“What is so special about a shark’s immune system?”
That was the question posed to scientist Dr. Helen Dooley, who studies the evolution of the immune system. Much of her work focuses on understanding the immune responses of sharks, skates, rays, and chimera. “Basically, cartilaginous fishes are the furthest we can go back in evolutionary time and find an immune system based on the same molecules as humans. By studying shark immunity we can get an idea of the molecules and mechanisms that were present right at the beginning of this system, then trace the changes that have made to the system between then and the emergence of mammals (including humans),” she explained. Not only that, but researchers also get to understand how these ancient animals protect themselves from infection – which is now pertinent information as scientists assess the impact of various environmental changes upon their health and if it impacts their ability to survive.
A shark’s immune system is famous mainly because many believe that sharks don’t get cancer (a myth). This idea that they don’t get cancer seems to stem from scant clinical evidence that cartilage has anti-angiogenic properties (meaning it inhibits the development of blood vessels, crucial to the growth of tumors). Since shark skeletons are made of cartilage, people believed they couldn’t get the deadly disease. However growths have been documented in research papers and even photographs from divers, so while the incidence of cancer in sharks and their relatives may be low, it has been found in sharks. Dooley believes scientists will see greater rates of cancer in sharks as aquaria get better at keeping sharks for extended periods of time, as cancer is generally a disease of older animals (including humans). In fact, she reckons that due to competition for food, we just may not be seeing these sick animals in the wild.
But how do sharks seem to have an extremely low risk for cancer and infectious diseases? Perhaps it has something to do with their super-powered genomes? ”The short answer is we don’t know yet. Personally, I’m not sure we even have enough data yet to say this is true –in the wild a sick shark would die quickly if it can’t compete for food. So even for the few health studies that are being performed we have to assume they are biased towards relatively healthy animals. Even in captivity, it’s really hard to know if an animal is sick unless visually obvious or it stops eating for a while, but this happens for other reasons too (e.g. bullying from more dominant tank mates, small changes in color due to season, age, etc.). Add to that the fact that we don’t really know what makes sharks sick in the first place and it’s a bit of a mess,” commented Dooley.
What also can be a bit of a mess? Getting funding for this research… and getting shark blood to run the necessary tests! Thankfully, Dooley and her team have a fresh supply of shark blood for this kind of research. Like most studies involving animals, they went through rigorous vetting and ethics paperwork to make sure they were complying with keeping the animals safe and happy. For most of their studies, the team needs to look at the immune response in individual animals over time. Therefore, they keep a number of sharks under carefully controlled environmental conditions in the aquarium at The Institute of Marine and Environmental Technology (IMET), a joint University System of Maryland research institute. This is so that they can immunize and bleed the animals as needed. They get blood mainly from nurse sharks, Ginglymostoma cirratum, but they work with other species as well and all of the animals are used to handling. “It’s no worse for them than us getting our flu shot,” said Dooley. Sharks have quite a high pain tolerance if their mating
At IMET, Dooley’s team aims to understand when the different components of the immune system emerged and how they became integrated into the very complex protective network we find in humans. Yes, while many may think that understanding a shark’s immune system is just throwing money at a scientific curiosity, it can actually benefit of human medicine! Sharks are the most ancient animals to have a “human-like” immune system, meaning they provide a good starting point to understand the origins of the system as a whole. ”The analogy I like to use are the Harry Potter books – if we focus all our efforts on studying the immune system in humans it’s much like reading book 7 alone; you know the final outcome of the story but don’t appreciate how each character has developed and what forces drove them to that place,” clarified Dooley on a Inside IMET segment. “In our work we start at book one (i.e. with the sharks, skates and rays) and try to map the full story for each immune system component. We hope this information will help us better understand the human immune system and why it goes wrong, for example in autoimmune diseases such as rheumatoid arthritis.”
Another reason delving into the shark immune system helps humans in the long run is because of how each species is optimized to a particular environment and the pathogens it faces. This basically means that sharks have some immune molecules that humans do not (and vice-versa) due to their respective environments. Dooley and her team create synthetic forms of those molecules, later testing them for their utility as human therapeutics. Dooley further illuminated this theory by giving this example: “Imagine we find an immune molecule in sharks that it really good at killing bacteria. We might be able to use a synthetic version of this, that we have produced in the lab, to treat MRSA.”
Currently, scientists know that sharks have three different types of antibody (called isotypes). Two of these isotypes are very similar in structure to the antibodies found in mammals and other vertebrates, the third (IgNAR) is unique to elasmobranchs. It has a slightly different structure, composed of only heavy chains which makes the binding region smaller and easier to work with. Researchers also know that following infection (or immunization, which is designed to simulate infection) sharks use these antibodies to clear the invading pathogen. This occurs through similar mechanisms as in mammals but the response is much slower (months rather than weeks).
Hopefully sometime soon we can report on sharks helping heal a number of our ailments. For now, we haven’t cracked the “secrets” of shark antibodies or their immune system but we are making strides in the medical field thanks to these ancient predators.