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My last post was about purple bacteria. Keeping the color-science theme, this week I’d like to discuss a liquid which is blue, important, and very, very expensive.
A gallon of this liquid costs more than twice as much as Chanel No. 5 per gallon, which will cost you only $26,000. Yep. A gallon of this blue stuff will set you back $60,000 and it won’t smell nearly as nice.
The liquid? Horseshoe crab blood.
Ewww. What do you do with this liquid? It’s certainly not for drinking, and it is not used for watercolor painting. The recent video below from Business Insider tells the story well. If you are more interested in the science, also watch the video which follows.
Business Insider video
Scishow video
If you saw the videos (and really, it only takes a few minutes to see them both, and this critter has been around for 450 million years - do the math!), you now know that if you have ever had any sort of injection, your life may have been saved by this liquid. You also know that the supply of horseshoe crabs is limited and is falling. It's unclear how many of the crabs survive the bleeding.
This story is particularly meaningful to me as a Bay Stater who has spent many summers visiting Cape Cod and noting the decline in the number and health of horseshoe crabs quite personally.
A recent story from the Audubon Society talks about a heroic effort to create a synthetic alternative. It’s a project that may improve the function of the test aided by horseshoe crab blood and help protect this ancient animal from extinction after surviving for 450 million years and all sorts of dangers (but perhaps not surviving human intervention).
https://www.audubon.org/magazine/summer-2018/inside-biomedical-revolution-save-horseshoe-crabs
The problem solved by the crab’s blue blood goes something like this: When gram-negative bacteria like E. coli die, they shed endotoxins, which are everywhere—in water, soil, the human intestinal tract. Danger arises when high concentrations of the potent poisons enter a person’s spinal fluid or bloodstream, potentially causing fever, respiratory distress, septic shock, organ failure, and even death. As a result, injected drugs (for people and their pets) or implanted medical devices that come into contact with blood must be tested for endotoxin.
Horseshoe crab blood, exquisitely sensitive to endotoxin, clots in its presence. LAL, the assay made from horseshoe crab blood, ensures that millions of heart stents, pacemakers, joint and cataract replacements, and radioactive tracers in PET scans, along with millions of doses of flu vaccine, insulin, and intravenously delivered antibiotics and chemotherapies, are free of endotoxin. Manufacturers also must test the water and raw ingredients used in their manufacturing. To keep up with demand, companies that make LAL capture and release some 500,000 horseshoe crabs along the eastern seaboard of the United States every year. In Asia, most bled horseshoe crabs are ultimately killed.
Enter: Jay Bolden, a tall, thin scientist who seems to disappear in his lab coat. He works in a sparkling new lab at Eli Lilly’s sprawling technology development center in Indianapolis. For the last five years, in his lab far from the sea, he’s been steadily working to develop a product that will take biomedical pressure off horseshoe crabs. Building on research carried out in Singapore, and continued in Maryland, he’s been compiling evidence that a synthetic enzyme, recombinant factor C—rFC for short—can replace horseshoe crab blood in endotoxin tests. According to his work, rFC works just as well as LAL, is more efficient and cost-effective, and doesn’t require a live animal. “It will benefit Eli Lilly,” he says.
Bolden is a birder (a person who observes and photographs birds). It turns out, as is almost always the case in nature, that the horseshoe crab does not stand (or rather, crawl) alone. If it fails as a species, other species fail as well. In particular, birds such as the Red Knot rely on the eggs of the crab for sustenance in their migration pattern. This further motivated Bolden. From the article:
Bolden, aware that Asian horseshoe crabs taken for biomedical use are often bled to death, became concerned about “supply problems down the road” when he learned that Eli Lilly was planning to build a second manufacturing plant in China, one that would make insulin, which requires endotoxin testing.
“Here,” he recalls thinking, “I can have an impact. I can make a difference. I can be part of conservation.” His vocation and avocation came together.
If Ding in Singapore had started this relay to end the practice of bleeding horseshoe crabs, and passed the baton to Lonza’s Burgenson, then Bolden was ready for his turn at the track. But this lap, like the others, would take time. He pitched an Eli Lilly vice president on using rFC, and with his support, then sought approval from two of the company’s governance committees: the specifications committee, dealing with quality control, including tests for endotoxin, sterility and pH, and the water committee. Tremendous quantities of pharmaceutical-grade water—some of Eli Lilly’s water tanks are 12 feet wide and two stories tall—are required to manufacture injectable drugs and vaccines.
“When we got the green light,” he says, “we were off and running.”
The Atlantic article, The Last Days of the Blue Blood Harvest tells the story of how Eli Lily became a company committed to synthesizing horseshoe crab blood.
There is another way though—a way for modern medicine to make use of modern technology rather than the blood of an ancient animal. A synthetic substitute for horseshoe-crab blood has been available for 15 years. This is a story about how scientists quietly managed to outdo millions of years of evolution, and why it has taken the rest of the world so long to catch up.
Click here to learn more about the project to synthesize LAL and reduce the impact on the ancient horseshoe crab (and the other species – including humans – which it supports).
A very recently-published description of the synthesis is below:
Recombinant Factor C (rFC) – a synthetic substitute for LAL – was developed by Dr. Ling Ding and Dr. Bow Ho of the National University of Singapore in 1997.
Until recently the manufacturing and patents for rFC were licensed to Lonza – one of four LAL manufacturers in the United States and one of three rFC manufacturers in the world. With the expiration of patent protection in the U.S., there is now an economic incentive for additional suppliers to begin producing rFC. In turn, the addition of new rFC manufacturers will end an important barrier to adoption for the pharmaceutical industry, which has been hesitant to transition to the synthetic alternative without a robust number of suppliers.
Lingering doubt on the efficacy of rFC has also been an important barrier to adoption of rFC. Although there is now abundant evidence that the efficacy of the synthetic alternative is equivalent to or better than LAL, adoption of new technology is difficult and change has come slow to the industry. Since the development of the rFC test, numerous studies have been conducted to evaluate its efficacy and comparability to the LAL test for a wide variety of potential applications. Revive & Restore synthesized these studies to demonstrate that all available scientific evidence suggests that commercially-available rFC tests detect endotoxins with equivalent of better efficacy than the LAL test. In fact, rFC signals fewer false positives, which can be costly when they occur in the manufacturing process.
Revive & Restore’s efficacy review was published on May 10, 2018. We are optimistic that this will lead the pharmaceutical industry to live up to industry sustainability tenets and make the switch away from the unnecessary use of animals in the production of injectable medications.
Source: https://reviverestore.org/horseshoe-crab/#synbio
Other references:
https://www.sciencedaily.com/releases/2010/10/101004101330.htm
https://www.businessinsider.com/why-horseshoe-crab-blood-expensive-2018-8
https://blog.frontiersin.org/2018/08/15/marine-science-horses
https://www.theatlantic.com/science/archive/2018/05/blood-in-the-water/559229/
The Atlantic article, The Last Days of the Blue Blood Harvest tells the story of how Eli Lily became a company committed to synthesizing horseshoe crab blood.
https://www.audubon.org/magazine/summer-2018/inside-biomedical-revolution-save-horseshoe-crabs
Video from PBS: https://youtu.be/e8KlAmtIu1E
Posted
by Richard Maltzman
on: November 24, 2018 09:40 PM |
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