This Crab’s Blood May Have Saved Your Life

This Crab’s Blood May Have Saved Your Life


The horseshoe crab…it’s a living fossil
that has called Earth its home for almost half a billion years. It’s outlived dinosaurs and survived mass
extinctions and ice ages, but today it’s facing a new threat. Their adaptations have worked with the way
the Earth has changed and it’s only in recent years with humans bringing impacts to their
population that they’ve started to have declines. Rising sea levels, habitat loss and overharvesting
all threaten the population. But if you’ve ever had a vaccine, injection
or a medical implant, then you might not know that you’ve been relying on this prehistoric
creature’s blood to save your life. Now, after decades of waiting, a new synthetic
solution could change all of that. Here on our beaches on the Delaware Bay, it
is a place that people are witnessing a phenomena that they cannot see anywhere else. It is the equivalent of the wildebeests crossing
the Serengeti. In May and June here on the Delaware Bay where
we are right now, millions of crabs come out on a high tide to lay their eggs about six
inches deep in the sand, and they will stay in the sand and hatch in about a month. And horseshoe crab eggs are a really critical
part of the ecosystem here. If a single crab is laying almost 100,000
eggs, that is providing a food source for shorebirds, for gulls, for fish, for terrapins
and then all up the food chain for that. And then what happens with the horseshoe crabs
then trickles down to the whole ecosystem here. They just have managed to evolve with the
changing oceans and the changing land. The reason this crab has been able to evolve
for so long? Its blue blood. This copper-based blood contains special cells
called amebocytes, which are extremely sensitive to endotoxins. These are contaminants released from the cell
walls of harmful bacteria and they can cause life-threatening fever or toxic shock. As soon as the amebocytes detect any of these
endotoxins, the blood clots around the intruder, immobilizing it and protecting the crab from
infection. In the 1960s scientists found a way to harness
this unique superpower to make sure our medical supplies were free from contamination. And it replaced slower, more unpredictable
tests involving rabbits. The formula is called limulus amebocyte lysate,
or LAL, and relies on amebocytes taken from horseshoe crab blood. And so every year half a million crabs are
collected along the Atlantic coast, as well as across the eastern shores of Mexico and
China. A third of the crab’s blood is drawn before
they’re released back into the ocean. It’s estimated that 15% of crabs collected
die as a result of this bleeding process, which could mean the loss of 75,000 crabs
in the US every year. An alternative was found, however, almost
20 years ago here in Singapore. In the past say 20 to 30 years ago we managed
to collect 30 pieces in one afternoon, but now it is difficult to find even a few. In the mid-’80s Professor Ding Jeak Ling needed
LAL for work involving IVF embryos, but there was a problem. Singapore research was not very well funded. So because the LAL was so expensive, we had
to find a good way to understand how the horseshoe crab blood works. So, my research collaborator, also my husband,
together with our research students, went to the Kranji mudflats to look for horseshoe
crabs, and to bring a few samples back to the lab. We cleaned them, we tagged them, and we took
only a small volume of the blood, isolating the blood cells from the horseshoe crab and
we could produce our own equivalent of LAL. This synthetic equivalent is called recombinant
factor C, and it’s a clone of the main gene in a horseshoe crab’s blood, which is sensitive
to bacterial endotoxins. It was a moment of realization that it is
going to change the biomedical industry, and it’s going to save a very, very highly threatened
species. But the pharmaceutical companies didn’t
come around as quickly as Professor Ding had hoped. And so years and then decades passed. We’re a highly regulated industry. And to say we would like to market a new medicine…
a lot of people are reluctant to take a chance on trying something new. That’s until a scientist at pharmaceutical
company Eli Lilly with a particular hobby came along. Birding is a hobby of mine, so to go to Delaware
Bay and see the horseshoe crab spawning, it kind of put it all together for me. So the horseshoe crab is a keystone species
in its ecology obviously for its own sake but then for a lot of other animals that depend
on it. If we use RFC then there aren’t any crabs
that are affected, whether it’s mortality or whether there’s some behavioural effect
by taking the blood. Studies have shown that the RFC test is a more
effective and a potentially cheaper solution than LAL. Changing minds, however, remained the biggest
challenge. There’s been several times I was ready to
throw in the towel. So it’s been a difficult journey: to fight
internally, to fight externally. Nobody likes change but we think we’re doing
it for the right reasons. We have had success and we have the data at
the end of the day. Persistence paid off, and in 2018, the first
drug to use the recombinant factor C test was approved by the FDA, and Eli Lilly is
planning to transition 90% of its tests to the synthetic by the end of 2020. I think the consequence, if industry carries
on with bleeding crabs, is at some point there won’t be any. So there are real impacts to what we’re doing
and the longer we say, you know, they’ll be available forever… It’s likely not true. It is important that we as humans are playing
a role in protecting biodiversity and not impacting biodiversity. The synthetic version of the horseshoe crab
lysate used by pharmaceutical industry is going to have a major impact on horseshoe
crab conservation. It’s not the only factor that we need. We also need to continue with harvest limits
and with beach restoration. But reducing the need to harvest crabs for
the use of their blood will have a major impact.