Placeholder Image

字幕列表 影片播放

  • Every year hundreds of thousands  of horseshoe crabs arrive on the  

  • beaches of the Atlantic coast  of America to lay their eggs.  

  • And every year, hundreds of thousands  of horseshoe crabs are rounded up and  

  • brought to the lab - not to be killed, but  for their blood to be carefully extracted.

  • These animals, often called living fossils, are  one of theoldestcreatures on the planet.  

  • They have remained nearly unchanged since they  first appeared on earth over 450 million years  

  • ago. This is due to some exceptionally effective  adaptations, and genes that code for remarkable  

  • molecules that have allowed the horseshoe  crab to survive, just as it is, for so long.

  • One of these ancient compounds is the reason  that hordes of these animals are dredged up  

  • from the ocean, jabbed with a hypodermic  needle, and their blue blood drained,  

  • processed, and sold. Their blood, made blue from  a copper-based oxygen-carrying molecule, is so  

  • valuable that it is the basis for a multi-million  dollar pharmaceutical industry. So valuable,  

  • that a single liter of it goes for around $16,000  - one of the most valuable liquids on earth.

  • Our reliance on these animals puts  immense pressure on a fragile ecosystem,  

  • and so far, scientists have struggled to  recreate this compound and its effects  

  • in the lab. What is it about this  primitive compound that we need  

  • so badly, and why can we only seem  to get it from this one creature?

  • The American horseshoe crab (on screen: Limulus  polyphemus) is an ancient, aquatic arthropod.  

  • They belong to their own class of animals, called  Merostomata, and are not actually crabs. They are  

  • more closely related to scorpions, with their  predecessors diverging from their arachnid  

  • cousins around 480 million years ago. Some  recent studies even suggest they are arachnids.  

  • The modern horseshoe crab as we know it has  technically only been around for 20 million years,  

  • but some of its early relatives, like Limulus  darwini, existed around 150 million years ago,  

  • and look nearly indistinguishable  from today’s horseshoe crabs.  

  • The iconic body plan has been around even longeremerging around 450 million years ago. The  

  • changes within the horseshoe crab group have been  shockingly minor in the big picture of evolution.

  • Here’s some perspective on just how long ago  horseshoe crabs came into existence. Pangea,  

  • the supercontinent of the past formed 335  million years ago and began to break apart  

  • about 175 million years ago. The non-avian  dinosaurs emerged 245 million years ago,  

  • and were wiped out 66 million years ago. The earth  descended into, and emerged from, 2 completely  

  • different ice ages since these crabs came aboutThe world has changed so much since then. And all  

  • the while horseshoe crabs have been here, crawling  along the seafloor, standing the test of time.

  • Some of the reason natural  selection has preserved them,  

  • pretty much as they are, is their hardy body plan.

  • Their hard shell, called a carapace, is an  exoskeleton so strong that only sharks or turtles  

  • can penetrate it. And guiding them through the  ocean depths are 9 eyes - 2 compound eyes which  

  • act much like our own eyes, 5 secondary simple  eyes on top of their shell which can detect UV  

  • light, and 2 ventral eyes located on their  underside, perhaps to help with orientation.  

  • Along with their complex circulatory system, 5  pairs of gills, and 12 bristled legs, evolution  

  • created them to be creatures extremely well  adapted to their particular environmental niche.

  • But beyond the physical traits that we can  observe, much of their survival is due to  

  • something we can’t see - their incredible, but  simple immune system. It’s protected them as a  

  • species from bacterial infection for eons. It  works in an entirely different way from ours,  

  • and in the late 1960s, we began to  harness its power for ourselves.

  • In 1968, two researchers at the  Marine Biological Laboratory in  

  • Massachusetts observed that blood cells  from horseshoe crabs vigorously clot in  

  • the presence of bacterial endotoxinWhen they published their paper,  

  • they had no idea that what they found would  revolutionise drug safety testing forever.

  • Pretty much every creature in the  world is vulnerable to bacterial  

  • infection - and the horseshoe crab is  no exception. Once an infection begins,  

  • bacteria can reproduce quickly, and many give off  toxins which damage specific tissues in the body.

  • Botulism, for example, is an illness caused byneurotoxic protein produced by a bacteria called  

  • Clostridium botulinum. The toxin can affect  your nerves, paralyze you, and even kill you.  

  • Toxins like this are called exotoxins. They  are released from live bacteria into the  

  • surrounding environment during an infectionBut, bacteria don’t have to release these  

  • exotoxins in order to be dangerous. In  fact, they don’t even have to be alive.

  • Once a bacteria is killed within the  body, they sometimes release endotoxins.  

  • Endotoxins are the lipid portions of  lipopolysaccharides (LPSs) that are  

  • part of the outer membrane of the cell wall of  some bacteria. The endotoxins are released when  

  • the bacteria die and the cell wall breaks apartThis toxin is a pyrogen - a fever causing agent.  

  • If it gets into the bloodstream, it can  lead to septic shock, and can be deadly.

  • But, fighting off these types of  infections is what immune systems are for.  

  • Immune systems have developed  to protect all different kinds  

  • of organisms from foreign pathogensAnd during the course of evolution,  

  • two different kinds of general immune system  emerged within multicellular organisms.

  • Humans and many other vertebrates have adaptive  immune systems that protect us by strategically  

  • mounting a defense against invading bacteriaIt is activated by exposure to pathogens, and  

  • uses an immune memory to learn about the threat  and enhance the immune response accordingly.

  • But many invertebrates, including horseshoe  crabs, don’t have this adaptive immunity. Instead,  

  • they have an innate immune system, which attacks  based on the identification of general threat.

  • The basis for a horseshoe crab’s immune  response are cells called granular amoebocytes.  

  • When bacteria come into contact  with a horseshoe crab’s blood,  

  • they trigger an enzyme cascademediated by these amoebocytes,  

  • which causes the blood in the immediate area  of the infection to clot into a gel. The gel  

  • surrounds and isolates the infection from the rest  of the crab, and the pathogens are neutralized.

  • The clotting from granular  amoebocytes is a simple,  

  • but very effective way for the horseshoe  crab to defend itself from infection.  

  • And, as researchers began to realize in  the 1960s, it’s a very effective way for  

  • us to detect the presence of toxins in places  where we really, really don’t want them to be.

  • When creating injectable healthcare products  like vaccines, medical implants, and IVs, it is  

  • imperative that they are free of any invading  microbes. It’s easy enough to sterilize the  

  • solutions or devices by blasting them with heatradiation, or gas that is deadly to bacteria.  

  • But killing bacteria isn’t enough to make these  products safe. If certain bacteria was present  

  • before sterilization, the endotoxin will remainand can lead to severe consequences if injected.

  • Historically, pharmaceutical companies  got around this problem with huge colonies  

  • of rabbits - needed for what’s  called the rabbit pyrogen test.  

  • To see if a product or drug is contaminated  with endotoxin, three (unlucky) rabbits would  

  • be injected with a small amount of the  drug or product in question and monitored  

  • for four hours. Rabbits have a similar pyrogen  tolerance to humans, so if any develop a fever,  

  • the batch would be considered to be contaminated  with bacterial endotoxin. This is an effective  

  • way of preventing endotoxins from accidentally  being injected into the public, but because it  

  • is an in-vivo test - meaning done inside a living  organism- it’s very time-consuming and expensive.

  • So when researchers noticed the  clotting effect of the horseshoe  

  • crab’s amoebocytes in the presence of  endotoxin, they realized it could be  

  • an in vitro way of spotting contamination  - a much cheaper, easier, and faster test.

  • This in vitro test is called the LAL test  - limulus amoebocyte lysate. Limulus being  

  • limulus polyphemus, the american horseshoe crabThis test has become the worldwide standard for  

  • screening for bacterial contamination. It is  capable of detecting endotoxin at significantly  

  • lower levels than the rabbit pyrogen testToday, every drug certified by the FDA must  

  • be tested using LAL, as do surgical implants  such as pacemakers and prosthetic devices.

  • After the horseshoe crabs are  brought to the lab, the tissue  

  • around their heart is pierced with a needle  and up to 30 percent of their blood is drained.  

  • The amoebocytes in the blood are then  extracted from that for the LAL test.

  • Upon exposure to endotoxins, the  amebocytes undergo a rapid enzyme cascade  

  • that causes the cells to stick  together and form a thick clot.  

  • This clot can form in around 90  seconds, giving a nearly instant result.

  • Weve never found anything that is as  sensitive in detecting endotoxin than  

  • the horseshoe crab’s amoebocytes. If there  are dangerous bacterial endotoxinseven  

  • at a concentration of one part per trillion  - a clot will form and can be detected.

  • This is great news for us. Pretty much every  single person who has ever had an injection  

  • of any sort has been protected because of this  compound from this strange, ancient creature. The  

  • only problem is that for this test to be readily  available, pharmaceutical companies need a large  

  • supply of the blood of live crabs - which, as  you’d guess, is not such great news for the crabs.

  • In theory, the process of extracting blood  from the horseshoe crabs does not kill them.  

  • It’s sort of like blood donation, albeitnonconsensual one. And once their blood is taken,  

  • the crabs are released in a new location so they  do not accidentally get caught a second time,  

  • ensuring they have a chance to recoverTheir blood volume rebounds in about a  

  • week - and the LAL industry states that there  are no long term ill effects for the crabs.

  • They measured mortality rates of less than 3%.  But conservationists tell a different story.  

  • Between 10 and 30 percent of the bled animalsaccording to varying estimates, actually die.  

  • And 30% of the animals per year dying equates  to losses in the hundreds of thousands.

  • And this isn’t just bad for the horseshoe crabbut for the entire ecosystem in which they live.  

  • Many other species of animals rely on  the horseshoe crabseggs for food,  

  • like shorebirds and turtles.

  • So the obvious question is - why haven’t  scientists made a synthetic alternative to LAL?

  • Since the 1970s they have certainly  been trying - and luckily for the  

  • crabs they have started to have some success.

  • In 1995, scientists from the National  University of Singapore were finally able to  

  • identify and isolate the gene responsible for the  endotoxin-sensitive protein called Factor C – the  

  • most important component in the LAL testand  produce it in yeast. Several years after that,  

  • they were able to create a rapid endotoxin  test based on this recombinant protein.

  • But despite these advances, these synthetic  tests are still not widely available.  

  • They have been adopted extremely slowly  due to regulatory and safety concerns.  

  • Europe did not recognize the synthetic protein  as an alternate endotoxin detection until 2015,  

  • and the FDA in the US did not approve the first  drug that used an endotoxin test based on the  

  • synthetic protein until 2018. And earlier this  year, the American Pharmacopeia, which sets the  

  • scientific standards for drugs and other products  in the U.S., declined to place the synthetic  

  • protein on equal footing with crab lysateclaiming that its safety is still unproven.

  • For now, we still need the horseshoe  crab and their baby blue blood.  

  • But as more and more studies come out that  demonstrate the safety of the synthetic  

  • version of the endotoxin test, the horseshoe  crabs can breathe a bit of a sigh of relief.  

  • While they still face threats from  overfishing for bait and habitat destruction,  

  • the adoption of this technology will  relieve at least one major pressure.

  • Our medical need for horseshoe crabs is what has  started to push these animals towards extinction  

  • in recent decades, but this is not the first time  they have faced such a profound threat. Since the  

  • first days of the horseshoe crab’s ancestorthey have faced - and survived - all FIVE  

  • mass extinctions. These extinction events  are defined as the loss of least 75 percent  

  • of species, happening in the geological blink  of an eye. Volcanoes erupting, oceans warming,  

  • ice sheets forming, or oceans acidifying  - the great die-offs result from a perfect  

  • storm of multiple calamities. The horseshoe  crab and its ancestors were one of the few  

  • creatures to survive - but if so many things  die, how does life rebound to flourish again?

  • This is the question that researchers at the  University of Oslo are trying to understand,  

  • and is the focus of the documentaryBreakthroughRecovering From Extinctionon CuriosityStream.  

  • They are pioneering an investigation  about what survived, and what emerged  

  • after the largest mass extinction on  our planet, 252 million years ago..

  • This is one of many paleontology documentaries  on CuriosityStream, which are all really good.  

  • And now, CuriosityStream has partnered  with us to offer an incredible deal.  

  • By signing up to CuriosityStream you now also get  a subscription to Nebula. Nebula is a streaming  

  • platform made by me and several other educational  YouTube content creators. It's a place where we  

  • can upload our videos ad free, and a place where  we can experiment with new, original content.

  • The original content is the best part of Nebula.  

  • Series like the Logistics of D-Day, or  the gameshow Money made by Tom Scott,  

  • or Brain Craft’s series Questionable  Advice. Series you can’t get anywhere else!

  • So by signing up at  curiositystream.com/realscience,  

  • you will get a subscription to CuriostyStream  and a subscription to Nebula, for just $14.79  

  • for the entire year. Signing up is also  the best way to support this channel,  

  • and all of your favorite  educational content creators.

  • Thanks for watching, and if you would like to  see more from me the links to my instagram,  

  • twitter, and patreon are below.

  • you

Every year hundreds of thousands  of horseshoe crabs arrive on the  

字幕與單字

影片操作 你可以在這邊進行「影片」的調整,以及「字幕」的顯示

B2 中高級 美國腔

为什么马蹄蟹血如此珍贵(Why Horseshoe Crab Blood Is So Valuable)

  • 5 1
    joey joey 發佈於 2021 年 06 月 09 日
影片單字