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In this fascinating new review, researchers Polina A. Loseva and Vadim N. Gladyshev discuss “The beginning of becoming a human.”

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For centuries, the question of when human life commences has perplexed philosophers, theologians, and scientists alike. With the advent of modern reproductive technologies and groundbreaking scientific advancements, this profound inquiry has taken on renewed urgency and complexity. In a fascinating new review paper, researchers Polina A. Loseva and Vadim N. Gladyshev from Harvard Medical School delved into this intricate subject, exploring the multifaceted perspectives that have shaped our understanding of life’s origins. On May 6, 2024, their review was published on the cover of Aging’s Volume 16, Issue 9, entitled, “The beginning of becoming a human.” Below, this article breaks down their chronological review of the various ways life has been defined: movement, fusion, self-sufficiency, uniqueness, and now, aging.

Life Defined by Movement: The Quickening

Historically, the notion of life’s inception was inextricably linked to the first perceptible movements of the fetus within the womb, a phenomenon known as “quickening.” In 18th-century England, this milestone was so pivotal that it could even pardon a pregnant woman sentenced to hanging. However, as our comprehension of embryonic development deepened, it became evident that quickening is an unreliable indicator, as the timing varies widely among individuals and is largely dependent on maternal factors.

Life Defined by Fusion: The Conception Conundrum

Another perspective posits that life begins at the moment of conception, when the egg and sperm fuse, forming a unique genetic entity distinct from its progenitors. However, this definition encounters challenges, as the newly formed zygote lacks a fully assembled nucleus and functional genome initially. Furthermore, the ability to split or combine embryos during the early stages raises philosophical quandaries about the individuality and uniqueness of life.

Life Defined by Self-Sufficiency: Viability and Technological Advancement

As medical technologies advanced, the definition of life’s beginning shifted towards the point at which the fetus could theoretically survive outside the womb, albeit with medical intervention. This threshold, known as “viability,” has been a moving target, continually redefined as neonatal care capabilities improve. However, with the advent of artificial womb systems, this criterion may become increasingly ambiguous.

In the midst of the heated debates surrounding reproductive technologies and embryonic experimentation in the 1980s, the Warnock Committee was tasked with establishing ethical boundaries. Their landmark report introduced the “14-day rule,” a compromise that prohibited the cultivation or experimentation on human embryos beyond 14 days after fertilization. While the rationale behind this specific timeframe was somewhat arbitrary, it struck a delicate balance between scientific progress and ethical considerations.

Life Defined by Uniqueness: The Gastrulation Milestone

Remarkably, the 14-day stage coincides with a pivotal developmental event known as gastrulation, during which the embryo transitions from a single-layered structure to a three-layered disc that prefigures the body plan of a vertebrate organism. This transformation not only establishes the embryo’s anterior-posterior, dorsal-ventral, and left-right axes but also marks the point at which the embryo becomes increasingly resistant to splitting or combining, solidifying its individuality.

As scientific capabilities advanced, the ability to culture human embryos beyond the 14-day threshold became a reality, reigniting discussions about revising the Warnock Committee’s guidelines. Proponents argued that this boundary was arbitrary and that our improved understanding of neural development warranted an extension. Others proposed alternative timeframes, such as 22 days (when the nervous system begins to form) or 28 days (when abortions are typically not performed). Ultimately, the International Society for Stem Cell Research (ISSCR) opted for a case-by-case approach, with individual oversight committees evaluating each experiment’s merits.

Life Defined by Aging: A Paradigm Shift

Intriguingly, recent studies have shed light on an overlooked aspect of embryonic development: the onset of aging. By employing epigenetic clocks and other molecular biomarkers, researchers have discovered that the “ground zero” point of aging coincides remarkably with the 14-day stage, marking the transition from a rejuvenated state to the commencement of the aging process. This finding not only reinforces the significance of this developmental milestone but also prompts a reconsideration of life’s beginnings from the perspective of aging trajectories.

The 14++ Conundrum: Navigating Ethical and Scientific Imperatives

As the debate surrounding the 14-day rule continues to evolve, a paradoxical situation has emerged: the scientific consensus on the beginning of life remains elusive, while the ethical boundaries are subject to ongoing reevaluation and case-by-case determinations. This dichotomy underscores the need for a broader discussion involving not only embryologists but also bioethicists, legal experts, and diverse societal stakeholders.

Rather than seeking a definitive answer to the question of when human life begins, a more holistic approach may be to consider the emergence of different levels of life organization during embryonic development. These levels could encompass the cellular, organismal, and human life levels, each with its own unique characteristics and potential boundaries. By recognizing the complexity and multidimensionality of this process, we may gain a deeper appreciation for the intricate tapestry that weaves together the beginnings of human existence.

Synthetic Embryos: Witnessing the Emergence of Life In Vitro

While the 14-day stage may not represent the ultimate boundary for human life, it emerges as a compelling candidate for the transition to organismal life. At this juncture, the embryo exhibits signs of self/non-self discrimination, with cells organized into layers that prefigure the body plan. Concurrently, the rejuvenation processes conclude, and the aging trajectory commences for the somatic cells. This confluence of events suggests that the 14-day stage marks the emergence of a living organism, even if it may not yet possess all the attributes of a human being.

Recent breakthroughs in the generation of synthetic embryos, or “embryoids,” from pluripotent stem cells have opened up unprecedented opportunities to witness the emergence of organismal life in vitro. By recapitulating the early stages of human development, including gastrulation and the formation of embryonic layers, these synthetic models offer a unique window into the intricate processes underlying the transition from a collection of cells to an organized, living entity.

The Path Forward: Embracing Complexity and Collaboration

As we continue to unravel the enigma of life’s beginnings, it is evident that a multidisciplinary approach is essential. Collaboration among embryologists, bioethicists, legal scholars, and diverse stakeholders will be crucial in navigating the ethical and scientific complexities that arise. By embracing the nuances and respecting the perspectives of various disciplines, we can collectively chart a course that harmonizes scientific progress with ethical considerations, ultimately deepening our understanding of the profound journey that culminates in the emergence of a human being.

Click here to read the full review paper published in Aging.

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Aging is an open-access, traditional, peer-reviewed journal that publishes high-impact papers in all fields of aging research. All papers are available to readers (at no cost and free of subscription barriers) in bi-monthly issues at Aging-US.com.

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