Mechanics of human embryo compaction

The shaping of the human embryo begins with compaction, during which cells come into close contact and form a tighter structure. Assisted reproductive technology (ART) studies suggest that human embryos fail compaction primarily because of defective adhesion. Based on our current understanding of animal morphogenesis, other morphogenetic engines, such as cell contractility, could be involved in shaping the human embryo. However, the molecular, cellular and physical mechanisms driving human embryo morphogenesis remain uncharacterized. Using micropipette aspiration on human embryos donated to research, we have mapped cell surface tensions during compaction. This reveals a 4-fold increase of tension at the cell-medium interface while cell-cell contacts keep a steady tension. Comparison between human and mouse reveals qualitatively similar but quantitively different mechanical strategies, with human embryos being mechanically least efficient. Inhibition of cell contractility and cell-cell adhesion in human embryos reveal that only contractility controls the surface tension responsible for compaction. Interestingly, if both cellular processes are required for compaction, they exhibit distinct mechanical signatures when faulty. Analyzing the mechanical signature of naturally failing embryos, we find evidence that non-compacting embryos or partially compacting embryos with excluded cells have defective contractility. Together, our study reveals that an evolutionarily conserved increase in cell contractility is required to generate the forces driving the first morphogenetic movement shaping the human body.

Intraluminal duodenal “windsock” diverticulum; Case Report and discussion

Intraluminal duodenal diverticulum (IDD) is a rare developmental anomaly usually found in the second portion of the duodenum. The cause appears to be a failure of recanalization of the occluded foregut lumen of the human embryo, resulting in a fenestrated mucosal membrane [1]. A small aperture in this diaphragm will gradually cause it to elongate caudally in response to duodenal peristalsis to form the so called “wind-sock” configuration. Symptoms are nonspecific and generally depend on the degree of duodenal obstruction; 25% of cases are associated with GI bleeding. In most documented cases, IDD was diagnosed radiologically, but the value of endoscopy for diagnosis and treatment has been amply demonstrated.

論人體胚胎研究“軟法”修改之正當性

LANGUAGE NOTE | Document text in Chinese; abstract also in English. This commentary briefly discusses the substantive and procedural justifications for amending the longstanding 14-day rule, a soft-law limitation on the culturing of human embryos. The 14-day rule was established on the basis of general recognition of the human embryo's special status, accompanied by widespread public conversation and engagement. In principle, amending this rule would require the same substantive and procedural justifications. However, such justifications were absent prior to the lifting of the rule by the ISSCR in its 2021 guidelines. This article also discusses the value and importance of the 14-day rule to the development of human embryo research in the last three decades. Discarding the rule without the proper substantive and procedural justifications is likely to damage public trust and confidence in future human embryo research.

生物醫學技術發展應該改變14天法則限制嗎？

LANGUAGE NOTE | Document text in Chinese; abstract also in English. Developments in research have made culturing human embryos beyond the 14-day limit seem technologically feasible. In the article “Emerging Human Embryo Research Technologies, the 14-day Rule, and the Special Status of the Embryo,” the authors examine a proposal for new human embryo and embryoid research guidelines by reviewing the history of the 14-day limit and emerging areas of research that are impacted by these guidelines. However, as noted by the authors, changes in science policy should not be developed solely by scientists. Instead, policy development should reflect the reality of science as a public endeavor. After 40 years of consensus, any attempts to revoke the 14-day limit on the in vitro culturing of human embryos should rely on public and stakeholder engagement.

善治視角下的人類胚胎研究政策的制訂

LANGUAGE NOTE | Document text in Chinese; abstract also in English. 人類胚胎研究的“十四天規則”作為一條重要的倫理原則已實施四十餘年，被很多國家立法採納。近年來，隨著胚胎技術的飛速發展，科學家們對“十四天規則”提出了新的挑戰，也是對相關的倫理研究和公共政策的制訂提出的挑戰，即我們該怎樣看待人類胚胎研究的公共政策？Ana S litis等在〈新興人體胚胎研究技術、十四天規則和胚胎的特殊地位〉（馬修斯、洛伊、伊爾蒂斯2021）一文中鼓勵科學家從促進善治的角度來看待人類胚胎和胚狀體的研究政策，但並未深入探討其原因和意義，本文主要從善治的特徵出發通過對人類胚胎研究政策制訂中如何實現的探討而對該文的上述核心觀點進行回應。 In the article “Emerging Human Embryo Research Technologies, the 14-day Rule, and the Special Status of the Embryo,” one of the authors' core aims is to encourage scientists to look at human embryo research policy from the perspective of promoting good governance. Starting with the characteristics of good governance, this paper responds to Iltis et al. by discussing how to realize good governance in the formulation of human embryo research policy.

改變“14天規則”：生命倫理學與公眾參與的再平衡

LANGUAGE NOTE | Document text in Chinese; abstract also in English. This article argues that the ISSCR's changes to the 14-day rule should be welcomed. In the future of human embryo research oversight in China, bioethics and public engagement should be fully balanced. This is essential to safeguard the public's trust in science.

新興人體胚胎研究技術、 十四天規則和胚胎的特殊地位

LANGUAGE NOTE | Document text in English ; abstract also in Chinese. 胚胎研究的＂十四天規則＂已經在國際上實施了幾十年。當前，很多科學家正在挑戰這一限制，因為技術進步使得人類胚胎和胚胎的細胞模型可以培養到其早期發育階段的後期。一些學者質疑人們長期以來持有的胚胎研究應該受到限制的信念，即超過十四天的胚胎研究是不道德的，他們開始提出替代性指導方針。本文通過回顧“十四天規則”的歷史和受這一規則影響的新興研究領域的情況，審查一項新的關於人類胚胎和類胚胎的指南。我們表明社會和政治哲學、形而上學和倫理學所關注的問題對於解釋和應用新的建議或開發替代方案具有核心作用。至關重要的是，科學家在突破十四天的限制去做任何研究之前，應該制訂明確的、深思熟慮的、且有文化敏感性的指導方針，包括具體限制和監督程式，以確保科學能夠適當地回應社會的需求和價值判斷。 After 40 years of abiding by an international guideline that barred human embryo research beyond day 14 of embryonic development, many scientists are now challenging this limit due to technological advances suggesting that embryos and cell-based models of embryos can be cultured to later points in early development. Some scholars have questioned the long-held belief that research beyond 14 days is unethical and have begun proposing alternative guidelines for research. In this paper, we examine a proposal for new human embryo and embryoid guidelines by reviewing the history of the 14-day limit and emerging areas of research that are impacted by these guidelines. We then show how social and political philosophy, metaphysics, and ethics are central to interpreting and applying these new recommendations or developing alternatives. Before conducting any research beyond day 14, scientists must develop clear, thoughtful, and culturally sensitive guidelines that include limitations and oversight procedures to ensure that science responds to societal needs and values.

前言：科技興趣、超越人類與倫理限制

LANGUAGE NOTE | Document text in Chinese; abstract also in English. 人類正處於前所未有的技術高速發展時代。特別是，NBIC技術（納米技術、生物技術、資訊技術和認知科學）彙集起來的發展，使得人類改造自身、進而超越自身的夢想不斷接近現實，但也為我們敲響了倫理學的警鐘：如果我們對生命技術的不斷突破和廣泛應用所牽涉的倫理價值缺乏充分的考量並施以必要的限制，那麼技術就無法得到有利的發展和公平的應用，甚至造成過分追求那些具有不可逆結果或不可逆傷害的生命技術的後果，使得現代生物醫學成為人類幸福的一種“錯誤承諾”。本期的兩篇主題論文以及十六篇評論文章，正是著力於探討這些影響深遠的生命倫理問題。 This issue of the journal contains two thematic papers, namely “Emerging Human Embryo Research Technologies, the 14-day Rule, and the Special Status of the Embryo” by Kirstin R. W. Matthews, Sam Lowe, and Ana S. Iltis, and “A Confucian Reflection on Transhumanism: How to Regulate Our Posthuman Future?” by Wang Jue, in addition to 16 commentary essays on ethical issues associated with rapidly developing biomedical technologies. The authors argue that scientific interests should not be the main driver of technological breakthroughs and applications. Rather, ethical commitments embedded in cultural traditions should play a positive role through public participation in legitimate policymaking.

在中國的科研倫理規範體系建設中重視公眾參與

LANGUAGE NOTE | Document text in Chinese; abstract also in English. It is an inspiring idea that public participation should be the key factor for determining the human embryo research policy. However, public participation is missing from the Chinese government's vision of an ethics regulation system for scientific research. This article argues that to develop human embryo research policy for China and a new regulation system globally, the most important tasks may be to set rules for public participation and to understand the views on human embryo and cell-based embryo research ethics held by different stakeholders and the Chinese public.