Science Focus (Issue 33)

making the task of understanding the organ more manageable [10]. For example, some researchers harness brain organoids to trace how brain cells develop and migrate in the fetus, while others connect a few brain organoids to investigate how pain signals travel from our skin to our brain [10]. More importantly, to be able to model a disease in rodents, scientists need to know the cause of it, and that takes about a year [9]. Patient-derived organoids can speed up the process significantly, allowing scientists to move faster when developing a model. In brain organoid research, scientists have already used brain organoids derived from patients to model Alzheimer's disease and Parkison’s disease [6]. Perhaps a more exciting is the application of organoids in drug screening. For a long time, poor assessment of drug toxicity in the preclinical stage has been a major cause behind the failure of many drug developments [6]. This is particularly true for cancer therapies, which may have severe, sometimes lethal side effects. To this end, drug efficacy and toxicity can be better studied by comparing the response of organoids that are derived from normal and cancer cells from the same patients [6]. The End of Lab Rats? So where does this leave us? Are organoids the end of "you're a lab rat?" Not yet. Model organisms still have unique value in the scientific community. With a large body of work and laboratory techniques already established, animal models allow a low-cost way for fundamental research [9]. While the potential for organoids in precision and regenerative medicine is widely recognized, the field of organoids is still in its infancy, with major technical bottlenecks ahead and limited clinical outcomes. However, regulatory progress has been made with the passing of the “FDA (Food and Drug Administration) Modernization Act 2.0” in the United States. It authorizes the use of “new approach methodologies,” including organoids and 使用實驗老鼠的弊病 當有人被迫參與試驗新事物時,人們常開玩笑說:「你 被人拿來當白老鼠。」過往數十年,新藥在進行人體試驗 前,都會先在大鼠和小鼠等囓齒動物上進行初步臨床測 試。然而,以動物為模型仍有兩大難題。首先是道德上的 取捨:藥物測試帶來的好處,是否抵得過動物承受的痛 苦?我們能否在研究中減少使用脊椎動物?其次是科學 上的難題:大鼠能充分模擬人類嗎?科學家一直用大小 鼠模擬哺乳動物複雜的生理與病理過程,這是基於操控 人類體內活動的蛋白質大多亦存在於大小鼠身上,它們 都是在演化過程得以保留的蛋白質。可是,要準確地以 動物模型預測藥物在人體上的效用仍然困難 [1]。 若我們能以人類細胞培養出人體器官模型,又會怎 樣呢? 甚麽是類器官? 類器官(organoid)是可以自我成形的三維迷你細 胞團,在某程度上能模擬真實器官。「類器官」一詞由兩 部分組成:「器官」(organ)是指一群執行共同特定功 能的細胞及組織,「類」(-oid)則表示與特定物件的相 似性,在此即指「類似器官的東西」。 那麼,類器官就是具有正常器官形狀的迷你版器官 嗎?這個描述並不準確。正如你可能知道,器官具有特定 形狀和內部結構,就像小腸是管狀結構。然而,小腸類器 官在顯微鏡下並不是彎曲的管道。事實上,作為史上第 一個類器官,它是中空的球狀囊泡,表面帶有芽狀突出 物。儘管整體結構與小腸彎曲的管狀外形毫不相似,但 AI-based computational models, as alternatives to the compulsory animal testing to support an investigational new drug application [11, 12]. This enables new drugs to be tested in a more effective and human-relevant way [12]. In April 2025, the FDA further announced a roadmap to phase out animal studies in the next three to five years [11]. The end of lab rats – in clinical trials – might not be that far away, after all.

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