NATURE | Crash: A Tale of Two Species | Blue Blood | PBS
Where (and when) do horseshoe crabs evolve?
The evolution of the horseshoe crab extends back far before the dawn of human civilization, before the dinosaurs, before flowering plants... back to the era in our planet's history when visible life first appeared.
Our Evolution section traces the development of the horseshoe crab from the Paleozoic Era and provides an overview of the changes to our planet's geology, climate, flora and fauna from 540 million years ago to the present. Toward the end of the Cenozoic Era, beginning with the Holocene (11,000 BC to the Present), we look specifically at the evolution and development of the Delaware Bay.
If you've ever had a flu shot, know someone with a pace maker or joint replacement, or have given your pet a rabies vaccination, you owe a debt of gratitude to the horseshoe crab. Vaccines, injectable drugs, intravenous solutions, and implantable medical devices, both for humans and animals, are quality checked for safety using a test that comes from the blood of horseshoe crabs.
How does horseshoe crab blood protect the public health?
Humans can become sick if exposed to bacterial endotoxin. It is especially dangerous if endotoxin enters our blood stream directly, such as from an injectable drug. Given this, drugs and medical devices that come in contact with our blood stream are tested to help assure they do not contain harmful levels of endotoxin.
Like other animals, the horseshoe crab has an immune and blood coagulation system that protects it against infection. Inside the horseshoe crab’s blood cell (called the amebocyte) are the protiens of its blood clotting system. These proteins are released in response to the presence of unwanted organisms like Gram negative bacteria and cause its blood to clot around the injury and bacteria, protecting the animal from further harm.
Endotoxin Testing: LAL and TAL
Research on horseshoe crabs showed that their blood is very sensitive to endotoxin, which is a component of Gram-negative bacteria like E. coli. In the 1960s (see timeline), Frederik Bang and Jack Levin developed a test from Limulus polyphemus blood that detected the presence of endotoxin. This test, based on the fact that the blood of the horseshoe crab gels or clots when it comes in contact with endotoxin, was called the Limulus amebocyte lysate (LAL)test and was commercialized in the United States in the 1970s. In Asia, there is a similar test called TAL which takes its name from an Asian species of crab, Tachypleus tridentatus.
The LAL and TAL test methods have advanced since the early days, all with the purpose of helping to make injectable drugs, vaccines, and medical devices safer for humans and animals. In addition to the use of their blood for an endotoxin test such as the gel clot test, the horseshoe crab's DNA has been used to develop a recombinant test method for endotoxin. Even as alternatives are being developed that will retire or reduce the use of horseshoe crab blood, we will always be indebted to the horseshoe crab's contribution to our health.
In addition, a version of the LAL test has been clear by FDA as a test to aid in the diagnosis of invasive fungal infections. This test takes advantage of the fact that the horseshoe crabs blood clotting system responds to (1→3)-β-glucans as well as to endotoxins. (1→3)-β-glucans are a cell wall component of a wide range of fungi. A glucan test can indicate the presence (or absence) of a fungal infection within a couple of hours of drawing a patient’s blood sample so that appropriate treatment can begin promptly. Conventional methods of diagnosis can take days of even weeks to give a definitive result.