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Biochemistry

Marine life: Coming to a PharmaSea near you!

Paper: Jaspars M, Pascale D De, Andersen JH, Reyes F, Crawford AD, Ianora A (2016) The marine biodiscovery pipeline and ocean medicines of tomorrow. J Mar Biol Assoc UK 96:151–158 (Open Access!)

People have been using medicines made from the ocean’s residents ever since ancient times. Coastal Asian cultures have eaten seaweeds since 1400 BC, which helped them introduce the necessary nutrient iodine into their diets to help prevent goiter. Cod liver oil was all the rage as a nutritional supplement for northern Europeans in the early 20th century to help prevent rickets. The Irish folk medicine tradition uses the seaweed Irish moss (Chrondus crispus) to soothe colds, sore throats, and chest infections. But that’s all in the past, right? Modern medicine comes from chemists in labs around the world?

Not quite. Ocean life is crucial to our development of new pharmaceutical drugs. There are over 28,000 potential compounds that have been isolated from marine organisms that could be the next cure for a variety of diseases, and more are being discovered every year. Right now, there is a large push to make those compounds into functioning drugs available to the public. Recent technological advances in sciences such as genomics and proteomics (studying the genome and the proteins of an organism, respectively) have made it economically feasible to isolate the compound from the animal, and then develop the drugs in labs.

This paper, a collaboration among five different EU countries, was put together by the PharmaSea program. PharmaSea is an international effort by 24 institutions for drug discovery. Their specific focus is to find new compounds from marine organisms to treat bacterial infections, inflammation, and diseases such as Alzheimer’s. This unique program is targeting some of the most extreme regions of the ocean – hydrothermal vents and deep ocean trenches – to try to find those compounds.

Figure 1 – A hydrothermal vent system, maybe the source of our next medicines? Source: Wikimedia Commons

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Why look at marine organisms, especially those adapted to extreme habitats, for new drugs? The ocean is inherently difficult and hostile to live in – lots of predators in a 3D environment that can vary in terms of temperature, salinity, and pressure. As a response, marine organisms have evolved a lot of secondary metabolites (the prime compounds to look at for drug discovery) to help them survive. Secondary metabolites are compounds the organism synthesizes to defend against disease, parasites, or predators. A common example is penicillin – a drug made from the Penicillium fungi – that kills certain types of bacteria by interfering with their ability to create a cell wall. (Click for a cool video!)

Because the ocean environment is so different from the terrestrial environment, many of the compounds these marine animals have evolved have no terrestrial equivalent. Animals that live in extreme systems, like hydrothermal vents, are even more likely to contain these special secondary metabolites. Their environments are even harder to live in than the rest of the ocean because of the high pressure, low temperatures, high concentrations of hazardous chemicals, and zero light availability.

The PharmaSea program is using innovative technologies like remotely operated vehicles to probe the deep sea for new animals to isolate compounds from. They’re focusing their energies on marine microorganisms for two reasons: (1) they’re easier to collect, and (2) they’re easier to propagate in the lab. Once a microorganism is found, it goes through cultivation with different stressors (bacteria viruses, tumors, etc). If it survives the stressors, it goes though additional testing for antibiotic resistance. If the compound has a neural component, it is tested on zebrafish larvae (easier to culture than lab mice!) to see how they behave with the compound. There is a lot of screening that goes into finding exactly which compounds are likely to be effective in pharmaceuticals.

The PharmaSea program is looking to expand the development of marine organism-based drugs, but so far, there have been a few discovered that are already being used. Marine animals are very good at destroying non-native cells – lots of parasites in the ocean – so one major category of marine-derived drugs are anti-cancer medications. There are anti-cancer drugs out there made from sponges and tunicates that have successfully treated non-Hodgkin’s lymphoma and ovarian cancer. Another compound, isolated from a cone snail, eases severe pain in patients who didn’t respond to other drugs. Still others come from fish oils, and have been in trials to reduce triglycerides, which would aid patients with obesity, diabetes, and atherosclerosis.

Figure 2 - Medicines and their little known sources: marine life!

Figure 2 – Medicines and their little known sources: marine life! Source: Jaspars et al. 2016.

 

 

 

 

 

 

 

 

 

 

 

Another major area of research is in nutraceuticals and cosmeceuticals – compounds that aren’t for clinical use, but are nutritional supplements. You’ve likely heard of omega-3 fatty acids, which come from krill oil, but there are so many more health benefits associated with these marine-derived compounds. Carotenoid pigments from algae are said to be anti-aging, astaxanthin from shellfish shells is said to be an antioxidant and anti-inflammatory, and marine collagen peptides from fishes are said to have anti-hypertension properties.

Figure 3 - Nutraceuticals and pharmaceuticals with their lesser known sources: more marine life!

Figure 3 – Nutraceuticals and pharmaceuticals with their lesser known sources: more marine life! Source: Jaspars et al. 2016.

 

 

 

 

 

 

 

 

 

 

 

 

 

The paper ends with a nod to preservation and conservation, as it should. When we think about all the pharmaceuticals that we could cultivate from these marine organisms, it makes sense to preserve our ocean environment. In terms of hydrothermal vents, in many instances, we don’t even know what pollution does to these systems because they were only discovered thirty years ago. Just one more thing to think about as we talk about conserving the ocean’s biodiversity – the cure for cancer may be threatened due to pollution and climate change effects, and we won’t even know until we find it.

Engage: What products in your home are made from algae or marine compounds? Hint: check this link for a list of what to look for.

Bonus: If you’re interested in learning more about various marine-based nutritional supplements, check out examine.com, a site that synthesizes and breaks down peer-reviewed literature to tell you if what you’re taking is effective or not. Here’s the link to their page on fish oil to get you started. Enjoy!

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