The special blood of the lugworm
Innovation can be found in the places you would least expect. Have you ever looked at a worm and thought ‘this is a lifesaver’? No? Well, then you would be like almost everyone on the planet. But one curious biologist looked at a particular marine worm, a worm that had a previously hidden secret, and found that it could change medicine forever…
Squiggles in the sand: the calling card of a lifesaver
The lugworm is a curious little creature, an aquatic worm that made its appearance on Earth around 450 million years ago.
Lugworms (Arenicola marina) are polychaeta marine worms found in coastal regions of Britain and North-western Europe.[1] Their habitat are the sandy beaches, 20cm below the surface because the sand is still wet from the tide.[2] It even leaves its calling card on the beaches, the squiggles of feces on the beach in a little pile, known as casts.[3]
Avid anglers will know that these marine worms are commonly used as fish bait, most precisely for the seabass. But they have a more innovative and significant use in medicine. This use could change medicine and the treatment of those needing transplants…[4]
Medicinal properties: a ‘universal’ donor
They have a set of gills to breathe underwater and grow to be about 25cm in size. It is their respiration which holds the key, more specifically the way in which oxygen is carried in their blood.
Back in 2000, researcher Dr Franck Zal started looking into the miracles of Mother Nature, he knew that biology has the secret solution to many of our medicinal problems. He spent many weekends on the beaches in Brittany and the humble lugworm took his notice. The lugworm can hold its breath for six hours when the tide goes out, and Dr Zal wished to know more. He began looking at lugworms to research their properties, ultimately to see if there could be a secret to be unlocked in their blood. For context, this discovery was of real importance as in 2003 Madcow disease and HIV had led to a crisis in the shortage of blood supply across the globe.[5]
His hopes were high, and the results were fruitful. He found that his hypothesis was correct in that lugworm blood was compatible with that of human blood.[6] In human blood, oxygen is carried around by red blood cells containing hemoglobin, however lugworms have hemoglobin directly dissolved in the blood and not included in Red Blood cells.[7]
But if the blood differs from human, how is it useful for human medicine? Well, the blood of a lugworm is 40 times more oxygen-rich that the blood of a human.[8] The lugworm hemoglobin protein holds 156 oxygen molecules at a time.[9] It is for that reason that the lugworm is a universal donor for all human blood types.[10]
Dr Zal established his own biotech company, and trialled his product, HEMO2life®, with a major test from 2016 to 2018. After storing kidneys in HEMO2life®, 60 patients underwent transplants, and the patients recovered faster and had improved renal function compared to traditional electrolyte preservation furthermore, lifespan of the patient four years after transplantation was higher with HEMO2life®, 98.3% against 86% with the standard of care.[11]
This will improve the longevity of transplants, increasing the time for an organ to be donated and then transplanted.
Lugworm haemoglobin has continued to be used in transplants, including that of a full-face transplant. In 2018, Jérôme Hamon, became the first person ever to undergo a second full face transplant.
Discoveries lurking just beneath the surface: innovation within nature
We spoke to Dr Zal on our podcast. His sights are on the future, with one of his aims to use the lugworm blood to create safe and successful full blood transfusions. Dr Zal explained that the powder of haemoglobin from lugworm blood is combined PPI water to create the equivalent of a blood bag for a blood transfusion centre. This blood can keep the blood viable for 5 years at room temperature instead of 42 days and four degrees Celsius, for blood donation.
In 2019, Sir Peter Ratcliffe became Nobel Prize laureate for his discovery of how cells sense and adapt to oxygen availability, and Zal’s discovery delivered proof of this. The lugworm has learnt to take the dissolved oxygen from seawater and bond it to the haemoglobin molecule at low tide.
He left us with an important piece of advice for researchers and scientists within the life sciences: if you want to find innovation, return to the nature. He quoted da Vinci’s ‘Take inspiration from nature’. To Zal, biodiversity is the library of innovation. So, next time you are out at the beach, woods, dessert, or city, try to ask yourself questions that nobody has ever asked you about: Why is this tree here, why is this mussel here, why is this bird living here?
“Discovery consists of looking at the same thing as everyone else and thinking something different.” — Albert Szent Gyorgi
References:
[1] The Brackish-Water Fauna of Northwestern Europe, By R. J. Barnes, Richard S. K. Barnes. P.35
[2] The Brackish-Water Fauna of Northwestern Europe, By R. J. Barnes, Richard S. K. Barnes. P.21
[3] Wells, G. P. “The mode of life of Arenicola marina L.” Journal of the Marine Biological Association of the United Kingdom 26, no. 2 (1945): 197.
[4] Lodhi, Sirat*,†; Stone, John P.*,†,‡,§; Entwistle, Timothy R.*,†,‡,§; Fildes, James E.*,†,‡,§ The Use of Hemoglobin-Based Oxygen Carriers in Ex Vivo Machine Perfusion of Donor Organs for Transplantation, ASAIO Journal: April 2022 — Volume 68 — Issue 4 — p 461–470
[5] Mad Cow Disease Restricts Blood Donation (webmd.com)
[6] Rousselot, Morgane, Eric Delpy, Christophe Drieu La Rochelle, Vincent Lagente, Ralph Pirow, Jean‐François Rees, Agnès Hagege, Dominique Le Guen, Stéphane Hourdez, and Franck Zal. “Arenicola marina extracellular hemoglobin: a new promising blood substitute.” Biotechnology Journal: Healthcare Nutrition Technology 1, no. 3 (2006): 333–345.
[7] Toulmond, André. “Tide-related changes of blood respiratory variables in the lugworm Arenicola marina (L.).” Respiration physiology 19, no. 2 (1973): 130–144.
[8] Stam, Kevin. “The Long-Held Secret Of Lugworms.”
[9] Lugworm Blood, Coming Soon to a Pharmacy Near You | Hakai Magazine
[10] Animals to humans, how blood saves lives :: Understanding Animal Research
[11] HEMO2life as a protective additiv… preview & related info | Mendeley
