改善科学与重建公众对公共卫生的信任 | Dr. Jay Bhattacharya

改善科学与重建公众对公共卫生的信任 | Jay Bhattacharya 博士

摘要

Jay Bhattacharya 博士现任美国国立卫生研究院（NIH）院长，曾任斯坦福大学卫生政策教授。他在本次对话中探讨了美国生物医学研究资助体系中存在的结构性问题、新冠疫情政策失误所导致的公众对科学信任的侵蚀，以及他对改革 NIH 的愿景。对话还涵盖了纳税人资金如何流经大学体系、美国人为何为处方药支付远高于世界其他地区的价格，以及目前正在推进的哪些具体变革将使科学更加透明、富有创新性和问责性。

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核心要点

• 美国人均预期寿命自 2012 年起陷入停滞 —— 欧洲国家在同期持续进步，而美国在疫情前已趋于平稳，直至 2024 年才恢复至 2019 年的水平，表明现行生物医学研究模式未能完成其核心使命。
• NIH 资助的研究论文将于今年七月起向公众免费开放 —— 这一政策由前任 NIH 院长启动，确保纳税人无需购买期刊订阅即可阅读由其资助的科学成果。
• 美国人为同种药物支付的费用是欧洲人的 2 至 10 倍，实际上是通过高药价为全球制药研发提供补贴 —— Bhattacharya 博士称这一安排难以为继。
• NIH 同行评审（研究小组）体系在结构上偏向渐进式、“安全”的科学，而非大胆、高风险的假设 —— 这是该机构近几十年突破性发现减少的关键原因。
• 基础研究将在现任院长领导下继续作为受保护的优先领域 —— 据 Bhattacharya 博士表示，担忧其被纯应用研究所取代的说法并无依据。
• 复现危机正在被积极应对 —— NIH 推出了新举措，旨在尽早核实研究发现并激励复现研究，以确保知识基础的准确性。
• 间接成本（IDC）结构将研究资金集中于沿海精英大学，使同等才华的科学家在财力较弱的机构处于不利地位 —— 现任政府正在重新审视这一结构性问题。
• 科学资助的地域多样性与思想多元性有助于遏制群体思维，产出更丰富、更具创新性的科学成果。
• 现行药品专利与定价体系（由《Bayh-Dole 法案》塑造）初衷是加速基础科学成果转化为可用疗法，但结果却使美国人为全球制药研发管线提供资金，自身却所获甚少。

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详细笔记

NIH 使命与基础研究的角色

• NIH 的既定使命是增进美国人民的健康与寿命。
• NIH 被视为全球首屈一指的生物医学研究机构，几乎参与了每一种获批药物和健康指南的研发过程。
• NIH 预算中相当大一部分用于资助基础研究 —— 即非针对特定疾病或治疗目标的发现性研究。
• 基础研究产生深远下游影响的历史案例：
  • Watson、Crick、Franklin 与 DNA 双螺旋结构 —— 当时无法申请专利，却奠定了现代生物学的全部基础。
  • Hubel 与 Wiesel 的视觉皮层研究 —— 直接催生了儿童白内障、斜视和眼睑下垂的早期矫正手术方案，挽救了数百万人的视力。
  • 细胞生物学与线粒体研究 —— 为几乎所有现代癌症治疗奠定了必要的理论基础。
• Bhattacharya 博士明确表示：在其领导下，基础科学将继续作为 NIH 核心投资组合的重要组成部分；现任政府没有任何指示表明情况将有所改变。

复现危机

• 复现危机是指科学发现无法被独立重复验证的现象。
• NIH 正在开发新举措，旨在在研究过程早期核实研究发现，并激励复现研究，以确保科学知识基础的可靠性。

研究成果开放获取

• 在前任 NIH 院长 Monica Bertagnolli 领导下，已制定政策要求 NIH 资助的研究在发表时即向公众免费开放 —— 此前计划于 2025 年 12 月实施。
• Bhattacharya 博士将实施日期提前至 2025 年 7 月。
• 目前，《自然》等期刊发表一篇论文约收取 12,000 美元，同时向读者收取每篇 30 至 100 美元的阅读费 —— 尽管这些研究已由纳税人资助。
• 此次开放获取转变不仅被定性为公平问题，更被视为公众参与科学的根本保障。

间接成本（IDC）与研究基础设施

• 当科学家获得 NIH 资助（例如每年 100 万美元）时，所在大学还会在此基础上额外获得一定比例的间接成本补偿 —— 在斯坦福大学，这一比例约为 55%（即每 100 万美元资助对应约 55 万美元间接费用）。
• 间接成本旨在覆盖固定基础设施支出：建筑维护、放射性材料处理、实验室维护、行政管理等。
• 特朗普政府曾试图将所有机构的间接成本统一上限设定为 15% —— 此举随后被法院裁定中止，目前仍在诉讼中（Bhattacharya 博士婉拒就法律事务本身置评）。
• 现行间接成本模式的关键结构性问题：
  • 形成棘轮效应：需要资助才能获得间接成本支持，但需要基础设施才能吸引能够赢得资助的科学家。
  • 将联邦研究经费集中在少数精英大学，这些大学多位于沿海地区。
  • 未能区分高固定成本实验室（如涉及放射性材料的湿实验室）与低固定成本”笔记本电脑实验室”（如流行病学、卫生经济学研究）。
• EPSCOR/IDEAS 项目为 NIH 资金分布末位 25 个州的研究机构提供竞争优势 —— Bhattacharya 博士支持将其作为应对地域集中问题的有效工具。

同行评审、科学群体思维与激励大胆科学

• NIH 资助由研究小组进行评审 —— 由专家同行组成的评审委员会对申请项目评分，并为他们认为最具价值的项目发声。
• 该体系的结构内嵌了保守主义倾向：评审人倾向于支持可能成功的项目，这意味着资金流向渐进式（“按部就班”）科学，而非大胆、高风险的假设性研究。
• 与风险投资模式相比：在硅谷，50 个投注中有 49 个失败但有一个实现颠覆性突破，被认为是高度成功的投资组合。NIH 模式所激励的恰恰相反。
• Bhattacharya 博士援引了一位 Salk 研究所科学家的框架：两种科学 —— 检验大胆假设（大多数会失败，但成功案例将产生深远影响）vs. 渐进式工作（结果可靠，但整体投资组合影响有限）。
• 研究小组中的地域多样性在一定程度上缓解了沿海地区的群体思维，但并不能从根本上解决创新问题。

美国人均预期寿命与慢性病危机

• 美国人均预期寿命自 2012 年至 2019 年基本停滞，而欧洲国家在此期间持续改善。
• 疫情期间预期寿命急剧下降，直至 2024 年才恢复至 2019 年水平。
• 瑞典的预期寿命于 2020 年有所下降，但在 2021 至 2022 年间恢复至疫情前的上升趋势。
• 尽管生物医学取得了重大进展，美国仍未能应对其慢性病危机 —— 肥胖、抑郁症、代谢疾病 —— 这是预期寿命差距的主要驱动因素。
• 当代美国儿童的预期寿命和健康状况预计将不及其父母一代。
• Bhattacharya 博士将整个行业将重心置于疾病管理而非疾病预防的现状，定性为对现行优先事项的严重控诉。

药品定价：美国人为何支付更多

• 美国人为相同处方药支付的费用是欧洲人的 2 至 10 倍。
• 这背后涉及一种隐性的全球安排：
  • NIH（纳税人）资助基础及应用研究。
  • 制药公司资助后期第三阶段临床试验，但通过美国溢价定价收回成本。
  • 欧洲国家以接近边际成本的价格谈判，对研发费用贡献甚微。
  • 《Bayh-Dole 法案》（1980 年代）允许对 NIH 资助的发现申请专利，以激励私营部门将基础研究成果转化为可上市疗法 —— 这是在价格与转化速度之间所作的刻意权衡。
• 结果是：美国纳税人成为全球制药研发管线的主要资助方。
• 制药公司利润估计有三分之二至四分之三来自美国市场。
• 制药公司的研发方向自然向美国健康问题靠拢（肥胖症、抑郁症、代谢疾病），而非其他地区的优先健康需求。

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English Original 英文原文

Improving Science & Restoring Trust in Public Health | Dr. Jay Bhattacharya

Summary

Dr. Jay Bhattacharya, Director of the National Institutes of Health and former Stanford Professor of Health Policy, discusses the structural problems plaguing American biomedical research funding, the erosion of public trust in science following COVID-19 policy failures, and his vision for reforming the NIH. The conversation covers how taxpayer dollars flow through universities, why Americans pay dramatically more for prescription drugs than the rest of the world, and what concrete changes are underway to make science more transparent, innovative, and accountable.

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Key Takeaways

• American life expectancy has been stagnant since 2012 — while European countries showed gains, the U.S. flatlined before the pandemic and only recovered to 2019 levels in 2024, indicating the current biomedical research model is not meeting its core mission.
• NIH-funded research papers will be freely available to the public starting July — accelerating a policy initiated by the previous NIH director, ensuring taxpayers can read the science they paid for without purchasing journal subscriptions.
• Americans pay 2–10x more for the same drugs as Europeans, effectively subsidizing global pharmaceutical R&D through higher drug prices — an arrangement Dr. Bhattacharya calls unsustainable.
• The NIH peer review (study section) system structurally favors incremental, “safe” science over bold, high-risk hypotheses — a key reason the agency has generated fewer breakthrough discoveries in recent decades.
• Basic research will remain a protected priority at the NIH under the current director — fears of it being gutted in favor of applied-only research are unfounded, according to Dr. Bhattacharya.
• The replication crisis is being actively addressed through new NIH initiatives designed to verify findings early and incentivize replication, ensuring the knowledge base is accurate.
• Indirect cost (IDC) structures concentrate research funding on coastal elite universities, disadvantaging equally talented scientists at less wealthy institutions — a structural problem the administration is reconsidering.
• Geographic and intellectual diversity in science funding combats groupthink and produces richer, more innovative science.
• The current drug patent and pricing system (shaped by the Bayh-Dole Act) was designed to accelerate translation of basic science into usable treatments, but has resulted in Americans funding the world’s pharmaceutical R&D pipeline with little direct benefit.

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Detailed Notes

NIH Mission and the Role of Basic Research

• The stated mission of the NIH is to advance the health and longevity of the American people.
• The NIH is considered the world’s premier biomedical research institution, with a role in developing nearly every approved drug and health guideline.
• A substantial portion of the NIH budget funds basic research — discoveries made without a specific disease or treatment in mind.
• Historical examples of basic research with enormous downstream impact:
  • Watson, Crick, Franklin, and the double helix — unpatenatable at the time, yet foundational to all of modern biology.
  • Hubel and Wiesel’s visual cortex studies — led directly to early corrective surgery protocols for cataracts, strabismus, and drooping eyelids in children, saving the vision of millions.
  • Cell biology and mitochondria research — laid the necessary groundwork for essentially all modern cancer treatments.
• Dr. Bhattacharya explicitly confirmed: basic science will remain a core part of the NIH portfolio under his leadership; no directive from the current administration has suggested otherwise.

The Replication Crisis

• The replication crisis refers to scientific findings that cannot be independently reproduced.
• New NIH initiatives are being developed to verify findings early in the research process and to incentivize replication studies, with the goal of ensuring the scientific knowledge base is reliable.

Open Access to Research

• Under previous NIH director Monica Bertagnolli, a policy was established requiring that NIH-funded research be freely available to the public upon publication — previously scheduled for December 2025.
• Dr. Bhattacharya moved the implementation date to July 2025.
• Currently, journals such as Nature charge approximately **$12,000topublishapaper\ast \ast ,thenchargereaders$30–$100 per article — despite that research having been funded by taxpayers.
• This open-access shift is framed as essential not just for fairness but for public engagement with science.

Indirect Costs (IDC) and Research Infrastructure

• When a scientist receives an NIH grant (e.g., $1million/year),thehomeuniversityreceivesan\ast \ast additionalpercentageontop\ast \ast forso-calledindirectcosts—atStanford,approximately55$550,000 per $1M grant).
• Indirect costs are meant to cover fixed infrastructure expenses: buildings, radioactive material disposal, lab maintenance, administrative handling.
• The Trump administration attempted to cap IDC at a flat 15% across all institutions — this was subsequently blocked by court order and is currently in litigation (Dr. Bhattacharya declined to comment on the legal matter itself).
• Key structural problems with the current IDC model:
  • Creates a ratchet effect: you need grants to get IDC support, but you need infrastructure to attract grant-winning scientists.
  • Concentrates federal research dollars at a small number of elite, predominantly coastal universities.
  • Does not differentiate between high fixed-cost labs (e.g., wet labs with radioactive materials) and low fixed-cost “laptop labs” (e.g., epidemiology, health economics).
• The EPSCOR/IDEAS program provides a competitive advantage to research institutions in the bottom 25 states by NIH funding distribution — Dr. Bhattacharya endorsed this as a tool to counteract geographic concentration.

Peer Review, Scientific Groupthink, and Incentivizing Bold Science

• NIH grants are evaluated by study sections — panels of expert peers who score proposals and advocate for those they find most meritorious.
• The system’s structure embeds conservatism: reviewers implicitly favor grants likely to succeed, which means funding incremental (“turning the crank”) science over bold, high-risk hypotheses.
• Contrast with venture capital model: in Silicon Valley, a portfolio where 49 of 50 bets fail but one becomes transformative is considered highly successful. The NIH model incentivizes the opposite.
• Dr. Bhattacharya referenced a Salk Institute scientist’s framing: two types of science — testing bold hypotheses (most will fail, but hits are spectacular) vs. incremental work (reliable, but low-impact portfolio-wide).
• Geographic diversity in study sections partially mitigates coastal groupthink, but does not fully solve the innovation problem.

American Life Expectancy and the Chronic Disease Crisis

• U.S. life expectancy was essentially flat from 2012–2019, while European countries continued to improve.
• Life expectancy dropped sharply during the pandemic and only returned to 2019 levels in 2024.
• Sweden’s life expectancy dipped in 2020 but recovered to its prior upward trend by 2021–2022.
• Despite significant biomedical advances, the U.S. has failed to address its chronic disease crisis — obesity, depression, metabolic disease — which drives much of the life expectancy gap.
• The current generation of American children is projected to live shorter, less healthy lives than their parents.
• Dr. Bhattacharya characterized the entire industry’s focus on disease management over prevention as an indictment of current priorities.

Drug Pricing: Why Americans Pay More

• Americans pay 2–10x more for the same prescription drugs as Europeans.
• The reason involves an implicit global arrangement:
  • NIH (taxpayers) funds basic and applied research.
  • Drug companies fund late-stage Phase 3 clinical trials, but recover those costs through premium U.S. pricing.
  • European countries negotiate prices at or near marginal cost, contributing little to R&D expenses.
  • The Bayh-Dole Act (1980s) enabled patents on NIH-funded discoveries to incentivize the private sector to develop basic findings into marketable treatments — a deliberate trade-off between price and speed of translation.
• Result: American taxpayers are the primary financiers of the global pharmaceutical R&D pipeline.
• Drug company profits are estimated at two-thirds to three-quarters from the U.S. market.
• Drug company R&D naturally aligns to American health problems (obesity, depression, metabolic disease) rather than a