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“Over the oxygen supply of the body carbon dioxide spreads its protecting wings.”- Friedrich Miescher, Swiss physiologist, 1885 “在身体的氧气供应上，二氧化碳展开了它的保护翅膀。”- Friedrich Miescher，瑞士生理学家，1885 年
To reach useful simplicities, we usually have to sift through the accumulated rationalizations previous generations have produced to justify doing things their way. If we could start with an accurate understanding of what life is, and what we are doing here, science could be built up deductively as well as by the accumulation of evidence. But the fact that we have grown up amid false and unworkable models of what life is, means that we have to lean heavily on evidence, building up new models inductively, imaginatively, and scientifically. Textbooks and professional journals can be useful if they are seen as monuments to past beliefs, and not as authorities to be accepted. Examining the dogmatic models of life and the world in which life exists, we can better understand the nature of the existing barriers to constructive work. 为了达到有用的简单性，我们通常必须筛选前几代人积累的合理化理由，以证明按他们的方式行事是合理的。如果我们能够从准确理解生命是什么以及我们在这里做什么开始，科学就可以通过演绎和证据积累来建立。但事实上，我们是在错误和行不通的生活模型中长大的，这意味着我们必须严重依赖证据，以归纳、想象和科学的方式建立新的模型。如果教科书和专业期刊被视为过去信仰的纪念碑，而不是被接受的权威，它们就会很有用。通过检查生命和生命所在的世界的教条主义模型，我们可以更好地理解在做建设性工作的的时候存在哪些障碍。
The Central Dogma of the molecular geneticists, in their own words, was that information flows only from DNA to RNA, and from RNA to protein, never in the other direction. The Central Dogma was formulated to suppress forever the Lamarckian idea of the inheritance of acquired characters, that Weismann's amputation of the tails of a multitude of mice had attempted to deal with earlier in the history of genetics. 分子遗传学家的**中心法则**，用他们自己的话说，是信息只从 DNA 流向 RNA，从 RNA 流向蛋白质，绝不会向另一个方向流动。中央法则的制定是为了永远压制拉马克的获得性特征遗传的思想，在遗传学历史早期魏斯曼的老鼠尾巴切割实验试图来做这件事情。
The Central Dogma continues to be influential, even after a series of revisions. Until the 1990s, the only “practical” fruit of genetics had been genocide, but now it has become possible to insert genes into bacteria, and to use the bacteria to produce industrial quantities of specific proteins. In principle, that could be useful, although bovine growth hormone poses a threat to the health of both people and cows, human growth hormone poses a threat to athletes and old people, and human insulin could increase the number of treated diabetics. A deranged culture will put anything cheap to bad use. The ability to make organisms produce foreign proteins confirms that information can flow from DNA to protein, but as that technology was being developed, the discovery of retroviruses showed that the Central Dogma of molecular genetics was wrong, RNA is a very significant template for the production of DNA. And the scrapie prion shows that proteins can be infectious, passing along information without nucleic acids as the agent of transmission. The directed mutations demonstrated by John Cairns and others have thoroughly destroyed the Central Dogma of molecular genetics, even as it applied to the simplest organisms, but molecular genetics survives as an industrial and forensic technology. 即使经过一系列修订，中心法则仍然具有影响力。直到 1990 年代，遗传学唯一“实用”的成果是种族灭绝，但现在已经有可能将基因插入细菌中，并利用细菌生产工业数量的特定蛋白质。原则上，这可能是有用的，虽然牛生长激素对人和奶牛的健康构成威胁，但人类生长激素对运动员和老年人构成威胁，而人胰岛素可能会增加接受治疗的糖尿病患者的数量。一个错乱的文化会把任何便宜的东西都糟蹋了。使生物体产生外源蛋白质的能力证实了信息可以从 DNA 流向蛋白质，但随着这项技术的发展，逆转录病毒的发现表明分子遗传学的中心法则是错误的，RNA是生产DNA的非常重要的模板。痒病朊病毒表明蛋白质具有传染性，在没有核酸作为传播媒介的情况下传递信息。约翰凯恩斯和其他人展示的定向突变彻底破坏了分子遗传学的中心法则，即使它适用于最简单的生物，但分子遗传学作为一种工业和法医技术仍然存在。
Although evidence suggests that about 2% of human diseases involve the inheritance of an abnormal protein, the exact way the disease develops is never as clear as the geneticists would imply. And the major diseases, cancer, diabetes, heart disease, Alzheimer's, epilepsy, depression, etc., that are so often blamed on “genes,” are so poorly understood that it is arbitrary and crazy to talk about the way genes “cause” them. People who had never had a problem with diabetes in their culture, very soon suffered from the same rate of diabetes as their neighbors when they immigrated into Israel and began eating the European style diet. The interesting thing about the genetic explanation for disease is how its proponents can believe what they are saying. If you read Konrad Lorenz's writings on racial hygiene, you can imagine that he might have really come to believe what he was saying, even if it was an invention that earned him personal prestige and revenge against people who were reluctant to accept his ideas of cultural excellence and inferiority. When I listened to Gunther Stent praising the doctrine he had taken straight from Konrad Lorenz's original genocide papers, I wondered how a German who had escaped the holocaust with his Jewish family when he was nine years old could talk about those doctrines without anger, and without pointing out the purpose for which they had been created. In the audience, a professor who had been a refugee from Hungary defended the doctrine, saying that a man and his work have nothing to do with each other, though the whole content of the doctrine was that a man and his work are identical, because his behavior is determined by his genes. These were mature, internationally known intellectuals, who made the most amazingly self-contradictory statements without embarrassment, because they were committed, for some deep, mysterious reason, to the doctrine of genetic determinism. If these refugees could espouse the rationale for “racial hygiene” as their own, I suppose it isn't so hard to understand that people can devote their life to studying the genetics of diabetes, even though diabetes has appeared suddenly in one generation of immigrants when their diet was suddenly changed, a massive fact that bluntly contradicts the genetic doctrine. There is something very deep in our culture that loves genetics. 尽管有证据表明大约 2% 的人类疾病涉及异常蛋白质的遗传，但疾病发展的确切方式从未像遗传学家所暗示的那样清楚。 而那些经常被归咎于“基因”的重大疾病，癌症、糖尿病、心脏病、阿尔茨海默氏症、癫痫、抑郁症等，人们对其知之甚少，以至于谈论基因“导致”的方式是武断和疯狂的。 在他们的文化中从未患过糖尿病的人，当他们移民到以色列并开始吃欧式饮食时，很快就患上了与邻居相同的糖尿病。 关于疾病的遗传解释的有趣之处在于其支持者如何相信他们所说的话。 如果您阅读康拉德·洛伦兹 (Konrad Lorenz) 关于种族卫生的著作，您可以想象他可能真的开始相信他所说的话，即使这项发明为他赢得了个人声望并报复了那些不愿接受他的文化卓越和自卑观念的人。 当我听到冈瑟·斯坦特 (Gunther Stent) 称赞他直接从康拉德·洛伦茨 (Konrad Lorenz) 的原始种族灭绝论文中摘取的教义时，我想知道一个在九岁时与他的犹太家庭一起逃离大屠杀的德国人如何能够不愤怒地谈论这些教义，而且没有 指出创建它们的目的。 在台下，一位曾是匈牙利难民的教授为这个学说辩护，说一个人和他的工作没有任何关系，尽管这个学说的全部内容是一个人和他的工作是相同的，因为 他的行为是由他的基因决定的。 这些都是成熟的、国际知名的知识分子，他们毫不尴尬地发表了最令人惊讶的自相矛盾的言论，因为他们出于某种深刻而神秘的原因，信奉遗传决定论的学说。 如果这些难民能把“种族卫生”的理由作为自己的理由，我想就不难理解人们可以毕生致力于研究糖尿病的遗传学，即使糖尿病在一代移民中突然出现 当他们的饮食突然改变时，这是一个与遗传学说相矛盾的巨大事实。 在我们的文化中，有一种非常喜欢遗传学的东西。
One of the cultural trends that makes genetic determinism attractive is the theory of radical individualism, something that has grown up with protestant christianity, according to some historians. Roger Williams' work in nutrition seemed to be powered by this idea of individual genetic uniqueness, and in his case, the idea led him to some useful insights–he suggested that the environment could be adjusted to suit the highly specific needs of the individual. This idea led to the widespread belief that nutritional supplements might be needed by a large part of the population. Extreme nurturing of the deviant individual is the opposite extreme from the Lorenzian-Hitlerian solution, of eliminating everyone who wasn't a perfect Aryan specimen. 根据一些历史学家的说法，使基因决定论具有吸引力的文化趋势之一是激进的个人主义理论，这种理论是随着新教基督教而发展起来的。罗杰威廉姆斯在营养方面的工作似乎受到个体遗传独特性这一想法的推动，在他的案例中，这一想法使他获得了一些有用的见解——他建议可以调整环境以适应个体高度特定的需求. 这个想法导致人们普遍认为，大部分人口可能需要营养补充剂。对异常个体的极端培养与洛伦兹-希特勒的解决方案相反，即消灭所有不是完美雅利安样本的人。
But Williams' genetic doctrine assumed that our nutritional needs were primarily inborn, determined by our unique genes. However, there is a famous experiment in which rats were made deficient in riboflavin, and when their corneal tissue showed evidence of the vitamin deficiency, they were given a standard diet. However, the standard diet no longer met the needs of their eye tissue, and during the remainder of the observation period, only a dose of riboflavin several times higher than normal would prevent the signs of deficiency. A developmental change had taken place in the cornea, making its vitamin B2 requirement abnormally high. If we accept the epigenetic, developmental idea of metabolic requirements, our idea of nurturing environmental support would consider the long-range effects of environmental adequacy, and would consider that much disease could be prevented by prenatal support, and by avoiding extreme deficiencies at any time. Williams himself emphasized the importance of prenatal nutrition in disease prevention, so he wasn't a genetic totalitarian; combining the idea of unique genetic individuality with the recognition that malnutrition causes disease, led him to believe in the necessity for nutitional adequacy, rather than to the extermination of the sick, weak, or different individuals. 但是威廉姆斯的遗传学说假设我们的营养需求主要是与生俱来的，由我们独特的基因决定。然而，有一个著名的实验，在实验中，老鼠缺乏核黄素，当它们的角膜组织显示出维生素缺乏的迹象时，就会给它们标准饮食。然而，标准饮食不再满足他们眼部组织的需要，在观察期的剩余时间里，只有比正常水平高几倍的核黄素剂量才能防止缺乏的迹象。角膜发生了发育变化，使其对维生素 B2 的需求异常高。如果我们接受代谢需求的表观遗传和发育观念，我们培育环境支持的观念将考虑环境充足性的长期影响，并且会认为可以通过产前支持和随时避免极端缺陷来预防许多疾病。威廉姆斯本人强调产前营养对疾病预防的重要性，因此他不是遗传极权主义者；将独特的遗传个体的想法与营养不良导致疾病的认识相结合，使他相信营养充足的必要性，而不是消灭生病、虚弱或不同的个体。
The idea of “genetic determinism” says that our traits are the result of the specific proteins that are produced by our specific genes. The doctrine allows for some gradations, such as “half a dose” of a trait, but in practice it becomes a purely subjective accounting for everything in terms of mysterious degrees of “penetrance” of genes, and interactions with unknown factors. Proteins, that supposedly express our genetic constitution, include enzymes, structural proteins, antibodies, and a variety of protein hormones and peptide regulatory molecules. Every protein, including the smallest peptide (except certain cyclic peptides), contains at least one amine group, and usually several. Amine groups react spontaneously with carbon dioxide, to form carbamino groups, and they can also react, nonenzymically, with sugars, in the reaction called glycation or glycosylation. These chemical changes alter the functions of the proteins, so that hormones and their “receptors,” tubules and filaments, enzymes and synthetic systems, all behave differently under their influences. (The proteins' electrical charge, relationship to water and fats, and shape, change quickly and reversibly as the concentration of carbon dioxide changes; in the absence of carbon dioxide, these properties tend to change irreversibly under the influence of metabolic stress.) “遗传决定论”的想法是说我们的特征是由我们的特定基因产生的特定蛋白质的结果。 该学说允许一些等级，例如“半剂量”的性状，但在实践中，就基因“外显率”的神秘程度以及与未知因素的相互作用而言，它变成了对一切的纯粹主观的解释。 蛋白质，据推测表达我们的遗传构成，包括酶、结构蛋白、抗体以及各种蛋白质激素和肽调节分子。 每一种蛋白质，包括最小的肽（某些环肽除外），都至少含有一个胺基团，通常有几个。 胺基团与二氧化碳自发反应，形成氨基甲酸基团，并且它们也可以在称为糖基化或糖基化的反应中以非酶促方式与糖反应。 这些化学变化改变了蛋白质的功能，因此激素及其“受体”、小管和细丝、酶和合成系统在它们的影响下都表现不同。 （蛋白质的电荷、与水和脂肪的关系以及形状会随着二氧化碳浓度的变化而快速且可逆地变化；在没有二氧化碳的情况下，这些特性往往会在代谢压力的影响下发生不可逆的变化。）
This is the clearest, and the most powerful, instance of metabolic influence on biological structure. That makes it very remarkable that it has been the subject of so few publications. I think the absence of discussion of this fundamental biological principle can be understood only in relation to the great importance it has for a new understanding of development and inheritance–it is an easily documented process that will invalidate some of the most deeply held beliefs of most of the people who are influential in science and politics. 这是代谢对生物结构影响的最清楚、最有力的例子。 这非常得了不起，但是只有非常少的出版物来讨论这个主题。 我认为，对这一基本生物学原理缺乏讨论，只能从它对重新认识发展和遗传的巨大重要性来理解——这是一个很容易记录的过程，它将使大多数在科学和政治上有影响力的人最根深蒂固的一些信念失效。
I will continue discussing some of these implications in newsletters on imprinting, degenerative diseases, heart attacks, high blood pressure, and other special biological questions, but I think the most important work that remains to be done is to work out the exact mechanisms by which metabolic energy, expressed largely by factors such as the ratio of carbon dioxide to lactic acid, guides both development and evolution. These ideas will have to take into account the actual resources of the world, as well as the internal processes and resources of the organism. Each development in the organism, whether it leads to maturation or to degeneration, consists of responses to and interactions with specific environments. 我将继续在关于印记、退行性疾病、心脏病发作、高血压和其他特殊生物学问题的时事通讯中讨论其中的一些影响，但我认为仍有待完成的最重要的工作是找出代谢能量（主要由二氧化碳与乳酸的比率等因素表达）指导发育和进化的确切机制。 这些想法必须考虑到世界的实际资源，以及有机体的内部过程和资源。 生物体的每一次发展，无论是导致成熟还是退化，都包括对特定环境的反应和相互作用。
Curiosity, esthetics, creativity, and stimulation are necessarily and deeply linked to metabolic efficiency and structural-anatomical development. For example, the known effects of stimulation and success (or isolation and depression) on brain anatomy and function should be linked meaningfully with metabolic, hormonal and dietary processes. There is a large amount of information available that could be put to practical use, but there are still important ideological barriers to be overcome. Marshalling the information needed to optimize our own development runs counter to the program of our technical-scientific culture, which prefers to believe that degeneration is programmed, while emergent evolution is unforeseeable. But, if an optimization project is presented as a way to forestall the “programmed degeneration,” it might succeed in becoming part of the culture. 好奇心、美学、创造力和刺激与代谢效率和结构解剖学发展密切相关。 例如，刺激和成功（或孤立和抑郁）对大脑解剖结构和功能的已知影响应该与代谢、荷尔蒙和饮食过程有意义地联系起来。 有大量可用信息可以付诸实践，但仍有重要的意识形态障碍需要克服。 整理优化我们自身发展所需的信息与我们的技术科学文化的计划背道而驰，后者更愿意相信退化是程序化的，而紧急进化是不可预见的。 但是，如果一个优化项目被提出来阻止“程序性退化”，它可能会成功地成为文化的一部分。
Vernadsky's idea of the Noosphere differs from the Gaia hypothesis (that the world is a self-regulating organism-like system) in the intrinsic directionality of Vernadsky's Noosphere, which makes the course of human society crucial for the fate of the planet. It proposes that planets, like organisms, are going somewhere. The Gaia hypothesis is increasingly being interpreted as a justification for feeling no responsibility for the effects of technology on the environment, and some people are expressing that view of the world as essentially a justification for any vandalism that may come along. Kary Mullis, for example, says that mass extinctions of organisms have occurred in the past, and so it's just natural for species to become extinct, and it isn't appropriate to be concerned about the extinctions that are being caused by civilization's technological depredations. Vernadsky 的 Noosphere 想法与 Gaia 假设（世界是一个自我调节的有机体系统）的不同之处在于 Vernadsky 的 Noosphere 的内在方向性，这使得人类社会的进程对地球的命运至关重要。它提出行星，就像有机体一样，会去某个地方。盖亚假说越来越多地被解释为对技术对环境的影响不承担任何责任的理由，并且一些人将这种世界观表示为可能发生的任何破坏行为的基本理由。例如，Kary Mullis 说，过去曾发生过生物的大规模灭绝，因此物种灭绝是很自然的，而事实并非如此。
In the Noosphere, global warming and increased carbon dioxide would represent an advance toward a higher state of “metabolism” of the world, and this would support the emergence of new biological forms from those existing. But if whole systems of life are destroyed before that happens, the biological achievements of the past could be lost irretrievably; there is no guarantee that the system will continue to work, if major sectors are deleted from the interacting systems. Even in terms of the Gaia conception, that the earth is like an organism, consider what the loss of genetic complexity means for an organism. Sometimes, for example, things that happen to an individual lead to sterility several generations later, although the procedure didn't seem lethal for the individual or its immediate descendants. 在 Noosphere 中，全球变暖和二氧化碳增加将代表世界向更高“代谢”状态的进步，这将支持从现有生物形式中出现新的生物形式。但是，如果整个生命系统在此之前被摧毁，过去的生物学成就可能无法挽回。如果从交互系统中删除主要部门，则无法保证该系统将继续工作。即使根据盖亚的概念，地球就像一个有机体，考虑一下遗传复杂性的丧失对有机体意味着什么。例如，有时发生在一个人身上的事情会在几代后导致不育，尽管这个过程对个人或其直系后代来说似乎并不致命。
The whole idea of “evolution” is that the past is preserved within the present, or that the present is built upon the accomplishments of the past. The idea that evolution has been “random,” and that the world is simply self-regulating, might seem liberating to those who hate the idea that they might be intrinsically responsible for anything outside of themselves, but it is liberating only in the way that a vandal's manifesto might be, declaring the world to be their playground. “进化”的整个概念是过去保存在现在中，或者现在建立在过去的成就之上。进化是“随机的”以及世界只是自我调节的想法，对于那些讨厌他们可能对自身以外的任何事物负有内在责任的想法的人来说，这似乎是一种解放，但它只是在解放的方式下破坏者的宣言可能是，宣布世界是他们的游乐场。
The problem with such a manifesto of irresponsibility is simply that it is built upon the same system of cultural assumptions that produced Nazi eugenics, and that those assumptions are false. The political assumptions of the people who controlled scientific institutions were built into a set of pseudo-scientific doctrines, which continue to be valued for their political and philosophical implications. 这种不负责任宣言的问题在于，它建立在产生纳粹优生学的同一文化假设系统之上，而这些假设是错误的。控制科学机构的人的政治假设被构建成一套伪科学学说，这些学说因其政治和哲学含义而继续受到重视。
For hundreds or thousands of years, the therapeutic value of carbonated mineral springs has been known. The belief that it was the water's lively gas content that made it therapeutic led Joseph Priestley to investigate ways to make artificially carbonated water, and in the process he discovered oxygen. Carbonated water had its medical vogue in the 19th century, but the modern medical establishment has chosen to define itself in a way that glorifies “dangerous,” “powerful” treatments, and ridicules “natural” and mild approaches. The motivation is obvious–to maintain a monopoly, there must be some reason to exclude the general public from “the practice of medicine.” Witch doctors maintained their monopoly by working with frightening ghost-powers, and modern medicine uses its technical mystifications to the same purpose.vAlthough the medical profession hasn't lost its legal monopoly on health care, corporate interests have come to control the way medicine is practiced, and the way research is done in all the fields related to medicine. 数百或数千年来，碳酸矿泉的治疗价值已为人所知。 约瑟夫·普里斯特利 (Joseph Priestley) 相信是水中活泼的气体含量使其具有治疗作用，因此研究了制造人工碳酸水的方法，并在此过程中发现了氧气。 碳酸水在 19 世纪曾风靡一时，但现代医疗机构选择以一种美化“危险”、“强大”疗法并嘲笑“自然”和温和方法的方式来定义自己。 动机是显而易见的——为了保持垄断，必须有某种理由将公众排除在“行医”之外。 巫医通过与可怕的幽灵力量合作来维持其垄断地位，而现代医学也将其技术神秘性用于同一目的。尽管医学界并未失去对医疗保健的合法垄断，但企业利益已经开始控制医学的发展方式 实践，以及在与医学相关的所有领域进行研究的方式。
The fact that carbon dioxide therapy is extremely safe has led to the official doctrine that it can't be effective. The results reviewed by Yandell Henderson in the Cyclopedia of Medicine in 1940 were so impressive that carbon dioxide therapy would have been as commonly used and as well known as oxygen therapy, radiation treatments, sulfa drugs, barbiturates, and digitalis, but it was completely lacking in the thrilling mystique of those dangerous treatments. 二氧化碳疗法极其安全的事实导致官方学说认为它无效。扬德尔·亨德森 (Yandell Henderson) 在 1940 年在《医学百科全书》(Cyclopedia of Medicine) 中评论的结果令人印象深刻，以至于二氧化碳疗法本来可以与氧气疗法、放射疗法、磺胺类药物、巴比妥类药物和洋地黄一样常用且广为人知，但完全缺乏在那些危险治疗的惊心动魄的神秘感中。
Henderson assumed that carbon dioxide use was becoming a permanent part of medicine, to be used with anesthesia to prevent cessation of spontaneous breathing, during recovery from surgery to prevent shock and pneumonia, for stimulating respiration in newborns, and for resuscitating drowning or suffocation victims, as well as for treatment of heart disease and some neurological conditions (see below). However, its use in surgery and resuscitation has probably decreased since he wrote, despite occasional publications pointing out the dangers involved in the use of oxygen without carbon dioxide.
亨德森假设二氧化碳的使用正在成为药物的永久组成部分，与麻醉一起使用以防止自主呼吸停止，在手术恢复期间用于预防休克和肺炎，用于刺激新生儿的呼吸，以及用于复苏溺水或窒息的受害者，以及治疗心脏病和一些神经系统疾病（见下文）。然而，自从他写这篇文章以来，它在手术和复苏中的使用可能已经减少，尽管偶尔有出版物指出在没有二氧化碳的情况下使用氧气所涉及的危险。
REFERENCES
O. Rahn, “Protozoa need carbon dioxide for growth,” Growth 5, 197-199, 1941. “ On page 113 of this volume, the statement of Valley and Rettger that all bacteria need carbon dioxide for growth had been shown to apply to young as well as old cells.” “…it is possible…to remove it as rapidly as it is produced, and under these circumstances, bacteria cannot multiply.” 在本卷的第 113 页，Valley 和 Rettger 关于所有细菌都需要二氧化碳才能生长的声明已被证明适用于年轻和年老的细胞。”“……有可能……尽快将其去除当它产生时，在这种情况下，细菌无法繁殖。”
Y. Henderson, “Carbon Dioxide,” Cyclopedia of Medicine, 1940. “ (详情见回复) Before considering these matters, it will be best that the mind be cleared of certain deep rooted misconceptions that have long opposed the truth and impeded its applications. It will be seen that carbon dioxide is truly the breath of life.” “The human mind is inherently inclined to take a moralistic view of nature. Prior to the modern scientific era, which only goes back a generation or two, if indeed it can be said as yet even to have begun in popular thought, nearly every problem was viewed as an alternative between good and evil, righteousness and sin, God and the Devil. This superstitious slant still distorts the conceptions of health and disease; indeed, it is mainly derived from the experience of physical suffering. Lavoisier contributed unintentionally to this conception when he defined the life supporting character of oxygen and the suffocating power of carbon dioxide. Accordingly, for more than a century after his death, and even now in the field of respiration and related functions, oxygen typifies the Good and carbon dioxide is still regarded as a spirit of Evil. There could scarcely be a greater misconception of the true biological relations of these gases.” “Carbon dioxide is the chief hormone of the entire body; it is the only one that is produced by every tissue and that probably acts on every organ. In the regulation of the functions of the body, carbon dioxide exerts at least 3 well defined influences: (1) It is one of the prime factors in the acid-base balance of the blood. (2) It is the principal control of respiration. (3) It exerts an essential tonic influence upon the heart and peripheral circulation.” “A frog's muscle will contract effectively and repeatedly under suitable stimulation in an atmosphere of pure nitrogen. In contraction, a muscle produces lactic acid, partly by reconversion into sugar. In other words, oxygen is not one of the primary factors in muscular work. The reserve store of oxygen in the body is small. Vigorous breathing does not take place before an exertion; the exertion is first made and then the oxygen needed to clear the system in preparation for another exertion is absorbed. The demand for oxygen for this scavenging of waste and restoration of power is termed by A.V. Hill the “oxygen deficit” of exercise.” “On the other hand, present knowledge indicates that carbon dioxide is an absolutely essential component of protoplasm. It is one of the factors in the balance of alkali and acid for the maintenance of the normal pH of the tissues. Acapnia, that is diminution of the normal content of carbon dioxide, involves therefore, a disturbance of one of the fundamental conditions of life.” “These observations upon the circulation showed also that in animals reduced to a state of shock the carbon dioxide of the blood, or as it now be generally termed, the “alkaline reserve,” is greatly reduced. This experimental result was later confirmed by the observations of Cannon upon wounded soldiers during the war.” “Catatonia.—Finally, mention may be made of the extraordinary observations reported by the late A.S. Lovenhart, in which he found that inhalation of carbon dioxide to cases of catatonia induced a temporary restoration of intelligence and mental responsiveness. The simplest explanation of the results in these cases is attained by postulating an habitual contraction of blood-vessels in the brain of the catatonic patient, similar to that in the heart and limbs of the cases discussed in the previous section. If this view is correct, the beneficial effects of the inhalation are due to improvement in the circulation in the brain under the influence of carbon dioxide upon the finer blood vessels.”
Vojnosanit Pregl 1996 Jul-Aug;53(4):261-74. Carbon dioxide inhibits the generation of active forms of oxygen in human and animal cells and the significance of the phenomenon in biology and medicine]. Boljevic S, Kogan AH, Gracev SV, Jelisejeva SV, Daniljak IG
Carbon dioxide (CO2) influence in generation of active oxygen forms (AOF) in human mononuclear cells (blood phagocytes and alveolar macrophages) and animal cells (tissue phagocytes, parenchymal and interstitial cells of liver, kidney, lung, brain and stomach) was investigated. The AOF generation was examined by the methods of chemiluminiscence (CL) using luminol, lucigenin and NBT (nitro blue tetrazolium) reaction. It was established that CO2 in concentrations similar to those in blood (5.1%, pCO2 37.5 mmHg) and at high concentrations (8.2%, pCO2 60 mmHg; 20%, pCO2 146 mmHg) showed pronounced inhibitory effect on the AOF generation in all the studied cells (usually reducing it 2 to 4 times). Those results were obtained not only after the direct contact of isolated cells with CO2, but also after the whole body exposure to CO2. Besides, it was established that venous blood gas mixture (CO2 - 45 mmHg, +O2 - 39 mmHg, + N2 - 646 mmHg) inhibited the AOF generation in cited cells more than the arterial blood gas mixture (CO2 - 40 mmHg, + O2 - 95 mmHg, + N2 - 595 mmHg). Carbon dioxide action mechanism was developed partially through the inhibition of the OAF generation in mitochondria and through deceleration of NADPH oxidative activity. Finally, it was established that CO2 led to the better coordination of oxidation and phosphorylation and increased the phosphorylation velocity in liver mitochondria. The results clearly confirmed the general property of CO2 to inhibit significantly the AOF generation in all the cell types. This favors the new explanation of the well-known evolutionary paradox: the Earth life and organisms preservation when the oxygen, that shows toxic effects on the cells through the AOF, occurs in the atmosphere. The results can also be used to explain in a new way the vasodilating effect of CO2 and the favorable hypercapnotherapy influence on the course of some bronchial asthma forms. The results are probably significant for the analysis of important bio-ecological problem, such as the increase of CO2 concentration in the atmosphere and its effect on the humans and animals.
研究了二氧化碳 (CO2) 对人类单核细胞（血液吞噬细胞和肺泡巨噬细胞）和动物细胞（组织吞噬细胞、肝、肾、肺、脑和胃的实质和间质细胞）中活性氧形式 (AOF) 产生的影响. 通过使用鲁米诺、光泽精和 NBT（硝基蓝四唑）反应的化学发光 (CL) 方法检查 AOF 的产生。已经确定，浓度与血液中浓度相似（5.1%，pCO2 37.5 mmHg）和高浓度（8.2%，pCO2 60 mmHg；20%，pCO2 146 mmHg）的 CO2 对所有的 AOF 生成都有明显的抑制作用。研究细胞（通常减少 2 到 4 倍）。这些结果不仅是在分离的细胞与 CO2 直接接触后获得的，而且是在全身暴露于 CO2 之后获得的。除了，已确定静脉血气混合物（CO2 - 45 mmHg，+O2 - 39 mmHg，+ N2 - 646 mmHg）比动脉血气混合物（CO2 - 40 mmHg，+ O2 - 95 mmHg，+ N2 - 595 mmHg）。二氧化碳的作用机制部分是通过抑制线粒体中 OAF 的产生和 NADPH 氧化活性的减速来发展的。最后，确定 CO2 导致氧化和磷酸化的更好协调，并增加了肝线粒体的磷酸化速度。结果清楚地证实了 CO2 在所有细胞类型中显着抑制 AOF 生成的一般特性。这有利于对众所周知的进化悖论的新解释：当氧气、通过 AOF 显示出对细胞的毒性作用，发生在大气中。结果也可用于以新的方式解释 CO2 的血管舒张作用和对某些支气管哮喘病程的有利影响。研究结果可能对分析重要的生物生态问题具有重要意义，例如大气中CO2浓度的增加及其对人类和动物的影响。
Aviakosm Ekolog Med 1997;31(6):56-9. [Functional activity of peripheral blood neutrophils of rats during combined effects of hypoxia, hypercapnia and cooling]. Baev VI, Kuprava MV
Functional activity of neutrophilic leukocytes was studied in blood of rats immediately following single and repeated gradual increase in carbon dioxide and decrease in oxygen concentrations with the ambient temperature at 2 to 3 degrees C. Phagocytic activity was shown to alter as the number of phagocyticneutrophilic granulocytes, absorptivity or the phagocytic index, and the coefficient of phagocytosis completeness were elevated and levels of oxygen-dependent and oxygen-independent metabolism were reduced. 在 2 至 3 摄氏度的环境温度下，随着二氧化碳浓度的单次和重复逐渐增加和氧气浓度的降低，立即在大鼠血液中研究中性粒细胞的功能活性。吞噬活性显示为随着吞噬中性粒细胞的数量而改变、吸收率或吞噬指数和吞噬作用完整性系数升高，氧依赖性和非氧依赖性代谢水平降低。
Izv Akad Nauk Ser Biol 1997 Mar-Apr;(2):204-17. Carbon dioxide--a universal inhibitor of the generation of active oxygen forms by cells]. Kogan AKh, Grachev SV, Eliseeva SV, Bolevich S
Studies were carried out on blood phagocytes and alveolar macrophages of 96 humans, on the cells of the viscera and tissue phagocytes (liver, brain, myocardium, lungs, kidneys, stomach, and skeletal muscle), and liver mitochondria of 186 random bred white mice. Generation of the active oxygen forms was determined using different methods after direct effect of CO2 on the cells and biopsies and indirect effect of CO2 on the integral organism. The results obtained suggest that CO2 at a tension close to that observed in the blood (37.0 mm Hg) and high tensions (60 or 146 mm Hg) is a potent inhibitor of generation of the active oxygen forms by the cells and mitochondria of the human and tissues. The mechanism of CO2 effect appears to be realized, partially, through inhibition of the NADPH-oxidase activity. The results are important for deciphering of a paradox of evolution, life preservation upon appearance of oxygen in the atmosphere and succession of anaerobiosis by aerobiosis, and elucidation of some other problems of biology and medicine, as well as analysis of the global bioecological problem, such as ever increasing CO2 content in the atmosphere.
对96人的血液吞噬细胞和肺泡巨噬细胞进行了研究，对186只随机饲养的白鼠的内脏和组织吞噬细胞（肝、脑、心肌、肺、肾、胃和骨骼肌）和肝线粒体进行了研究. 在 CO2 对细胞和活组织检查的直接影响和 CO2 对整体生物的间接影响之后，使用不同的方法确定活性氧形式的产生。获得的结果表明，在接近于血液中观察到的压力 (37.0 毫米汞柱) 和高压力 (60 或 146 毫米汞柱) 的 CO2 是人类细胞和线粒体产生活性氧形式的有效抑制剂和组织。CO2 效应的机制似乎部分是通过抑制 NADPH 氧化酶活性来实现的。
Ukr Biokhim Zh 1978 Mar-Apr;50(2):150-4.. Content of adenine nucleotides and creatinephosphate in brain, myocardium, liver and skeletal muscle under combined action of hypercapnia, hypoxia and cooling]. Baev VI, Drukina MA
Cooling of rats under conditions of hypercapina and hypoxia induced no changes in the content of adenine nucleotides in the brain and skeletal muscles and decreased their concentration in the liver and myocardium. The content of creatine phosphate increased in the brain, but had no changes in the other tissues. 48 hours after cooling the amount of adenine nucleotides in the brain was higher as compared with the initial values, that was due to an increase in the ATP concentration; in the other tissues the contents of adenine nucleotides did not differ from that of the intact rats. The repeated action (48 hours after the first influences) caused no changes in the contents of adenine nucleotides in skeletal muscles and decreased them in the myocardium and liver. In the brain their amount and the content of creatinephosphate were increased as related to the intact rats. In the brain and myocardium the level of NADPH decreased after the first action and 48 hours after impact it restored up to the inital values. After repeated impact the level of NADPH in the brain restored up to initial values, in the myocardium it was increased.
在高碳酸血症和缺氧条件下对大鼠进行冷却后，大脑和骨骼肌中腺嘌呤核苷酸的含量没有变化，但它们在肝脏和心肌中的浓度降低。大脑中磷酸肌酸的含量增加，但其他组织中没有变化。冷却48小时后，大脑中腺嘌呤核苷酸的数量比初始值高，这是由于ATP浓度增加所致；在其他组织中，腺嘌呤核苷酸的含量与完整大鼠的没有差异。重复动作（第一次影响后 48 小时）导致骨骼肌中腺嘌呤核苷酸的含量没有变化，而心肌和肝脏中的腺嘌呤核苷酸含量减少。在大脑中，它们的数量和磷酸肌酸的含量与完整大鼠有关。在大脑和心肌中，NADPH 水平在第一个动作后下降，在撞击后 48 小时恢复到初始值。经过反复冲击，大脑中的 NADPH 水平恢复到初始值，心肌中的 NADPH 水平增加。
Fiziol Zh SSSR 1978 Oct;64(10):1456-62. Role of CO2 fixation in increasing the body's resistance to acute hypoxia]. Baev VI, Vasil'ev VV, Nikolaeva EN
In rats, the phenomenon of considerable increase in resistance to acute hypoxia observed after 2-hour stay under conditions of gradually increasing concentration of CO2, decreasing concentration of O2, And external cooling at 2–3 degrees seems to be based mainly on changes in concentration of CO2 (ACCORDINGLY, PCO2 and other forms of CO2 in the blood). The high resistance to acute hypoxia develops as well after subcutaneous or i.v. administration of 1.0 ml of water solution (169.2 mg/200 g) NaHCO2, (NH4)2SO4, MgSO4, MnSO4, and ZnSO4 (in proportion: 35 : 5 : 2 : 0.15 : 0.15, resp.) or after 1-hour effect of increased hypercapnia and hypoxia without cooling.
大鼠在CO2浓度逐渐升高、O2浓度逐渐降低、AN和2–3度外降温条件下，停留2小时后观察到的对急性缺氧的抵抗力显着增加的现象似乎主要是基于CO2 浓度（相应地，血液中的 PCO2 和其他形式的 CO2）。在皮下或静脉注射 1.0 ml NaHCO2、(NH4)2SO4、MgSO4、MnSO4 和 ZnSO4（比例：35 : 5 : 2 : 0.15 : 0.15，分别）或在不冷却的情况下增加高碳酸血症和缺氧 1 小时后。
Vopr Med Khim 1976 Jan-Feb;22(1):37-41 Pyridine nucleotide content in the brain and myocardium of rats under combined effect of hypercapnia, hypoxia and cooling]. Baev VI, Drukina MA
In experiments with rats, subjected to single and repeated simultaneous effect of hypercapnia, hypoxia and cooling, contents of pyridine nucleotides (NAD, NADP, NAD-H2 and NADP-H2) and macroergic substances were studied and also the activity of dehydrogenases of the pentose pathway was determined in brain and myocardium. In brain NADP was not practically determined and in heart its content was increased after the first and the second treatments. Content of NADP-H2 was distinctly decreased in both tissues after the single treatment. NAD was not altered in the tissues in all the periods studied. The amount of NAD-H2 was decreased in brain after the single treatment and it was increased in myocardium after the repeated one. In the activity of dehydrogenases marked alterations were not observed. Total macroergic substances were not altered in brain after the single treatment and after the repeated one they were increased mainly due to the ATP increase. In myocardium total macroergic substances were decreased after the both treatments.
在大鼠实验中，在高碳酸血症、缺氧和冷却的单一和重复同时作用下，研究了吡啶核苷酸（NAD、NADP、NAD-H2 和 NADP-H2）和大能物质的含量以及戊糖脱氢酶的活性在脑和心肌中确定了通路。在脑中 NADP 没有实际确定，在第一次和第二次治疗后，它在心脏中的含量增加。单次处理后两种组织中NADP-H2的含量均明显降低。在所有研究期间，组织中的 NAD 没有改变。单次治疗后脑内NAD-H2含量减少，重复治疗后心肌内NAD-H2含量增加。在脱氢酶的活性中没有观察到显着的改变。单次治疗后大脑中的总巨能物质没有改变，重复治疗后它们增加主要是由于ATP增加。两种治疗后心肌中总的巨能物质均减少。
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