3.1. Interventionist Framework

In order for a factor to be selected as a cause of some explanatory target, it needs to pass a second step of causal selection, which ensures that the factor has at least some causal control over this target. What does it mean to say that a factor has causal control? Consider a minimal notion of causal control, which is specified by the following interventionist criterion and motivated by Woodward’s (Reference Woodward2003) interventionist account of causation:Footnote ⁴

In this framework, variables represent properties that can take on different values and arrows represent relationships of direct causal control. Variables are the relata of causal relationships, and they represent various properties of interest. Suppose that variable X is a light switch on the wall, which can take on one of two values (0,1) representing the switch being down or up. Variable Y represents a light bulb, which can take on the values (0,1) representing whether the light is off or on. The IC relies on the notion of an ideal intervention. An ideal intervention involves an unconfounded experimental manipulation of X with respect to Y in which changes in Y are produced by changes in X and not through any other variable. In other words, as shown in figure 2, this intervention (a) is not correlated with another variable W that has causal control over Y, (b) it does not directly have causal control over Y, and (c) it does not have causal control over any of the intermediate variables between X and Y. Intervening on the light switch in this manner reveals that it has causal control over the light being on or off. In explaining why the light is on or off, we appeal to the state of the switch, because it provides causal control over this outcome.Footnote ⁵

Figure 2.

Causal control and ideal intervention (Woodward Reference Woodward2003).

3.2. Selecting Causes: Metabolites

In the glycolysis example there appear to be numerous factors with causal control over the manufacture of a final product.Footnote ⁶ At the very least, these factors appear to include metabolic substrates, enzymes, cofactors, and other regulatory molecules (ATP, NAD⁺). The interventionist notion of causal control clarifies which factors should be selected as causes in this case and the rationale underlying this assessment. One set of factors that are cited in explanations of glycolysis is the sequence of metabolites represented along the glycolytic pathway. In this section, I provide an analysis of the reasoning that guides the selection of these factors. In discussing this rationale, I introduce three main features of the pathway concept. In this context, the pathway concept represents a sequence of factors with (i) causal control, (ii) material continuity, and a (iii) fixed order of steps that are shared across some large domain of systems.

First, consider glucose, which is the starting point of glycolysis and the starting material for this manufacturing process. Glucose has causal control over the manufacture of pyruvate, but its causal control is indirect in the sense that it operates through a set of metabolic intermediates. Each of these intermediates involves a relationship of direct causal control in which an upstream substrate controls manufacture of a downstream product. Consider the first step of glycolysis, where glucose is converted into G6P. Suppose that the background circumstances S contain the hexokinase enzyme and available ATP. In these circumstances, glucose provides causal control over G6P in the sense captured by the IC—changing the value of glucose from present to absent provides causal control over whether G6P is formed. In this situation, the presence of glucose results in G6P formation, while the absence of glucose prevents it. This is similar to a factory assembly line where the relevant workers and tools for a given step are present but the starting material for the step is either supplied or withheld. The availability of the substrate controls whether the immediately downstream product is formed. The same relationship of direct causal control holds for the second step of glycolysis. The product of each step provides causal control over the next step in the pathway, and so on, until the final product is reached.

This identifies a chain of metabolites with causal control from glucose to pyruvate. These relationships of direct causal control can be represented with arrows and variables, as shown in figure 3, which represents the first three steps of glycolysis. In this diagram, X₁ represents glucose, X₂ represents G6P, X₃ represents F6P, and Y represents F1,6BP. If the enzymes, cofactors, and other regulatory molecules for this process were present, supplying glucose would result in the sequential production of each metabolite in the pathway until pyruvate was formed. In this environment, supplying or removing glucose provides causal control over whether pyruvate is formed. This is similar to a factory assembly line where all workers and tools are present but the initial starting material is either supplied or withheld. If starting material is supplied the final product can be made, and if it is not, production will not occur. In fact, this reasoning clarifies a strategy that biological systems use to control these manufacturing processes. Biological systems often sequester and compartmentalize starting materials as a way to keep them away from enzymes until the product in question is needed. Intervening on starting materials in this way controls whether the manufacturing process takes place.

Figure 3.

Sequence or chain of factors with causal control.

In addition to causal control, the sequence of metabolites along the glycolytic pathway has a second important feature. These factors have a type of material continuity in which a significant amount of material from each upstream step carries over to the immediately downstream product. It makes sense that pathway factors have this feature in light of the manufacturing context, because the focus is on explaining how a material substance is changed into a material product. The pathway variables capture changes in a material entity as it undergoes this process. In fact, biologists exploit the material continuity of these processes in order to study and understand them. One way they do this is with tracer experiments, which involve supplying a biological system with tagged starting material and watching it flow through the pathway. By stopping this process intermittently and collecting tagged material, the metabolic intermediates and their location along the pathway can be identified. One of the first uses of this technique revealed the metabolic steps of photosynthesis in plants. In these experiments, plants were supplied with tagged carbon isotopes (¹⁴CO₂), and the tag was identified, successively, in a chain of metabolic intermediates.Footnote ⁷ Tracer experiments provide other types of information about metabolic pathways, such as the flow or flux of material through the pathway, and they are viewed as “perhaps the single most important technique in unravelling the complexities of metabolism” (Rogers Reference Rogers2011, 48).

A third feature of the pathway concept is that it captures the sense in which metabolic processes involve a fixed order of steps. What do I mean by a fixed order? In order to clarify this, consider the manufacture of a house. Building a house involves many steps that often need to take place in a particular order: the foundation needs to be poured before the house is framed, and the house needs to be framed before the roof is added. Engineers refer to these fixed relations as “mandatory dependencies” because the particular sequence of dependency relationships is fixed or mandatory. They claim that these relations are constrained by “hard logic” (Kerzner Reference Kerzner2009, 501) because they identify a fixed ordering that is “required as a part of the nature of the work” and cannot be changed (Newell Reference Newell2005, 49). These differ from “discretionary dependencies” that hold between outcomes that are ordered on the basis of personal preferences and that are not fixed by the nature of the project itself. As discretionary dependencies represent a preferential ordering that can be changed, engineers claim that this ordering involves “soft logic” or “preferential logic” (Kerzner Reference Kerzner2009, 501).

Metabolic pathways involve sequences of steps that are similar to “mandatory dependencies” in the sense that they capture an ordering that is fixed by the nature of a biological system. This fixed order is sometimes referred to as a “processing chain” that involves “a number of steps which must occur in a certain order” (Bell Reference Bell2008, 113). In terms of carrying out glycolysis, biological systems have to follow a particular order of steps. As shown in figure 3, glucose must first be converted into G6P, which must be converted into F6P, which must be converted into F1,6BP, and so on. While it is possible to imagine other routes through which glucose could be converted into F1,6BP the only available route in living systems is represented in figure 1. In both biochemistry and ordinary life manufacturing contexts, the pathway concept is used to represent a fixed order of steps in the manufacture of some final product. Not only is this order fixed, but in the case of glycolysis it is nearly universal across all life forms. This sequence of factors will be selected as causes of glycolysis in nearly all organisms because these factors provide causal control over this process in these systems.

4.1. Selecting Enzymes: Interacting Causes

A straightforward answer to this question involves viewing enzymes and substrates as interacting causes with respect to product manufacture.Footnote ⁸ This can be clarified with an ordinary life example in which we want to explain what causes a flashlight (Y) to turn on and off. Consider two candidate causes, represented in figure 4, which include the flashlight’s battery (X) and on/off switch (Z). The switch has causal control over whether the light is on or off, but only when the battery is present. When the battery is present, intervening on the switch turns the light on and off. The battery also has causal control over the flashlight’s being on/off, but only when the switch is left in the on position. When the switch is left on, intervening on the battery (by removing it and replacing it) causes the flashlight to turn on and off. Both of these factors have causal control over the outcome, but their control depends on the other factor. This is what it means to say that these factors are interacting causes with respect to some outcome. Explaining whether the flashlight is on or off involves appealing to both factors, because both are required to gain causal control over this contrastive focus. Notice that the causal control of these factors individually is uneven—each factor alone can reliably turn the flashlight off, but both are required to turn it on. As the contrastive focus involves both states of the flashlight, and both factors are required for one of these states (i.e., the on state), gaining complete causal control over this target requires both factors.

Figure 4.

Directed acyclic graph of flashlight battery (X), switch (Z), and bulb (Y).

It is natural to view metabolic substrates and enzymes as interacting causes with respect to product manufacture. However, unlike the flashlight example, the metabolic case involves a sequence of many interacting causes, as shown in figure 5. Each step in the pathway identifies a substrate-enzyme pair that are interacting causes with respect to the immediately downstream product. The enzyme and substrate each have causal control over formation of the product where the causal control of each factor depends on the other. When the relevant enzyme is present, changing whether the substrate is available or not controls whether the product is formed. Likewise, when the substrate is present, changing whether the enzyme is available or not controls whether the product is formed. Explaining glycolysis involves citing the pair of interacting causes at each step in the ordered sequence from beginning to the end. This clarifies why scientists cite sequences of enzymes and substrates in these explanations and how there is a principled rationale for doing so—these are factors that provide causal control over formation of the final product.

Figure 5.

Directed acyclic graph of metabolites (X₁, X₂, X₃, Y) and enzymes (Z₁, Z₂, Z₃).

Scientists exploit the causal control of enzymes to study and understand metabolic processes. One such strategy involves examining biological systems with defective enzymes that lead to metabolic disorders or “inborn errors of metabolism.” When a metabolic enzyme is absent or nonfunctional, this blocks a step in the pathway resulting in a buildup of upstream material. The buildup of particular types of material can be used to identify the metabolites along the pathway and the enzymes they are associated with. In fact, the initial discovery of many metabolic disorders has involved identifying a pathological accumulation of metabolic materials. Scientists compare these disorders to disrupted factory assembly lines. They state that nonfunctional enzymes “cause an accumulation of an intermediate, in much the same way as a missing worker on an assembly line halts production at that point” (Windelspecht Reference Windelspecht2007, 55). Other experiments involve selectively inhibiting enzymes to identify their substrates and location along the pathway. As enzymes are proteins produced by genes, one way to manipulate them is to introduce gene mutations into an organism.Footnote ⁹ This experimental strategy was used in twentieth-century research that helped establish the fields of molecular biology and biochemistry. For example, these experimental methods were used in Beadle and Tatum’s (Reference Beadle and Tatum1941) Noble Prize–winning work on metabolic pathways in Neurospora and Beadle and Ephrussi’s (Reference Beadle and Ephrussi1937) research on biosynthetic eye color pathways in Drosophila. These studies led to the one gene–one enzyme hypothesis, which provided one of the first and most convincing explanations for how genes influence phenotypes, that is, through enzymes, which regulate metabolic pathways (Morange Reference Morange1998, 21). Hull’s (Reference Hull1974) diagram in figure 6 depicts these relationships between genes, enzymes, and metabolites and bears some similarities to the causal graph in figure 5. (I discuss the role of genes in these explanations in the next section.) In these experiments, metabolic pathways are studied with strategies that exploit the causal control of enzymes, the location of enzymes and substrates in a causal chain, and the flow of material along the pathway.

Figure 6.

Metabolic pathway (Hull Reference Hull1974, 29).

Metabolites and enzymes receive the most attention in explanations of metabolic processes. However, other factors are also frequently cited, such as enzyme cofactors and accessory substrates (e.g., ATP, NADPH). The interacting cause framework provides a promising approach to include many of these other factors—in many cases, they are additional interacting causes that allow for causal control over product formation.

4.2. General Speed

I have used the notion of an interacting cause to clarify why enzymes and substrates are selected as causes of metabolic processes. This is because intervening on both of these factors allows for causal control over the manufacture of a final product. There is a puzzle with this analysis. In the case of glycolysis, there is a sense in which metabolic substrates have causal control over product formation without enzymes. Let me clarify. Glycolysis is an exergonic reaction in the sense that it results in a net release of energy. Exergonic reactions are referred to as “spontaneous processes” because their thermodynamic favorability means that they can occur spontaneously without any outside factors or catalysts. This means that glucose can transform into pyruvate without the help of enzymes. If glucose and the glycolytic intermediates have causal control over pyruvate manufacture without enzymes, why are enzymes cited in explanations of this process? It turns out that just knowing that a process is spontaneous provides no information about the speed that it takes the process to occur. In the case of glycolysis, the transformation of glucose into pyruvate would take somewhere on the order of billions of years without enzymes. The following quote discusses this point in the context of glycolysis:

This helps to clarify the type of causal control that matters in the second step of causal selection. Selected factors need to have causal control that operates within a timescale set by the context of inquiry. If a factor fails to meet this standard it will not be selected because its control does not show up at the relevant timescale and, thus, is of little (to no) use in controlling and explaining the outcome within this time frame. In the case of metabolic processes, the relevant timescale is milliseconds to minutes. Metabolic processes need to operate at this scale in order for living organisms to sustain life and functionality. Organisms need to react to their environments, break down materials, and grow at particular speeds in order to survive. Metabolites alone do not have causal control that meets this standard. Without enzymes, they manufacture products far too slowly with respect to the time frame of interest. Enzymes are selected in addition to metabolites, because they increase the speed of causal control that these factors have over product formation, such that it occurs within the relevant timescale of interest. This consideration can be formulated as follows. In order for factors to be selected as the causes of an outcome, they need to meet a general speed principle, which ensures that the speed of their causal control over the outcome fits within some general time range specified by the context of inquiry. This clarifies why both enzymes and metabolites are cited in explanations of glycolysis, as opposed to just metabolites alone. It is not just that both are required to gain causal control over pyruvate manufacture but that their causal control meets this general speed principle.Footnote ¹⁰

Another example helps to support these points and suggests their general role in causal reasoning. Consider the conversion of diamond to graphite, which is another spontaneous process. Although this process is spontaneous, it takes over a billion years to manifest at normal conditions. In ordinary life and scientific contexts, we usually deny that this process occurs. Scientists claim that while “diamonds are thermodynamically unstable with respect to graphite … the rate of conversion … is so slow, that for all practical purposes, it does not occur” (Woodbury Reference Woodbury2012, 10, emphasis added). This reaction is viewed as “negligible at standard conditions” (Fecht, Brühne, and Gluche Reference Fecht, Brühne and Gluche2014, xi, emphasis added) because “it cannot be observed over any practical period of time” (OpenStax 2016, 236, emphasis added). We tend to deny that diamond alone decomposes into graphite, because this decomposition does not occur on a timescale relevant to human life, which is our default timescale in these situations. The only way to see this decomposition at this timescale is to subject diamond to extremely high heat or high pressure. When we want to explain this process on a timescale relevant to human life, we appeal to all these factors (diamond and high heat or high pressure) because they provide causal control at this scale. If the context of inquiry assumed a larger timescale (e.g., one at the geological or cosmological level), we would be more likely to just cite diamond as the sole cause of this conversion, because its causal control does manifest at these larger time frames. This reveals that our selection of causes is relative to an assumed time frame of interest. This is likely to be a general consideration that applies to causal reasoning in many cases, both within and outside of biology.

The general speed principle clarifies pragmatic and objective considerations that figure in causal selection. If we want to control the manufacture of a product in a living system or in some ordinary life context, identifying factors that take billions of years to influence these systems is not useful to us. We can target and intervene on these factors, but we will never see and enjoy the results of their causal control. While there is a sense in which metabolites alone have causal control over pyruvate, their control is not “useful” for biological systems because it is too slow to operate within the required time frame of interest. The same goes for the diamond-graphite example. While diamond alone does technically transform into graphite, this causal relationship is not useful to us because it does not occur within a “practical period of time” given various constraints (like the length of our life spans). This is not a “merely pragmatic” consideration in the sense of being arbitrary, subjective, or audience relative. It is a pragmatic consideration in the sense of utility and usefulness—causes that take billions of years to produce their effects are (typically) not going to be of use to us, especially not if our goal is to control or change outcomes during our lifetimes.Footnote ¹¹ This suggests that our selection of causes is relative to a practical goal in which causes need to meet some general time frame specified by the context of interest. Once this time frame is specified, there are objective facts about what factors meet it and what factors do not. Whether a factor meets this specification is not dictated by our personal or subjective preferences. Our personal preferences do not determine how fast high pressure converts diamond into graphite or how fast enzymes break glucose down into pyruvate. The speed of the causal control these factors exhibit is determined by objective facts about these entities and their nature in the world.

5.1. Specificity

In the glycolysis example, scientists want to explain how a particular product is produced. Biological organisms need to manufacture particular products in order to carry out various functions and sustain life. Minor alterations in the makeup of a product can completely change its functional capacity or render it nonfunctional in ways that lead to deleterious outcomes and even death. For example, minor changes in the stereochemical structure of amino acids and the amino acid sequence of proteins are known to cause various diseases. For these reasons it matters that a very particular product is produced, and scientists want to explain what causes the manufacture of one product and not another.

Each step in the glycolytic pathway involves the conversion of an upstream substrate into a downstream product. For every upstream substrate there are many downstream products that it could be converted into. For example, the first step of glycolysis captures the conversion of glucose into G6P, but glucose can also be converted into many other types of products. It could be converted into G5P, or it could be rearranged into the five-carbon sugar fructose or split into two three-carbon molecules (among many other possibilities). Factors that explain this first step of glycolysis should explain why glucose is converted into G6P and not into these other products. This explanation is provided, in part, by the fact that the enzyme at this step has specific causal control. There are two important ways in which enzymes have specific causal control: first, (a) they only interact with specific substrates as opposed to others, and second, (b) they only produce specific products as opposed to others.Footnote ¹² Both of these notions are suggested by scientists’s claims that “enzymes are highly specific both in the reactions they catalyze and in their choice of reactants which are called substrates” (Berg et al. Reference Berg, Tymoczko and Stryer2012, 220). I will briefly discuss these two types of specificity and their relevance to causal selection.

First, a represents specificity at the level of interacting causes in the sense of having to do with the particular factors that interact together to provide causal control over an outcome. The enzyme at the first step of glycolysis (hexokinase) exhibits this specificity in the sense that it only interacts with a particular type of substrate (i.e., six-carbon sugars). This enzyme interacts with six-carbon sugars and not with other molecules like five-carbon sugars, four-carbon sugars, or six-carbon nonsugars. But, b has to do with specificity in the sense of producing a particular outcome. Enzymes exhibit specificity in this sense because they produce particular products from some range of potential products. The enzyme at the first step of glycolysis produces G6P, as opposed to G5P, fructose, or two three-carbon molecules. This enzyme adds a specific component (a phosphate group) to a specific location (carbon 6) of a specific substrate (glucose), which results in a specific product (G6P). Both types of specificity, a and b, are relative to some class of alternatives. In a the enzyme interacts with a particular substrate among a set of alternatives, and in b the enzyme makes a particular product among a set of alternatives.

The glycolytic pathway, like other metabolic pathways, represents a causal sequence of specific metabolic substances. These substances are particular chemicals and biomolecules, which are represented in fine-grained molecular detail. Impressively, this sequence of metabolites is common to glycolysis in nearly all biological systems. What this means is that explaining glycolysis in any living organism will involve appealing to these factors because they provide causal control over this process in all organisms. The universal relevance of these causal factors is partly why they receive so much attention and why they are so useful in biological explanation. It also explains why these pathways are said to be “conserved” across living systems and representative of a “unity of life” at the biochemical level. But, enzymes in these pathways are not universal in this sense and are not represented in fine-grained molecular detail. This is because there is no single molecularly distinct enzyme that catalyzes each step in all organisms. Instead, there are families of molecularly diverse enzymes in which each enzyme in the family catalyzes the same chemical reaction. The enzymes in these families are called isozymes or isoforms, as they are “different proteins that catalyze the same reaction” (Nelson and Cox Reference Nelson and Cox2008, 583). The criterion that groups together a family of enzymes is their specificity in the senses of a and b and not their shared molecular detail. If the goal is to explain glycolysis in all living organisms, the enzyme variable represents an isoenzyme family. Alternatively, if the goal is to explain glycolysis in a particular system (e.g., a tissue, cell), the enzyme variable represents a particular enzyme from the family.Footnote ¹³ In both cases, the enzyme variable represents a factor that has specific causal control in the senses of a and b; it just differs in whether it represents a molecularly distinct enzyme or an enzyme family.

Enzymes are selected in explanations of metabolic manufacturing processes, not just because they have causal control over product formation but because they have causal control that is specific, in the senses of a and b. These types of causal control explain why specific causal factors interact and which specific products they produce. In particular, the specificity of enzymes in the sense of b explains how an enzyme-substrate pair produces a specific product from some range of alternative products. As product specificity matters for biological functioning and makes up an important feature of the explanandum in this context, enzymes are selected as causal factors, in part, because they explain this feature of the outcome of interest.

5.2. Particular Speed

In the glycolysis case, another feature of the explanatory target that scientists want to explain is the rate of product manufacture. Biological organisms have to make (and degrade) products at very particular speeds, in order to sustain life and proper functioning. For example, immediate and sustained physical activity requires the rapid conversion of energy-rich products into available energy. Additionally, responding to environmental stimuli requires extremely fast nerve signaling, which is facilitated by the speed of neurotransmitter degradation. In other cases, the functionality of a process requires that it not operate too fast relative to some time frame. For example, enzymes that cleave DNA (e.g., restriction endonucleases) need to be slower than those processes that protect it (e.g., methylation), otherwise DNA would be destroyed before it could figure in transcription or other activities (Berg et al. Reference Berg, Tymoczko and Stryer2012, a9). For these reasons the particular rate of production matters, and scientists often want to explain what causes these processes to operate at one rate and not another.

What explains the rate at which a metabolic process manufactures some final product? In metabolic pathways the rate of product manufacture depends on the particular speed of the enzymes in the pathway. This is similar to a factory assembly line in the sense that the speed of making a final product depends on the speed of each step in the line. As these steps occur in sequential fashion—where a downstream step only occurs once an upstream step is completed—production is no faster than the slowest step. In fact, if each step in the pathway is saturated with material the rate of production is approximately determined by the slowest step, which is called the “rate-determining” or “rate-limiting” step. The enzyme at this step is called the “pacemaker enzyme” because it sets the pace of production and the flow (or flux) of material through the pathway. Because of their important role in determining the rate of manufacture, biological systems often target pacemaker enzymes in an effort to control flux through a pathway. In order for the pacemaker enzyme to determine total rate of product manufacture, all other pathway steps should have their respective enzymes, which is why all enzymes in a pathway are often cited in these explanations.

This analysis has characterized causal selection as a three-step procedure, which clarifies why particular factors are selected as the main causes of some outcome. What about background factors that are not selected? What does this analysis say about the distinction between these factors and the selected causes? Consider a set of factors that seem to be causally relevant to metabolic outcomes but that are not typically cited in explaining these outcomes: temperature, pH, and genes. All of these factors might seem causally relevant to these metabolic processes in the sense that their presence is necessary for them to occur. Metabolic outcomes require particular ranges of temperature and pH, and they require genes, which produce the enzymes that operate at each step. Why are these factors not typically cited as important causes of these processes? My analysis suggests that they are not selected because they either fail to (a) provide any causal control over the outcome of interest or fail to provide (b) particular kinds of causal control. This is captured by the fact that these factors fail to advance through the causal selection procedure. Temperature and pH are backgrounded (or not selected) because they do not pass the second step—they do not provide control over the final metabolic outcome of interest. Both need to be present in a particular range for these processes to take place, but alternations of these conditions do not significantly influence metabolic outcomes in living organisms.Footnote ¹⁴ Genes, however, are backgrounded when they do not pass the final step—in particular, when they fail to provide causal control that meets the particular speed criterion. However, genes are sometimes cited in explanations of metabolic outcomes. Why is this?

Scientists sometimes appeal to genes in explaining metabolic processes, but they distinguish their explanatory relevance from enzymes. Scientists claim that genes have “coarse control” over metabolic processes in the sense that their control is “less immediately responsive” (Rogers Reference Rogers2011, 64, 178). Enzymes, however, have “fine control” over these processes because they have “immediate effects” on product manufacture (63, 170). This distinction can be understood with the notion of the particular speed of a factor’s causal control, and it clarifies why genes are sometimes cited in explanations of metabolic processes and sometimes not. Relative to the speed at which enzymes catalyze reactions, genes take a much longer time to produce proteins. If the goal is to explain the speed of a metabolic manufacturing process, genes are unlikely to be cited because they produce enzymes at slow rate that does not capture or explain the speed of these processes. More specifically, it is often assumed that genes have already made enzymes that are present and prepared to catalyze a reaction. In this case, the faster “fine control” of enzymes explains the responsive nature of these processes. That being said, genes do control the amount of available enzyme, which does influence the rate of manufacture in a longer-term sense. If the goal is to explain the changes in a metabolic process over a longer time frame, genes are more likely to be cited because their slower “coarse control” operates at this scale and explains these changes.

This section has clarified additional reasons that guide the selection of enzymes as causes of metabolic processes. These reasons have to do with particular types of causal control that these factors have over an explanatory target. Enzymes are cited in addition to substrates because they have particular types of causal control that explain important features of this target. The specificity of enzymes and the particular speed of their causal control explain how metabolic processes create specific products and the rate at which these products are manufactured.