Putting the Bite on Cancer

Q: Is it true that sharks don't get cancer? I've heard that their immune system is more advanced than was previously thought.

- Charles

Chicago, IL

A: While it is not true that sharks do not develop cancer, they do have a remarkable cancer shield. Of the thousands of fish tumors in the collections of the Smithsonian Institution, only about 15 are from elasmobranchs (The Smithsonian is an amazing place - where else can one go to see thousands of fish tumors?), and only two of these are thought to have been malignant.

A tumor can be thought of as an uncontrolled cellular growth. To support their very high metabolism, tumors secrete a hormone called 'angiogenin' which causes nearby blood vessels to grow new branches that surround the tumor, bringing in nutrients and carrying away waste products (this last is likely to be the mechanism of metastasis - where part of a tumor breaks away and establishes another cancerous colony elsewhere in the body). Research by Dr. Robert Langer of M.I.T. and other workers has revealed a promising anti-tumor agent obtainable in quantity from shark cartilage. Shark cartilage, it turns out, contains a compound antagonistic to the effects of angiogenin, called (cleverly enough) 'angiogenin inhibitor' - which does just what it sounds like: inhibits the formation of new blood vessels so that the proto-tumor starves or 'chokes' in its own waste products.

Regarding the shark immune system: yes, it is now known to be much more sophisticated than was previously thought. This sophistication is surprising only to those not familiar with elasmobranchs, which are undeniably ancient but also highly evolved and anything but primitive.

Basically, sharks seem to possess only one class of broad-spectrum serum antibody - similar to that found in human infants. In humans, this broad-spectrum class of antibody is replaced by more specific antibodies as the child matures and is exposed to a greater variety of pathogens. Conversely, sharks retain their non-specific immune response throughout their lives. This generalized immune system is one of the reasons sharks are able to detoxify many potentially harmful compounds quickly without need of prior exposure. Sharks injected with carcinogens, coliform bacteria, and - most recently - exotic fungal toxins at concentrations that would kill most vertebrates outright, have detoxified these pathogens and survived apparently without ill effects.

It has even been suggested that sharks may represent the Great Grey Hope in our fight against HIV and AIDS. This was originally 'poo-pooed', as no one could see why a shark would develop an immune response to something it is very unlikely to encounter. However, considering the generalist nature of the shark immune system, perhaps this would be a worthwhile research area after all.

One final thing: if you were to dissect most any vertebrate, you would find a simple and straight-forward, one-to-one correlation among organ systems (a heart is a heart; a liver a liver; a spleen a spleen; etc.). Sharks have all the internal organs one would expect of a gill-breathing vertebrate ... and something 'extra'. Called an 'epigonal organ', one lies underneath each of the kidneys and is quite unique to elasmobranchs. Think of it: here we have a complete, well-developed paired organ, yet we do not know where it comes from ... or even much about what it does. Based on unpublished data from some of my colleagues, the epigonal organ seems to be composed of lymphoidal tissue (and is thus mesodermal in derivation), and seems to be concerned with hemopoetic (bloodcell-forming) functions. Recent data also indicate that the epigonal organ is the site of T-cell differentiation in elasmobranchs, and thus plays an important role in the immune system of these fishes. Without long bones to serve as a site for leucocyte development, sharks have jury-rigged a scrap of available tissue to assume that function.

Are elasmobranchs amazing critters, or what?