25), such

safeguards can enable non-decomposable problem definition and the protection of indigenous

knowledge through patents.

A Phased Approach for Innovation The foregoing discussion can be encapsulated in a phased approach towards the innovation of

commercially viable marine-based nutraceuticals; this is depicted in Figure 3. A viable point

of departure for the search for ideas would be traditional/folkloric medicinal knowledge

bases, used in conjunction with epidemiological data. As Figure 3 suggests, the recognized

health conditions (ethno-medicine) as well as the manner in which marine organisms are used

to treat those health conditions (medical ethno-biology) would comprise the principal data for

the ethno-pharmacologist (Berlin & Berlin, 2005). In turn, the ethno-pharmacologist would

define and investigate relevant problems such as: what active principle in shark’s liver

extract, as used by Japanese fishermen, explains its efficacy in the treatment of oily skin and

liver toxicity?

Place Figure 3 about here. The resulting ideas would need to be screened, first on the basis of the size of the

potential market(s), be it the treatment of acne or liver disorder. It is important to thereafter

vet the ideas for the feasibility of extraction given that extraction needs to be a viable fallback

route for the manufacture of the nutraceutical. This process would involve aquaculturists and

possibly also natural product chemists, who would furnish indicative yield factors of the

25

relevant secondary metabolite(s) (such as sodium scymnol sulphate).

Then, one needs to scientifically document the therapeutic efficacy of the marine

extract(s). This would involve collaboration between natural product chemists (who would

participate in the extraction) and the relevant specialist medical, pharmacological, and

clinical researchers, as suggested by that traditional/folkloric medicinal knowledge which

occasioned the inquiry in the first instance.

It is important to investigate, in parallel, the viability of industrial-scale synthesis for fully

realizing the commercial potential of the nutraceutical. This would require the prior

identification of any ‘marker’ metabolite(s) in the marine extract(s), as well as the structural

elucidation of those metabolite(s).

SUMMARY With recourse to two case studies, one being the principal case study and the other serving as

an auxiliary, we have examined the innovation of marine-based nutraceuticals as well as the

role of the embedding context of marine biotechnology. While several potential pitfalls

thwart the fullest realization of the business potential of promising leads, it is yet possible to

discover and develop commercially viable marine natural products that serve various niches.

The key is to manage the risk of development by enabling collaboration across several

disciplines and to conserve capital by initiating the search for meaningful problem definitions

through epidemiological and traditional/folkloric medicinal knowledge, which has seemingly

been underutilized for this purpose.

Our investigation also highlights the differential aspects of the successful innovation of

marine-based nutraceuticals as compared with functional foods such as ProViva. A major

consideration in the former is the need for a fallback route, i.e. extraction from the source

organism that is grown through aquaculture/fermentation, given the relatively high likelihood

of failure of industrial-scale synthesis. In turn, the imperative of a viable fallback entails the

participation of scientists from aquaculture and allied areas early in the discovery process.

26

Two directions for further research are suggested by the present study. The first speaks to

additional investigations of innovations in the functional food/nutraceuticals space that

highlight the influence of context and thereby clarify the situational aspect of the

management of innovation. The other direction speaks to the specification of institutional

structures and mechanisms whereby the intellectual property of indigenous peoples is

protected and inter-disciplinary collaboration is gainfully realized, with particular emphasis

on ethno-pharmacology, given that it will likely be the hub of meaningful problem

definitions.

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FIGURE 1. A progression of challenges in developing therapeutic agents from marine

bioactives (based on Faulkner, 2000).

The logistics of expeditions for collecting organisms

Harvesting and handling several kilo-tonnes of biomass, owing to low yields of compounds

The isolation and structural elucidation of marine extracts

Complexity of synthesis

Need for successful formulation of the compound for in vivo use

Constraints on harvest volumes due to considerations of sustainability and biodiversity conservation

32

33

FIGURE 2

A Knowledge Networking Perspective of the Innovation and Commercialization of Lyprinol®

(Following Langlais, Janasik, & Bruun, 2004)

Action KN Mode Result KR 1 Natural product chemistry.

TC 1 Why are fractions not stable?

Collaboration with other researchers having prior experience with natural product extracts.

Translational Formation of KR 2. Identification of the need for a stabilizer through a pharmacological screen for bioactivity.

KR 2 KR1 plus pharmacology.

TC 2 How can GLM powder extract be stabilized?

Drawing upon prior research into folkloric preservatives.

Translational Formation of KR 3. The development of a stabilizer and subsequent successful extraction of active fractions.

KR 3 KR 2 plus folkloric wisdom.

TC 3 How can the anti-inflammatory potency of the extracted fractions be verified?

Enlisting the services of a rheumatologist for conducting in vitro tests of anti-inflammatory fractions.

Pioneer/ Modular

Formation of KR 4. The concurrent extraction of fractions and in vitro testing that confirmed potency.

KR 4 KR 3 plus rheumatology.

TC 4 How can the therapeutic potency of the fractions be confirmed?

Collaboration with a medical researcher with experience in in vivo testing of anti-inflammatory compounds.

Pioneer Formation of KR 5. Confirmation of Lyprinol®’s potency when administered in vivo.

KR 5 KR 4 plus experimentalist medical researchers.

TC 5 How can the efficacy of Lyprinol® be scientifically documented?

Contracting medical researchers worldwide to conduct clinical tests for arthritis and later, asthma.

Modular Formation of KR 6. Successful, randomized controlled trials of Lyprinol®.

KR 6 KR 5 plus clinical researchers, including specialists in complementary therapies.

TC 6 How can Lyprinol® be successfully commercialized as a nutraceutical?

Value-chain partnerships with investors, marketers of nutraceutical products, functional food and nutrition specialists, etc.

Modular Commercialization of Lyprinol®, development of markets, continued clinical research, pursuance of registration as a drug, etc.

Legend: KR - Knowledge Regime; TC – Transepistemic Challenge; KN – Knowledge

Networking.

Ethno-medicine

Screen ideas on the basis of the size of the potential market(s)

As applicable, evaluate the feasibility of farming the source organism(s) and/or harvesting them in the wild in a sustainable manner

Medical ethno-biology

Ethnopharmacology

Ideas for marine extracts with commercial potential as nutraceuticals

In collaboration with natural product chemists and aquaculturists, screen ideas on the basis of yield factors and cost, besides the reliability and scalability of farming/harvesting the source organism(s)

1. Establish scientific documentation of the therapeutic efficacy of the marine extract(s) through research collaboration between natural product chemists and relevant specialist medical, pharmacological, and clinical researchers as suggested by traditional/folkloric medicine.2. Embark on the search for ‘marker’ metabolites and if they can be isolated and elucidated, investigate methods for industrial-scale synthesis.

FIGURE 3. A Suggested Phased Approach for the Innovation of Commercially Viable Marine Nutraceuticals(drawing partly from Figure I of Berlin &Berlin, 2005, p. 238).

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i Sourced from www.dictionary.com, September 2004. ii Sourced from http://www.nzmfa.co.nz/industryinfo.asp, August 2006. iii Sourced from www.lyprinol.com, September 2004. iv www.mcfarlane.co.nz (sourced September 2004). v Sourced from www.lyprinol.com, September 2004. vi Sourced from www.lyprinol.com, September 2004. vii In contrast with primary metabolites, secondary metabolites are made for purposes other than sustaining the

producing cell or organism. viii http://www.2beaut.com/ketsugo_article.html (sourced April 2005). ix http://www.csiro.au/index.asp?type=activity&id=isolutrol&stylesheet=aboutCSIROActivity (sourced April

2005). x http://www.2beaut.com/ketsugo_article.html (sourced April 2005). xi Sourced April 2006.

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