There is growing agreement among scientists that the world may face catastrophic climatic developments in the coming decades, caused primarily by the massive emission of greenhouse gases such as CO₂ and methane. Many governments are already beginning to face the challenge on how to manage and minimize the calamitous effects. The topic is a complex interplay of many facets, and the sheer size of the successive meetings of the Conference of Parties─UN Climate Change, with tens of thousands of attendees, bears witness that the management of the ongoing climate change will require a massive input of creative ideas and resources. The topic is central to the ability of humans to survive on Earth, so minimization and mitigation of climate change will be the driver for several decisions in the next decades. It is clear that we are at the beginning of a new modern industrial revolution which will completely change the way we live and how our economies function. The coming decades will experience a massive shift to renewable energies, with replacement of energy-intensive chemical manufacturing processes such as the Haber–Bosch ammonia synthesis and the petrol-based polymer industry by renewable materials and sustainable technologies. We will also have to find strategies on how to deal with limiting supplies of critical elements such as P, Pd, and Li, and critically, the construction industry will have to find replacements for concrete. These are massive challenges and will amount to a new analogous industrial revolution that requires unabated efforts in defining our future economies that will alter the fabric of our societies. Health (new medicines) and materials (to improve living standards) are central to modern human existence. Transforming science, engineering, and technologies should play a critical role by providing solutions and new opportunities. Toward this end, chemistry will play a vital and decisive role as the central science, since the material world is dependent on finite chemical resources on and within Earth. We need to acknowledge the fact that the ability of humankind to continue living on this planet depends on chemists and their creativity to bring forward solutions. The chemical community should responsibly and proudly embrace this responsibility. How will all these demands effect the production and affordability of medicines? Let us look at how the existing processes and prevailing industrial revolution will affect the production of different types of medicines and what the decarbonized industrial landscape will mean for the manufacture of these. One should never forget that medicines should not only extend patients’ lifetimes but also improve the quality of our lives. Medicines cover a vast range of different modalities, each associated with characteristic production technologies. Very importantly, all technologies are associated with widely varying business models. Let us keep in mind that the economics of a recently launched, patent-protected antibody–drug conjugate has nothing in common with that of a blood-pressure-lowering generic medicine available in the market for decades. The sharply different economic models have stark consequences, and it is regrettable that both public and private companies blur this line in communication. This confusion may be explained by the fact that the preparation of a classical generic medicine is done using the same sophisticated high technology by highly skilled experts, often in the factory of the inventor next to an innovative new drug with a very different business model behind it. However, it is also a fact that the preparation of generic medicines is not a high-margin business. New modalities are highly complex─the effort required to prepare an antibody–drug conjugate is massively more complex than that for production of a classical drug. Similar complexity exists for a small synthetic oligonucleotide, where the synthesis of a building block alone requires more synthetic effort than for many small-molecule drugs. The intricacies require the extensive use of energy and solvents that generate vast amounts of waste─in other words, it is far from being benign and sustainable. While ideas abound on how to improve the sustainability of biologics, oligonucleotides, and peptides, it is fair to say that these modalities will never become easy to produce, and they will always have a problematic carbon footprint. It is likely that modern biomolecular medicines will be used when they provide therapeutic benefits in wealthy societies, despite their high cost and poor environmental footprint. From a global point of view, one can look at these as a luxury that society decides to indulge in. The vast majority of medicines in all countries, irrespective of their wealth, are still the classical drugs. Essentially, these are small-molecule drugs, usually prepared solely by chemical routes or by chemical derivatization of a natural product made by fermentation or by isolation from a plant. While every year pharmaceutical research adds new compounds to the list, the number of essential medicines is largely fixed. (1) These drugs will be prescribed to patients for years and decades to come, simply because they offer an efficient, efficacious, safe, cost-effective, and proven way to treat diseases. Small-molecule medicines are the bedrock of our medical system. It is thus important to focus on how they are produced and what we can expect for the production in the future. Many important medicines were discovered beginning in the middle of the last century, and their discovery reflects the chemistry available at that time. Enabling innovative reactions led to accessing vast chemical space in new drugs, such as the Suzuki coupling leading to biaryl drugs. The structures of the target drugs also reflect the chemistry and the starting materials available at the time of their discovery. It is no surprise that almost all available starting materials stem exclusively from geological petrol via the steam cracker, meaning that the bulk of our important medicines result from old chemistry with deep origin in fossil fuels. While it is important to fully follow the value chain back to the basic starting materials, it is not sufficient to go back in a synthesis to, e.g., thiophene to realize that thiophene is prepared in a high-temperature gas-phase reaction from butadiene and sulfur to arrive at the root of the material. Only a full knowledge of the value chain allows full control and risk management. The business drive to rely on starting materials of increasing complexity has created opaque supply chains with an inherently higher risk, as the global supply of a drug may depend on a tiny number of factories preparing a specific chemical. We currently do not have a full global picture of the supply chain for our essential drugs, risking the supply recklessly. This is the opposite of a diversified and derisked supply chain, something societies should demand given the importance of drugs for our health. A look into a complex global supply chain going back to petroleum-based chemistry that was developed decades ago does not bode well for the resulting carbon footprint of the production of medicines. This is reflected in the statistics that the production of drugs is perhaps responsible for approximately 1% of the global CO₂ emissions. (2,3) Access to medicines will be challenged by an important additional hurdle. The chemical feedstock was shifted from coal tar to petrol more than 100 years ago, and we are currently witnessing a new shift away from petrol to bio-based and renewable materials. This change is necessary and will provide functional equivalents to many of the products that we use in our daily lives. Replacing terephthalic acid with the corresponding furan-based dicarboxylic acid will result in an essentially functional equivalent polymer, which is bio-derived and biodegradable, i.e., independent of petrol as a starting point. Similar substitution of a phenyl group with a furan will not work for a pharmaceutical drug and is not that simple. The structures of the medicines that are the bedrock of our medical system cannot be altered without significant impact on their biological function, and we will need to continue producing them even when the whole supply chain has switched from petrol-based to bio-based products. Chemistry in general, but especially process chemistry, will be the central science to enable the transformation of supply chains toward sustainability. (4) Organic process research and development is the science that allows the safe, reliable, and economic preparation of bulk amounts of drugs in high quality while maintaining a very high environmental standard. It is important to note that this science is neither practiced nor generally taught at universities─its art is almost exclusively practiced in industrial laboratories. This creates a strange situation where industry hires university graduates who were trained in relevant areas but different from what is central to process chemistry and then trains them to become process chemists. There is also a growing disconnect between the perception of challenges in academia and what is necessarily important for industrial process research. This may have been unproductive and undesirable in the past, but it has to change now. Industry simply does not have the skills or the means to drive the shift from a petrol-based supply chain to one based on bio-derived starting materials. Industry certainly will not be able to discover sustainable reagents and reaction conditions for a large set of transformations or to find catalysts based on first-row transition metals (available in abundant amounts on our planet). It will be decisive for the academic world, too, to embrace such great challenges and to focus on delivering solutions. Overall, we will need a fundamental change in the way chemistry is taught, challenges are defined, and research is done, both in universities and industry─but rightly, it has to start in academia. Many things will have to change to achieve this goal. The concept of green chemistry was put forward over 25 years ago. Paul Anastas and John Warner coauthored the groundbreaking book Green Chemistry: Theory and Practice, (5) and it is a fascinating exercise to reread the book for all the insight and wisdom that came with the creation and definition of green chemistry. The holistic concept has shaped the chemistry discussion for the last two decades, and the 12 principles of green chemistry are put up in many chemists’ offices. It is striking to see the wisdom of the principles of green chemistry asking for the design of biodegradable products when we are facing a global crisis because of the pollution caused by the “forever” chemicals. The world would be in a much better state had the warnings been heeded earlier. Nevertheless, after 25 years it is important to reflect on whether we need an update of the 12 principles of green chemistry. From today’s perspective, one could argue that it is not necessarily true that catalysis is always better than a resolution, e.g., if one compares a dynamic resolution with concomitant racemization to an Ir-catalyzed reaction requiring a high catalyst loading. The 12 principles put a strong emphasis on the safety and toxicity of chemicals. The well-being of everyone working with chemicals is paramount, but it is possible to work with very toxic chemicals safely when the appropriate measures are taken. A good example is the industrial synthesis of the amino acid methionine, which is made on huge scale from HCN, acrolein, and methanethiol, all of which are very toxic and dangerous compounds. Chemists and chemical engineers know how to handle dangerous chemicals, and their use should be encouraged when they enable production with a decreased carbon footprint. We believe that an update of the 12 principles of green chemistry is needed for the topic of drug substance production and that this update must provide strong quantitative guidance allowing an objective and quantifiable measure for sustainability. We therefore propose the following three principles of green chemistry for API production: Understand the supply chain. Fully map and understand the synthesis of an API going back all the way to the basic starting materials (steam cracker, fermentation product) and include all reagents and catalysts in this analysis. Evaluate the greenhouse gas emissions. Determine full greenhouse gas output for all routes going back to the basic starting materials (6) and use this output as a new metric to evaluate a synthetic procedure in addition to traditional approaches such as PMI, yield, number of steps, and cost. Minimize environmental impact, including greenhouse gases. Invent chemistry that enables short preparation of drug substances with minimal greenhouse emissions. What differentiates these three principles from the conventional way of working? The first rule will create full transparency by creating the awareness of the real and objective complexity of a route. It has become a bad habit to start chemistry with the “commercially available starting material” without answering the question of what effort was invested to prepare that material. Such a strategy is problematic because it obscures the real impact of a route and outsources the synthetic challenge to an unknown producer with an unknown CO₂ and environmental footprint. The second rule provides the metrics by which we have to measure our activities in organic chemistry. It is an old adage that one has to measure things when one wants to change them. The classical metrics in organic chemistry had been the number of steps and the overall yield from a commercial starting material, and these metrics simply do not capture what is mandatory for chemists to deliver in order to achieve the required decarbonization. What is currently missing is an agreed system that allows the calculation of the CO₂ footprint with relative ease and in a globally consistent and agreed manner. Such a system will get away from “greenwashing”, where the pretense of an environmentally good approach is created. The third rule asks for a radical change the way chemists work. Curiosity-driven research to answer fundamental questions is important and needs to continue, maybe even much more than currently allowed by the academic funding system. One may regret it, but much publicly funded research has been done for some purpose designed to ultimately bring economic benefits to the country funding the research. Virtually any natural product synthesis will argue that the compound to be synthesized possesses some virtuous properties and that the total synthesis is necessary in order to benefit from the properties of the compound. The reality is that the compound was synthesized because the chemist considered the compound to be interesting and it allowed the researcher to develop and demonstrate new synthetic strategies and to demonstrate her or his creativity, inventiveness, and persistence at solving very challenging problems. In order to achieve the decarbonization of API production, it will be necessary to bring the same scientific brilliance to our real-world problems. The questions concern “industrial” research, as they have a practical underpinning, but they have nothing to do with the often-used image of industrial research as a minor tweaking of known methods for economic gains. The challenges are daunting. It is a good assumption that the production of all of our medicines is working close to the optimum in the frame of the known chemistry, and there is little benefit in minor changes. We have to invent chemistry that does not exist and is not imagined today, which demands not just a gradual change or improvement but a reinvention of what is possible. Moreover, failure is not an option─we must succeed in decarbonizing the production of medicines, and we need to change the raw material basis from petrol-based to bio-based materials. We must do this for real─just greenwashing is not good enough. Is there a simple recipe for finding the answers? The authors think that there is. Natural product chemistry flourished because the brightest and most ambitious organic chemists went into the tough field. Funding agencies should do the same with medicines: ask for novel approaches that allow scientists to shine with the metrics of minimized carbon footprint. It is sure that the chemical community will come with solutions that we cannot even imagine today. Giving human creativity resources in the form of funding while defining strict metrics of what needs to be achieved will provide the answers we need, just as it always has throughout humankind’s history. Bio-based starting materials are central to decarbonizing the chemical industry and making it sustainable. The focus is naturally on the preparation of materials that will find use in bulk products, based on the correct assumption that the biggest steps to decarbonization can be achieved by replacing the current petrol-based starting materials and products with new components that are bio-derived. The number of compounds that can be derived efficiently and effectively from straw or wood, from efficient fermentation, and from creative enzymic approaches is steadily increasing in an impressive manner. The new developments will provide a new set of available starting materials, just as the steam cracker changed what was available from coal-tar-derived chemistry. What will be needed is the translation of these compounds with efficient methods into what should be the foundation of new chemistry leading to medicines. This is far from trivial. We are facing a grand challenge that must be solved to secure the supply of medicines to patients in the decades to come. We can be optimistic that the chemical community has the skills to rise to the challenge and that politics has understood the need, so that funding agencies will support this research. A key aspect is that politics and funding agencies must create and define a globally accepted and uniform system to measure CO₂ emission in order to enable a strict application of objective metrics. Such a system is a prerequisite, and global funding agencies should see to the establishment of such as system. Innovation in the field of medicines is often protected by patents, which allow the patent grantee to stop others from applying the invention. The search for new drugs depends on the ability to protect the invention with a patent, as this is the way to justify the highly risky and expensive investment to look for new drugs. The situation is different for the production of generic medicines. Margins are much lower, and there should be an incentive to have the lowest-carbon-footprint technologies widely known and widely used. A potential solution to this need would be compulsory licensing under fair and equitable terms to all producers that meet a set of social and environmental standards. We believe that the goal of decarbonizing and securing the production of medicines for the coming generations can be achieved. The political decision is basically quite simple: funding agencies need to ask for research addressing technologies for sustainable API production but strictly using the three principles for sustainable API production as guidance. The technical challenge is everything but simple and will require innovation of the highest level─but chemists thrive on tough challenges and have an excellent track record for delivering solutions. We have all reason to be optimistic─we just need to start the journey. This article references 6 other publications. U.S. healthcare causes ca. 7% of U.S. emissions of CO₂. See: Of these emissions, 14% are emitted as result of drug production (tenofovir as an example). See: This article has not yet been cited by other publications.

中文翻译：

---

绿色化学原则的扩展：包括温室气体和碳足迹


科学家们越来越一致认为，未来几十年世界可能面临灾难性的气候发展，这主要是由 CO₂ 和甲烷等温室气体的大量排放引起的。许多政府已经开始面临如何管理和减少灾难性影响的挑战。这个话题是多方面的复杂相互作用，联合国气候变化会议连续召开的会议规模庞大，有数万名与会者，这证明管理正在进行的气候变化将需要大量的创意和资源投入。该主题是人类在地球上生存能力的核心，因此最小化和缓解气候变化将成为未来几十年多项决策的驱动力。很明显，我们正处于一场新的现代工业革命的开端，它将彻底改变我们的生活方式和经济运作方式。未来几十年，可再生能源将发生向可再生能源的巨大转变，可再生材料和可持续技术将取代能源密集型化学制造工艺，例如 Haber-Bosch 氨合成和汽油基聚合物工业。我们还必须找到如何应对 P、Pd 和 Li 等关键元素供应受限的策略，而至关重要的是，建筑业将不得不寻找混凝土的替代品。这些都是巨大的挑战，将相当于一场新的类似工业革命，需要有增无减的努力来定义我们将改变我们社会结构的未来经济。健康（新药）和材料（提高生活水平）是现代人类生存的核心。 通过提供解决方案和新机会，科学、工程和技术转型应该发挥关键作用。为此，化学作为中心科学将发挥至关重要和决定性的作用，因为物质世界依赖于地球上和地球内部有限的化学资源。我们需要承认这样一个事实，即人类继续在这个星球上生活的能力取决于化学家及其创造力来提出解决方案。化学界应该负责任地、自豪地承担这一责任。所有这些需求将如何影响药品的生产和可负担性？让我们看看现有流程和流行的工业革命将如何影响不同类型药物的生产，以及脱碳工业格局对这些药物的制造意味着什么。我们永远不应该忘记，药物不仅应该延长患者的寿命，还应该提高我们的生活质量。药物涵盖多种不同的方式，每种方式都与独特的生产技术有关。非常重要的是，所有技术都与千差万别的商业模式相关联。让我们记住，最近推出的受专利保护的抗体-药物偶联物的经济性与几十年来市场上可用的降血压仿制药的经济性没有任何共同之处。截然不同的经济模式会产生明显的后果，令人遗憾的是，公共和私营公司都在沟通中模糊了这条界限。 这种混淆可能是因为经典仿制药的制备是由高技能专家使用相同的复杂高科技完成的，通常在发明人的工厂中，紧挨着一种商业模式截然不同的创新新药。然而，仿制药的制备并不是一项高利润的业务，这也是一个事实。新模式非常复杂，制备抗体-药物偶联物所需的工作量比生产经典药物要复杂得多。小合成寡核苷酸也存在类似的复杂性，其中仅合成一个结构单元就比许多小分子药物需要更多的合成工作。这些错综复杂的问题需要广泛使用能源和溶剂，从而产生大量废物，换句话说，这远非良性和可持续的。虽然关于如何提高生物制剂、寡核苷酸和肽的可持续性的想法比比皆是，但公平地说，这些模式永远不会变得容易生产，而且它们总是会产生有问题的碳足迹。当现代生物分子药物在富裕社会提供治疗益处时，很可能会使用现代生物分子药物，尽管它们成本高且对环境的影响很差。从全球的角度来看，人们可以将这些视为社会决定沉迷于其中的奢侈品。所有国家的绝大多数药物，无论其财富如何，仍然是经典药物。从本质上讲，这些是小分子药物，通常仅通过化学途径或通过发酵或从植物中分离制成的天然产物的化学衍生化制备。 虽然每年药物研究都会向清单中添加新的化合物，但基本药物的数量在很大程度上是固定的。（1） 这些药物将在未来几年和几十年内为患者开具处方，仅仅是因为它们提供了一种高效、有效、安全、经济且行之有效的疾病治疗方法。小分子药物是我们医疗系统的基石。因此，重要的是要关注它们的生产方式以及我们对未来生产的期望。许多重要的药物从上世纪中叶开始被发现，它们的发现反映了当时可用的化学成分。实现创新反应导致新药获得巨大的化学空间，例如导致联芳基药物的 Suzuki 偶联。目标药物的结构也反映了其发现时可用的化学性质和起始材料。毫不奇怪，几乎所有可用的起始材料都完全来自通过蒸汽裂解装置的地质汽油，这意味着我们的大部分重要药物都来自深深源自化石燃料的古老化学成分。虽然完全遵循价值链回到基本起始材料很重要，但在合成中回到例如噻吩是不够的，要意识到噻吩是由丁二烯和硫在高温气相反应中制备的，以到达材料的根源。只有全面了解价值链才能进行全面控制和风险管理。依赖日益复杂的起始材料的商业驱动力创造了不透明的供应链，本质上具有更高的风险，因为药物的全球供应可能取决于少数准备特定化学品的工厂。 我们目前没有关于我们基本药物供应链的全球全面情况，这不计后果地冒着供应的风险。这与多元化和去风险的供应链相反，鉴于药物对我们健康的重要性，社会应该要求这样做。回顾几十年前开发的石油化学，复杂的全球供应链对于药品生产产生的碳足迹来说并不是一个好兆头。这反映在统计数据中，药物生产可能占全球二氧化碳排放量的 1% 左右。（2,3） 获得药物将面临一个重要的额外障碍。100 多年前，化学原料从煤焦油转向汽油，我们目前正在目睹从汽油到生物基和可再生材料的新转变。这种变化是必要的，它将为我们日常生活中使用的许多产品提供等效的功能。用相应的呋喃基二羧酸代替对苯二甲酸将产生一种本质上功能等效的聚合物，该聚合物是生物衍生和可生物降解的，即独立于汽油作为起点。用呋喃取代苯基的类似方法不适用于药物，而且也不是那么简单。作为我们医疗系统基石的药物结构无法在不对其生物功能产生重大影响的情况下改变，即使整个供应链已从汽油基产品转向生物基产品，我们也需要继续生产它们。一般来说，化学，尤其是过程化学，将成为实现供应链向可持续发展转型的核心科学。 （4） 有机工艺研究和开发是一门科学，它允许安全、可靠和经济地制备高质量的大量药物，同时保持非常高的环境标准。值得注意的是，这门科学既不在大学里实践，也不在大学里普遍教授——它的艺术几乎完全在工业实验室中实践。这造成了一种奇怪的情况，即工业界雇用了接受过相关领域培训但与加工化学的核心不同的大学毕业生，然后培训他们成为加工化学家。学术界对挑战的看法与工业过程研究的必要重要性之间也存在越来越大的脱节。这在过去可能是无益且不可取的，但现在必须改变。工业界根本没有技能或手段来推动从基于汽油的供应链转变为基于生物衍生的原材料的供应链。工业界肯定无法为大量转化发现可持续的试剂和反应条件，也无法找到基于第一排过渡金属（地球上有大量）的催化剂。学术界也必须接受如此巨大的挑战并专注于提供解决方案。总的来说，我们需要从根本上改变大学和工业界的化学教学方式、定义挑战和进行研究的方式——但正确地，它必须从学术界开始。要实现这一目标，必须做出许多改变。绿色化学的概念是在 25 年前提出的。 Paul Anastas 和 John Warner 合著了开创性的著作《绿色化学：理论与实践》（Green Chemistry： Theory and Practice），（5） 重读这本书，了解绿色化学的创造和定义所带来的所有见解和智慧，这是一个引人入胜的练习。整体概念塑造了过去二十年的化学讨论，绿色化学的 12 项原则被许多化学家的办公室提出。令人震惊的是，当我们因“永久”化学品造成的污染而面临全球危机时，绿色化学原则要求设计可生物降解产品的智慧。如果早点注意到这些警告，世界将处于一个更好的状态。尽管如此，25 年后，重要的是要反思我们是否需要更新绿色化学的 12 项原则。从今天的角度来看，人们可能会争辩说，催化并不总是比分离更好，例如，如果将伴随外消旋化的动态分离与需要高催化剂负载的 Ir 催化反应进行比较。这 12 项原则非常强调化学品的安全性和毒性。与化学品打交道的每个人的福祉都至关重要，但采取适当措施后，可以安全地使用剧毒化学品。一个很好的例子是氨基酸蛋氨酸的工业合成，它是由 HCN、丙烯醛和甲硫醇大规模制造的，所有这些都是剧毒和危险的化合物。化学家和化学工程师知道如何处理危险化学品，当它们能够减少碳足迹的生产时，应鼓励使用它们。 我们认为，原料药生产主题需要更新绿色化学的 12 项原则，并且此更新必须提供强有力的定量指导，以便对可持续性进行客观和可量化的衡量。因此，我们提出了以下三个用于 API 生产的绿色化学原则：了解供应链。全面映射和了解 API 的合成，一直追溯到基本起始材料（蒸汽裂解装置、发酵产物），并将所有试剂和催化剂纳入此分析。评估温室气体排放。确定所有途径的温室气体总产量，可追溯到基本起始材料 （6），并将此产量用作新指标，以评估除 PMI、产量、步骤数和成本等传统方法外的合成程序。最大限度地减少环境影响，包括温室气体。发明化学方法，以最少的温室气体排放实现原料药的短制备。这三项原则与传统的工作方式有什么区别？第一条规则将通过建立对路线的真实和客观复杂性的认识来创建完全透明。从“市售起始材料”开始化学反应，而不回答为制备该材料投入了多少精力的问题，这已经成为一个坏习惯。这样的策略是有问题的，因为它掩盖了路线的真正影响，并将合成挑战外包给 CO₂ 和环境足迹未知的未知生产商。第二条规则提供了我们必须用来衡量有机化学活动的指标。有一句古老的谚语说，当一个人想改变事物时，就必须衡量它们。 有机化学中的经典指标是商业起始材料的步骤数和总产量，而这些指标根本无法捕捉化学家为了实现所需的脱碳而必须提供的内容。目前缺少的是一个商定的系统，该系统允许以全球一致和商定的方式相对容易地计算 CO₂ 足迹。这样的系统将摆脱“漂绿”，在漂绿中，创造了一种对环境有益的方法的幌子。第三条规则要求从根本上改变化学家的工作方式。以好奇心为导向的研究来回答基本问题很重要，需要继续下去，甚至可能比目前学术资助系统允许的还要多得多。人们可能会后悔，但许多公共资助的研究都是出于某种目的，旨在最终为资助研究的国家带来经济利益。实际上，任何天然产物合成都会争辩说，要合成的化合物具有一些良性，并且为了从化合物的特性中受益，完全合成是必要的。现实情况是，合成这种化合物是因为化学家认为这种化合物很有趣，它允许研究人员开发和展示新的合成策略，并展示她或他在解决非常具有挑战性的问题时的创造力、创造力和毅力。为了实现 API 生产的脱碳，有必要为我们的现实问题带来同样的科学光彩。 这些问题涉及“工业”研究，因为它们有实际的基础，但它们与工业研究的经常被使用的形象无关，即工业研究是对已知方法的微小调整以获得经济利益。挑战令人生畏。这是一个很好的假设，即我们所有药物的生产都在已知化学的框架内接近最佳状态，微小的变化几乎没有好处。我们必须发明不存在且今天无法想象的化学反应，这不仅需要逐步改变或改进，还需要重新创造可能的东西。此外，失败不是一种选择——我们必须成功地实现药品生产的脱碳，我们需要将原材料基础从汽油基材料转变为生物基材料。我们必须真正地这样做——仅仅漂绿是不够的。有没有一个简单的方法来寻找答案？作者认为有。天然产物化学之所以蓬勃发展，是因为最聪明、最雄心勃勃的有机化学家进入了这个艰难的领域。资助机构也应该对药物做同样的事情：寻求新的方法，让科学家能够在最大限度地减少碳足迹的指标上大放异彩。可以肯定的是，化学界将带来我们今天甚至无法想象的解决方案。以资金的形式为人类创造力提供资源，同时定义需要实现的严格指标，这将提供我们需要的答案，就像人类历史上一贯的答案一样。生物基原料是化工行业脱碳和可持续发展的核心。重点自然是准备用于散装产品的材料，基于正确的假设，即通过用生物衍生的新成分取代目前的汽油基起始材料和产品，可以实现脱碳的最大步骤。可以从秸秆或木材、高效发酵和创造性酶方法中高效和有效地衍生的化合物数量正在以令人印象深刻的方式稳步增加。新的发展将提供一套新的可用起始材料，就像蒸汽裂解装置改变了煤焦油衍生化学的可用材料一样。需要的是用有效的方法将这些化合物转化为导致药物的新化学的基础。这绝非微不足道。我们正面临着一项必须解决的巨大挑战，以确保未来几十年向患者供应药物。我们可以乐观地认为，化学界有能力应对挑战，并且政治界已经理解了这种需求，因此资助机构将支持这项研究。一个关键方面是，政治和资助机构必须创建并定义一个全球公认的统一系统来测量 CO₂ 排放，以便能够严格应用客观指标。这样的系统是前提，全球资助机构应该确保建立这样的系统。医药领域的创新通常受到专利的保护，专利授权人可以阻止他人应用该发明。 寻找新药取决于通过专利保护发明的能力，因为这是证明寻找新药的高风险和昂贵投资是合理的方式。仿制药的生产情况有所不同。利润率要低得多，应该有动力让最低碳足迹的技术广为人知并得到广泛使用。满足这一需求的潜在解决方案是在公平公正的条款下向所有符合一系列社会和环境标准的生产者提供强制许可。我们相信，为子孙后代实现脱碳和确保药品生产的目标可以实现。政治决定基本上很简单：资助机构需要要求研究可持续 API 生产技术，但严格使用可持续 API 生产的三项原则作为指导。技术挑战绝非简单，需要最高水平的创新，但化学家们在严峻的挑战中茁壮成长，并且在提供解决方案方面拥有出色的记录。我们都有理由保持乐观——我们只需要开始这段旅程。本文引用了其他 6 篇出版物。美国医疗保健造成的 CO₂ 排放量约占美国排放量的 7%。请参阅：在这些排放物中，14% 是由于药物生产而排放的（例如替诺福韦）。请参阅：本文尚未被其他出版物引用。