The Good, Part the First: Basic Science Offers Insights Once More. T cells, integral components of the immune system, are crucial for establishing self-tolerance and adaptive immune responses. These cells originate from the thymus, an organ in mammals that significantly reduces in size during a process known as involution in early life.
For many years, scientists have pursued a deeper understanding of how the thymus can regenerate. A recent study published in Science marks a significant breakthrough in our knowledge of vertebrate thymus growth and restoration:
Editor’s Summary. Although acute injury and age-related decline can result in diminished thymic and immune function, the adult mammalian thymus maintains a limited ability to regenerate. Czarkwiani et al. discovered that juvenile axolotls can completely regenerate their thymus after total removal. This thymic regeneration was linked to the restoration of morphological and transcriptional features. Interestingly, while the key mammalian thymic transcription factor FOXN1 is generally vital for thymus development, it proved to be non-essential for thymus regeneration. Instead, single-cell transcriptomics identified the growth factor midkine as a likely driver of the regeneration process. Future research on axolotls could lead to new therapeutic strategies aimed at encouraging thymus regrowth.
The study, while intricate, presents compelling arguments. Developmental pathways in vertebrates are significantly conserved, suggesting that though the amphibian model may not directly provide solutions, it outlines a potential path forward. For those steeped in traditional biology, the experimental model utilized in this research is particularly fascinating. The axolotl, often regarded as one of the cutest non-mammalian creatures, alongside other amphibians, sea urchins, starfish, and fruit flies, has long been a focal point in developmental biology, tracing back to the time when the field was termed embryology, prior to our understanding of genes.
Regrettably, like many species, the axolotl is currently classified as critically endangered, with its sole natural habitat confined to a small wetland in Mexico City:
An ancient wetland system of islands and canals that predates the Aztecs continues to endure quietly in Mexico City.
These wetlands, nestled within North America’s most populous city, harbor one of the most recognizable—and endangered—species on the planet: the axolotl.
Recent surveys have confirmed the fears of scientists and local residents alike: the charming salamander is nearing extinction in its natural habitat, primarily due to habitat loss, pollution, and the introduction of invasive fish species that prey on it.
Conducted by the Ecological Restoration Laboratory of the National Autonomous University of Mexico (UNAM) in collaboration with Conservation International-Mexico, this comprehensive survey covered 115 monitoring sites across the 2,500-hectare (6,180-acre) Xochimilco Protected Area, a UNESCO World Heritage Site renowned for its canals and farm islands, known as chinampas.
The University of Kentucky hosts the Ambystoma Genetic Stock Center, but ensuring wild populations flourish is crucial. The extinction of this one population in Mexico City would be irreversible.
The Good, Part the Second: Body-Produced Cancer Killer Cells Show Promise in Treating Multiple Myeloma. A significant advancement has been made in CAR-T cell therapy, demonstrating over twelve years ago that these engineered immune cells can be created within patients instead of in a lab and subsequently administered back to the patient:
Engineered immune cells that specifically target cancer cells can be lifesaving; however, timely treatment remains crucial. Traditionally, T cells are harvested from patients and modified through genetic manipulation—a slow and costly procedure. Developing the cells directly within the body promises to be a quicker approach, and initial clinical data indicate this method may be effective. In one of the first trials, this technique induced in vivo CAR-T cells in four patients with multiple myeloma, successfully clearing malignant cells from their bone marrow.
Presented at the American Society of Hematology (ASH) annual meeting, the results, while preliminary, are “truly impressive,” remarks cancer biologist Bin He from the Houston Methodist Research Institute, who is not involved in the study. This trial marks the second instance this year to report positive outcomes from in vivo CAR-T cells for multiple myeloma. In a previous study, patients experienced significant side effects, likely due to the viral vectors used to deliver necessary genes to the immune cells. Yet, in this new trial, complications were less severe, even with similar viral classes involved. “The question is no longer whether this can be achieved,” states Yvonne Chen, a cancer immunotherapy researcher at UCLA. “Now, the focus is on whether we can meet effective treatment levels and ensure patient safety.”
CAR-T cells, which were recognized as part of Science’s 2013 Breakthrough of the Year, were first approved by U.S. regulators in 2017 and have since become standard therapies for several blood cancers, including multiple myeloma. Specialized centers transform a patient’s T cells into cancer-fighting agents by exposing them to viruses that introduce the CAR gene. Researchers are actively exploring applications against solid tumors, autoimmune disorders, and other conditions.
However, some patients succumb to their cancers during the month it typically takes to produce CAR-T cells. Additionally, the treatment often costs hundreds of thousands of dollars, making it inaccessible to many. Before receiving the upgraded T cells, patients usually undergo risky chemotherapy to eliminate their natural T cells.
This context has heightened researchers’ enthusiasm for the groundbreaking potential of producing these cells within patients. “The field is progressively transitioning from ex vivo to in vivo CAR-T cells,” remarks immunobioengineer Matthias Stephan from the Fred Hutchinson Cancer Center.
Gene therapy has been a topic of interest for over three decades. The challenges associated with gene therapy are practical rather than theoretical. When using lab-created CAR-T cells, infusion can sometimes trigger an overwhelming immune response, putting the patient at risk. This risk is significantly reduced with CAR-T cells produced in the patient’s body.
Despite not fully resolving all issues with CAR-T therapy, the fact that these cells can be generated in situ eliminates the need for harvesting, modifying, culturing, and reintroducing them, simplifying the process, reducing costs, speeding up treatment, and likely enhancing safety.
Since the declaration of the War on Cancer by President Nixon in 1971, urged by the resolute Mary Lasker, this type of therapy was fervently hoped for, yet its attainment remained uncertain. However, as we move into 2025, we witness the results of sustained support for incremental research funded by institutions like the National Institutes of Health and the American Cancer Society. Such research does not conform to transient political climates, and it never will. Progress requires perseverance—likely out of every project that seems successful, many fall short, yet each failure teaches us valuable lessons contributing to cures like that for multiple myeloma.
Traditional CAR-T cells have allowed numerous multiple myeloma patients to prolong their remission periods for over five years. Whether the in vivo methods will deliver similar lasting results remains to be seen. Nonetheless, the field is advancing rapidly. “Patients should feel hopeful.”
Indeed, they should.
The Good, Part the Third: Tailored mRNA Vaccines Revolutionizing Cancer Treatment. Once more, the term mRNA arises in an article from Scientific American: Personalized mRNA Vaccines Will Revolutionize Cancer Treatment—If Funding Cuts Don’t Doom Them. In the coming years, there may be challenges ahead. However, breakthroughs are on the horizon, provided societal stability remains intact. Research on mRNA’s effectiveness against pancreatic cancer has been previously discussed and shows promising results!
Upon the removal of Barbara Brigham’s cancerous pancreatic tumor in fall 2020, a researcher was promptly alerted to assess the pathology department beneath Memorial Sloan Kettering’s main hospital in New York City. Now 79 years old, Brigham was recuperating until she could return home to Shelter Island, located at the eastern tip of Long Island. Meanwhile, her tumor and parts of her pancreas underwent an intricate 24-hour laboratory process. Hospital personnel assigned the tissue sample a unique identification number and bar code, extracting a small piece to be frozen at –80 degrees Celsius. They applied formalin to prevent any degradation and placed it in a machine that would gradually substitute the water in the cells with alcohol.
Next, laboratory staff affixed the pancreas to a foam block, employed a high-resolution camera for imaging, and meticulously excised tumor tissue into thin slices for examination. After detailing the tumor under a microscope, it would take more than 50 individuals’ expertise to navigate it through the lab processes. Yet, this was merely a prelude.
The real groundbreaking moment occurred approximately two months later, when Brigham returned to receive a vaccine specifically designed to target the mutations distinguishing her tumor from healthy tissue. This vaccine, comprised of messenger RNA (mRNA) encased in minute lipid particles, essentially provided her immune system with genetic instructions to identify and target the unique proteins produced by her cancerous cells. In essence, it was a personalized therapeutic intervention.
This narrative mirrors the CAR-T therapy journey, as in this instance, the patient’s pancreatic tumor—originally deemed life-threatening—was utilized to derive antigens which, through mRNA vaccination, enabled her body to recognize and combat the cancer. Remarkable! And while it shows promise, the challenge remains to ensure consistent efficacy in the treatments moving forward. Despite this potential, progress in mRNA therapy must not fall prey to the current societal stigma surrounding it.
The journey to this point is marked not only by tragedy but also by absurdity. While mRNA vaccines against COVID-19 have shown substantial effectiveness in mitigating disease severity, the communication surrounding their efficacy has been flawed. First, the tragedy:
If scientific and political leaders had been transparent, they might have stated: We can produce these vaccines rapidly and on demand, but we cannot guarantee their effectiveness against the pandemic due to the historical nature of coronaviruses in evading immune responses. Nevertheless, in conjunction with non-pharmaceutical interventions such as masking, social distancing, enhancing ventilation, and fast-tracking antiviral drug research, we could mitigate the pandemic’s severity while also advancing towards a long-term solution.
Now to the farce, where our current scientific and political authorities have thrust mRNA into a realm of scorn for various unfounded reasons. Despite the strong foundational principles of mRNA therapeutics since the late 1980s, this reflects a troubling trend in contemporary discourse:
Data from Brigham’s trial also indicated that mRNA vaccines may hold promise for a broad spectrum of cancers. While pancreatic cancer is often characterized by a low mutation rate, the initial findings on personalized mRNA vaccines originated from investigations into melanoma—selected due to its high mutability. An earlier phase 2 trial found that patients receiving a personalized mRNA vaccine alongside immune checkpoint inhibitors saw their risk of death or recurrence cut nearly in half compared to those treated solely with checkpoint inhibitors. Ongoing trials are focusing on kidney and bladder cancers as well as lung cancer, positioning the vaccine as an adjunct to surgery and standard therapeutic drugs. Its purpose is to prepare the immune system to detect abnormal proteins stemming from mutations and eliminate residual malignancies that might survive traditional treatments, subsequently alleviating recurrences.
The path forward seems fraught with obstacles before we illuminate the way ahead. There may be additional delays, but the dawn will inevitably emerge. We must consider how many lives may be lost during our indecision. Perhaps we will see innovations such as pull-up bars in airports; at least there’s that small comfort.
The Good, Part the Fourth: The Marvelous Strength of Spider Silk. Remarkably, the strongest spider silk known to exist is produced exclusively by female spiders. The tagline, “Bark spider silk is stronger than steel, though males produce a weaker variant,” exemplifies the ingenuity of nature.
Bark spiders exhibit exceptional engineering abilities, spinning webs that span entire rivers in Madagascar. Their silk, renowned for its superior strength, has been revealed through recent studies published in Integrative Zoology, showing that only females weave the most resilient webs.
Researchers conducted strength tests on the silk from two bark spider species (Caerostris darwini and C. kuntneri). Utilizing a microscope, they measured the silk strands’ diameter and then applied varying tensions until they broke. Evidence shows that the silk produced by female spiders can be more than double the strength of that made by males.
Biochemistry enthusiasts in the NC community will recognize the science behind spider silk’s impressive tensile strength. Examinations of the silk from bark spiders could lead to advancements in materials for skin regeneration after injuries or illnesses. Basic scientific inquiry continually enriches our understanding, even if predicting which research will yield practical results remains a challenge. Nonetheless, the very presence of spiders still gives me the creeps. Snakes? No problem. Yet, the sight of spiders makes me hesitant. That caver shown here demonstrates remarkable courage.
The Bad, Part the Fifth: The Persistent Dilemma of Plastic Pollution. We all recognize that plastic pollution is a blight on our planet. Yet, it’s vital to acknowledge that oil and gas companies are determined to transform fossil fuels into a growing mountain of plastic packaging and products to maintain their profit margins.
In 2018, at a resort in Dubai, Amin Nasser, CEO of Saudi Aramco, articulated his vision for the future before an audience of petrochemical executives. Rather than focusing on energy, he outlined plans to invest $100 billion to expand plastic and petrochemical production.
According to Nasser, with a growing global population increasingly capable of purchasing power, demand for petrochemicals—which include plastics and their components, making up about 80 percent of such chemicals—will contribute nearly half of the oil demand growth by mid-century. Nearly all virgin plastics are derived from fossil fuels. He asserted that “the tremendous growth in chemicals demand provides us with an excellent opportunity.”
Since then, Saudi Aramco has acquired a majority stake in the country’s petrochemical firm SABIC and has embarked on major plastic projects across China, alongside constructing new petrochemical plants from South Korea to the Texas coast. By the 2030s, Aramco plans to convert over a third of its crude output into petrochemicals—a substantial increase within just 15 years.
While the sector has framed its shift to plastics as a response to consumer demand for a material critical to modern living, it is evident that another motive is at play: as industries pivot away from fossil fuels due to climate-related concerns, they see plastic as a safeguard for profitability. Increasing production of plastic and petrochemicals, as Nasser suggests, will establish “a reliable destination for Saudi Aramco’s future oil production.” An industry analyst elaborated on the strategy, stating, “The overarching imperative is to avoid being forced to leave oil in the ground as demand for fuels declines.”
The Market remains oblivious to long-term consequences, despite our profound awareness of plastic’s dangers and the apprehension regarding its widespread usage:
Designed to resist decomposition, plastic breaks down into minuscule fragments that infiltrate our air, water, and food supplies. Scientists have detected these microplastics in human blood, semen, breast milk, bone marrow, and placentas. Only now are we beginning to understand the implications of these tiny particles for human health and environmental wellbeing. Recent research has uncovered microplastics in tissues from human kidneys, livers, and brains. Moreover, in a study of dementia patients’ brains, significantly higher accumulations were found compared to those without the disease. Subsequently, another study observed microplastics in neck-artery plaque in nearly 60 percent of participants tested; three years later, individuals with microplastics in their samples faced a 4.5 times higher risk of experiencing heart attacks, strokes, and mortality.
In my community, single-use plastic bottles remain rampant. A particularly egregious example is at my usual golf course, which, after renovations, replaced six water jugs meant for refilling personal bottles with branded plastic bottles filled with tap water—excessively ending up in landfills. My inquiries regarding this shift have generally been met with bewilderment.
The Ugly, Part the Sixth: The Enigma of Human Social Behavior. In A Headless Mystery, the findings reveal that a wave of mass brutality accompanied the decline of the first pan-European culture.
In 2017, archaeologists excavating a Slovak wheat field unearthed four headless skeletons. These burials belonged to one of Europe’s earliest farming communities, dating back over 7,000 years. While interring individuals near settlements was standard practice at that time, the absence of heads was not.
Year after year, researchers have returned to this site, uncovering increasing numbers of headless skeletons around Vráble, a village located 100 kilometers east of Bratislava. “Wherever we began digging, we stumbled upon bones. Regardless of where we stood or sat, we found remains,” notes Katharina Fuchs, a biological anthropologist from Kiel University (KU), who has participated in excavations at Vráble each summer since 2021. In the summer of 2022, she and colleagues managed to recover skeletal remains of 34 individuals, stacked atop one another in a space roughly the size of a parking spot. With the exception of one child, none bore heads.
This community, known as the Linear Pottery culture (or LBK), had descended from the people who initiated plant and animal domestication in Anatolia around 9000 B.C.E. By 5500 B.C.E., they had reached present-day Hungary and continued to propagate across Europe. The LBK farmers flourished for over 400 years, establishing settlements across a substantial stretch of fertile land reaching as far west as the Paris Basin.
Then, something went tragically awry. Vráble, alongside numerous mass graves scattered throughout Europe, indicates a surge of brutality around 5000 B.C.E., coinciding with the abrupt disappearance of countless LBK settlements across the continent. Following these events, vast segments of the continent remained uninhabited for centuries. Other communities transitioned peacefully, with continued agricultural activity, but altered housing and pottery styles. “The LBK represents the first farmers and the first large-scale pan-European culture, marking the first recorded instances of persistent violence,” observes Christian Meyer, an osteoarchaeologist specializing in LBK mass graves.
While we cannot truly comprehend the motivations of our early human counterparts from the Linear Pottery Culture who filled graves with headless corpses, characterizing their actions as brutal seems fitting. Inexplicable, indeed, yet not altogether uncommon even when viewed through the lens of contemporary standards.
Until next week!
