 Okay, so for our first talk of the afternoon, Daniel, you and historian, I have to say that you out of the ground, I have to say, when we were designing this workshop with Shao Shao says, we have to invite the historian. We have to invite the historian. At least one historian in every workshop, because historians are great. So what happens when you hire me? Sorry. So I was really happy to comply. I have to say that Daniel was less keen because he was not sure how he could contribute to a philosophy on causation, but of course usually historians under rape themselves. So we will listen, Daniel, on discussing ending epigenesis cell and protoplasma as developmental agents, 1828 to 1850. Gosh, I gave you a set of dates that I didn't hold to at all. That's a historian. Thank you so much, Alexander and Charles for inviting me. It's really lovely to be here. I, in my defense, I feel like I know something about causation, but I don't know what ontic causation is, and maybe you can still help me out with that a little bit. So I work on, I have a project right now that's funded by the German Research Foundation on the history of the first century of cell and protoplasm theory. Now people, actually can I get a show of hints? Do most of you know the basic history of cell theory? Like when cell theory started? No? Okay, no is a good answer. That's an answer I've been wondering. So, right, most of us know what cells are, but what was protoplasm, and one of my big points in the project is that these two theories together were important to think about as two parts of one larger theory in this first century. So around 1900, you would have said that there were three or four foundational theories in biology. Darwin's theory of evolution by natural selection is the really obvious one. Cell theory is still fundamental for us today. They would have also said protoplasm theory, and some people would have also added Heckel's biogenetic law, but I'm not going to make a picture of its phylogeny. Now, what was protoplasm theory? And the past tense is important here. So protoplasm theory, at its most basic, held that there was a certain part of the cell that was alive, and that that part was referred to as the living substance or living matter in many different languages. So here's Ernst Heckel writing in 1868, quote, one of the greatest achievements in modern biology and one of the richest in results is the protoplasm theory of the Sarkoge theory, the theory that the protein contents of animal and plant cells are identical, and that in both cases this protinaceous material is the original active substrate of all vital phenomena. Th Huxley had this famous formulation whereby protoplasm was the physical basis of life, quote, even those who are aware that matter and life are inseparably connected may not be prepared for the conclusion plainly suggested by the phrase physical basis or matter of life, that there is some kind of matter which is common to all living beings. Claude Bernard in 1878 wrote, quote, that the living matter independent of all form of morphis or rather monomorphis is the protoplasm. Nevertheless, protoplasm is not yet a living being, it lacks a form that characterizes the distinct being. It is the ideal matter of the living being or the agent of life. It exhibits to us in the state of nakedness in whatever is universal and persistent throughout its varieties and its forms. The famous 1911 encyclopedia Britannica, if you look in the entry life, it merely said life, the popular name for the activity peculiar protoplasm. And to indicate that its concept about 30 years later was either dead or retired, if you look in the 1848 edition of the same encyclopedia, it says merely life, see biology. So in the project, one of my main goals is to try to track this development from being a central theory in biology to being not even worth discussing in a simple encyclopedia. But today, I want to focus on this period here, the 1840s. What happened in the 1840s to make this concept come about? Now, obviously, the term was invented then, this was the first decade of the cell theory, but I was trying to come up with better reasons for why I should start a historical investigation at this particular point. So in the project as a whole, I have two main arguments, and the first is borrowed from Hans Rheinberger, that biologists constantly confronted the limitations of the optimal microscope, first by studying the microscope as a physical system, and second by analyzing their micro-technique. So the suite of section fixation, staining, and preservation techniques required for biological microscopy. And so, Karen, what I was talking about earlier, you have the tool, and then you have methods and methodologies. So that's a distinction that is important. So what I'm going to do today, the big empirical portion of what I want to present to you today is early cell theory. How did it come about? And in particular, I'm going to pay attention to two parts of early debates in cell theory. When Matthias, Sleidon, and Théodore Schwann came up with cell theory in 1838, their theory for how cells generated was called free cell formation or flyet cell development. And the basics of the theory was that the nucleus first coagulates out from a structural substance and then the cell as a whole coagulates around the nucleus. Now, obviously, now we, with a couple of rare exceptions, we don't hold this to be true. Now we hold that cells multiplied by division. And this was the theory that came along in the 1840s, but only in a very protracted way. I'm going to show you some of the difficulties that it. When I originally pitched this talk to Alexander, I was thinking I would make these two strong arguments, but I'm going to make them moderate suggestions instead. So I'm going to moderately suggest that cell and protoplasm theory together marked the end of its older era of biology in which the concept of life itself was defined by its identity with organization and the transcendental causes of that organization. For example, vital forces or potentialities. And for those of you who know your cons, this is the conti-marginal. I'm going to further our, mildly, moderately suggest that cell division and protoplasm theory marked the beginning of a modern age in biology in which the concept of life becomes indexed to matter theory. So essentially that you make it possible for Thuxley to say physical basis or material of life. I have three terminological points to make, two and a half. I'm going to say, but botanist is going to make sense, I'm going to say the word anatomist to refer to medical anatomists, pathologists, and comparative zoologists as a group. I'm also, I'm going to talk about cell plant cells. I want to use the words membrane and wall interchangeably, and if you want to know more about that, I can tell you a lot about that if you want. Okay, having said that, in any standard outlines of the history of cell theory, you'll get at best all three of these points and usually two out of the three, right? So in the standard outline of the history of cell theory, Matias, slide in 1838, comes up with a plant cell theory. He meets with Teodor Schwann and Teodor Schwann generalizes the plant cell theory to be true for plants and animals, and that's published in 1839. Second, either in 1841 or in 1842 or in 1844 or in 1846, or in 1851 or 54 or 55, Carl Nagley or some other botanist suggests that plant cells divide. And then Robert Riemach in 1851 or 52 or 54 or 55, declares that animal cells divide and Rudolf Vierkoff in 1855 popularized the doctrine on this cellula a cellula, every cell from every other cell. I looked at Jen Saps, Genesis was in history, biology textbook. I looked at fields and yons, the 6th century, the third edition, which is excellent. I looked at François Jean-Cos, what's the title of that in French Leveux Logique de Vivant, and they all only have two of them. So I'm going to give you a lot more than the two of them today. All right. So the idea that the idea of cells and pores as being a feature in biological, biological structure, of course came from Robert Pokes micrographia in 1665. From 1665 until 1803, anatomists would say that something had a cellular texture or that something was cellular as an adjective. It would have made no sense for anyone to say that something was made of cells until 1803 because this cell was not an individual unit. This only happened in 1803 with Jean-Pierre Gauchet's Histoire de Comptez, in which he took filamentous algae, shoved them apart into individual what he called Le Loge, and said that these were individualized, individualized plants, complete with the powers of metabolism and reproduction. By the 1830s, botanists had generally agreed that there were two or three different kinds of fundamental units in plants. Cells, spiral fibers, and elongated vessels. So Julius Mayen said there were these three kinds. Some people said that there were only cells and vessels. Some people said there were only cells and fibers. Some people thought, actually, I did think that cells were basically what you had, but these were the three. In anatomy, does anyone want to take a guess for how many different fundamental units they had? Anyone? So Javier B. Schott in 1801, in the anatomy general, proposes 21 different tissue types as being fundamental to the animal body, of which number one was the cellular system of tissue. This started to change in anatomy and botany alike as more biologists started to notice the existence of the nucleus. The first major work on the natural history of the cell nucleus was by the Czech anatomy designer, John Perpinia, who studied what he called the scar or the germinal vesicle of chickens. And the chicken cell, I mean, now recognize that he was, in fact, looking at and studying the nucleus. The term nucleus comes from Robert Brown in either 1831 or 1833, depending on how you count it, in which he was studying, conducting a study of the reproduction of organs, and incidentally mentioned that he thought that the nucleus was a structure common in cells across the entire organ. So this is noticing the ubiquity and commonality of the nucleus. He also thought that the nucleus had something to do with pollen, so this is an image of pollen, and the process of fertilization in plants. But he seems to have only talked about this in private conversation. He never published this. So the immediate catalyst for cell failure as a whole occurred when Robert Brown traveled to Berlin to meet a friend from Humboldt and the botanist Johann Horkel. Horkel had a student who was also his nephew, named Matthias Schleiden, who also happened to be studying plant reproduction in the process of fertilization. We know that Schleiden and Humboldt both were particularly thrilled by Brown's visit to Berlin, and Brown is apparently so impressed by Schleiden and Schleiden's Berlin-made microscope that he bought one for himself before he left for his next stop in Vienna. For the next year, Schleiden refocused his research on the plant ovaries, the pollen, and the process of reproduction, following Brown's advice and paying particular attention to the nucleus. In October 1837, a year after meeting Brown, Schleiden met with Theodor Schwan, a student of the great physiologist Johannes Müller. Schleiden told Schwan about his research on cell nuclei. They got very excited, and Schwan took Schleiden to the anatomical theater of the University of Berlin, where he looked at cell nuclei in Schwan's preparations of embryonic frog cartilage. In the spring of 1838, Schleiden published his version of the theory as an article in Johannes Müller's The Ashi for Anatomy Physiology, a missing chapter in the medicine, which, if you think about it, is kind of a weird place to publish a botany article. Schwan was faced with a larger empirical challenge and published his book in four installments, the first of which was delivered in August 1838. So, in summary, there were four parts of the Schleiden and Schwan cell theory. The first one was uncontroversial, to any that a cell consists of a membrane enclosing the nucleus. This was the definition of the cell. The second two points would have been common or well understood for botanists, but would have been very challenging to analysis. First, that cells are biological individuals, and that all plants and animals are ultimately composed of cells. That the cell is the only fundamental unit for all the organisms. Finally, they both agree that cells are generated from the nucleus, from the nucleus in a cytoglastema by free cell formation, that is, by coagulation. This would have been very familiar to anatomists, but was slightly less familiar with botany. And this will become apparent as I keep going. So, what was the cell theory in their own words? If you look at passage two on the handout, so here's Schleiden's review. Right. Each cell leads a double life, an entirely independent one belonging to its own development alone, and an incidental one, insofar that it has become an integrated part of the planet. Here's how he describes how cells form. In the pollen tube and the ovule, minute mucus granules originate in the gum, upon which a thus far homogenous solution of gum becomes opalescent or even opaque within the larger mass of granules. Single, larger, more sharply defined granules, here in figure two, now become very apparent in this mass. Very soon afterwards, the cytoglasts occur, that was his word for the nucleus, down here, appearing as granular coagulations around the granules. As soon as the cytoglasts have attained their full size, a delicate, transparent vessel rises upon their surface. This is the yon cell. So it proceeds in figure one to show how you initially start with a solution of gum, in which the cytoglasts coagulate, and then the cells start to balloon outwards until they reach their full size, and then they mature by harming here in figure nine. Schwan basically takes this, and even just quotes Schleiden often in his own book, so passage number four. There is in the first instance a structuralist substance present, which is sometimes quite fluid at others more or less gelatinous. This substance possesses within itself in a greater or lesser measure, according to its chemical qualities and the degree of its vitality, a capacity to occasion the production of cells. When this takes place, the nucleus of usually appears to be formed first, that's figure 12 here, and then a cell around it, figure 11. The cell, when once formed, continues to grow by its own individual powers, but is at the same time directed by the influence of the entire organism in such manner as the design of the whole requires. This is the fundamental phenomenon of all animal and plant vegetative growth. We will name this substance in which the cells are formed, the cell germinating material, or cytoglasty. So to reiterate the cells, sorry, it is important for us to realize that this is a theoretical schema, because technologically speaking, neither Schleiden nor Schwan could have been observing this under the microscope in real time. This was not a problem of optical quality, it only has to do with the fact that these tissues had to be cut thinly enough to be transparent and therefore usable as a microscope specimen. Only then can the microscope hope that the section is sufficiently uninjured, that they look like they are in a natural state. Furthermore, once extracted, there is a finite time to observe the specimen before it dries out or decays. Therefore, seeing a process like cell formation was a matter of making many discrete observations and inferring a sequence. There was no way for anyone to watch, in real time, a cell dividing or generating out of the sight of lastima. Our visual culture in the 20th and now 21st centuries has primed us to imagine mitosis and fission in cinematic or stop motion style. In the 19th century, not only did biologists lack the technology to produce motion pictures of living cells in action, biologists inferred the sequence of cellular life by examining prepared specimens that would ultimately, cumulatively, show the cellular life of many stages. Every time we see a sequence in a diagram and read a description of a sequence process, we need to understand it as having come out of the scientist's visual system as a whole, and thus we need to understand it as an argument for how to link discrete observations to discrete objects. Thus, in 1842, Schleiden openly admitted to having never seen cell multiplication himself that he had, quote, never been so fortunate as to observe a complete series of cells in this course of development. All of these images, in other words, need to be read as schematic and argumentative, unless explicitly indicated that cannot be viewed as serial observations of one object in development. Together in the text, these kinds of images are arguments by their authors that these many observations of many individual objects ought to be interpreted as stages in a developmental series. Now, historical retrospective has not been time to Schleiden and Schleiden at all. Already in 1875, you could read that, quote, one will hardly find a single correct observation in Schleiden's theory. On the 100th anniversary of the cell theory, John Carling wrote that it was fantastic and erroneous, purely a hypothesis spun out of mid-air, and Jen Sapp in the text of Genesis from 2003 wrote, quote, if much of what is credited to Schleiden and Schwann has been stated by others before them, and if their assertions of a regeneration of cells was simply wrong, why are they credited as phenomena of cell theory? But I would argue that we have to remember that from 1838 to at least 1846, about two or three, almost at that age, I'm not doing math at all today, Schleiden and Schwann cell theories were greeted enthusiastically and free cell formation was widely. Now, nor did Schleiden and Schwann simply come up with this on their own. They relied on a very familiar schema of generation as a process of coagulation and development. So Schleiden said that plant cells are generated in gum, sugar, or starch, which is a whole other topic, boring to tears with that one. If you ask me in Q&A, Schleiden, by contrast, used this weird term cytoblastema, and aside from calling it a gelatinous structuralist substance, he was very evasive about its other qualities. I was very surprised when I realized that no other historian has bothered to look for where this term cytoblastema comes from, even though a lot has been written on Schleiden, so I went and looked. What I found was that if you took the cytoblastema off of the word and just looked for blastema, the first person to use this word was Johannes Mohler, Schwann's teacher, the one who published the Schleiden cell theory, and one of the most important comparative physiologists of its time. It is a vaguely Greek term that he used as a term to substitute for the German time shop. So here's passage six. Every organized body is composed of fluids and of solids. There are the first star in one point of view, the materials, and in the other, I'm sorry, that's number five. In the embryo, the germinal material time shop in Oregon, which we have called the blastema, the nature of this germinal material can be seen particularly clearly in the development of the glands, in the glands, it is a gelatinous, semi-transparent matter. It forms a kind of atmosphere around the glandular tubules, which is initially very disfuse and is absorbed by the glandular system as it grows. And in five years earlier in 1830, he simply calls the primordial material a gelatinous material. Through Mohler's influence, the term blastema became quite common in 1830's physiology. We find many indications of it by many other physiologists, including by Daniel Valentin. So this is passage seven. On the handout, quote, the blastema consists of a gelatinous or gummy mass, tenacious, uniform, transparent homogenous, and embedded in larger or smaller granules. This blastematic mass in every bud of the plant embryo is contained in the center, which according to the authority of Sia Wolf, we call the point of vegetation. Thus, the terms blastema and time shop had very little theoretical content. It was merely a gelatinous precursor material that coagulated into tissues and organs during development. Svan never bothered to explain the site of blastema in terms of its chemistry or structure, and Mohler never bothered to explain the blastema in terms of its chemistry or structure either. This was, I would argue, a legacy of the epigenetic theories of biological development going well back into the 18th century, back to Cosmar Friedrich Fulf, back to Blumenbach, back to Kant, and the German Romantic biologists as well. And there happens to be a gigantic literature on this. All of the philosophy of the organism people will go back to Kant if not earlier. That's about half of this list here. The literature on this tends to frame this in terms of the epigenesis versus pre-formation debates. And to really radically oversimplify this, inspired from the first microscopic studies of microorganisms, in the first part of the 18th century, physiologists tried to introduce Cartesian mechanics to explain generation. That is, they used matter in motion as the proximate material cause. The best Cartesian explanation for biological generation was pre-formation. That is that God, the clockmaker, puts each embryo inside of every other embryo. This is the famous term on Bois Mont, or for Chauchelon. And then the history of nature starts. And at some finite point in the future, the history of nature will end with the judgment. I'm still surprised that anyone thought this was a good idea. And that was what happened in the late 18th century as well. So in the late second half of the 18th century, anyone who was unsatisfied with this pre-formation theory started to develop immaterial theories of the causes of generation. So they posited vital forces, the inner drive, its soul meant divining dimension. The list goes on and on. And I would argue that one of the reasons there's so much scholarship on this is because biologists in this period had lots and lots of options to explore once they all agreed that matter theory did not provide the answers they were looking. That matter theory was too impoverished to explain something as complicated and recurring as generation and reproduction. The blastema is just a fluid. An ohad parnas here as a historian gives this list of something like a dozen different names that a dozen different biologists gave to this fluid, all of which were unorganized, simple structuralists and themselves not alive. By the 1820s, as historians have shown, German morphologists by and large held to epigenetic theories of development, but rather than talk about vital forces, they simply described developmental sequences and sought to derive general laws of development by induction. By and largely, they also stopped talking about causes. So what Schleiden and Schwann did was they took a very familiar and widely accepted explanatory schema of coagulation of unorganized nonliving fluid and focus it down to the cellular level. That is all free-cell information was. The claim, however, was not just that cells were the fundamental units of plant and animal life, but that free cell formation was the general law of development as such. When biologists eventually started to propose cell division in the 1840s, they were aware that they were challenging not just a part of cell theory, but also the prevailing epigenetic theory of generation as a whole. And they did so with roughly the same methodological strictures that Schleiden and Schwann faced, namely the challenge of crafting a developmental argument from the street, rather than serial observations. The first claim that plant cells divide came from the botanist Hugo Moll in 1835. So this is three years before Schleiden and Schwann. However, during this period, botanists had more or less an understanding that there were many ways for cells to generate and Moll added division to a pile of existing. So Moll examined filamentous algae and basically argued that you never see half-grown cells in a filamentous algae, but you do see these bumps, these humps, and these protrusions. And at some point you will also see branching off from the main filament another protrusion at this time with a dividing wall. He conjectured that he argued that they go that the sequence goes in this order from a hump to a bump to a projection to a divided cell. So this is passage eight on the handout. This is not the passive voice in this passage. A constriction appears protruding in the interior of the cell, which constricts the green mass inside the alpha filament, i.e., a ring-shaped partition that is perforated. In 1841, now this is three years after Schleiden and Schwann's theory, the botanist Franz Unger became the first to botanist avoid some objections to free cell formation. In 1844, he produced these diagrams, which I find incredibly unconvincing, in which he says that these partitions here, they seem thinner than the rest of them. So I think Moll's scheme of division might hold for other plants as well. This is a very short comment almost in the context of a larger discussion. You can see a similar thing happens in anatomy. So famously, Robert Riemach in 1841 becomes the first anatomist to reject free cell formation, although he wasn't able to publish this diagram until 1851, 10 years later. And you'll notice this is not a developmental sequence. These are individual observations of things, objects which he claims are cells hot in the middle of dividing. This is not a process. When we play the historians' game of who said it, first we point to Unger in 1841, and Riemach, the dates vary because most people don't read all of Riemach, uh, let's see. This highly descriptive approach was typical for German biologists. Oh, I have a whole version of my tongue. The theory of cell division was first, sorry, let me go back a step. So how did this change? I would argue, my apologies, I would argue that I should have the right version of my text. Of any botanist who was active in the 1830s and 40s, the one best prepared to examine Shledon's theory in detail was Hugo Moll. In his 1835 theory of cell division was well known, but actually his most important work was on the maturation and growth of woody plant cells. In older plant cells, especially in the stem of the wood, what you see under the microscope in what was very easily seen by many botanists was that it has these spiral structures, these dots, or these pits, and that they vary in shape and appearance depending on how thick and how old the cell is. And botanists had actually spent about two decades arguing what the relationship between all these structures were, what order they formed, and what order they formed. So here is Moll speaking, writing in 1837. Again, to give you a flavor of this descriptive mode in morphology. Quote, since we do not find the membrane originally fibrous and later homogenous in any cell, but because conversely, the striations and the occurrence of fibers are the result of the further developments of cells, it follows that the organic substance is not uniformly deposited, but rather in particular places in greater or smaller quantities, such that if these irregularities reach a higher degree, then no organic substance will be deposited. They're all between places at which a stronger deposition takes place, and these more intense depositions either proceed either in the direction of a spiral or in the direction of a net of contents. Now this is a 169 word German sentence that I spent quite a long time translating, because it was very, which was very difficult, but you can get a sense of how much work is being put into not ascribing causes and not ascribing a mechanism to this development. This changed with two papers in 1844, one by Hugo Moll and the other by Carla. So I'll start with the 1844, with Moll's paper. First, in 1844, Moll found that if you put younger plant tissues in alcohol or acid for a short time and then stain it with iodine, one can identify a loose, brown or yellow colored lobby object that has separated inside of the cell, sometimes still attached to the algorithm. Additionally, when you apply acids to fully grown plant cells, and this was well known, what you get initially is that it separates into rings. And if you let it sit in the acid for long enough, it will separate into lobes with the rings. What he argued in 1844 was a scheme of development by which a young cell consists of a solid membrane solid membrane at close to full size with what he called the primordial uterus or the primordial ischia, lining the outside, lining the inner side of the young cell membrane. As the cell grows, matures the cell, let's see, as the plant cell matures, the primordial deposits successive layers of woody material along the interior of the cell wall, except at these points at which the primordial uterus is still attached to the outer most cell wall. That was his argument for how the cell matures, and that is his argument for why the pits ended lobes of cell wall material appears. In other words, Moll argued that the primordial uterus was the agent of cellular growth that was initially an inner lining of the cell wall. It deposited the successive layers of this woody cell wall material, retreating inwards as it did so. The primordial uterical, in other words, was a small part of the cell that in its organismal context was responsible for creating the bulk mass of the whole plant or even the whole tree. At the same time, as Moll published his primordial uterical theory, the botanist Carl Nagling developed the theory of cell division that specified what he called a schlime as the agent inside of the cell. Whereas earlier, Moll had suggested that the partition basically just grows inward in cutting this plant cell in two. Nagling, by contrast, argues that the interior schlime of the cell creates this partition. The schlime inside of the cell first constricts or sometimes even divides completely at the site of the constriction, and at the site of this constriction, the living schlime deposits cell wall material. So this is passage 11. So no hit, he's going to describe parts of the contents of the plant cell as alive and parts of the plant cell cell as either injured or dead. It often happens that a portion of the cell contents is so injured that it becomes incapable of performing further functions. Then, that portion of the living layer of mucus, the laban's cryptic schlime shaped, contracts into the new independent hole and completes its message. The dying cell contents lie outside this restored cell. So in this diagram on the left, here are the dying cell contents. Here are the living cell contents, and it is depositing a new cell wall around itself to close itself off from the dying, injured and potentially pathological. Let's see. Indeed, in Nagling's general language, as everyone else I've mentioned so far, Nagling's illustrations are highly schematic and argumentative. What is also interesting, not only novel, is that Nagling claimed to have observed filamentous algae in a kind of serial observation, and this is passage 12. So he claims to have observed that, quote, each secondary cell contains in its center around its transplant states the nucleus. The cell contents consist of a nearly homogenous and colorless schlime. So that's number 13 here. After a few days, this acquires a green color in granules. At this point, it also becomes clear that the septa dividing the two samples did not proceed from the parent cell, but were produced as parts of each particular daughter cell in the interior of the cell. In Nagling's general language, we find remarkable and repeated indications that the cell had schlime that is endowed with vital power in contrast to the parts of the cell. A year later, Moll raced to try to catch up with Nagling's observations and revised the cell division scheme, making it very clear that yes, it is the interior primordial utricle that constricts the rest of the cell, and the outer most cell wall of the cell membrane is formed by the primordial utricle. As he later wrote, it was not until I had discovered the primordial utricle that I was able to trace accurately the processes and the formation of this dividing sample. Finally, in 1846, Moll recognized that his primordial utricle was more or less the same as Nagling's schlime or schlime shaped, but Moll complained that the word schlime was too ambiguous. It was a word that was at too many popular and other scientific connotations, so instead he proposed the word protoplasm to distinguish this special living substance from the other non-living substances in the cell. This is passage 13. Since this viscous fluid precedes the first solid formations that indicate the future cells wherever they are to be formed, since we must further suppose that it supplies the material for the formation of the nucleus in the primordial utricle, and that these are both the closest and closest spatial connection with it, and also react in an analogous way to iodine, that therefore its organization is the process that initiates the formation of the new cell, i.e. cell division, in light of these physiological functions, I trust it is justified if I propose to designate this substance by the word protoplasm. Finally, it was these botanical terms that Robert Riemach termed to in the 1850s in an attempt to convince anatomists that division was also the rule for anatomies. In 1852, for example, he attacked Schwann's free cell formation first by noting work by Mullen-Nagley in plants, and then deploying their agents as well, the primordial utricle and the protoplasm, to argue that the cells, animal cells also multiply by division. This is passage 14. The following of the A is the first example of endogenous cell formation, which is based on the fact that after division of a nucleus, the protoplasm divides together with the inner membrane, primordial schlauch, without the participation of the outer cellular membrane. That he has, in other words, taken the developmental schema that Mullen-Nagley introduced in 1844 to 1906 and transported it to animals as an attempt to convince anatomists that the cell is divided. So, some concluding thoughts. Now, I know my title, I think epigenesis is a bit broad, because epigenesis means something more than just vital forces and collagulation, but I do think there's something really important that's happening in the 1840s. Something very important about these claims that protoplasm or the schline is a structuralist unorganized substance that is itself alive and active and back to which all biological processes can be traced. Eighteenth-century epigenesis would have rejected this idea outright. In fact, there is a big convincing scholarship that has shown that biology as such and the concepts of the living and life itself owe their existence to the study of the body as a whole than the parts that constitute it. We read in 1801 in Bichard's general anatomy, for example. I don't know if you can read this back there, but so this is the English version. There are in nature two classes of beings, two classes of properties, two classes of sciences. The beings are either organic or inorganic. The property is vital or non-vital and the sciences, physiological or physical. Animals and vegetables are organic. Minerals are inorganic. Now, we have a different notion of what inorganic means today thanks to the success of 1820s and 1830s organic chemistry, which is the chemistry of living substances. In the German, it says, there are in nature two classes of things, es gibt in der Natur zwei Klassen von Wesen, zwei Klassen von Eigenschaften, zwei Klassen von Wissenschaft. Die Wesen sind organisiert oder unorganisiert. Die Eigenschaften, die Tale oder nicht die Tale. The things are organized or unorganized. The property is vital or non-vital. The sciences, physiological or physical. The animals and plants, die Tiere und Flassen sind organisiert. What man calls minerals are unorganized. To what is this organization of? How is this organization caused? Repeatedly. These are the questions that 18th century epigeneticists and 19th century biologists were supposed to solve. Cell division, cell theory and protoplasm theories did not solve the problem of how the whole organism unfolds. Unlike 18th century epigenesists, I think neither cell theory nor cell division or protoplasm theory will be able to answer that question. Rather, we see in this moment that what qualifies as a developmental cause has changed. 18th century epigeneticists were supposed to invoke forces, ends or adaptations. Protoplasm and cell theory in the 1840s would invoke material constitutions and material processes. It might even go out on a limb to argue that a more diffuse cultural materialism that helped to uphold in the 1840s. Europe had much to do with an increasingly robust or at least more confidence in matter theory than it had been in the case in the 18th century. We see this confidence in matter theory reflected in the dry technical work of Morley Green and Riemach at the threshold of empirical research. Again, so this is, I get to show you vacation photos. This is at the Natural History London right before COVID, traveling right before COVID was really funny. I don't know if you can see this, but this, whatever it is, asks, what are we made of? And the answer at the Deutsches Museum Munich, you are chemistry, la vie, c'est la vie, c'est la chemie. And I would argue that this is a product of the 1840s. I have a difficulty to understand exactly what is the proto-basma. Yeah. Okay, so, so correctly, they put cells in acid, they see that some part dies. It's already dead. It's already dead. It separates off. It separates off and they say, okay, what's, what's, what stays there? What is still around must be the matter of everything or the cause of life or something like that. Yep, okay. And if they do it in acid even longer, it goes, how, how could, so how did they understand that stuff? So what I'm trying to note here is that the process by which we get away from this old explanatory schema where we rely on forces or forces or ends, like the structure of the argument is that you, you, you put this in acid. You see this thing that you haven't been able to see before. Yes. We've known about this. I'm just going to argue that this creates this. Okay. Here's what this will be. I have found a new part of the cell. I argue that it's okay. It's the thing that does this. So the acid is like a revelator. And it's done. Okay. And like, this doesn't happen in nature, right? That's the interesting thing about all of this. This only happens by artifice. But what you do is if you look at this artificial formation and you say, this was here before. And in its natural state, here's what it looked like. Here's why you couldn't see it before. And this is what it does. And this is alive. And this is the living part of it. Thank you very much for that really, really interesting question. So I'm really struck by how you, you know, be characterized by genesis on the one hand, which appeals to these sort of transcendental vital forces. And then a more kind of picture this. I'm not familiar to a modern ear, right, which would be this sort of matter theory. And I'm especially struck by that because I wonder, you know, I think certainly in the case of, well, okay. So I wonder if actually you see both of those kinds of ways of thinking at play in the work of Isaac Newton. And so I'm specifically thinking of the optics, where he's thinking about, he's doing matter theory, but he's wondering how active principles feature into matter theory. And sometimes he thinks maybe they're super added, sometimes he thinks maybe they're actually inherent to the matter. And so clearly we have more of an applied matter theory in terms of biology, but I'm wondering if you see Newton and the Cambridge Platonist as kind of playing intellectually in sets for role. So interestingly, it has nothing to do with the Cambridge Platonist. It has to do with the French and Dutch Newtonians. In the famous German preformation versus epigenesis debates, Albrecht Holler trains in the Netherlands. And Carl Friedrich Wolf trains with someone who studied mathematics. And so you have very direct lineages of the Newtonian of the optics and Cartesian taking hold in the arch-preformationist of his time, Albrecht Holler, debating endlessly the same empirical observations with his rival Kaspar Friedrich Wolf, who very directly learns his physics from the Newtonians of the pre-capital. It's kind of amazing that people have been able to trace these kinds of influences, but it's right there. And we do know about Holler's background. We can also say that, yes, this was also a Cartesian. Preformation was also derived from Cartesian ideas as well. It's very, yeah, very cool. I wanted to ask about, how to put it, there's this funky undercurrent of agency type talk that runs around through here. And I just wanted to ask you to like riff on this a little bit, because I think this is really interesting. And I kind of don't know what to do with it, and I've never really known what to do with it in these kinds of contexts. And so, yeah, like, help me know what to do with it. In this context, it just means this is the thing that does the thing. This is the cause. Right? There's all sorts of this new materialists, hand-wavy stuff that I've got really into, and I've become very familiar with it. And I do think there is a strong reason why one should claim that matter has agency or has an active and less than, sorry, more than just a passive role in anything. Right? But what we see here is the appearance of agency talk and causation talk in the 1840s in strong regards to the impulse to get all of it out at the expense of your own intelligence. Right? That long passage by Mulberry's like torturously describing the development of the plant cell without positing what's causing it, what's doing what, what are the mechanisms. That's hard to write. It's hard to write like that. And it becomes easier to posit that something's active. And Claude Bernard, for his many faults at his meeting, for his many shortcomings, he identifies this in the language of agency. It's, it's, so what I make of it is they're saying, oh, this is the part that does the stuff. Everything else. This is especially important in plant anatomy. That this is the part that is alive and does everything that you're interested in as a physiologist. And this stuff has been created by the living stuff. Right? The plant cell wall itself is not alive. The cell contents are alive. Even though, if you're a botanist, you do study the whole thing. It is a whole system. But one part of this is alive. And botanists are the only people who still use the word for the pleasant today. You also hear this term protoplast that is a legacy of this 19th century context. Follow up on this actually. Isn't the term agent or agent also used in a chemical sense? So not in the sense of being an acting entity, but in the sense of being chemically active or having a chemical power to transform other chemical stuffs. I mean, that's, I guess, that's an old sense of the term agent. It's still sometimes used. What it's used in, read it. So read it or read it. It's a very common term in today's chemistry and was common in the 19th century as well. Whether, I don't know if Bernard is, so in this particular passage, I don't think he's talking about this in purely chemical terms. Because somewhere in between these three dots, here he does talk about chemistry. And he doesn't talk about the agency of chemistry or chemical agency in that technical sense. He really is expand, talking about protoplast in this expansive way. Let me follow up. But then that opens up an interesting question, right? So for these authors, what is the relationship with chemistry at this point? So I think it is worth seeing that the biologists come up with this active, this part of the matter is active. They make this big change in their own understanding of matter theory practically without any input from chemistry. And if that mold will explicitly argue chemical, we know biologists do not understand chemistry and chemists do not understand botany. We must direct a strong variation between them. But nevertheless, he's able to talk about matter and make these modifications to matter theory that everyone else will also say, well, yeah, sure, but the chemistry is there. We're going to go there. So chemistry, the chemistry of the living matter, the structural chemistry, the physical chemistry of the living matter starts very soon. Still on this quote of Fuban, was it, of course, your absolute threat that agent of life is a very strong, very strong expression, but just it's or the matter of the ideal life being, not the matter of life, of the ideal life being. So it must be, it's why he says it's common to every different form, a specific form of life. So Bernard and Heckel also, unlike some of the more radical physiologists, will say that every living organism has a form, also. This is, so this isn't a paper I've peer reviewed recently and should come out in the next some months. Bernard, Bernard in this, in this particular moment is trying to separate the sciences of physiology and morphology, or at least try to understand what the relationship these sciences are. And he will say the science of protoplasm is the science of chemistry, it's the science of mechanisms, it's the science of material processes. And the sciences of form are inductive, they're based on laws, they're not based on experiments. Okay. Now just the science of diversity is non-experimental. Which was also true earlier. I mean, he's basically admitting to the fact that taxonomy, evolution, and development are still intractable to him as a physiologist. So there's this tension in Bernard really, really fascinating. I'm really curious to see how this author responds to my peer review comments. Boy, that paper was rough. But yeah, that's a super interesting feature. And Hackle also talks about it. So is Bernard at this point in time read what? Oh, Bernard's dead. This was published posthumously. Okay. So when is Bernard saying that physiology and morphology are intractable to him? Cannot, cannot. Were they cannot meet? Yes. When is he saying that? He simply says that physiology, and by which he means chemical and physical physiology, cannot apprehend why essentially the organism forms in this way. When does his question is when? Around when, when he asks the idea? Oh, 1870. Okay, so it is. So I guess the reason I'm wondering about that is because this is post Darwin's famous marriage of teleology and morphology. The great arbiter of the Joffrey Kubey debate. So I'm just wondering if Bernard's like engaging with that at all? Yeah, he definitely is. He is asking himself, where's the role, what is the role of physiology? And his conclusion is basically when he, so this is again in the paper today that I reviewed, not my own research, but when he writes in the 1860s, he's more optimistic about a meeting point between the two experimentally. By the 1870s, he is not only quite ill, but he's more pessimistic. And the movie is trying to be just to cleave it off into a separate domain of science. Hi. Could you explain a little about Bernard, the notion of milieu? The milieu, yeah. Because today, they use Bernard milieu as some kind of grandparent or grandfather of the boundary condition notion. And the idea of the a form that characterizes the organism is very, is very based on the notion of the milieu that is great today as constructions and sets. So an organism from some, from some altars is like a constriction set of relations between particles or molecules. And I'm sorry, what? Between a constriction sets of interaction between molecules. Okay. They constrain this. There is a mutual constraints between them. And that is what they think is a form. So I think that the idea of a form that characterizes the organism in Bernard is basically the idea of boundary condition or conditions, internal and external boundary conditions. It's not the form of like unseen philosophy or the form of like... He is very much talking about the whole organism. He is talking about a whole organism. So one thing to notice about the milieu interior is that the milieu interior is a static structure that he can access as a physiologist using chemical and physical tools. And he's saying, we can study form in these ways, like we study matter. We can study the physiology of the organism in these ways. But why does the organism have the shape that it does? What are those causal relationships? He will say, I may be able to study the milieu interior. I may be able to say profound things about the maintenance of the organism. But I cannot explain using those tools, the formation of that organism, from... He draws that line. So I would caution you by saying that Bernard is very useful to many philosophers, but if you read Bernard as a historical actor, but he is engaged in a lot of issues that are not just him, but are part of the larger debate about what is the future of biology going to be. Even what is biology as such, which... So my boss argues that there's no such thing as biology. I beg to differ. But this is about the identity of which direction the life sciences are going to go in. And he is proposing, along with many other people at this point, that there are two directions for them to go to. And that some meeting will happen maybe in the future, but he is unable to see it. He is quite deeply pessimistic about this aspect of biology in the 1870s. We'll also say that the concept of the molecule is a very different, difficult one, and I've done some work on that. If you read some of the people at this time, the word molecule is indistinguishable from Descartes corposal. They still use that concept. Just out of curiosity, I don't know much about this period in the history of biology. So but I've looked at debates that start just a little bit later, namely the Driesch-Ruh versus Ruh debate about vitalism and the mosaic theory of development and preformation and epigenesis. Actually, I'm just curious how do you get from the sort of camps that you've drawn out, so the organizationalists versus the Schlein theorists, if you allow me? How do you get from that debate to the Ruh-Driesch-Ruh debate? So essentially what Driesch is saying is matter theory is no longer adequate to explain what I think needs to be explained. So for me, this is not about chemistry can actually explain x, y, or z, but it has a lot to do with your confidence that matter theory is the domain in which you must answer these questions. And Driesch will come along and say no, matter theory is not the domain in which we can answer these questions. And frankly, I think at that moment he's probably right. One of my big arguments is that it is through these kinds of technical explorations of what is happening under the microscope as you've stated fits your preparation samples that biologists are learning what's possible to think about in chemistry and physics. And when the Driesch-Ruh debates are happening, it's getting quite challenging and biologists are having a hard time keeping up with what physicists and chemists are making. You tempted us to ask you about walls versus membranes. Because that's a really interesting, yeah, yeah, there's almost this idea. I mean, do we know that it almost sounds like there's a sense at this point that the walls in some sense really don't belong to the cell right now? So where to start? If you look in the litter, so the first time someone makes the distinction between the plant cell wall and the plant cell membrane, do you want to guess? Later than I think I'm guessing. Does anyone want to guess? 18, 77. Okay. Right. I don't know what you're suggesting. Right. But that distinction has to be made. And before that distinction is made, the terminology is interchangeable partly because membrane, I think membrane is a Greek-ish term and wall is a dramatic term. And so in many languages, they become interchangeable depending on how sophisticated one wants to sound. Right. And in 1877, the LaHelm-Pfeffer says no. The wall is a rigid structure and he does the famous osmosis experiments to determine that a membrane composed of anything, which is soft, can be responsible for developing somewhere between at least six atmospheres of pressure with a one percentual resolution. I think I have those numbers wrong. And on this basis, he analogizes the plant cell must also have a membrane, right? That a membrane is essential for osmotic function and that the wall is necessary to keep that osmotic function from essentially blowing the plant cell up, which is what would happen with six atmospheres of pressure. That's, I wrote a marketplace. Okay, okay. It's quite a journey and it has a lot to do with the status of analogy in biological argument, whether you can analogize between physical experiments and biological experiments. The membrane as we know it as a lipid bilayer with some stuff around it, that has a thickness of six to 12 nanometers. The resolution limit of the microscope, of the optical microscope, just in pure physics terms, it's 250 nanometers. So what was the object that they were calling the membrane before electron microscopy? Well, it was just whatever was on the outside. And in 1860, with protoplasm theory, the, many of the anatomists knew this and therefore argued that the membrane is an optional accessory to the cell, to the protoplasm. You mean that it's not visible in plant cells because an animal cells do it? No, it is. The membrane. The lipid bilayer membrane with its attendant parts. Well, you just see it as too little, too little, What you're seeing, if you're seeing two lines in an optical microscope, that is an illusion created by the three-dimensional structure of the cell under those physical conditions. Resolution-wise, that those two lines are impossible to see under the optical microscope. What you're seeing, so there was this question about essentially bubbles, right? There was, like, does a little bubble on a microscope slide, does that have a membrane? Is that a membranous structure or is it simply a pocket space? Because it looks like there is a structure there. And depending on when you're pointing to invisible chemistry, yes, there is a structure there. But that is an atomic structure. You are not seeing the membrane. You are seeing the optical effects of the refraction, of the change in refraction, the change in refractive index between the cell and the surrounding me. Yeah, it's kind of wild. You would see all the same thing with just a drop of water. Yes. And one, two, in the previous slides, there was auto-blasphemy, but there was the expression protein contents. Yeah, protein content. At that period, what they had in mind when they said protein content? I'm a little orange. Okay. I do know they mean nitrogenous contents. What exactly they mean? I would actually have to go back to the German to make sure if you're saying protein or ice, because but it's just an impossible word to translate. The word protein is coined by Jan Gertmulder, I think in 1836. What he means by protein and what we mean by protein are obviously worlds of art, but I don't actually know what those gradations are. Or whether they think there's one protein or many proteins. This is a whole thing that I tried to plural contents. Yeah. One more question. Let's thank our speaker and