Marine natural products drug discovery – new drugs from the sea

“The oceans offer enormous biological diversity with unique metabolic and physiological capabilities that ensure survival in diverse habitats and the potential to produce an enormous diversity of metabolites not found in terrestrial organisms.”

This is paraphrase of the rationale that is used at the beginning of almost any marine drug discovery venture. I have written stuff like this myself, but I have a problem with it.

While the inherent diversity and uniqueness of marine life is true and this is almost certainly matched by chemical diversity, is this enough to form the basis of a drug discovery venture? Yes – If you have an unlimited supply of money and no fixed timelines. In the real world we need more than the big picture to develop a proposition for a drug discovery venture that has realistic chance of success.

Marine natural products drug discovery is bioprospecting, which like any kind of prospecting, should not be a completely random process. Before we start looking for gold we need to know where is a good place to look, we need to know how to look, we need to know what we are looking for, and we need to know that someone will buy it if we find it. This sounds obvious? What does this mean for marine drug discovery:

What to look for? – This is probably the most important question in drug discovery, and defines the direction you will take with the other questions – it gives focus. Drug discovery needs to be driven by targeting a particular chemistry or biological activity, preferably both. For example at GlycoMar we target glycomolecules with anti-inflammatory activity, and have good biological reasons for that focus. The answer to this will depend on your aim: an academic doing research can select almost any chemistry or activity that they wish and build a rational justification for funding that research, but this selection should also consider the practical considerations in the next two questions. For a commercial venture there should be careful consideration of the application: the disease indication being targeted, or maybe a particular personal care application. This requires deep knowledge of the application, which then defines the biological activity being sought and perhaps the chemistry that might deliver that activity. This knowledge is really key and links to my previous post about knowing your market. This is why marine drug discovery should be an interdisciplinary pursuit linking chemists, marine biologist, pharmacologists, and clinicians.

Where to look? – Marine biodiversity is enormous and mostly unknown, so we need some method for selecting organisms to work on. For example, we may pick a group of organisms that is particularly rich in the chemistry we seek. We should only pick organisms that we can get enough of, at a reasonable cost, without destroying the diversity that we rely on and taking full account of national and international rules on biodiversity. Perhaps we will only pick organisms that are suitable for future production, such as fermentable microorganisms. We may pick organisms that are used in traditional medicine and are therefore likely to have some beneficial properties. There is an almost endless basis for deciding where to look, some of which is defined by your geography and resources, but the opportunity inherent in marine bioprospecting means you can almost always find a good place to look.

How to look? – Accessing marine biodiversity can be enormously expensive and slow, so we need a practical mechanism for getting hold samples and we need practical mechanisms for processing these samples. For example, working on extremophiles from deep ocean vents is an attractive idea, but can you afford the ROV that is required to go down there and will that produce enough samples and will you be able to resupply if needed. Once you have your samples the extraction process needs to make enough ‘product’ for characterisation, at a reasonable cost and in a reasonable timeframe.

Does someone want what I am looking for? – this is mostly answered when you have considered ‘what to look for’, but goes beyond that. Its important not only to have an application, but to have one that someone wants. If you are successful and find a new drug, how will you progress from that initial discovery? For an academic this may be less of a concern, but you do need to know that you will produce science that is publishable. In a commercial drug discovery the answer will probably be that nobody wants a newly discovered drug, they want one that has gone through development and successfully reached phase 1, II or III of clinical development.  This defines how much money you need, how long it will take and probably defines your business model.

My argument, therefore, is for a carefully thought through approach to marine natural products research and development. I don’t think there is a right answer, except that the answers should give focus and be rational. Luck will still be involved but we need to increase the chance of success.

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