We Can Use Horseshoe Crabs To Keep Us Safe
September 11, 2022 at 5:05 p.m.
By Max [email protected]
The material is horseshoe crab blood obtained by capturing the crabs, shipping them to Charles River, a company in Charleston, S.C., then strapping the crabs to steel countertops and subsequent draining about a third of it. The crabs are then returned to the ocean. This liquid is vital for America’s biomedical industry. (A liter sells for as much at $15,000.) The blood is the only known natural source of limulus amebocyte lysate (LAL), an extract that detects endotoxin.
Drug and device firms use LAL to ensure the safety of their products, including antibiotics, anticancer drugs, heart stents, insulin and vaccines by detecting the presence of foreign organisms. The immune cells in the crab’s blood clot around toxic bacteria, giving a visual signal of unwanted contamination. Water used in the processing of drugs or devices is frequently the culprit.
Endotoxin
Endotoxins, also called lipopolysacchride or LPS, are the component of the outer membrane of gram-negative bacteria and are released into the circulation upon disruption of the intact bacteria (death, cell lysis). Endotoxin is commonly found everywhere in our environment and it is the most significant pyrogen in parenteral drugs and medical devices. (Pyrogens can cause fevers.)
Endotoxins are also present in the digestive system. Their presence in the blood stream may cause septic reactions with a variety of symptoms such as fever, hypotension, nausea, shivering and shock. The Food and Drug Administration (FDA) regulates the acceptable level of endotoxin contamination with medical devices to be 0.5 endotoxin units/ml. There have been few reports of endotoxin contamination with the use of cardiovascular and other devices. As mentioned earlier, the most conspicuous source of endotoxin may actually be the water used in cleaning procedures since distillation and deionizing columns do not remove endotoxin.
Horseshoe Crabs
The four species of horseshoe crabs, the only living representatives of an entire Class of organisms, have already provided scientists with a window into the past as well as yielding valuable insight concerning the chemistry of life, the nature of vision, and some of the intricacies of nervous system development. Their unique blood, eyes, genetic material, and basic structure continue to provide priceless knowledge that far outweighs their value when killed as a commodity.
Direct predation by people, incidental killing of large numbers trapped in nets and trawls, and vast depletion of their shoreline habitats, from beaches to productive offshore waters, have combined in the past few decades to threaten these amazingly durable animals with extinction.
Physiological Effects
As Dr. Lewis Thomas describes in his book “A Long Line of Cells,” “Gram negative bacteria display lipopolysaccharide endotoxin in their cell walls, and those molecules are read by our tissues as the worst of bad news. When we sense lipopolysaccharide, we are likely to turn on every defense at our disposal, we will bomb, defoliate, blockade, seal off and destroy all the tissues in the area.
Leucocytes become more actively phagocytic, release lysosomal enzymes, turn sticky and aggregate together in dense masses, occluding capillaries and shutting off the blood supply. Complement is switched on at the right point in its sequence to release chemotactic signals, calling in leucocytes from everywhere. Vessels become hyperactive to epinephrine so the physiologic concentrations suddenly possess necrotizing or death causing properties. Pyrogen is released from leucocytes, adding fever to hemorrhage, necrosis and shock. It is a shambles.”
Availability
According to the International Union for Conservation of Nature, horseshoe crabs are vulnerable to extinction. It blamed overharvesting for use as food, bait and biomedical testing, as well as habitat loss as the cause. As crab numbers fall and demand for LAL rises, America’s biomedical industry will face a crunch. Billions of COVID-19 vaccinations have relied on it, but so do plenty of routine surgical procedures such as hip replacements, whose numbers continue to grow. Charles River estimates that 55% of injectable pharmaceuticals and implanted devices globally are tested for the extract produced at their facility.
Final Thoughts
Fortunately, there is a synthetic alternative to LAL already available, which in Europe is rapidly replacing crab blood as the industry standard for testing. In 2003, Lonza, a Swiss biotech company, cloned crab DNA to create recombinant factor C (RFC). Jay Bolden, a biologist, pioneered the use of RFC in America at Eli Lilly. In a study published in 2017, Mr. Bolden found that RFC detected endotoxins as well as LAL, or even better. The test turned up fewer false positives and was cheaper to produce. Unfortunately, the United States Pharmacopeia has been reluctant to add the synthetic substance to its list of approved materials.
Max Sherman is a medical writer and pharmacist retired from the medical device industry. His new book “Science Snippets” is available from Amazon and other book sellers. It contains a number of previously published columns. He can be reached by email at [email protected].
The material is horseshoe crab blood obtained by capturing the crabs, shipping them to Charles River, a company in Charleston, S.C., then strapping the crabs to steel countertops and subsequent draining about a third of it. The crabs are then returned to the ocean. This liquid is vital for America’s biomedical industry. (A liter sells for as much at $15,000.) The blood is the only known natural source of limulus amebocyte lysate (LAL), an extract that detects endotoxin.
Drug and device firms use LAL to ensure the safety of their products, including antibiotics, anticancer drugs, heart stents, insulin and vaccines by detecting the presence of foreign organisms. The immune cells in the crab’s blood clot around toxic bacteria, giving a visual signal of unwanted contamination. Water used in the processing of drugs or devices is frequently the culprit.
Endotoxin
Endotoxins, also called lipopolysacchride or LPS, are the component of the outer membrane of gram-negative bacteria and are released into the circulation upon disruption of the intact bacteria (death, cell lysis). Endotoxin is commonly found everywhere in our environment and it is the most significant pyrogen in parenteral drugs and medical devices. (Pyrogens can cause fevers.)
Endotoxins are also present in the digestive system. Their presence in the blood stream may cause septic reactions with a variety of symptoms such as fever, hypotension, nausea, shivering and shock. The Food and Drug Administration (FDA) regulates the acceptable level of endotoxin contamination with medical devices to be 0.5 endotoxin units/ml. There have been few reports of endotoxin contamination with the use of cardiovascular and other devices. As mentioned earlier, the most conspicuous source of endotoxin may actually be the water used in cleaning procedures since distillation and deionizing columns do not remove endotoxin.
Horseshoe Crabs
The four species of horseshoe crabs, the only living representatives of an entire Class of organisms, have already provided scientists with a window into the past as well as yielding valuable insight concerning the chemistry of life, the nature of vision, and some of the intricacies of nervous system development. Their unique blood, eyes, genetic material, and basic structure continue to provide priceless knowledge that far outweighs their value when killed as a commodity.
Direct predation by people, incidental killing of large numbers trapped in nets and trawls, and vast depletion of their shoreline habitats, from beaches to productive offshore waters, have combined in the past few decades to threaten these amazingly durable animals with extinction.
Physiological Effects
As Dr. Lewis Thomas describes in his book “A Long Line of Cells,” “Gram negative bacteria display lipopolysaccharide endotoxin in their cell walls, and those molecules are read by our tissues as the worst of bad news. When we sense lipopolysaccharide, we are likely to turn on every defense at our disposal, we will bomb, defoliate, blockade, seal off and destroy all the tissues in the area.
Leucocytes become more actively phagocytic, release lysosomal enzymes, turn sticky and aggregate together in dense masses, occluding capillaries and shutting off the blood supply. Complement is switched on at the right point in its sequence to release chemotactic signals, calling in leucocytes from everywhere. Vessels become hyperactive to epinephrine so the physiologic concentrations suddenly possess necrotizing or death causing properties. Pyrogen is released from leucocytes, adding fever to hemorrhage, necrosis and shock. It is a shambles.”
Availability
According to the International Union for Conservation of Nature, horseshoe crabs are vulnerable to extinction. It blamed overharvesting for use as food, bait and biomedical testing, as well as habitat loss as the cause. As crab numbers fall and demand for LAL rises, America’s biomedical industry will face a crunch. Billions of COVID-19 vaccinations have relied on it, but so do plenty of routine surgical procedures such as hip replacements, whose numbers continue to grow. Charles River estimates that 55% of injectable pharmaceuticals and implanted devices globally are tested for the extract produced at their facility.
Final Thoughts
Fortunately, there is a synthetic alternative to LAL already available, which in Europe is rapidly replacing crab blood as the industry standard for testing. In 2003, Lonza, a Swiss biotech company, cloned crab DNA to create recombinant factor C (RFC). Jay Bolden, a biologist, pioneered the use of RFC in America at Eli Lilly. In a study published in 2017, Mr. Bolden found that RFC detected endotoxins as well as LAL, or even better. The test turned up fewer false positives and was cheaper to produce. Unfortunately, the United States Pharmacopeia has been reluctant to add the synthetic substance to its list of approved materials.
Max Sherman is a medical writer and pharmacist retired from the medical device industry. His new book “Science Snippets” is available from Amazon and other book sellers. It contains a number of previously published columns. He can be reached by email at [email protected].
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