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Inspired by Frank Herbert's Dune:

Action Joe is kept prisoner in Doctor Evil's prison. Doctor Evil knows that Joe's escape is inevitable. So he decides to introduce poison to Joe's body. Joe gets his antidote in his daily food rations.

Once Joe stops eating antidote he should die, regardless of how much of the antidote he has eaten.

Things to consider:

  • The person to be given the poison is a classical action hero (a physically active guy who is well above average in all metrics).
  • The antidote should be something considered "not poison" so that Joe has no chance of realising he is being fed antidote.
  • The antidote has to be consumed (eaten).
  • The quality of food is going to be classic "prison food", so the antidote can be something generally untasty.
  • The poison is introduced to Joe'sbody while he is unconcious, so there are almost no limitations except one: introducing poison to a body should make as few body marks as possible (say injection is OK, but general surgery is not).

I know that a similar premise was used in Jurassic Park but there the dinosaurs were genetically modified. I feel that modifying Joe is also beyond plausibility.

And as stated above: the poison and antidote should be something plausible. No hard science is required.

Also, later in the story not only is Joe is going to escape (surprise, surprise), but he should know about his condition. So bonus points for mentioning some cure which cures Joe forever.

EDIT: Dr. Evil's motivation: he is going to offer for Joe to work for him. But the Dr. is not stupid and assumes that Joe will betray him and/or escape at the first possible moment. Also, Dr. Evil is cruel by nature, so he wants to kill Joe once Joe is not needed, without actually being accused of the killing.

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Comments are not for extended discussion; this conversation has been moved to chat. – Monica Cellio Mar 6 at 23:18
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What is the question? – Daniel Mar 7 at 15:54
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To quote Dr. Strangelove: "But, the whole point of a Doomsday Machine is lost....if you KEEP IT A SECRET!" How is the poison effective at preventing escape attempts if the hero is unaware that it exists? – Muuski Mar 7 at 16:36
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Just a note, in Jurassic Park the dinosaurs were engineered to not be able to create the amino acid lysine. It is revieled at the end of the book that some dinosaurs did escape, and were surviving by eating crops that were high in lysine. Interestingly enough, no animals are able to produce lysine, and so it is an essential amino acid that must be acquired from food for every living creature, including us. – AndyD273 Mar 7 at 17:56
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@Muuski My reading of the question is that Dr. Evil isn't interested in keeping our hero in prison as much as making sure our hero is dead. – Kevin Mar 8 at 4:57

28 Answers 28

up vote 61 down vote accepted

This is actually pretty straightforward. The toxin is targeted at a critical organ or function, and the "antidote" is not actually an antidote, but rather provides the same effect as the now-missing organ.

A simple example would be a toxin which comprehensively destroys the Islets of Langerhans, while the "antidote" is insulin.

A slightly less common case would be thyroid/thyroxine. In fact, Dorothy L. Sayers wrote a Lord Peter Wimsey story, "The Incredible Elopement of Lord Peter Wimsey" about a sadist who punishes his wife's possible infidelity by withholding her thyroxine tablets (she has hypothyroidism) for long periods, turning her into a cretin.

EDIT FOR THE SAKE OF HONESTY - Sayers was either mistaken or taking literary liberties. Hypothyroidism in adults does not produce cretinism. It's a developmental issue, so my example is not actually correct. But I enjoyed the story a great deal, so I won't delete it.

There is, of course, a drawback here - these conditions are known and the counteracting medications readily available. Here is where authorial license comes in. There are any number of brain functions which might be controlled by an as-yet-undiscovered chemical. Oliver Sacks has written an excellent book "Awakenings" about sleeping sickness patients whose condition was caused by dopamine deficiency, and feeding L-DOPA (a dopamine precursor) made amazing improvements. At least temporarily. Likewise, destruction of the substantia nigra (or at least dopaminergic neurons in the pars compacta) produces Parkinson's. A toxin would be asserted to be able to destroy some critical function, and the prison (or more probably the central government which administers the prison) is in possession of some secret therapeutic material which will provide function.

EDIT - It has been suggested that I address the possibility of recovery. I see at least 2 possibilities.

The first is that the damage produced by the toxin is temporary. With supportive treatment the affected function will recover. To put it a bit inaccurately, it's not the disease that kills, it's the symptoms, and if you keep the symptoms from killing the body will eventually recover from the disease. An example might be tetanus: the cause of death is not organ destruction, but rather asphyxiation or heart failure due to sustained muscular contraction. Keep the blood oxygenated and the patient will (probably) recover. Another example would be the Milwaukee Protocol for rabies, in which the patient is put in an induced coma to prevent (more or less) brain damage while the immune system gets control of the virus. Note that this example is iffy - one study suggests an expected 8% success rate. At any rate, in this version of things the replacement medication only needs to be continued for a limited duration. Of course, this implies that the toxin will need to be readministered at regular intervals if Joe is expected to be a prisoner for a long time, but frankly I don't see this as an overwhelming problem. Joe is, after all, a prisoner and at the mercy of the EO.

The second possibility is as straightforward as the original suggestion: transplant. One experimental therapy for neurological conditions such as Parkinson's is the transplant of fetal brain tissue, which is hoped to replace reduced function in the affected portion of the brain. The author can have any amount of fun developing the mechanism and pitfalls of the process - compatibility (note that fetal tissue is somewhat different), sources, recovery therapy,etc).

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Diabetes. And dopamine is the wonder drug. Plus one. – Mazura Mar 4 at 16:49
    
You get so close here... – Shalvenay Mar 5 at 2:01
    
Nice Answer. But I think there is a problem here: while the OP has not specifically stated this, I assume that after a given while the protagonist is to be healed/cured completely. Your suggestions would make him dependent on medicine for the rest of his life. – fgysin Mar 7 at 11:58
    
@fgysin - See edit. – WhatRoughBeast Mar 7 at 15:05
    
As a side not regarding the book you mentioned: hypothyroidism does not lead to cretinism in adults. It may be the case for children born from a mother with untreated hypothyroidism. – WoJ Mar 7 at 15:56

What about Decompression Sickness? Joe could be kept in a prison kept at a high air pressure - both the toxin and the antidote against the effects of ambient air pressure - (needs not be underwater, even though divers in real world are most aware of this). Joe could be unconscious while his prison is being pressurized, and he will never be the wiser: it won't leave any marks.

Depending on the pressure, suddenly escaping from the pressurized environment would be highly unpleasant, harmful, or even fatal. The most obvious cure would be slow decompression, which can take a lot of time (and needs the necessary equipment).

Building such a prison, one would have to design it so that an escapee does not have access to the airlock (or at least the pump) and will have no other choice than to emerge into normal air pressure at once. Well, perhaps disguising the airlock as an elevator... when you enter a certain secret code, it follows the slow decompression protocol, but when an escapee who does not know it just presses "ground level", it depressurizes rapidly to ambient pressure and opens to the outside world.

Of course, access to Joe from the outside world would be through that airlock, which for humans may take a lot of time because of the same reasons. But not for robots or other mechanical means of delivering his food. Food in airtight packages (bags, bottles, etc.) would give the game away as the contents inside the package would have much less pressure than outside and so be squashed flat.

He could be in contact with his captor (and other humans) through CCTV (etc.). No physical contact. Except maybe in emergencies, e.g. medical treatment, where the personnel could reach him fairly quickly, but will need to go through lengthy decomp when they leave.

It would probably take some good money and specialized skills to build the prison (think spaceships or deep-sea vessels), but in a way that it is not obviously a high-pressure container to its inhabitant. But could be done, e.g. housing box made with conventional materials and techniques, inside a large high-pressure (round) cylinder. Or an old (still sound and tight) submarine hull could be repurposed if one has a handy one lying around...

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-1 The problem of this is that in the end it's no different then any other prison in that case: Everybody going in and out have to go through the same procedures and if you can escape then you're perfectly fine. I mean, a far cheaper way is rigging the prison with mines as soon as he leaves his room or something. – David Mulder Mar 6 at 15:35
    
I like this, building it underground would make it easier to handle the high pressure and make elevators and such things appear more 'innocent'. Making it so that only one prisoner is affected would be more difficult. Developing some other plausible gas that is only fed to Joe's cell that saturates his blood would make him more susceptible to drop in pressure even if other prisoners and visitors are just on the safe side of decompression from plain Nitrogen narcosis. Staff would be aware and cure is very slow decompression and removal of dissolved gas. – KalleMP Mar 6 at 20:21
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Also how can protagonist Joe work for Doctor Evil? I assume he'll have to leave his cell for this... – fgysin Mar 7 at 12:00

I'm not sure if this one meets your rules or not:

Instead of a poison/antidote, how about something addictive with lethal withdrawal symptoms? (Note that there are things close to this in the pharmacy--once your body adapts to them if you suddenly take them away it can't adjust fast enough and you might die.)

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A real world example is alcohol. I used to work in an addiction research lab and for several studies we had active alcoholics as participants. Many had to have dangerously high blood alcohol levels in order to function. They also couldn't take part in longer studies because of the risk of withdrawals. – bob0the0mighty Mar 4 at 19:50
    
A fictional example is found in Patrick Cave's The Selected: a man is kept under the control of an evil master by his addiction to a drug ("the Lady"), which he must take every day or else die. – rand al'thor Mar 5 at 20:40
    
Methadone is a great candidate: it's used to treat heroin addiction, but withdrawal is potentially lethal - even moreso than heroin. (And, for bonus points, it doesn't have an obvious "high.") With a sufficiently-high daily dose of methadone, withdrawal can be nigh-guaranteed to be deadly. It can be treated later by gradually reducing the dosage of methadone - or by switching to heroin or other opiates and then trying to kick that habit. – Paul Marshall Mar 7 at 19:33
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The antidote is the poison. – PyRulez Mar 8 at 2:53

Nanobot. A normal poison would be sooner or later flushed out of Joe's body, while nanobot can reproduce themselves in his system. The antidote would be just a way to keep them in standby, without it, things get messy.

Joe can be cured later by any kind of low yield EMP pulse, a blood replacement from his beloved Joe Bond's girls or his pet bantha.

Some dissease would work more or less the same way, but to be powerful enough, it would need heavy biological engineering.

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Nanobots are always the answer! – thanby Mar 4 at 15:47
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The poison and antidote should be something plausible. No hard science is required Maybe Nanobots is still too expensive or futuristic for this story. (I know it actually exists, but it's expensive and not as relevant as we planned) – Carlos2W Mar 4 at 21:20
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@thanby: Nanomachines, son! – Joshua Snider Mar 5 at 9:04
    
There was a TV show where a victim had been "poisoned" by very simple nanobots. When triggered, these nanobots would start binding to each other, clogging up the circulatory system. Filtering the blood wasn't useful as they were largely made of carbon and would reproduce. It seems to me that an anti-trigger could also be used, i.e., the nanobots would activate when lack of a signal was detected. This could be in the form of a easily broken down chemical introduced in food. – Ouroborus Mar 6 at 8:19
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@thanby Someone here has played too much Metal Gear Solid 4. youtu.be/7kNrIn8H32c – Nicolas Daoust Mar 7 at 19:58

The tricky part is that most antidotes remove the poison. We have to be clever.

If the poison actually caused Joe to develop an autoimmune disease, his own immune system would become the real poison. The antidote could then be immunosuppressants.

If you want a cure, you could play with the idea of trying to re-teach the immune system not to hate itself. I do know this is done with allergies, where you slowly introduce allergens to try to get the immune system used to them, but its unclear whether this could work with a particular poison generated autoimmune issue.

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This is both not doable and does not fit the scenario. 1) We can't deliberately cause autoimmune diseases in humans. 2) We can't cure autoimmune disease. 3) Autoimmune treatments are not antidote-like. The side effects of the most benign ones are still pretty severe with long-term usage (Cushing's). They can be deadly in themselves. 4) The chronic autoimmune diseases are rarely deadly. When they end fatally, they need to go for years without treatment. – rumtscho Mar 4 at 15:08
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@rumtscho: whereas we make self-reproducing death-dealing nanobots all the time ;-) – Steve Jessop Mar 4 at 16:01
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@rumtscho Organ transplant recipients often have to take a cocktail of immunosuppressants to avoid organ rejection. You might do e.g. a heart transplant, and even deliberately choose a not particularly compatible donor to ensure that without a thorough medication the recipient would soon experience a fatal heart failure. – Peteris Mar 4 at 16:07
    
wouldn't you call something like this a disease. we already take medications (antidotes) for certain diseases daily and if we do not, we have adverse and possibly life threatening side effects. They usually can not be removed as well. – Ryan Mar 4 at 16:36
    
@Peteris That's not a bad start but the OP said he wanted to avoid the surgery route because it would be more easily detectable – thanby Mar 4 at 16:49

There are many fat-soluble toxic chemicals (mercury, DDT, tetraethyllead, etc.). These will be absorbed by the body's fatty tissues. While embedded in fat, they might not cause an immediate health threat. However, when the victim is physically active, the body burns the fat and releases these toxic chemicals into the bloodstream, resulting in a sudden toxic dose of the poison. Our hero would need an immediate dose of some sort of antidote that neutralizes the toxin's effect (chelation therapy for heavy metal poisoning, for example). He would also probably need small doses of antidote over longer periods of time even with low activity, since some of the poison will make it to the bloodstream regardless.

This is similar to what you're looking for, but it depends on the hero's physical exertion, rather than just leaving the prison. Since Joe is your typical action hero type, this might put a damper on his thrilling heroics. It might even prevent escape if that escape is physically strenuous.

I would guess that Joe could cure himself later on by a controlled release of the toxins. Exercise together with a carefully regulated antidote regime would release the poison and neutralize it so that his body could eliminate it. This would be a long process, as Joe would essentially need to burn off all of his fat, then put it back on to get back into fighting shape.

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This has merit, the antidote is supplied with the toxin, the antidote is something to keep him idle and lethargic so he keeps gaining weight on prison food, once out he is running and not eating the fat cells are consumed and toxins are released. – KalleMP Mar 6 at 20:29
    
A simpler way to use the same poisons: The victim is fed rich, high calorie foods laced with the poison for a while to cause them to gain weight in the form of fat that has the toxin(s) bound in it. Then they have to keep eating a high calorie diet (which no longer needs to be tainted) to prevent the toxin from being released. – Todd Wilcox Mar 6 at 22:36

The answer to this question sits on the shelf at the BBEG's local hardware store. It's called d-CON.

No, seriously. The second-generation superwarfarins (such as brodifacoum) are exactly the poison you seek -- they have a long half-life in the body (in the weeks to months range) due to being highly fat soluble, are capable of being quite insidiously lethal due to their mode of action, and can easily be antagonized by a steady diet of green vegetables (as said vegetables are high in vitamin K, which counteracts the effects of coumadins).

However, if Joe gets out and reverts back to his fast-food-eating ways...he'll be in the hospital or worse.

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This sounds great, but do you know of any evidence that the levels of Vitamin K in food are sufficient to counteract superwarfarin poisoning? – Obie 2.0 Mar 5 at 2:01
    
@Jonah -- they're enough that warfarin patients need to take their diet into account to avoid throwing off its effects. Considering the main difference between warfarin and the superwarfarins in terms of pharmacokinetics is their half-life in the body, as I understand it...it's not a stretch that 3 wilted spinach salads a day would be enough to keep someone alive in the face of superwarfarin poisoning (you'd be eating >10x times your RDA in vitamin K) – Shalvenay Mar 5 at 2:03

Most poisons need to be continually reintroduced in order for the antidote to continue to be necessary. Otherwise the poison will be flushed out of the system over time, or completely negated by the antidote. What I'd propose is a two-part system. You have two poisons, A and B which work independently. Basically, you give the prisoner a dose of Poison A and Antidote B in their breakfast, and Poison B and Antidote A in their dinner. So long as they eat both meals every day (and they most likely will or else they'll starve - make sure there's no other way to get food), they will continue to have one or the other poison in their system, but it won't kill them. The first time they skip a meal, the poison from the previous meal will still be in their system and kill them (or at least make them very sick - you might need to miss 2 antidote doses for it to actually be fatal).

The way to get out of this is for Joe to figure out that it's coming from the food (maybe he's forced to skip a meal for some other reason and he gets sick, and does the math), and slowly wean himself off of the meals. (Possibly figure out which part of each meal is poisoned, and which has the antidotes - is it the bread? The water? The potatoes? Maybe they mix it up every day so it's not obvious, but there's a pattern he can detect over time if he's really observant.) He'd suffer from malnutrition, and possible minor side effects of the poisons from taking a lower dose of the antidote, so it wouldn't be easy. He might be able to live by catching rats or other vermin to use as an alternative food source.

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You can even mix the antidote and poison, so he has to either keep consuming it, or to pick his poison. – PyRulez Mar 8 at 2:56

The opposite of Cort Ammon's answer:

Keep him in a sterile environment and feed him immunosuppresants. After a while, he will develop severe immunodeficiency (you can remove the drugs at this point) and in case he escapes, meeting with other people will infect him with all sorts of lethal infections (flu can be fatal).

Quick medical action and correct diagnosis can save his life, but recovery will be probably long and non-trivial.

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You could have a retro virus, use it to somehow cause a disease that causes the body to go into a state where the blood is constantly coagulating, meaning that the daily doses of antidote would be anti-coagulants meaning that he wouldn't be cured, it'd be suppressing the coagulation.

This disease here would do the trick, but you'd have to bump it up to 11 on the aggressiveness scale.

This could be introduced by messing with Joes DNA, using a retro virus which would leave no marks (I'm assuming the evil genius is intelligent enough to be up-to-date in gene manipulation). This would also be the route of the cure, as if Dr Evil believes he can turn Joe, he wouldn't want Joe to be dependant on the antidote for the rest of his life. So he would keep a copy of Joes original DNA somewhere to repair the damaged DNA in Joe.

This article on reprogramming cells shows that it is used to treat a whole host(sorry) of viral infections. It might help with the plausability of modifying Joe.

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what about if the poison is actually a toxin that, destroys certain kinds of cells, or the ability for the cells to produce certain vitamins or amino-acids.. this should mean that if the subject does not take that regular amount of vitamins his body would shut down and die.

Imagine if you will, a poison that destroys your Pancreas, without a daily regular dose of insulin you will die.

of course the true effect of the poison should be something that is not easily diagnosed by a doctor.. and if you need something really credible you should maybe ask a biologists.. else just refer to some amino acid/enzime.. and make it sound plausable

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I'm not aware of anything that does this currently but the basic idea makes sense. Especially if it destroys a specific organ that can just be surgically replaced later on to provide the cure. – thanby Mar 4 at 15:49

You could postulate any kind of chronic infection which releases a toxin. In real life this could be something like Clostridium botulinum which kills through the release of a potent neurotoxin and is treated with an injectable anti-toxin.

It's easy enough to imagine a genetically modified organism being implanted into Joe (e.g. as part of a meal so that it colonizes Joe's gut). It then releases a toxin that can be treated with a nutritional supplement (e.g. like warfarin being treated with vitamin K).

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The other answers are correct, there's no direct way to do what you are looking for as a "poison". It might be possible with some form of chronic illness or the very innovative high pressure area.

There is an alternative though, which is that you actually make the antidote the problem. Find something that has really nasty withdrawal symptoms and then pump his system full of that. So long as he keeps taking it he is fine but if you remove it then the withdrawal kills him.

That's closest to what you seem to want in that it doesn't require any special architecture or facilities, just something to keep slipping him a daily dose of the substance.

The cure would be weaning him off it gradually (i.e. he gathers a stash and takes it with him then takes gradually reducing dosages) possible accompanied by medical care and/or something to mitigate the withdrawal.

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I was going to comment on the same type of thing. I don't know if there's a drug available today that would be unnoticeable but many less-savory (read: human trafficking) organizations keep their "merchandise" around by intentionally hooking them on narcotics and then using the addiction to control them. The trick would be getting Action Joe physically addicted to something without him realizing it. – thanby Mar 4 at 16:39

Posted this as a comment but realized it's actually more of an answer. There are already several good ones but I just wanted to throw this out there in case it inspires you.

Neuromancer has a somewhat similar plot device wherein a character is implanted with tiny toxin sacs that slowly degrade and they must remain loyal to another character in order to get the cure. This could be modified a bit to fit your scenario.

The toxin sacs are tiny, maybe they contain something extremely lethal like botulinum, so you don't need much to kill Joe. This means they would leave virtually no scarring from being implanted and could even go somewhere out-of-sight like the back of his neck next to his spinal cord (the ideal place since botulinum is a neurotoxin). Now in Neuromancer the sacs degraded over a long period of time, but in this case maybe they break down much faster. They're made from organic tissue so the body could be actively trying to absorb them.

The "antidote" could either be some protein that binds to the sacs to "replenish" them, or it could be a chemical that prevents the body from absorbing them in the first place. Either way, within days of stopping the antidote the sacs would be absorbed and the toxin released. The total cure would simply be locating and removing them, which would be a delicate but ultimately not-impossible thing to do once Joe knows about them.

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Also good answer. If Dr Evil is very evil he could have layers of sacs that are prevented from activating after various delays by a number of different chemicals (just in case Joe figures one out) with various toxins inside each, chem or bio.. – KalleMP Mar 6 at 20:37

How about a large internal parasite?

Joe has let's say a worm inside of him that he is unaware of (attached to the intestines perhaps).

This worm produces a waste product that is toxic to Joe and would kill him. Joe consumes the antidote to this toxin to stay alive.

If Joe ever finds out about the worm and has it surgically removed he no longer gets regular doses of the toxin and is permanently cured.

The parasite could even have been fed to Joe without him realizing it to initially administer the poison.

I have been told by exterminators that some mouse poisons are rendered inert by cat food. (This helps reduce incidents of pets being killed accidentally during an extermination, but means you have to also prevent the mice from having access to the cat food.) So I can imagine similar toxins in humans having antidotes present naturally in a specific diet.

Or perhaps the parasite simply has a knack for reducing Joe's ability to absorb vitamin C resulting in scurvy unless Joe consumes vitamin C in shockingly large quantities.

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Normally parasites don't kill their hosts, except of bridging ones. – enkryptor Mar 4 at 17:16
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true, but such a parasite could have been engineered by Dr. Evil, or the intended host could have been not human. The ticks in Australia can be fatal to cats and dogs while not fatal to kangaroos. It is at least believable that a tapeworm that normally has a komodo dragon as its host might be fatal to a human host. – YoungJohn Mar 4 at 17:25
    
I wonder if the mouse toxin-cat food is a fairytale made up by exterminators to placate customers. The antidote may be something that prevents the parasite from multiplying and/or creating toxins. Malaria and quinine seem to fit the bill quite well here except a recurrence after stopping treatment is not rapid in current strains, perhaps something new from dr evil. – KalleMP Mar 6 at 20:33

I don't know of an actual substance that works like this but I can think of a mechanism by which you can justify it.

This poison would have to be something that the body can't clear out. Maybe it deposits in the body somehow or the kidneys and liver can't clean it from the blood. Something like that.

Then, it has to work via some very specific chemical pathway in the body. Maybe it latches on to some kind of receptor in the cells. However, this might be the hard part. Mostly because of the way the antidote would have to work.

Finally, the antidote would have to be something that wouldn't degrade the poison. The way to do that is to have some sort of substance that blocks the chemical pathway that the poison takes (like a receptor agonist). It competes for the cellular receptor and gets preferential treatment.

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That's a plausible way to do it if you're willing to do a little "Chemical A and Chemical B" hand-waving (the reader probably doesn't want to know what the exact chemical structure is anyways). The trick would be explaining how Joe figured out a cure in time to save himself. Liver transplant and a blood transfusion maybe? – thanby Mar 4 at 16:45
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Dialysis if it's constantly in his blood. Surgical removal of the deposits if not. I figured Dr. Evil probably had to take an evil pharmacokinetics and evil biochemistry class at evil medical school so he could probably devise an Action Joe Cell Receptor Antagonist. Unless his doctorate is in evil art history. – Jake Mar 4 at 17:12

No Poison at all.

You don't need to poison him. You need to make him believe he was poisoned.

Give him a real poison, and let him suffer the first effects. After that, apply the antidote in a visible form (injection is best), and let him know that this will stop the toxin from working for a while. Which is a lie, but he doesn't need to know that.

After that, give him poisoned food, and let he feel once more the effects of the poison before applying the antidote. Do this a few times until he believes that he was poisoned in that manner. Once he believes he is poisoned with your special poison, do the offer for work. If he accepts, you start providing him a stronger dose of the 'antidote', which will hold the effects of the poison at bay for a longer time - a day, a week, you choose.

At this point, you just brainwashed him into working for you, and don't need the poison anymore - just making him believe he is poisoned will be enough.

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placebo works just as well as medicines is most cases, no reason why placebo poison wouldn't work too! – gbjbaanb Mar 8 at 13:35

Inject him with a small explosive device near the brain stem. The device is constantly listening for a radio signal that is being transmitted around his cell, like a dead mans switch.

The device could be small enough that it could be put in with a needle, similar to how animals are tagged with RFID chips.
The explosive itself could be very small since it wouldn't need to blow his head off, just mess up the brain stem.
The explosive could also be used to drive a spike or something like a miniature gun, or even break the capsule and release some toxin.

When Joe escapes his cell and goes outside the range of the radio transmitter the explosive triggers, killing him.

You could let him know that it's there by watching another prisoner try to escape, or DE could give him a warning by injecting a dog or some other animal and throwing a ball for it to chase down the hall.

Joe could make a daring escape by hooking the transmitter to a battery pack and taking it with him. This adds to the suspense by needing to make sure that the battery doesn't come unhooked, and also he has to get somewhere safe where the device can be removed before the battery dies

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I was going to suggest some kind of electric shock collar, but explosives are much more interesting. – Pharap Mar 7 at 23:54

Instead of a poison, a disease. You need something with two forms, one that hides out and one that's active. The "antidote" is a treatment for the active form of the disease but it can't touch the part that's hiding. (As for what looks like this--how about some sort of spore-forming bacteria? Many antibiotics can't touch the spores. Take one of those and turn up the lethality.)

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Two poisons, a lethal does of anticoagulant and a does of blood‐clot promoting drugs, these should cancel each other out, but one should have a significantly longer half life than the other. If he does not take the two poisons then the longer lasting one will out way the other and he will die.

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The radiation poisoning from The Expanse series. It is grounded in reality with just a hint of the fantastical (i.e. meds exist that can "counter" new cancers that are constantly popping up). Ultimately, the body is beyond "reapir" so the meds effectively become the antidote. Since the infection method is a high dose of radiation, Joe will never see it coming!

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  • damage Joe's pancreas. He will require insulin to stay alive. Con: insulin is digested, so Dr Evil have to invent prodrug ("a biologically inactive compound which can be metabolized in the body to produce a drug").

  • make Joe allergic. Dr Evil puts some "bags" under Joe skin to slowly release allergen. Antidote is antihistamine drug.

  • genetically modify bacteria to produce deadly toxin in absence of some substantion. Place bacteria in Joe's intestines.

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Easiest answer is the physically calming effects of benzodiazepines. Adding some to food would get him physically addicted. As soon as he is un-able to get his now life saving medication he will die.

Also, getting action joe addicted to any sort of drug would be the best answer, causing him as much physical degeneration as possible is probably best in the long run.

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What about multiple poisons?

When Joe eats his breakfast cereal, he eats Antidote A and Poison B. For his lunch he gets Poison C with Antidote B and for dinner Antidote C and Poison A. And next day entire circle starts again.

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Infect him with bacteria or parasites that require a protein that humans do not have or produce but is common in many foods. Then only give the character enough of that protein to preserve the life of the organism. If he is no longer supplied with this food he will eat a different diet high in this protein and allow the infection to grow.

Contact with allergens while in a weak state causes an allergy to it. http://www.webmd.com/allergies/guide/chronic-allergies-causes#1 Maybe he could be injured by something he does not suspect is related and then exposed to allergens.

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Well There is always the clasic arsenic poisoning. Joe could be fed it in low doses constantly and once he stopped it would have the desired effect of his demise. An example would be the Arsenic Eaters of Styria. article found here another example found here.

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Maybe a bit out of the box, but what about a small device is put in the body (not sure if possible without general surgery) that checks for a trace chemical that is given to the person, something that stays in the blood for a short period of time but is not common, if it is not present in the blood, then the device explodes.

Got this idea from the movie Crank, where the person needs adrenaline (which he can produce himself by doing dangerous things) so the difference here is that the character would need something that is supplied externally.

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A lot of suggestions have been offered, but none seem acceptable on all requirements. So here is an even more whacky suggestion.

What about a poison that poisons the mind, rather than the body? I'm talking of something like Stockholm syndrome. A notable example in real life is Patty Hearst.

Anybody with some knowledge of the appropriate science and the necessary means can apply the biological run-of-the-mill type of evil if needs be. To pull off this sort of psychological manipulation would to my mind require a whole deeper, darker level of calculating heartless Evilness, spelled with a capital letter. It also has the potential to turn just another action novel into a profound psycho-thriller...

Let's look at the requirements:

  1. Science-based: well, one can argue that psychology is "not really" hard science. On the other hand, this sort of thing has already happened and is documented (see references above). "Making it work" will leave a lot of leeway to the story-teller, much more than a (possibly implausible) chemical/biological/physical action would.
  2. Joe working for Dr E: once Joe is indoctrinated initially during his captivity, he should be a reliable minion to do Dr E's bidding. Not much risk in releasing him into the wild.
  3. Dr E cruelly killing off Joe: He might not need to do that in the end. On the other hand, an antagonist capable of inculcating a subject with Stockholm Syndrome, could also quite conceivably be capable of implanting suggestions of sufficient guilt or worthlessness so that the subject commits suicide, or otherwise destroys himself (e.g. alcoholism/drugs).
  4. Antidote enabling Joe to escape: Well, Dr E might underestimate Joe's psychological clued-up-ness (because he is this stereotypical all-physical action jock with not much intelligence, see), so once Joe catches on to the mind games Dr E is busy playing on him, it's all cat-and-mouse subterfuge and counter-subterfuge from then on, potentially leaving the reader to guess "has he or hasn't he" until the end. But as said, that is a whole different story-telling ball game.
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