Why sharks are important to the study of human health
Dr Blake Chapman
Dr Blake Chapman
IT’S ONLY BEEN a few days since we lost my grandmother to cancer. Her disease progressed quickly, rapidly transforming her from a strong, independent, constantly cheerful person to someone who could no longer perform even the most basic of functions on her own. While I am still trying to cope with the loss, her story is not unique.
As a society, we lose 48,000 people to cancer every year in Australia and another 43,500 to cardiovascular disease (which can result in heart attack and stroke). It is projected that at current rates, 1 in 2 Australians will be diagnosed with cancer by the age of 85 and most people over the age of 65 years are currently living with long-term cardiovascular disease. These statistics are staggering, but what do they have to do with sharks?
Sharks are nature’s survivors. Relatives of the shark species we have swimming around in the oceans today have been in existence for around 450 million years. They survived the evolution and extinction of the dinosaurs, and pre-date just about every other vertebrate currently in existence. It appears that they have even been around longer than trees. It’s not that sharks have it easier than other species, they have just been able to evolve, adapt and diversify, where others have not.
When we think of shark survival techniques, we would most likely jump to images of large, serrated teeth or draw on information we may have heard about their highly refined sensory systems. But there is much more to these animals below their thick, largely impenetrable surface.
While few external similarities are apparent between sharks and humans, sharks are the most primitive vertebrates to possess all of the components of the same immune system that we use. That being said, there are still some significant differences between shark and human immunology, starting at the source. We produce red blood cells, platelets and white blood cells from our bone marrow; sharks, as cartilaginous fish that lack true bone, don’t have bone marrow. Instead, they have specialised epigonal and Leydig organs, which are completely unique to sharks and their closely related species.
Despite our differences, sharks are providing some truly notable outcomes for human health. Among these are promising preliminary and early stage clinical results against a variety of human diseases.
Sharks produce really small antibodies (about half the size of what we typically see), often called nanobodies. Interestingly, nanobodies are also produced by llamas, camels and their relatives. The advantages of these small proteins is that they are easier to make, they are more durable and they can get into things more easily, even when loaded with therapeutic cargo (e.g. drugs). As a result, they are being investigated for drug delivery into cells and tissues that human-sized antibodies cannot get into.
A recently developed formulation based on nurse shark antibodies has shown promising preliminary results as a transport system that can more efficiently carry human antibodies across the blood brain barrier. The potential for this capability is huge! This system is now being investigated for delivering therapeutic agents into the brain to fight Parkinson’s and Alzheimer’s diseases.
Another new drug has been developed based on the structure of wobbegong shark antibodies. Preliminary trials on animal models showed extremely encouraging results in the ability for the drug to reduce fibrosis in the lungs and liver. It is hoped that the anti-inflammatory and anti-fibrotic properties of the new drug will be similarly effective in reducing collagen build-up in the lungs of humans suffering from pulmonary fibrosis. This respiratory disease is currently incurable and is fatal.
The same drug has also been proposed as an option for the treatment of age-related macular degeneration and fibrosis diseases of the liver, skin and kidney.
Although these drugs have shown promise, they are still in the development and/or clinical stages, and are not yet available for human use.
A first-of-its-kind patch that incorporates components of shark cartilage (among other things, including cow collagen) has now been approved by the US Food and Drug Administration for the treatment of diabetic foot ulcers, with further proven effectiveness in treating third-degree burns. The patch aids in the permanent and rapid regeneration of skin tissue. The shark component of the design stems from the inclusion of chondroitin-6-sulfate, which serves to reduce blood clotting and inflammation.
Amazingly, a steroid derived from a shark has been shown to increase the regeneration rate of bone and tissue amputations in fish and improved heart function and survival rates of mice with induced heart attacks.
In another area of research, the ability of certain species of sharks to survive in low oxygen environments is being looked at for potential solutions to the same condition for humans. What can cause reduced oxygen availability for humans? Heart attacks, strokes, brain tumours, low blood pressure, anaphylaxis and complications for babies during birth, just to name a few. It is hoped that the physiological mechanisms used by these sharks might lead to therapeutic advances and counteractive measures for human application.
And finally, while not actually containing any biological shark material, the design of shark skin is also being examined for human health benefits. A new micropattern surface design is being trialled for objects that are regularly in contact with easily transferrable pathogens – for example, hospital bed rails. The design was shown to be effective in reducing the surface load of a number of bacterial species in lab tests, supporting further investigation into real-world application trials. One particular advantage of this strategy is that it is based on simple physical surface modification, rather than the more conventional strategy of (at times) harmful chemical treatments.
In modern society, sharks are overwhelmingly seen as threats to human livelihood. However, medical research is now giving us literally hundreds of thousands of reasons every year why we should instead be considering these animals to be potential life-savers.