Crab Wars: A Tale of Horseshoe Crabs, Bioterrorism, and Human Health

by Bill Sargent

Surviving almost unmolested for 300 million years, the horseshoe crab is now the object of an intense legal and ethical struggle involving marine biologists, environmentalists, US government officials, biotechnologists, and international corporations. The source of this friction is the discovery 25 years ago that the blood of these ancient creatures serves as the basis for the most reliable test for the deadly and ubiquitous gram-negative bacteria. These bacteria are responsible for life-threatening diseases like menengitis, typhoid, E. coli, Legionnaire’s Disease and toxic shock syndrome. Because every drug certified by the FDA must be tested using the horseshoe crab derivative known as Limulus lysate, a multimillion dollar industry has emerged involving the license to “bleed” horseshoe crabs and the rights to their breeding grounds. Since his youthful fascination with these ancient creatures, William Sargent has spent much of his life observing, studying, and collecting horseshoe crabs. As a result, he presents a thoroughly accessible insider’s guide to the discovery of the lysate test, the exploitation of the crabs at the hands of multinational pharmaceutical conglomerates, local fishing interests, and the legal and governmental wrangling over the creatures’ ultimate fate. In the end, the story of the horseshoe crab is a sobering reflection on the unintended consequences of scientific progress and the danger of self-regulated industries controlling a limited natural resource.

Genres: Nonfiction, Science, Environment, Biology, History, Health, Animals

208 pages, Paperback

First published January 1, 2002

Reviews

[Ned · Rating 5 out of 5]

In case you are late to the party, the armor-plated creature called known as the horseshoe crab is in the throes of an explosive geopolitical debate. Ironic since these inscrutable animals “saw” the dinosaur come and go, and are one of the oldest “living fossils” on earth. Further, they are not even crabs and phylogenetically closer to spiders (I’ll spare you the genus / species nomenclature as that usually stops readers cold).

So, what’s all the hubbub? (as I write, suddenly occurs to me I need to look up the origin of that word) As it turns out, even this ancient organism is being consumed by man’s voracious appetite, along with the more traditional competition from fellow species. Biologics, notably Fred Bang, discovered they possess a primitive immune system where their blood clots to wall off and block bacterial infections, notably those of the gram-negative variety (E. coli, for example). These organisms are problematic for people, especially for those receiving parenteral (injected) drugs. Human bodies possess far more complicated immune systems, yet still retain the ability to aggressively respond to infections. And therein lies the problem. Without getting too technical (being a biochemist we are all about the exact chemical structures causing such reactions), the body can recognize not only the offending E. coli organisms, but also the otherwise harmless “bits” shed from them. During production of such drugs (e.g. insulin), the filters that remove bacteria are generally unable to remove endotoxin (their shed “bits’). As a consequence, all injectable drugs must be tested for pyrogens (the most likely type being endotoxin) to assure their absence. Without such tests, patients would be at risk of getting fevers or other more serious problems.

So, how does the horseshoe crab fit into this narrative? It turns out that what Fred Bang, and his eager young student (Jack Levin) discovered was that the horseshoe crab blood was exquisitely sensitive to endotoxin. A special way of preparing the blood was discovered and published, known today as LAL (limulus amebocyte lysate). It was soon industrialized and today is a thriving industry which is used to guarantee the lack of even very low levels of endotoxin in just about everyone one of the thousands of batches of drug. These types of drugs, including monoclonal antibodies, are the biggest sellers in the world today (e.g. Humira®). My connection to this topic started in 1993 when I personally began performing and attempting to improve this test in my role as laboratory scientist in the pharmaceutical industry. It has been a long journey, and is very topical today as there are many new issues that have arisen. Eventually my publications in scientific journals put me in contact with the very Jack Levin, Doctor Levin as he is known, and I count it one of my finest achievements to collaborate with this man. He is now a distinguished and highly revered scientist, with razor-sharp analytical instincts, who has worldwide respect for his part in protecting patients from fever. What stands out for me, however, is his humility and inquisitiveness – in our dinners together he always has many questions for me and listens and takes notes. A hallmark of all great scientists for me has always been their passion for learning, whatever the source, and their unwavering discipline for the highest standards of scientific conduct. “Show me the data” is what I expect from Dr. Levin, and do NOT fall in love with your opinions and speculations.

Back to the hubbub: It turns out birds and fisheries depend on the eggs laid in rare breeding cycles driven by the tides (and moon phases of course). The author describes beaches fairly covered with a skein of green eggs. I’m not a birder (a most voracious and indefatigable species themselves, as I’ve come to learn), but my LAL world has collided with theirs as I’ve learned that these eggs are especially critical for the survival of some bird species, in particular the red knot. This fist sized bird journeys from the southern pole to the north pole, and back, every year. They lose half of body weight halfway through the trip, and depend of the crab eggs being present when they are ready to refuel on particular beaches in the Atlantic seaboard. Without this, the species is in peril – and that is what the birders are consumed with. I was invited and had the pleasure of visiting such a place last year, to see the horseshoe crabs on the beach, and even saw a red knot or two, but they were a minority. They used to be in massive flocks, now they compete with less endangered species.

What is the controversy? The exact state of horseshoe crab populations is of great concern to those seeking their protection. Sargent’s book is just excellent in describing these “wars” – he goes back to the beginning and details the depletion of crabs used for bait (it turns out ground up female crabs are a delicacy for eels). The eel market, especially in Asia, is very profitable. The LAL industry has gone to great effort to not harm the crabs, by removing only a portion of their blood to make the lysate used for drug testing, and then returning the crabs to the ocean. Of course, there is debate about how much harm this does to the animals, but indisputably this is better than pulverizing them for bait. In the US this is a regulated activity but, due to the unique interplay and complexity of local, state and federal law, there are differing opinions about how effective this is. Sargent covers a great deal of the individuals involved in the LAL industry, the fishing industry, and just how these regulations are enacted and where the loopholes and noncompliance have occurred.

Sargent has done us a great service by detailing this story in colorful anecdotes and with interesting personalities. I know several of them, so it was a delight discovering the larger context of what these people have done. What comes to mind for me, and gives me hope, is the old axiom recently recycled by Barack Obama that the arc of the universe is long but ultimately bends to justice – I do have faith (in its purest meaning) that this is true. Also, I believe in progress, and that a technical breakthrough or two will ease tensions. Until then, I will do my part listening and learning from what science can teach from all corners of the debate, and continue to do my part to minimize man’s destructive tendency to the natural world and protect from harm people receiving our drugs.

Ironically this book was written in 2002 – yet the wars rage on with greater fervor than could likely have been imagined by this fine author. I splurged on a signed copy.

[Daniel Joshua · Rating 5 out of 5]

Absolutely loved this book. I would definitely recommend it. I started out thinking I was going to be in for a boring read; how wrong I was. The writing is excellent, especially since very specifically focused nonfiction books are usually not written so well.
I didn't agree with everything he said. I didn't think his standpoint on evolution was so hot, and his environmentalism was a tad hasty, however it was honest and well meant.
I learned a great deal from the book. I had no idea that the creatures were so essential to the healthcare industry. The process of catching, bleeding and, releasing the crabs was riveting.
Altogether a ripping good book!

[Johanna Haas · Rating 5 out of 5]

A horseshoe crab has saved your live, and you didn't even know it (their blood is used to test drugs for bacteria). William Sargent LOVES horseshoe crabs and this comes out in his writing on the development of the horseshoe crab industry and its intersection with environmentalism. Seriously, this book takes the driest topic and makes it really interesting.

[Jimmy · Rating 4 out of 5]

Sargent wrote the book just after 9/11. You can imagine him questioning if it was worth writing at that time. He felt he "was doing something important." He was "honoring an animal that has saved a million more human lives than died in the World Trade Center." He was trying to show that "all life was related."

Chapter 4: At an Ancient Orgy [June 21, 1957]

It is the first day of summer, longest day of the year, longest tide of the season. A large female horseshoe crab enacts a ritual that has lasted over 300 million years. A smaller male crab crawls toward her and does a brief circling dance before clasping her shell with modified mating claws.

As they go toward shore, they navigate other male suitors. They clamber over each other to clasp on to her carapace. By the time she reaches shore, two more males are holding on.

Thousands of crabs are on the beach. Each female is surrounded by 30 or 40 males. They are all climbing over each other. The female digs in the sand and deposits several thousand eggs. Other males compete to have their sperm fertilize the eggs. The water is filled with eggs, sperm, and perhaps pheromones.

It is over in 30 minutes. Thousands of crabs crawl back to the ocean. Those that don't make it back will die in the heat of the morning sun.

The next day Sargent goes back with a doctor studying the crabs. In six inches of sand they find 3,000 green eggs the size of a pinhead.

The crabs cannot see in the daytime. It was believed the pheromones attracted them. Eventually, scientists realized the crabs could not be giving off pheromones. Their eyes are made to see ultraviolet light during the full moon. Mystery apparently solved.

Part II: Commercialization. Chapter 5: The Conversation. [Woods Hole, Cape Cod, 1962]

Dr. Frederik Bang injected some bacteria into a horseshoe crab and it died. It had no immune system, but it seemed to be mounting a defense.

He finally got someone to show an interest in his experiments.

When they injected a crab with vibrio bacteria, the blood turned a bright cobalt blue. Too much bacteria will kill the crab. But with a small amount, it fights the infection and survives. Its primitive cells swarm to the area, coagulate, and immobilize the bacteria. They act like platelets in human blood.

Dr. Bang collaborated with Dr. Jack Levin. It proved to be one of the most fruitful in the history of applied science. They created a new way to test for bacteria. First they stabilized the amoebocyte cells and made lysate which could be used as a test for bacterial endotoxin.

They should have hired a good lawyer and applied for a patent. Instead they published their paper. They would lose millions of dollars in licensing fees.

Chapter 6: Bleeding the Crab [1969-1974]

Gram-negative bacteria are ubiquitous and lethal. They live in shallow waters with horseshoe crabs, and thrive in the human intestine where they usually do little harm. When they enter the human blood system, it's a problem. Trauma breaks the membranes between the gut and blood system. The bacteria get into the blood vessels and multiply. They release endotoxins that cause a raging fever. The person goes into septic shock and can die in 24 hours.

Researchers fold a crab along a hinge connecting the thoracic and abdominal segments. They insert a large needle into the crab's heart. A bluish-gray blood flows into a flask. Air turns it cobalt blue. Lysate was selling for $15,000 a quart.

Chapter 8: "Flugate" [1976]

This chapter reminded me so much of the Trump Administration.

A young recruit at Fort Dix dies of a virus "known to be found in pigs from Asia." People wonder if it is the same as "the Spanish flu" of 1918, which killed "up to 40 million people worldwide."

Sargent claims "Flus tend to start in Asia, then spread quickly around the world. They arise when farmers pick up the viruses from their poultry."

Scientists must then figure out "the exact mix of H and N proteins so that pharmaceutical companies can start producing vaccines for the new strain."

"Occasionally, however, something happens that is far more insidious. Instead of being passed from birds to humans, the flu virus ends up in pigs. . . . to create a far more serious dangerous illness." The Center for Disease Control "started to call the new strain by a more ominous name, the swine flu."

But 1976 was an election year for Gerald Ford. What better way to show what he could do than to "vaccinate every man, woman, and child" against the swine flu.

"The federal government urged pharmaceutical firms to start churning out massive quantities of vaccine." It took about 200,000 fertilized eggs to produce about 250 gallons of vaccine. Ford even convinced Congress to accept any liability.

"Then something went wrong. Ten days after the program's inception, people started to get sick from the shots. They developed fever, paralysis, and neurological disorders. Clearly, some vaccines had become contaminated by pyrogens. . . . Fifty-two people had died, six hundred had been impaired, and the government faced $1.7 billion dollars in lawsuits."

And "nothing became of the pandemic. . . . Not a single case of swine flu was ever reported outside of Fort Dix."

What does this have to do with horseshoe crabs? It was right after this that they found out that "the horseshoe crab test was faster, cheaper, easier to use, and several times more sensitive than the rabbit test." Rabbit colonies were dismantled and the crabs became valuable.

Part III: Environmental Conflicts
Chapter 11: Fishing for Bait: The Conch and Eel Fisheries

Fisherman could pluck mating crabs off the beach and stack them like cordwood. There would be hundreds of thousands of rotting corpses. The stench caused neighbors to complain. So it was smell rather than science that caused regulations to be put in place and enforced. Also, the economic value of horseshoe crabs helped to cause protections to be put in place. Lessons learned on how to save the environment. People are hard wired to care about the moment, food on the table, money coming in, and not too much about hard shelled crustaceans.

Chapter 12: A Day at the Beach: Red Knots and Horseshoe Crabs [Reed's Beach, New Jersey, May 29, 1985]

Red knots spend the summer above the Arctic Circle and the winter on Tierra del Fuego. In March they land in Brazil to feed on snails. They double their weight in a month and fly over the Atlantic to Dover Bay. They are now thin and emaciated. Their migration is timed perfectly to coincide with the phases of the moon and the breeding of horseshoe crabs.

They will spend two weeks on the beaches. Each bird eats 135,000 eggs. All together they gorge on 248 tons of fat and protein. The eggs are critical to the survival of the red knots.

Chapter 13: The Atlantic States Marine Fisheries Commission [Washington, D.C., 1996 to 1999]

This chapter discusses the battle between environmentalists and recreational fishermen. I keep repeating this to everyone I know. Regulations are necessary. The drop off in horseshoe crabs was dramatic. Something needed to be done. In the long run, laws and preservation benefit everyone.

We need to take the word "conservative" back from the so-called "conservative" movement because there is nothing conservative about it. It is a destructive disaster.

[Ellie · Rating 5 out of 5]

Loved this book so much! Although it was released in 2001, the history on Horseshoe Crabs and the Lysate industry that it constains is super interesting! Would highly recommend this book to anyone interested in Horseshoe Crabs!

[Darcey · Rating 4 out of 5]

This is a book about horseshoe crabs. It talks about their life cycles, their habitat, their unique biological properties, and their place in the ecosystem. But most of all, it talks about their commercial uses, and the environmentalist efforts to keep them from being fished out of existence. It was surprisingly worth reading.

From this book, I learned that horseshoe crabs have been around since before the dinosaurs, and they retain many "primitive" evolutionary features. One of these is their unique primitive immune system, where special blood cells surround invading bacteria and coagulate in order to destroy them.

Sometime in the 1960s, scientists discovered that you could use these special blood cells to make a solution, called lysate, which could be used to test for Gram-negative bacteria. (Gram-negative bacteria are a particularly dangerous type of bacteria; if they enter the bloodstream, they can cause sepsis.) The discovery of lysate was really important, since pharmaceutical companies needed to test vaccines and other medicines to make sure they didn't contain Gram-negative bacteria. Prior to lysate, they did this by injecting the vaccines into live rabbits and seeing if any developed a fever; this required keeping massive quantities of live rabbits in the drug-producing facilities. The introduction of lysate meant that pharmaceutical companies no longer needed to keep and kill all of these rabbits.

I would have thought that, once lysate was invented, companies would start producing it synthetically. Or maybe companies would keep big factory farms of horseshoe crabs in order to make it. But to my surprise, that's not how lysate is produced. Instead, it's made from wild crabs. Collectors go out to the beaches, take the crabs, and bring them to facilities for "bleeding". This is where you take a needle, stick it into a horsehoe crab's heart, extract some of the blood, and then return the horseshoe crab to the wild. So there are entire large facilities which bleed hundreds of wild crabs each day. I had no idea that anything like this existed, and was fascinated to learn it.

For the most part, bleeding the horseshoe crabs is a non-fatal process. The crabs are weakened, but most of them should be able to survive. But the lysate industry was still having environmental impacts. Enough crabs were dying that it was depleting their numbers. And the lysate facilities needed more crabs than the local beaches could provide, so they were trucking them in from out of state. Due to the distance of transport, these out-of-state horseshoe crabs were much less likely to survive.

But it wasn't just the lysate industry depleting the crab's numbers; fishermen also liked to catch them in order to chop them up and use them as bait. Between the lysate industry and the fishermen, the population of horseshoe crabs was severely declining. So environmentalists started fighting for regulations that would control the use of the crabs. The book described the back-and-forth as environmentalists fought for and won new regulations, but old regulations went out of effect, and the fishermen continually searched for loopholes to the rules. The book ended on a hopeful note, suggesting that the new regulations were actually proving effective, and were preserving the horseshoe crabs and restoring their numbers. Protecting them is essential partly for environmental reasons (for instance, a shorebird called the red knot eats their eggs during its passage from South America to the Arctic), and partly for public health reasons (since using live horseshoe crabs remains the only viable way of making lysate).

Anyway, I learned a lot from this book, both about horseshoe crabs themselves (did you know they have copper-based blood?!?!); and about how the lysate industry got up off the ground, and how it operates; and about the sort of legislative battles that go into protecting a given species. And I learned about the lives of field biologists, and professional crab harvesters, and the people who live on islands and run crab-bleeding facilities. It was one of these books that gave me a glimpse into how a totally other part of the world operates. Prior to reading it, I had no idea that any of this existed.

[Russ · Rating 3 out of 5]

A somewhat rambling account of the quest to make lysate from the cobalt blue blood of the horseshoe crab. There's a bit of science that explains how a primitive immune system was used to test for bacteria, rather than having to use live rabbits. Then there follows the account of the demise of the horseshoe crab, how that affected migratory bird populations that feed on their eggs, and what the future holds for one of the oldest living organisms on the planet.

[Laurie Cybulski · Rating 4 out of 5]

The dated style of this book wasn’t enough to detract from the story and modern history of horseshoe crab fishing.

The best chapters in the book are at the end where Sargent summarizes the establishment of preserves and the lawsuits that followed. I’m a bit horrified that I wasn’t following these stories then.

The books was written in 2001. Radiolab did a podcast on the crabs in 2020. I need to find the stuff in between.

[Stephen · Rating 4 out of 5]

This is right up my alley. Bill is a classmate, though I don't think I knew him. The horseshoe crab wars were/are so economically paltry, so medically critical, and so ecologically catastrophic that this is a nice picture of humanity writ small. Avaricious, idealistic and inadvertently destructive of something we didn't even know about until it was almost too late.

[Dane · Rating 3 out of 5]

The book gets 5 stars if you want a history of the “blood harvest”, the taking of horseshoe crabs blood. But the author was annoying with his opinions that seemed spiteful towards conservationists who are trying to save horseshoe crabs and the species who depend on them.

[Warren · Rating 4 out of 5]

This is a fascinating story of the history of the commercial uses of horseshoe crabs. From bait for conch fisherman to a blood source for medical companies who produce an indicator of harmful bacteria, the story of the harvest of this crab is well told. This is another example of the struggle to balance commercial use against environmental preservation. The crab is a part of an ecosystem that includes birds which migrate 8000 miles from the tip of South America to the arctic and depend critically on crab eggs as a fuel source to complete this trek. The only drawback is that the book was published in 2006 and leaves one wondering about the current health of the horseshoe crab stock. Oh well, this has prodded me to dig further to learn about this million year old creature.

[Amy · Rating 1 out of 5]

Had you ever seen horseshoe crabs wash up on the shore when you were younger? They aren't around anymore. This book explains why they've disappeared: they are being harvested for their copper-based blue blood which is used in medical testing to determine whether medicines are safe. The book is short and a bit choppy at times, but it raises some excellent points about science vs. nature and the biologists involved on either side of the dividing line.

It's too heavy on the business aspect of the "bleeding" industry, though. I wanted more info about the environment. Oh well.

[Everett · Rating 3 out of 5]

It's 2012, Sargent should be adding a post-post script. Has synthetic Lysate been developed? How have the crabs been doing since 2001? The author does an excellent job of speaking up for them without being inconsiderate of the people behind the industry, whose livelihood depends upon the crabs exploitation.

I myself have noticed a decline in horseshoe crabs over the past 30 years when I make my yearly visit to my birthplace in Stone Harbor, New Jersey. They are lovely little things and I am sorry to see them being exploited for our species advancement.

[Fishface · Rating 4 out of 5]

The true story of the enormous medical industry, and the associated shady machinations that sprang up around the humble Horseshoe Crab after someone discovered that a simple, powerful medical test could be made from the Crab's blood. Written by a true Crab aficionado who, by the way, is also a science writer.

[Tom · Rating 4 out of 5]

This book was incredibly fascinating. Not only was it very informative about horseshoe crabs, but it had all sorts of information about immunology, swine flu (the 1976 scare), bait markets, and bird migrations. A nice short read about a wonderfully simple and ancient animal.

[Chad · Rating 2 out of 5]

Guy didn't really have the chops to write as well as he wanted, and the structure was lacking. But it's a science book, so/there was as much information about horseshoe crabs and the horseshoe crab business as you would expect in 120 general interest pages.

[Diana · Rating 2 out of 5]

Somewhat stilting in its writing and overly prostelitizing in its message, still an interesting account of the fate of the horseshoe crab.

[Laura · Rating 4 out of 5]

The book was really choppy and jumped around a lot, but it was very interesting! I had no idea horseshoe crabs were so important.

[Abhishek · Rating 4 out of 5]

Wonderful when it dips into storytelling, dry when it lists agencies, court cases and names - but packed in such a small package this is a feat and I'm glad to have read it