The people of the world get into accidents and other traumas, some of which affect their spine, leading to spinal cord injuries (SCI). This damage to the spine leads to other disabilities like paralysis and lifelong back pain. These people with spinal cord injuries are more likely to die early and have a very high chance of being bed-ridden with some other complication of the injury. As for the treatment options, there are not many by traditional conservative medicine. Spine injuries are usually fixed by surgeries, and they, too, don't have a high success rate. So scientists are always on the lookout for some out-of-the-book solution that will help them understand the healing process and resolve the issues patients have been suffering; a treatment with no severe long-term complications, minimal hospital stay, and even minimal chance of relapse of the condition.
From horseshoe crab blood to limb regeneration in Axolotls, many inspirations can be found in marine ecosystems where animals show remarkable healing capacities. Another such example in marine life is lampreys. Sea Lamprey is a non-mammalian model for spinal cord regeneration. Nature has demonstrated successful regeneration for centuries, and Morgan et al. tested this capability by experimenting on sea lampreys. The team discovered that humans share genes with eel-like species that, if activated, could help us reverse spinal cord damage, even paralysis!
The horrifying subject
The lamprey in Latin means “stone licker” because of their characteristic long funnel-shaped face, with a mouth that pays homage to horror movies. Sea Lampreys are part of a very ancient lineage of the order of jawless fishes and are placed in the superclass of Cyclostomata. But they are not fishes; they belong to an ancient group which means they do not have scales, fins, or gills. Morphological records of this living fossil indicate that its physical features (size, shape, and structure) have been largely unchanged for about 400 million years.
There are 38 species of these fishes, and they are mostly parasitic. They bore holes in the skin of the fishes and suck their blood. They inhabit northern and western Atlantic waters. Some remain in the sea and some in freshwater, but some species move from the sea to the freshwaters for the purpose of breeding.
Lampreys are very famous in humans as food. Many kings and queens and aristocrats even were very fond of these jawless fishes. It is said that King Henry the 1 was so fond of them that he kept eating them well into his bad health against the advice of his physician. And is rumored to have died from an over-eating of lampreys. They are also very famous as pets, and they also have been part of folklore in Germany and Japan, where they were called “eight-eyed eels.”
But what makes them an interesting research subject is their extraordinary ability to regenerate. The lamprey has this ability to regenerate its spinal cord, and after regeneration, it starts swimming again as well.
It takes them around three months to repair and regain function after their spinal cord has been cut. Moreover, they can repair their cut spinal cord a second time at the same time as before.
What's even more important and interesting is that the genes that actively take part in the repair of the spinal cord in these lampreys are also found to be active in the peripheral nervous system of certain mammals.
Molecular recipe of spine regeneration
The first attempt to understand this extraordinary ability of regeneration was done by Dr. Selzer, who tried to translate this power of extraordinary regeneration into humans and in genetically engineered mice. But the added substances were inhibitory in nature and had no effect. That research was a dead end.
Research conducted by the scientist in the Eugene Bell Institute tells us how it is all done. They used RNA sequence to study the transcriptional profile of the spinal cords after the injury. The team took multiple samples from their brain and spinal cords multiple times during the regeneration of the cut spinal cord. Lampreys take some 10 to 12 weeks to fully regenerate their cut spine with full regain of the function.
The team found out that there were changes in the levels of transcription of different genes from the start towards to end of the regeneration process. This level of gene transcription is different as compared to the levels in lamprey with no spinal injury.
The author and Scientist at the Marine Biological Laboratory (MBL), Jennifer Morgan, say that “One of the most surprising findings from this study is the robust and complex transcriptional responses occurring in the lamprey brain after spinal cord injury (SCI). There were 238 newly differentially regulated transcripts in the spinal cord and 88 newly differentially expressed transcripts in the brain 12 weeks after the initial injury. As a result, dynamic changes in gene expression continue throughout the course of SCI recovery, even at late stages of behavioral recovery.” Morgan and her companions, Ona Bloom and Joseph Buxbaum, have been studying lampreys and their spinal cord recovery since 2009.
The study shows not a lot can be done to an injured spine externally; all the healing happens from within. And it was also seen by the scientists that the recovery has gene pathways like WnT involved. It is a pathway that works by negative regulation. An interesting thing here that should be noted is that this pathway is present in many species of mammals as well. The genes in this pathway are involved in cell proliferation and tissue development. And just to double-check, scientists at MBL treated the injured lamprey with some anti-Wnt. This test showed them that the lamprey could not regain the function of swimming after the regeneration.
And now the million-dollar question, is this research merely a curiosity quest that has led these scientists at the MBL to tediously and carefully record data and conduct tests? This research indicated that the expressed transcripts in the lamprey spine regeneration are also found in the peripheral nerves of mammals, and they carry out the function of repair as well. But the problem is that humans, when the spinal circuits are cut, do not grow back, and this is what is to be done to kick start the process of regeneration.
Spinal cord regeneration: Take two
In their recent research, the team found that the spine regeneration capacity in lamprey is not altered even after a repeated spinal cord transection. To test the resilience of regeneration in this non-mammalian vertebrate, the team cut its spinal cord in the same site for the second time. Jennifer and her team reported that the sea lampreys that had their spine severed twice recovered and regained normal swimming patterns “just as robustly as after initial spinal cord transection.” 11 weeks after second surgery and lampreys went from abnormal behaviors (like rapid head swaying, uncharacteristic body contractions, and smaller side-to-side swimming motions) to their standard swimming movements.
The team also acknowledges that while lampreys did recover their normal swimming patterns, the regenerated spinal cords didn’t return back to their pre-injured state. Instead, the lampreys showed remarkable nerve plasticity after both spinal cord injuries. The animal regenerated the transected and re-transected nerves in the spinal cords and formed a new network of synaptic connections between the nerve cells.
Humans and, if said broadly, mammals are complex creatures, and many processes are hard to understand and manipulate. While the lamprey is a simple creature with little blood, no bones, and few neurons, their simple organization might have helped them achieve this incredible power of healing. Perhaps there is more commonality to find between mammals and these ancient jawless fishes to use the understanding of repair to the advantage of mammals, say, humans. Perhaps someday, scientists might unlock the series of genes or that one master gene to help them understand the process properly.
Highly Conserved Molecular Pathways, Including Wnt Signaling, Promote Functional Recovery from Spinal Cord Injury in Lampreys (2018)
Regenerative capacity in the lamprey spinal cord is not altered after a repeated transection. (2019)
Nida Riaz is a freelance blogger based in Pakistan. She started writing about her passion for the environment when the world came to a stop in early 2020.