Introduction
The realm of biomedical science is ever-evolving, marked by groundbreaking technologies such as CRISPR. However, with great advancements come substantial responsibilities. This discussion explores the implications of gene editing trials, the surprising adaptations in plant evolution, and the intriguing genetic connections between Neanderthals and modern humans.
Part the First: If You Stretch Biomedical Science Too Far It Breaks, Every Time. Gene editing utilizing CRISPR technology has propelled biomedical science into new frontiers, earning Emanuelle Charpentier and Jennifer Doudna the Nobel Prize in Chemistry in 2020. The potential of CRISPR in treating genetic disorders is vast, but it necessitates careful and ethical application. Unfortunately, there have been tragic incidents that remind us of the risks involved: Once again, a child dies in gene-editing trial in China, rekindling debate on transparency and safety (HuidaGene, operating under relaxed regulations, was conducting a CRISPR trial on a boy with muscular dystrophy).
Last year, a lesser-known Chinese startup gained attention at the American Society for Gene and Cell Therapy’s annual convention in New Orleans.
During a presidential symposium, HuidaGene CEO Alvin Luk shared findings from one of the first trials assessing the effectiveness of CRISPR gene editing on children with Duchenne muscular dystrophy, a severe and fatal condition. Unlike U.S. initiatives that faced technical barriers, HuidaGene advanced rapidly, leveraging a regulatory framework that allows hospitals in China to initiate studies without extensive government oversight.
The outcomes from the initial two patients were underwhelming, and the therapy’s efficacy remained uncertain. However, Luk claimed the data suggested some benefit, prompting plans to test a higher dose, which was hoped to yield improved results.
Subsequently, HuidaGene ceased communication for 15 months, with no press releases issued. The CEO, Luk, quietly left, joined by Chief Technology Officer TJ Cradick, who had a brief tenure. In February, an update on a clinical trial registry indicated the study was “complete.”
The fate of the other participants remains ambiguous. However, following an extensive investigation by STAT and multiple inquiries, HuidaGene released an update.
The trial was halted after a young boy who received the experimental treatment passed away.
Fortunately, the cause of death was not directly attributed to the therapy itself. Instead, it stemmed from a severe immune response triggered by the viral vector dose (AAV, adeno-associated virus) employed in the treatment. This scenario echoes past tragedies, such as the death of Jesse Gelsinger in 1999, during gene therapy’s early trials, which was exacerbated by a high adenovirus vector dose, a risk likely not adequately considered beforehand.
While this incident raises significant concerns, broader issues in gene therapy warrant discussion. The early identification of disease genes led to the belief that such knowledge could directly translate to cures. This holds true in specific instances, such as with blood stem cells or liver-targeted therapies, which have proven effective for conditions like Hemophilia A and B (as mentioned previously here and here). In contrast, muscle tissue presents substantial challenges for gene editing, as delivering a functional dystrophin protein to the vast skeletal muscle network remains unattainable due to size limitations of viral vectors, necessitating the use of a mini-dystrophin.
Thus, while gene editing may serve as a promising intervention, achieving true cures remains elusive, particularly for skeletal muscle-related diseases, until improved technologies emerge. Whether HuidaGene’s protocol should have received approval is a question for Chinese regulatory bodies to consider. However, failures like those discussed here do little to cultivate public confidence in the scientific community, a matter for my colleagues at the forefront of research to reflect upon.
Part the Second: The Revenge of Kingdom Plantae. I once came across a humorous remark from a Texan who, when offered a salad alongside his substantial porterhouse steak, quipped, “Salad? Are you serious? Salad is what food eats!” Recently, while perusing Nature, I stumbled upon an article that reignited my fascination with biology, driven by the pure joy of discovering natural history. It turns out, that motivation might not have been the most beneficial for a scientific career, but some of us persist. One such intriguing study is the Identification of carnivory in the flowering plant Saxifraga via multidisciplinary evidence, which serves as a delightful rabbit hole for biology enthusiasts. For the sake of our discussion, the Abstract suffices:
The transformation from prey to predator is an extraordinary adaptive strategy shared by all carnivorous plants, allowing them to capture and digest various animal prey for essential nutrients (nitrogen, N). In this study, we report the discovery of carnivory in the alpine flowering plant Saxifraga candelabrum (Saxifragaceae; Saxifragales). Field experiments and herbarium investigations reveal that this plant actively attracts and captures insect prey via glandular hairs. Enzymatic analyses further confirm the plant’s ability to digest prey, and isotope labelling experiments using ¹⁵N-labelled insects demonstrate nitrogen transfer from prey to plant tissues, thereby confirming the carnivorous nature of this species. Genomic comparisons reveal significant genome-wide convergence in genes related to carnivory (e.g., leaf morphogenesis, digestion, and nutrition) across six independent origins of carnivory in diverse flowering plant lineages. Our findings provide conclusive evidence of carnivory in Saxifraga, addressing Charles Darwin’s long-standing hypothesis that certain Saxifraga species could exhibit carnivorous behavior, and suggest that carnivory may be more widespread among angiosperms than previously acknowledged.
Any paper mentioning Charles Darwin in its abstract deserves attention. The aforementioned study, while unconventional, is nonetheless captivating to biology aficionados:
Carnivorous plants can acquire nutrients (primarily nitrogen) by actively attracting, ensnaring, and ultimately digesting a variety of small animals, thus altering the predator-prey relationship between animals and plants. Understanding the independent evolution of carnivory under physiological and ecological constraints has long captivated biologists. Carnivory has evolved multiple times across angiosperms, encompassing members of 14 families. These plants can be categorized into five main types based on their trapping methods, including the well-known pitfall trap of pitcher plants, snap traps of Venus flytraps, sticky traps of sundews, suction traps of bladderworts, and eel-trap or lobster-trap mechanisms of corkscrew plants. Despite their diverse trapping strategies, most carnivorous plants engage in a common functional sequence during prey utilization, which includes attraction, capture, digestion, and nutrient absorption.
Is there practical value in such scientific inquiries? The answer remains elusive, highlighting the unpredictable nature of research. Studies on limpets have potential applications in developing strong underwater adhesives. The evolution of carnivory in plants has been largely incidental, with various groups employing distinct strategies. Could some fundamental chemistry yield useful knowledge? Only time will tell. During my own early scientific endeavors involving bioluminescent sea creatures, my colleagues were skeptical of the relevance. Yet our research culminated in pivotal advancements in cell biology, earning the Nobel Prize in Chemistry in 2008.
When we hear claims that funding will only support research aligning with current administration priorities, it invites contemplation about what knowledge may remain undiscovered under such a narrow strategy. The unpredictability of scientific inquiry often surpasses the foresight of even knowledgeable politicians and esteemed scientists alike.
Part the Third: The Neanderthal Muscle Head Gene. This topic is equally captivating and perhaps even more intriguing than the story of plants reclaiming agency over animals: Neanderthal growth gene turns modern humans into muscle heads:
Are your muscles impressive? If so, you might owe your athletic physique to your Neanderthal heritage. In a recent study published in Current Biology, researchers have identified a gene variant linked to human growth hormone that likely contributed to the stockier build of our Neanderthal relatives. Interestingly, some individuals today carry this ancestral variant, resulting from our historical interbreeding with Neanderthals, and they typically possess greater lean muscle mass than those with the common gene variation.
This research presents strong evidence that this gene variant “nudges human physiology closer to Neanderthals,” according to Michael Dannemann, a population geneticist who was not involved in the study. Nevertheless, he cautions against overinterpreting the findings: “We are not becoming Neanderthals due to a single genetic variant.”
Neanderthals and modern humans diverged from a shared ancestor around 500,000 years ago. As our lineage evolved in Africa, Neanderthals followed a similar trajectory in Europe and Asia until their extinction approximately 40,000 years ago. The robust skeletal structure—characterized by thick bones and broad muscle attachment sites—indicates that Neanderthals were more muscular than contemporary humans. Despite extensive research on ancient DNA over the past 15 years, pinpointing the genes responsible for this muscularity has proven challenging.
In reviewing the genetic distinctions between modern humans and Neanderthals, evolutionary anthropologist Hugo Zeberg at the Karolinska Institute identified a variant that regulates a crucial gene in the human growth hormone pathway. The pituitary gland releases this hormone into the bloodstream, interacting with muscle and bone cell receptors to instigate growth. An imbalance in growth hormone levels can lead to conditions like gigantism or dwarfism. This specific variant enhances the receptors’ responsiveness to growth hormones, amplifying the messages sent to cells.
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Zeberg and his colleagues conducted further analyses using ancient and modern genomes to determine the prevalence of this variant across different human populations. Their findings revealed that 94% of Neanderthal genomes carried the variant, compared to fewer than 10% in modern humans.
This gene variant was most frequently found in individuals of East Asian and South Asian descent (15% and 20%, respectively), while it was least common among those of European and Indigenous American ancestry (0.5% and 2%, respectively). It most likely entered modern human genomes from Neanderthals approximately 47,000 years ago during periods of interbreeding between the two groups.
As a final test, Zeberg’s team cultured cells expressing either gene variant and treated them with growth hormones. The cells carrying the Neanderthal version increased in size by roughly 40% compared to those with the more common modern human variant.
It won’t be long before someone approaches a lab seeking a CRISPR modification to their physique. However, it’s essential to recognize the complexity beyond this single gene difference—its effects are real and noteworthy. Moreover, paleogenomics plays a crucial role in unraveling such biological truths that hold promise for various applications. Lastly, I wonder: among the scientists involved in this project, who might possess the “Neanderthal” variant? You only get one guess:
Parting Shot: If Health Insurance Is Such a Good Idea, Why Are the Deductibles So High? Throughout this series, I have frequently suggested that health insurance represents a fundamental misconception, often confused with healthcare itself. Recent experiences have underscored this point. My partner and I benefit from employer-based health insurance, which we have utilized since February 2025. Our deductibles, recalling from memory, have been approximately: $3400, $3700, $2800, and $2200, not to mention various additional charges. Tomorrow, my share for a necessary procedure will amount to $820. Four years ago, the identical procedure that identified a tumor, which was later successfully treated, incurred no deductible. In Paris, the same procedure would only cost a few hundred dollars, presenting a more patient-friendly system.
Insurance is designed for improbable events, not inevitable ones. Debates might arise over the necessity of homeowner’s insurance when the home is owned by the occupants, but contesting the need for car insurance during a traffic stop or accident is futile. Refocusing on my deductible experience, last year, a rock chipped my windshield, resulting in a $250 deductible for a $1500 repair job (modern vehicles and their intricate sensor systems!). The sole time I’ve utilized my homeowner’s insurance was for hail damage to the roof, which also entailed a $500 deductible. For a typical family facing an unexpected $400 expense, both the windshield incident and roof repairs could be manageable.
Clearly, there is a significant imbalance at play, worsening annually. The solution is straightforward, but continues to elude us as long as individuals rely on insurances when addressing health care needs. That said, it’s important to acknowledge the unwavering dedication of nurses and the competent care provided by doctors and hospitals under challenging conditions.
Thank you for engaging with this concise discussion on this first Friday in August! I look forward to connecting with you next week. In the meantime, let’s continue striving for a better world in whatever ways we can manage.
