As a graduate student, I selected a mentor who was deeply committed to finding a cure for spinal cord injuries. He had survived a horrific car accident during childhood that left his family in tragedy; while he emerged unscathed, his sister tragically lost her life, and his mother suffered severe injuries. This pivotal moment ignited his lifelong quest to restore his mother’s mobility. He became a renowned researcher focused on unraveling the molecular processes that facilitate spinal cord regeneration.

His fascination with the growth of brain cells stemmed from the belief that understanding these mechanisms could potentially reverse nerve damage. Although his mother passed away before I joined his lab, his determination to assist others in similar situations remained undiminished. I was drawn to his lab, not just because of his unwavering passion, but also due to his innovative ideas. Among his theories is the intriguing notion that cancer could serve as a means to heal spinal cord injuries. Allow me to elaborate.

From Regeneration to Cancer When threatened, some lizards exhibit a remarkable defense mechanism where they shed their tails to escape predators, later regenerating the lost appendage. Humans, in contrast, possess limited self-healing abilities, particularly in regenerating complex tissues. This limitation has prompted scientists to investigate the genetic traits of certain animals to explore if we could enhance our healing processes. If we could mimic the regenerative capabilities of lizards, we might be able to regrow lost limbs, or if we took cues from zebrafish, we could potentially heal a damaged heart.

Sadly, our molecular genetics do not support extensive repair of critical injuries. Once a limb is lost, it is irretrievable, and significant cardiac damage often proves irreversible. However, we do have some regenerative capacity; for instance, skin cells can heal cuts due to their constant replenishment through cellular division. But this frequent regeneration carries a heightened risk of cancer.

Indeed, skin cancer constitutes roughly 40% of all tumors, making it the most prevalent cancer globally. This is because cancer results from uncontrolled cell division, and skin cells replicate frequently. Errors during cell division occur in about 2% of cases, which may seem negligible, but considering the daily division of skin cells, this error rate compounds. Statistically, there’s a 13% chance of a cell making an error during a week’s worth of divisions, escalating to nearly 99.9% over a year. Fortunately, not every mistake in cell division results in tumors, or we would face dire consequences.

The key takeaway is that a robust regenerative capacity and an increased cancer risk are interconnected — enhanced regeneration often leads to a higher likelihood of cancer. Some lizards have evolved unique anti-cancer adaptations to balance their regenerative abilities, whereas humans have not developed such mechanisms, thus limiting our capacity to regenerate limbs or mend severe injuries.

Regeneration in the Brain Our limited regenerative capabilities are particularly evident in the brain. With age, neurons lose the expression of genes responsible for synaptic plasticity, resulting in decreased flexibility. Consequently, young individuals can learn new languages effortlessly, while older adults may struggle for years without achieving fluency. This decline in cognitive adaptability is a common phenomenon as we age, with various learning processes becoming increasingly challenging.

While the decline in plasticity might seem disadvantageous, it is beneficial in some respects. In biology, the structure of cells directly correlates with their function. Disruption of neuronal structure, as seen in traumatic brain injuries, can lead to severe complications. Although our brains need to adapt for learning, excessive change can result in significant issues, affecting everything from memory to personality.

The structural stability of the brain, while advantageous, also limits its ability to rewire itself after injury. Severed spinal nerve cells cannot repair themselves, rendering severe spinal cord injuries untreatable. However, individuals with milder spinal cord injuries can fully recover, likely due to remaining nerves compensating for lost functions and retaining some growth capacity from their developmental stages.

Our spinal nerves never completely lose their ability to regenerate; rather, this capacity diminishes with age. This correlation between age and recovery rates from spinal cord injuries suggests that as we grow older, our chances of recovery decrease. Laboratory experiments further confirm this decline in growth ability as neurons mature. This realization prompted my mentor to propose a hypothesis: if genetic engineering could revert spinal cord neurons to a more youthful state, they might regain the ability to regenerate following injury.

Reactivating Regeneration Restoring severed nerves presents a straightforward solution for spinal cord injuries. However, the challenge lies in the intricate genetic expression networks that govern cellular function and development. Identifying the right genes to manipulate for the desired outcome is crucial, akin to navigating a room filled with countless dimmer switches where only a few control the lighting.

My mentor opted for a comprehensive approach known as high content screening. He compiled a list of genes that alter expression during neuronal development and utilized genetic editing techniques to overexpress these genes in millions of neurons. A specialized microscope and imaging algorithms allowed him to observe how each gene's expression influenced neuronal growth.

The findings yielded two significant insights: 1) genes that decrease in expression during development enhance neuronal growth when overexpressed, and 2) genes that increase in expression during development inhibit growth when overexpressed. Essentially, as neurons mature, they deactivate growth-promoting genes and activate those that inhibit growth. This process can be likened to easing off the accelerator and applying the brakes. While this revelation was not unexpected, it provided a solid foundation for validating the hypothesis that spinal cord nerves might regenerate if the growth-inhibiting genes could be turned back on, akin to a molecular fountain of youth.

Causing Cancer On Purpose Unfortunately, the concept of a fountain of youth is not feasible. The genes identified in the high content screen yielded minimal effects when transitioned from cell cultures to animal models. The underlying theory was sound, but the complexity of biological systems is often underestimated. Thus, my mentor returned to the drawing board, which coincided with my arrival in the lab. My initial task involved restarting the high content screening process, but with a novel twist — instead of pursuing rejuvenation, we aimed to induce a cancer-like state in neurons.

At first, this approach might seem counterintuitive, but it’s important to note that neurons cannot become malignant cancers like other cell types. Brain tumors, while serious, arise from glial cells, not neurons. Cancer occurs due to mutations that trigger uncontrolled cell division, but neurons are unique as they are terminally differentiated and do not divide. Therefore, neurons cannot directly cause cancerous tumors.

We theorized that genes associated with cancer might influence neuronal growth similarly to developmentally regulated genes. Specifically, we posited that creating a cancer-like environment in neurons could enhance their regenerative capacity. As previously mentioned, the relationship between strong regenerative ability and increased cancer risk suggests that cancer could potentially be harnessed to boost regeneration.

In line with this theory, I conducted my own high content screen focusing on genes frequently mutated in cancers. The results were promising, revealing nearly a dozen potential leads. However, with success comes complexity. We lacked the necessary tools to effectively test the impact of these cancer-inducing genes on neuronal growth. Our screening techniques relied on overexpression, but cancer-related genes are often underexpressed in tumor cells. We needed methods to disrupt the expression of these genes, which is more challenging than merely amplifying them. This led me to focus my thesis on employing CRISPR technology for knockout screening in neurons, a topic for another time.

From Cancer To The Future Whether cancer-like gene expression can stimulate the regeneration necessary to heal spinal cord injuries remains uncertain. Some initial results show promise, indicating that it could be effective when combined with other techniques. Looking ahead, I find the potential applications of this technology incredibly exciting. While I believe genetic editing, particularly CRISPR, is not yet suitable for human use, I envision a future where cancer-related epigenetics might be manipulated to enhance our body's regenerative capabilities or improve synaptic plasticity to boost learning.

At this juncture, the narrative lacks a definitive conclusion, but it fills me with optimism to know that dedicated and brilliant individuals are tackling some of the most challenging problems in the world. Although my mentor's mother passed away before he could assist her, he continues to strive toward his goal. Many individuals affected by lifelong disabilities stand to gain from his efforts, and I am confident his mother would be proud.