Consider one of the most famous modern examples of this problem, Gilbert Harman's "Brain-in-a-Vat" thought experiment. A descendant of Rene Descartes' "evil demon" hypothesis, this thought experiment is designed to motivate general skepticism about sense perception and the external world. What if, we are asked to imagine, you're not really here right now, but instead you are just a disembodied brain, suspended in fluid, with a complex computer stimulating your brain in all the right places to artificially create the experiences you take yourself to be having. For example, the computer could send signals to your visual cortex making you think you’re looking at a blog post on The Dance of Reason, when in fact you’re looking at no such thing, because you have no eyes. Hypothetically, the thought experiment says, there would be no way to tell the difference between a reality where your brain is directly stimulated in this way, and one where you actually have a body that interacts with the world at large. Given this indistinguishability, how can we ever really rely on our senses? How can we ever have any kind of empirical knowledge at all?
Many late-night hours have been spent trying to answer this skeptical riddle. As an intellectual puzzle, an amusing game to getting us thinking, or to kick start a conversation in an intro to philosophy course, it works just fine. But as a tool for trying to understand how humans know the world, it is deeply misleading.
The problem, in short, is that neurologically speaking conscious experience simply does not work the way this thought experiment presumes it does. The brain is a necessary, but not sufficient condition for having experiences. This is not because, as Descartes argued, we have some nonphysical aspect to our mental lives, but rather because a disembodied brain is physiologically incapable of producing the panoply of experiences that we all have every day.
Consider, for example, emotions. While the processing of emotions takes place in the brain the key ingredients that make up the neurocorrelates of emotions—hormones and neurotransmitters—are created by the endocrine system, the network of glands distributed throughout the body. Without these glands you would never feel love, anger, sorrow, joy, lust, hunger or disgust. The absence of these feelings would be a dead giveaway that you were a disembodied brain in a vat.
But it doesn’t stop there. In addition to an endocrine system, you would need circulatory and lymphatic systems to transport the hormones from the glands to the (very specific!) parts of the brain where they are needed in order to give rise to specific emotions. You would also need a digestive system to get the chemical precursors that fuel the endocrine system, while your integumentary system (skin, hair) is essential for flushing byproducts the other systems can’t use. Lastly, all those organs need to be supported by something, making a skeletal system indispensible as well.
In short, the only way to build a brain in a vat is to make the vat out of a human body.
I suspect two objections are occurring in your brain right now. First off, how do I know we need these systems to feel emotions? What if I only think that because the evil genius programming the computer controlling my brain has led me to believe this in the first place? Haven’t I failed to take the force of the skeptical argument seriously?
Okay, I reply, but how do we know we even need a brain in the first place? Why doesn’t the thought-experiment work if it’s just a vat and a computer? For that matter, how do we know there are such things as vats or computers or evil geniuses at all? In order to be expressible in language the thought experiment has to be grounded in something, some kind of experience that explains how our experiences might be systematically misled. If the skeptic can help themselves to a host of experience-based ideas to fund their thought experiment it seems disingenuous of them to object when I do the same to defund it.
The second objection charges me with taking the thought experiment too literally. The point of the thought experiment was to explore epistemology and the limits of our sense perception, not the neuroanatomical foundations of our emotions. We can acknowledge the facts about the physiological basis for hormones and still benefit from pondering fantastic hypotheticals such as these.
This objection precisely illustrates the problem with thought experiments I mentioned in the first paragraph. Epistemology is not bounded by the limits of our imaginations alone. Human beings come to know things by using our brains and bodies, and the empirical realities of those brains and bodies places constraints on what knowledge can be, how it can work, and how we can attain it. When we abstract away from real flesh-and-neuron human beings we are left with nothing human in our epistemology. Whatever is leftover has little bearing on anything worth caring about.
Thought experiments that are accountable only to our imaginations are unlikely to provide us with insight into complex topics like the true nature of minds, morality or metaphysics. As Daniel Dennett says, “The utility of a thought experiment is inversely proportional to the size of its departures from reality.” If we want to contemplate skepticism and the limits of sense perception, there are plenty of ways to engineer realistic thought experiments based on the real-world limitations of the human brain.
 Harman, Gilbert (1973). Thought, p5. Princeton University Press
 Descartes, René, (1641), The Meditations Concerning First Philosophy, (John Veitch trans., The Online Library of Liberty 1901 Meditation II, paragraph 2.
 Ironically, the endocrine system includes the pineal gland, which Rene Descartes speculated was the point of contact between our immaterial minds and our material brains. Rather than serving as a magic intermediary between two metaphysical planes, the pineal gland is part of what grounds the brain squarely within the body itself.
 It is only fair to mention that three parts of the endocrine system—the hypothalamus, the pituitary gland, and the pineal gland—are technically housed inside the brain. The supporter of the Brain-in-a-Vat argument could perhaps lay fair claim to these, as they would be included in the terms of the original thought experiment. None the less, the other parts of the endocrine system (including the thyroid, the adrenal glands, the gonads, and other glands) are distributed throughout the body placing them well out of play for the original thought experiment.
 Dennett, Daniel C. (2014), Intuition Pumps and Other Tools for Thinking, p.183, Norton, W.W. & Company, Inc.