Marek Cuhra
Institute of Marine Research, Bergen, Norway
Honourable colleagues,
The great American poet Thomas Alan Waits acknowledged the complexity and potential of our common language when he proclaimed that; fishing for a good time starts by throwing in your line.
I will throw in a few lines, since I have been given the opportunity to present views regarding new approaches in bioprospecting, and hopefully my lines will be short and concise. I have printed copies of what I will talk about as I attempt to outline the present efforts of Norwegian bioprospecting, and draw ecologically based perspectives towards some developing possibilities.
In short, the present efforts at isolating attractive bioactive chemical compounds from marine organisms, are being conducted along the main strategy which was founded more than a decade back in time; biological material is collected by trawling, dredging or diving in annual cruises along the Norwegian coast and in deeper waters within the Norwegian territories. In the laboratory ashore, the biological material is freeze dried and extracted. The extracts are tested in a range of cell-lines, – malignant human cells, normal human cells, various microorganisms and amongst those, such strains which demonstrate the most vicious antibiotic resistance. When effect is indicated through such simple screening, subsequent detailed analysis of isolate fractions and singular compounds will contribute to isolation of a potential pharmaceutical. But, as you surely understand, this is a simplified version of the story.
An alternative and more targeted approach in marine bioprospecting can be based in the ecological context of specific marine organisms, or of tissues, organ systems or body fluids in which biochemical mechanisms or compounds are either known or can be expected. Such a functional approach might identify the biochemical mechanisms responsible for certain observed abilities, such as the well-known anti-fouling properties of alcyonarian corals or the rapid and clean wound-healing and skin-repair of demersal fish.
Somewhat naïvely, the initial expectations were to harvest biochemical from the sea much in the same manner as we have for centuries harvested biochemical pharmaceutical ingredients from the botanical diversity of our planet. Researchers and representatives of marine-biopharma have presented politicians and investors with golden prospects of potential cures to grave diseases, including cancer. However, to date only a handful of functional pharmaceuticals have been developed from marine organisms.
Furthermore, after more than a decade of intensive bio-prospecting in the marine environment, we face new fundamental realisations. Importantly, we have recently reached an understanding of the importance of microbial symbionts, – the so-called microbiomes of various host organisms.
Organisms such as marine-sponges, fish and humans have specific societies of bacteria and other microorganism living in specific tissues or organ systems, – these are the vitally important microbiomes which aid in what we might describe as numerous micro-ecosystem-services; defence against potential pathogens, digestion of specific compounds, holobiont regulation and possibly some services which are rather difficult to explain, – it has even been suggested that in Homo sapiens the functionality of microbiomes is important for not only overall health, but mood and mental function as well. Although difficult to accept, such indications are being investigated at present.
Thus, we return to chemical ecology as a strategy to search for compounds. Chemical ecology is what helps organisms obtaining lunch without becoming lunch, and there are numerous important biochemical interactions in which marine organisms use chemical means to signal, attract mates, deter enemies and incapacitate predators. What we know at present is impressive, but even more astonishing is the realisation that in this subject, as in so many other subjects, our understanding is shallow and barely breaks the surface of that specific biological complexity.
Recently we understand that the trophic level supplied by such sponge reefs (sponge grounds) of species in the genus Geodia and others, has high ecological importance as an ecosystem service beyond the simple conversion of biomass from dissolved organic carbon or microbial origin. We also suspect that complex dialogue is taking place within the sponge holobiont of such species, as sophisticated prime line of immune system defences, antipredatory measures and cultivated tissues analogues of vegetable gardens. The medical qualities which ancient Chinese, Indian and Greek attributed to marine sponges are undoubtedly products of this biochemical complexity. Previously, when bioprospecting marine porifera, we have homogenized the entire holobiont and performed extraction from this. However, we have now begun stratifying the holobiont and testing distinct strata, – such as the exterior – or dermal – layers separate from the interior layers. Whether such simple differentiation will lead to anything but frustration, is still an open question.
In order to do groundbreaking research, move our field forward and truly solve the grand scientific enigmas, we must be able to acknowledge several aspects which we at present ignore at best, or which we at worst even counteract and oppose. Several of our fundamental assumptions must be revised, and we must be honest regarding potential and possibility of novel research fields.
In the near future marine microorganisms undoubdedly will be recognized for their enigmatic complexity and fundamental ecological importance. Microorganisms constitute a large part of global biomass, quoting a recent figure, an estimated 1.3 Gt marine carbon is contributed by bacteria. This is roughly the double of the global biomass of fish, which is estimated at 0.7 Gt (700 megaton).
Marine bacteria – as bacteria in general – are highly adaptable and the present efforts at developing strains which can utilize and degrade plastic waste is a reflection of that quality. From before we know that marine bacteria in the core microbiome of the deep water coral Lophelia pertusa include strains which can degrade and utilize hydrocarbons. Also, my own recent research presents soil bacteria adaptation to agriculture toxins as an important ecological driver for development of functional genes. Thus, it must be expected that as we speak, the galactic complexity of marine microbiology is evolving and adapting in response to changes in water chemistry, evolving mechanisms to deal with industrial effluents, residues of pharmaceuticals and other man-made pollutants.
I will spend a few minutes of this talk in accentuating my strong belief, that only diversity of academic background can help us form research-teams which can solve the present big challenges of natural science research. In several disciplines – such as genetics – we have worked ourselves into blind alleys and we need new ideas. As an example, we have recently initiated a project which will investigate analogue occurrence of semi-identical code in distantly related organism, speculating on new fundamental principles in heredity. One of the main problems with the academic socialisation, homogenisation and indoctrination which is performed at present, is the intolerance it poses to alternatives proposed by academic dissidents. Such dissidents must be allowed to contribute, even if their messages may be unpleasantly blunt, as in the situations when they correctly observe that the emperor has no clothes.
The previous time I gave a talk at an international conference, the subject was coral reef ecology and my presentation was entitled “the interval of biological normality”, – it was in 1995, in Newcastle, and it was well received. A Russian researcher was also there, Boris Preobrazhensky from the Pacific Institute of Geography in Vladivostok (maybe it has another name when translated from Russian now). I had the great privilege to spend some enlightening moments with professor Preobrazhensky, – we walked along the British coastline, observed natural phenomena and talked of various subjects. Although this is more than two decades back in time, I must say that these were important moments in my development as a scientist. To me – who had recently completed my masters of biology – professor Preobrazhensky stood out as an impressive academic capacity and a truly trans-disciplinary researcher. He had written a book on biological complexity of underwater landscapes and had interesting reflections on many of the issues, which I had previously strived to understand. And, like me, he was an active diver.
As an example, he taught me some new things on chemistry of marine waters. Also, some of his reflections made me understand that several widely accepted explanations and scientific dogma, are simply not correct. In a certain way, that introduced me to epistemology and – notably – agnotology.
However, we shall not talk of epistemology and agnotology here, although these subjects are so very important in all scientific work. This realization, though, is one which practitioners of the noble arts of natural sciences have to reach by themselves.
Many – if not most – are satisfied with the narrow focus of numbers and statistics, with little need to neither penetrate mentally into neighbouring academic fields nor to challenge themselves intellectually. And such professional decisions must be respected, – colleagues should be allowed to go about in their daily business and not be forced to fill their stressed minds with all sorts of adjacent disciplines, new complexities and revolutionary ideas.
I must say that our basic understanding of microorganisms will surely change dramatically within the coming decade. We will reach such realisations which today are nearly unspeakable. One might thus say that I should keep my tongue and not speak of purely hypothetical concepts – which I even admit are mostly based on little evidence other than own conclusions. However, being in the country which fostered such minds as Boris Mikhaylovich Kozo-Polansky who lived from 1890 to 1957, I feel that such comments are justified. Kozo-Polansky investigated cells living within other cells as symbionts and fathered the only much later accepted theories of symbiogenesis, theories which notably inspired the work of Lynn Margulis, who had to endure more than ten rejections of her manuscript on symbiogenesis, before those revolutionary ideas were recognized and received standing ovations in academic circles.
I will dare to say that a few aspects of microbiology are rapidly approaching realizations so clear to us at present, that we as a community simply have to acknowledge the coming advances. Here, I specifically think of two subjects, microbial taxonomy and microbial genetics. In a few years those subjects can become revolutionized by new realizations, primarily the concept of microbiomes as generators and providers of genomic elements and sorely needed code for metabolic processes needed to solve ecological challenges, – such as the presence of persistent or regularly inflowing pollutants and chemical disruptors.
The other issue, which might emerge relating to microbes and their taxonomy, will mean a complete revision of the concept of separate and distinct species as units of biological and genetic integrity. In the future we will see a new phylogenetic tree emerging, accentuating the importance of horizontal transfer of genes and supplementing and enhancing the present realization that most living diversity, is within the worlds of microbes. The idea which I hereby will attempt conveying
to you, speculates that microbes have an infinite number of species. The term “infinite” is so very absolute and heretic in the language of science, but here it must be used with some justification.
You can imagine the stems of the phylogenetic tree, as these stems and trunks are constantly sub-dividing into trillions-gazillions separate small branches. Recent estimates on the number of marine bacteria speculate at 1029 individual cells, but no researchers have dared to present estimates of species numbers. Possibly, because we cannot speak of traditional concepts such as species when it comes to bacteria. Possibly, we must acknowledge that the correct terms to use in microbial taxonomy are that of strains, and operational taxonomical units, the so-called OTUs.
The parent mother microbe exchanges her genetic code with not only close relatives, but with other microbes and higher organisms as well. This constant exchange of genes, through the well-established process of lateral or horizontal – gene transfer, is a main driving force in creating such diversity. But, also the mutability of the prokaryote plasmids, providing the adaptability which microbes demonstrate, be it towards antibiotics, agricultural pesticides or marine oil-spills.
For marine bioprospecting, the simple and primary goal is ecological approaches aimed at identifying ecological interactions in candidate holobionts, for subsequent harvesting and testing, but also with a wider perspective, such as employing microbial generators based on hosts modified via transgenesis. Simple expressions of such candidate genes for example coding for antimicrobial peptides are already routinely performed in model microbes such as E. coli, and surely the future will bring numerous advances there as well.
And here we reach conclusion regarding the ecological changes to our northern seas and the future of the harvestable marine resources which these seas will provide: we must realize that changes in water-chemistry, temperature and human activity, may profoundly affect the diversity of marine microorganisms. The sad fact of this matter is, that we have only limited reference knowledge of this diversity and these complex microbial ecosystems, and thus no benchmark to measure changes against.
Finally, I must say that I am excited to be here, as a representative of the small neighbour at the western shores. Although the recent statistics from the United Nations assessments of the Global Ocean Survey find that amongst the nations of this world, Norwegian marine research has the highest number of employees per hundred-thousand inhabitants, – still I find that numerous challenges to the marine ecosystems are neglected at present. Notably, this concerns marine microbiology, a subject where we have only limited understanding of the ecosystem services performed by bacteria.
Hopefully this will change. In the IMR the understanding of these things is developing rapidly, and it pleases me to notice the attention which many researchers are now giving to this important complexity.
I thank you for your attention and if any of you wish to discuss any of these things, I will be happy to enter into conversation. (final comments out of script on 1) diving, and 2) this, the authors first visit to Russia, 50 years after Russia visited him in Prague, Czechoslovakia).