Sharks are well known for their incredible resistance to disease. The exact reason for this resistance has always been a bit of a mystery. While performing research as a graduate student almost thirty years ago, John Marchalonis took several milliliters of blood from the heart of a shark. Marchalonis discovered two proteins, one large and one small, which could link together to form a Y-shaped structure. This Y-shaped structure, which consisted of the two proteins, had the ability to stick tightly to chemicals that did not belong inside the shark. This was an immune system response that would destroy the foreign invaders. This finding showed that sharks have disease-fighting antibodies that are similar to those found in humans.
Currently, as the head of Microbiology and Immunology at the University of Arizona, Marchalonis is still studying sharks, skates, rays and shark cousins. He is comparing them with humans in the hopes of uncovering some of the early stages in the evolution of the immune system. Even though sharks are vertebrates, our evolutionary paths went their separate ways over 400 million years ago. This may uncover possible answers to questions concerning the evolution of the immune system.
The immune response depends on antibodies and three other immune proteins known as T-Cell receptors (TCRs), MHC proteins and RAG proteins. Scientists have been unable to detect the presence of these proteins and antibodies in any group that evolved before sharks. This is one reason that sharks are being studied so heavily but, even with the presence of antibodies and other important proteins, sharks exhibit a rather sub-par immune system. There have been experiments in which sharks were injected with foreign proteins. The sharks did create antibodies to bind to the foreign proteins but the response did not improve upon repeated injections as it does in humans. Even with these findings, sharks are known to be very disease resistant. Contrary to popular belief, sharks do get cancer but it doesn’t happen easily. Scientists must somehow make sense of the shark’s rather substandard immune capacity. One possibility could be that sharks do not require the same immune system functions humans do in order to survive.
A human’s acquired immune system is made up of antibodies and T-Cells. The acquired immune system is responsible for recognizing foreign invaders and allows our body to make the distinction between self and non-self. Antibodies recognize antigens and bind to them. As antibodies bind to antigens, they essentially are being singled out for destruction. Humans can produce as many as one hundred million distinct antibodies, which allows for quite a bit of protection against foreign invaders.
As our body cuts and rejoins DNA to make up the Y-shaped antibodies (found in sharks as well) many tiny mistakes are made which leads to even more diversity. This diversity, along with DNA cutting, allows humans to fight off many different foreign invaders without requiring one dedicated gene to create each antibody and TCR. Even though a shark can cut DNA in a similar fashion to humans, they also have more light and heavy chain genes.
Sharks not only possess a remarkable immune system but also produce a steroid called squalamine. According to Mike Zasloff, President of Research of Magainin Pharmaceuticals, sharks rely less on TCRs and antibodies and more on squalamine. Squalamine, as well as other shark chemicals, are considered potent killers of many bacteria and also seem to ward of viral infections. Magainin Pharmaceuticals is trying to develop squalamine for commercial use in prescriptions like the health food stores which sell shark cartilage since the early 1990’s. Many companies and people have been quick to point out the benefits of shark cartilage even though most of the claims have not been proven by true scientific research. Unfortunately, sharks are being over fished worldwide because of the cartilage craze.
The research that John Marchalonis began is really just the beginning of a significant study. As the research has found, sharks are very resistant to infection and sickness. If these abilities can be brought to the human species, then we have a lot to look forward to. Less sickness and better resistance to viral infections are only two possible benefits that could come from Marchalonis’ research. There will always be a debate on ethics when DNA is concerned. Many religious sects do not believe in research involving DNA because they feel it is science’s way of “playing God”.
I feel that if this research can prevent sickness or be able to fight off infections, then science should pursue in the effort to do more research.
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