2024-刘颖-疾病概念与生物功能：基于分子适应论的自然主义探索

博论题目：疾病概念与生物功能——基于分子适应论的自然主义探索

答辩人：刘颖

指导老师：刘晓力

答辩时间：2024年5月25日

导论

0.1 不容忽视的疾病与健康界定

0.1.1 疾病概念理解的差异性

0.1.2 疾病界定决定医学边界

0.1.3 疾病界定的现实社会影响

0.1.4 对疾病概念的哲学分析

0.2 疾病界定下的生物功能

0.2.1 生物目的论与生物功能探究的兴起

0.2.2 功能在科学和哲学的讨论

0.3 研究方法

0.3.1 “哲学解释”的研究方法

0.3.2 本文创新之处

第1章 “什么是疾病”：自然主义与建构主义之争

1.1 “建构主义”代表学说及其反驳

1.1.1 定义与历史性论证

1.1.2 “家族相似”的诸多学说

1.1.3 “解构”建构主义的批评观点

1.2 “自然主义”代表学说及其反驳

1.2.1 “内稳态”与自然主义兴起

1.2.2 布尔斯的“生物统计学理论”

1.2.3 对自然主义的三大批判：社会意义缺失、价值隐含与统计质疑

1.3 “混合主义”代表学说及其反驳

1.3.1 韦克菲尔德的“有害功能失常论”

1.3.2 对混合主义的批评：理论融合之光还是混沌之源？

本章小节

第2章 疾病论域下的功能与生理学中的功能论

2.1 自然主义与混合主义的“功能性”困境

2.1.1 自然主义者布尔斯疾病理论的难题

2.1.2 布尔斯的发展者：疾病理论中的生物功能替换与困境

2.1.3 重启功能探索：对“功能失常”的语义分析

2.2 生理学中的功能论

2.2.1 生理学科学案例——循环系统中心房的功能

2.2.2 生命系统中的因果：康明斯的“因果角色论”

2.2.3 升级康明斯理论：戴维斯的“系统效果论”及其难题

本章小节

第3章 演化生物学中的功能论 93

3.1 演化科学案例研究——大蝙蝠亚目大睾丸的功能

3.1.1 霍斯肯的适应假设关联检验

3.1.2 费尔森斯丁的“系统发育独立对比法”检验

3.2 “溯因论”的代表学说

3.2.1功能的历史起源：赖特的“功能溯因论”

3.3.2 演化的历史：米利肯的“选择溯因论”

3.2.3 近期的选择压力：戈弗雷-史密斯的“近期选择溯因论”

本章小节

第4章 “组织理论”及其他功能理论

4.1 组织理论与科学案例

4.1.1 血糖负反馈功能案例

4.1.2 探究生命闭环因果：组织理论与其问题

4.2 其他的功能理论

4.2.1 对生存与繁殖的贡献：“目标贡献理论”及其问题

4.2.2 探究可能性和倾向性：“生命机会理论”及其问题

4.2.3 当前的效用与设计：“非历史选择理论”及其问题

本章小节

第5章 一种新的功能论：“分子适应功能论”

5.1 分子适应科学案例——膝关节软骨细胞调节的演化

5.1.1 人类直立行走演化历史

5.1.2 膝关节特异性调控元件的生物功能

5.1.3 调节元件的变异如何引发关节炎

5.2 分子适应功能理论及其跨学科背景

5.2.1 生理与演化的交汇：跨学科视野下的分子功能

5.2.2 基因组视野下对适应性分子的探究

5.2.3 定义与解释

5.3 分子适应功能的综合解释力

5.3.1 符合好的功能理论的标准

5.3.2 解决其他功能理论的难题

本章小节

第6章 一种新的疾病理论：“分子适应疾病理论”

6.1 分子适应疾病理论与科学背景

6.1.1 一般性定义

6.1.2 医学范式的转换与发展：对疾病概念内涵的拓展

6.2 分子适应疾病理论的解释力

6.2.1 新自然主义对疾病的理论解释力

6.2.2 对疾病争议性案例具有的解释力

本章小节

结语

参考文献

后记与致谢

摘要

“疾病”与“健康”是医学领域中的一对基础概念，也是医学哲学中讨论的核心议题。“什么是疾病”的探讨引发社会和学界广泛关注的大致原因有如下四点：一，在社会中，将日常生活中非医学问题“医学化”的倾向；二，在理论中，疾病成为医学伦理和疾病划界争议的焦点；三，在实践中，疾病观念深刻影响着对个体的感知、医学组织的架构、医疗与社会资源分配；四，在认知中，疾病在公众、医学专家和医学教育者中呈现出巨大的差异性。

医学哲学中参与对疾病刻画有诸多学派，如强调语言分析的英美哲学、突出权力结构的法国后现代主义、描述主观经验的现象学、聚焦社会价值的社会学等。这些学派大体可划分为“自然主义”和“建构主义”两大阵营。自然主义以客观、无价值的生物功能定义疾病，而建构主义基于社会文化价值给出疾病判断。

以布尔斯为代表的自然主义面临最大挑战是：第一，无法以立场宣称的无价值方式从自然类中挑选“疾病”，因为布尔斯生物统计方法其实渗透了价值判断；第二，无法提供对医学中“正常”规范的有效说明，布尔斯生物统计正常是基于特定人群中大多数的表现，这无法说明群体性患病经历。建构主义的困难在于既无法明确区分医学和非医学负面价值之间的差别，也很难不依赖于生物事实对何为疾病形成判断。

在自然主义路径下，疾病通常被定义为生物功能失常。生物功能理论分为六大流派：关注生理学功能使用的“因果角色论”、探索演化生物学功能的“溯因论”、强调生命闭环因果的“组织理论”、探索生存与繁殖贡献的“目标贡献理论”、发现可能性和倾向性的“生命机会理论”、关注当前效用和设计的“非历史选择理论”。几大流派各有优劣，迄今没有一个受到普遍认可的生物功能论。其中因果角色理论和溯因论是接受程度比较高的两个流派，前者的优势在于具有经验可验证性，但其无法提供对生物功能失常的说明也无法区分功能与意外，后者能提供一个很好的功能失常的规范性说明但面临无法被验证的挑战。

为克服生物功能论和疾病自然主义的困难，本文提出基于分子适应功能的分子适应疾病论，以应对这些诸多挑战。

通过探索基因组学、分子生物学、演化生物学等最新科学的成果，提出了一种新的功能理论——“分子适应功能论”，即生物功能是演化过程中适应性分子所发挥的作用。分子适应功能论能有效应对功能论中公认的三大重要挑战：第一，通过分子在演化中被选择的历史能提供功能的正常标准；第二，通过对演化史中适应性和非适应的区分，解决功能与偶然意外的区分难题；第三，通过分子层面的控制变量实验来验证功能，解决溯因论的验证性难题。

在分子适应功能论的基础上，我们继续追踪基因组医学、精准医学、演化医学等各领域的新发展，提出了“分子适应疾病理论”，即疾病是分子适应功能的失常。分子适应疾病理论能解决传统自然主义面临的两大挑战：一是如何在没有价值判断的情况下从自然类别中挑选出‘疾病’；二是如何解释在有害环境中出现的群体性疾病。应对第一大挑战，分子适应疾病理论仅从分子中挑选那些完全由自然选择决定的适应性部分，不涉及任何社会或人为价值。应对第二大挑战，分子适应疾病理论的疾病定义是一些演化史上的适应性分子无法发挥其作用，在有害环境中自然无法发挥，且不论患病群体的大小。我们的理论的另一个重要优势在于，它能够在分子层面上经验性地验证适应性，而不仅仅是基于假设。在应用层面，分子适应疾病理论提供了一套一致的标准来区分疾病和非疾病，使其能够判定如肥胖、同性恋、更年期综合症以及注意力缺陷多动障碍等争议性疾病案例。

关键词：疾病；功能论；自然主义；建构主义；分子适应理论

Abstract

“Disease”and “health”are fundamental concepts in medicine and a central topic of discussion in the philosophy of medicine. The discussion of“what is disease” has aroused widespread concern in society and academia for the following four general reasons: First, in society, the tendency to medicalize non-medical problems in daily life; second, in theory, disease is often the basic starting point for disputes over medical ethics and disease delimitation; third, in reality, the concept of disease has a profound impact on individual perception, the organizational structure of medicine, and the allocation of medical and social resources; fourth, in perception, disease shows great variability among the general public, medical experts, and medical educators.

There are many schools of thought involved in the portrayal of illness in the philosophy of medicine, such as analytical philosophy, which emphasizes linguistic analysis; French postmodernism, which highlights power structures; phenomenology, which describes subjective experience; and sociology, which focuses on social values. These schools of thought can be roughly divided into “naturalism” and “constructivism.”Naturalism defines disease regarding objective, value-free biological functions, while constructivism gives judgments about disease based on socio-cultural values.

The most significant challenges facing naturalists are: first, the inability to select diseases from natural categories in the value-free manner claimed by the position because Boorse's biostatistical theory is permeated by value judgments; second, the inability to provide a valid account of the norms in medicine; Second, it cannot provide an adequate explanation of the normal standards in medicine. Boorse's biostatistical definition of normality is based on the performance of the majority within a specific population, which fails to account for the experience of epidemic disease. The difficulty with constructivism is the inability to distinguish between medical and non-medical negative values and the difficulty of forming judgments about what constitutes disease without relying on biological facts.

To overcome the many difficulties faced by function theory and naturalism on disease, this paper attempts to address each challenge by giving a molecularly adaptation disease theory built on molecularly adaption function theory.

Under the naturalistic path, disease is usually defined as a biological malfunction. Theories of biological functioning are divided into six significant schools: “causal role theory,” which focuses on the use of physiological functions; “etiological theory,” which explores the functions of evolutionary biology; “organization theory,” which emphasizes the closed-loop causality of life; “goal contribution theory” which explores the contribution of survival and reproduction; “life chance theory” which discovers possibilities and predispositions; and “ahistorical theory” which focuses on current utility and design. However, each has its advantages and disadvantages, and so far, no universally recognized theory of biological function exists. The causal role theory has the advantage of empirical verifiability. Still, it cannot account for biological malfunction or distinguish between function and accident. In contrast, etiological theory offers an excellent normative account of malfunction but is not verifiable.

First, by exploring the results of the latest sciences, such as genomics, molecular biology, and evolutionary biology, we propose a new theory of function, “molecular adaptation theory,” in which biological function is a function of adaptive molecules during evolution. Molecular adaptation theory can effectively address three critical challenges recognized in functional theory: first, it can provide a normal criterion of function through the history of molecules being selected in evolution; second, it can solve the difficulty of distinguishing function from accidental accidents by distinguishing between adaptive and non-adaptive in the history of evolution; and third, it can solve the validation difficulty of etiological theories by verifying function through the experiments of controlled variables at the molecular level.

Secondly, based on molecular adaptation function theory, we continue to track the new developments in genomic medicine, precision medicine, evolutionary medicine, and other fields and put forward the“molecular adaptation theory disease theory,” i.e., the disease is a malfunction of molecular adaptive function. Molecular adaptation disease theory addresses two significant challenges facing traditional naturalism - selecting valueless natural classes and providing rational criteria for normal biological function. To address the first substantial challenge, molecular adaptation disease theory selects an adaptive fraction from all molecules determined solely by the value-free process of natural selection, which contains no social or anthropogenic values. In response to the second challenge, the molecular adaptation disease theory defines disease as the failure of evolutionary adaptive molecules to function in harmful environments, regardless of the size of the affected population. Another great advantage of our theory is the ability to empirically validate adaptations at the molecular level rather than remaining at the level of speculative hypotheses. At the practical level, the molecular adaptation disease theory provides a consistent set of criteria to differentiate between disease and non-disease, enabling the determination of contentious medical cases such as obesity, homosexuality, menopausal syndrome, and attention deficit hyperactivity disorder.

Key words: Disease; Function theory; Naturalism; Constructivism; Molecular Adaptation Theory