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In this near-future setting, biotechnology is slightly more advanced than our own. Genetic engineering is cheap as well, but due to an ecological disaster the environment just doesn't have enough calories to go around.

What I am looking for is a known chemical, drug, or (if necessary) a SPECIFIC genetic mutation (as in, a particular gene that has been identified by modern science) that allows people to survive on fewer calories. This mechanism may have side effects.

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This question asks for hard science. All answers to this question should be backed up by equations, empirical evidence, scientific papers, other citations, etc. Answers that do not satisfy this requirement might be removed. See the tag description for more information.

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    $\begingroup$ Such an additive would be a great way to make your car go twice as far on the same amount of fuel... In other words, how would it work? The human body uses about 2000 kcal / day just to stay alive and warm. I'm not saying that it is impossible; what I'm saying that it would be much more complicated than taking a pill or modifying one gene: you need to introduce complex modifications to the way the human body works. (And it is also highly dependent on what you want the humans to do and the environment in which they live.) $\endgroup$ – AlexP Sep 19 at 9:07
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    $\begingroup$ @AlexP Not everyone burns calories at the same rate; so-called "thrifty genes" cause people to retain more of what they eat (and causes obesity in modern times). I'm looking for a particular gene or medication that may cause the same effect. $\endgroup$ – IndigoFenix Sep 19 at 10:10
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    $\begingroup$ In this case you should edit the question and explain that a small reduction is fine; I thought you were looking for a large reduction. (Note than if all you want is reduce the caloric intake by 10 to 20% you can simply let your people eat less and lose weight.) $\endgroup$ – AlexP Sep 19 at 11:35
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    $\begingroup$ Comment cause I lack hard science reference, what if you come at it the other way. Instead of alter people to use less energy, alter people to produce more digestive enzymes and be better at converting plant matter into other essential nutrients like Gorillas etc. $\endgroup$ – Affe Sep 19 at 19:34
  • $\begingroup$ I feel like the questioner is looking for something like the difference between aerobic and anaerobic metabolism. An organism that has an aerobic metabolism can use oxygen to get significantly more energy from the same food as an anaerobic organism. Unfortunately I'm not aware of anything that allows a similar step up from aerobic metabolism. $\endgroup$ – Barry Haworth Sep 19 at 23:49
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GH1 gene

If the GH1 gene has problems in a person, this person will likely be much shorter because of a lack of growth hormone.

Smaller people consume fewer calories when idle (but more to walk the same distance as a tall person). So this could help in reducing global calorie intake if accompanied by other measures to diminish the need for physical effort (work from your bed, sports are bad, …).

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What you want to do is to decrease basal metabolic rate for humans. It is influenced by several factors, I just went through them one by one and came up with several ideas.

Reduce physical activity

Everyone goes to sleep

About 30% of BMR comes from physical activity, thermoregulation and digestion:

About 20% of one's energy expenditure comes from physical activity and another 10% from thermogenesis, or digestion of food (postprandial thermogenesis).

Assuming you have enough resources to take care of sleeping people you can put most of your population to sleep using any sleeping pill you like. Optimistically, this will lead to a 10% decrease in food intake.

As an alternative you can change sleeping patterns. A mutation in ADRB1 gene was reported to lead to a short sleep behaviour in mice. Possibly, you can "reverse" this kind of mutation to make people sleep 20-22 hours a day.

Reduce biomass

Female society

An average woman needs to eat about 20% less calories per day than an average man (2000 vs 2500 kcal). As a long term solution, you can move to a predominantly female society.

The good thing about this option is that it's achievable with modern technology (sex preselection). You can employ genetic engineering to thwart Fisher's principle and produce the disproportionate amount of females naturally.

Life without limbs

Legs amount to 33-37% of body mass. If the absolute goal is to reduce food intake your people can choose to use (hopefully, more efficient) artificial limbs instead of natural ones. This can be done with genetic engineering: tetra-amelia syndrome is a genetic disease (linked to a mutation in the WNT3 gene) that is characterized by the absence of all four limbs.

Other options and limitations

Unfortunately, without dramatic advances in biochemistry there's no safe way to improve the energy efficiency of a human body. I can see no easy way to sustain the same amount of biomass with a significantly lower amount of energy.

Saying that, there are other options that don't require drugs and mutations. For example, organized food rationing can have an enormous effect by itself. According to the Food and Agriculture Organization of the United Nations the minimum daily caloric intake is about 1,800 kcal. For comparison, average American consumes 3800 kcals a day.

So, you have a potential to decrease food consumption by 50% with a highly efficient food production and distribution system.

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    $\begingroup$ Regarding sleep: Maybe you could modify humans to go into some kind of hibernation state like squirrels or bears during winter with very low energy consumption. Arctic ground squirrels hibernate from early August to late April. “During hibernation, its brain temperature drops to just above freezing, its core body temperature reaches temperatures down to −2.9 °C (26.8 °F) and its heart rate drops to about one beat per minute” $\endgroup$ – Michael Sep 19 at 19:17
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    $\begingroup$ The 1800 kcal/day number is for a fully-functional human. If you're willing to lose things like the immune system or the ability to heal from injuries, you can drop calorie intake to about 800 kcal/day. $\endgroup$ – Mark Sep 19 at 22:00
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    $\begingroup$ I wonder if one could affect the baseline body temperature. I think thermoregulation is, what, 10% of the BMR... but we already have the technology to create decently thermoregulated spaces, so could probably get by with a much reduced ability to regulate temperatures internally. Coldblooded humans, fun. The other big energy sink I see is osmoregulation, controlling various concentrations. Most of it we can't do externally, but if everyone's food and drink was tightly regulated for electrolytes and salts, we might, again, be able to survive with a less efficient system. $\endgroup$ – Megha Sep 26 at 6:03
  • $\begingroup$ @Megha That's a cool idea! :) I was thinking about cold-blooded humans, but I couldn't estimate the effect of thermoregulation on biochemistry. As it turns out too many processes depend on it and I wanted to avoid redesigning human body from scratch. See this answer for a possible list of problems: worldbuilding.stackexchange.com/a/12764/325 $\endgroup$ – default locale Sep 26 at 6:16
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    $\begingroup$ @defaultlocale - that would be why I didn't make it an answer, I've no idea how it could be done (which seems to be what OP is most interested in). its fun to think about, though :) $\endgroup$ – Megha Sep 26 at 7:01
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In short, you can either decrease the minimum energy the body needs to function through thyroid hormone reduction, or increase the amount of energy you get from breathing by artificially upping respiration rates.

Anything that affects thyroid hormones will affect how much energy your body needs to function.

For the thyroid. Medication: Thiamazole. Gene mutation: Hasiomoto's Thyroiditis.

Thyroid hormones, amongst other things, regulate your body's BMR. This is the rate of energy usage for things like organ function, respiration, and so on. Lower BMR => lower energy usage => less food required.

However, considering the side effects of hair loss, muscle pain, lower red blood cell count, liver failure and thyroid cancer, maybe you might be interested in something else.

As for Hasiomoto's Thyroiditis, it's a horrifying inherited autoimmune disease that lowers the release of thyroid hormones. If anything, I'd use it as an example as to why you shouldn't use genetic engineering. The body is a well balanced machine, and genetic engineering sounds like a permanent solution to a temporary problem.

For respiration. Medication: Doxapram.

Doxapram increases the respiration rate of hospital patients. The effect of this is increased cellular respiration and greater ATP per unit time. Again, some severe side effects if wholly relied upon, but if biotech is more advanced then maybe it's something that can be introduced.

Hope this helps: your world sounds interesting, look forward to hearing more in the future.

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  • $\begingroup$ Increasing the rate of ATP generation won't change the overall balance of calories in to usable energy out, will it? You'll still have to eat the same amount as before. $\endgroup$ – Nuclear Wang Sep 19 at 19:49
  • $\begingroup$ Means your body burns through less energy whilst idle and whilst moving. You're right in saying lowering your BMR doesn't make your body more efficient. It just puts it on low-power mode, so to speak. $\endgroup$ – mcRobusta Sep 19 at 20:20
  • $\begingroup$ Still not following you - if it takes X calories to run a mile, it will still take X calories to run a mile on doxapram, no? $\endgroup$ – Nuclear Wang Sep 19 at 21:03
  • $\begingroup$ Yes, but in the case of doxapram you get more energy from respiring (i.e. breathing) and have to burn less in the form of stored energy, which comes from your food. X is the same, it just comes from different sources in different amounts. Thiamazole works by reducing your body's minimum energy requirements to stay alive, and doxapram increases the energy yield from breathing. In either case, you now have to put less food fuel in to get the same result. $\endgroup$ – mcRobusta Sep 20 at 5:55
  • $\begingroup$ More lost now - every bit of energy comes from food, you can't generate ATP by breathing alone, and you always get ~36 ATP per glucose, regardless of how quickly that happens. Are you talking about the efficiency differences between aerobic and anaerobic respiration? That would make sense, as increased breathing would allow your cells to perform the more efficient aerobic respiration for longer before switching to relatively inefficient anaerobic respiration. But that wouldn't be relevant during periods of rest, since the body only uses anaerobic respiration during physical exertion. $\endgroup$ – Nuclear Wang Sep 20 at 12:56
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Cocaine is well known for having, among the short term effects, a reduction of the sense of hunger.

I wasn't able to find the corresponding section in the English version of Wikipedia, so I quote the Italin version, which states

Gli effetti neuropsichiatrici sono estremamente vari:

  • Distorsione cognitiva e delle capacità recettive

  • sensazione di aumento delle percezioni

  • Accentuazione della reattività fisica e mentale
  • Riduzione dello stimolo di addormentarsi, della fame e della sete
  • Euforia (da cui l'uso passato come antidepressivo e come trattamento dalla tossicodipendenza da oppiacei)
  • Maggiore socievolezza e facilità di relazione
  • Infaticabilità
  • Incremento della libido

The bold text translate as "reduction of sleep, hunger and thirst stimulus".

Of course it just masks the hunger and has plenty of side effects, but since you are open to them, this is not an issue.

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    $\begingroup$ There are a lot of things that reduce appetite, but the person will still need the same amount of food to live, so it won't really help. Could be useful for staving off hunger though. $\endgroup$ – IndigoFenix Sep 19 at 10:06
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    $\begingroup$ @IndigoFenix, after the first days of fasting, the human body gets used to operate in low food intake regime. Cocaine might help in those first days. $\endgroup$ – L.Dutch - Reinstate Monica Sep 19 at 10:10
  • $\begingroup$ I would assume that cocaine increases the metabolsim and by that increases the nedded caloric intake... $\endgroup$ – Silent-Bob Sep 19 at 10:58
  • $\begingroup$ Actually most people nowadays who don't live in war-torn or famine-ridden areas do eat more than they need, so this might be the most efficient short-term solution. $\endgroup$ – Renan Sep 19 at 11:08
  • $\begingroup$ Wiki: "Stimulants have been used in medicine for many conditions including obesity, sleep disorders, mood disorders, impulse control disorders, asthma, nasal congestion and as anesthetics." - Google; stimulant : "There are several types of stimulants, including caffeine, nicotine, cocaine, amphetamines, and methamphetamines." $\endgroup$ – Mazura Sep 20 at 0:29
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Brain Hog/Fog

Well, you said "survive", and not "thrive", so run-of-the-mill starvation will solve your problem nicely. Others have observed that muscle mass has high BMR, which is why atrophying muscle is one of the first things the body does in response to starvation. But the single hands-down winner for specific energy consumption is the brain. It provides less than 5% of the body's mass, but consumes more than 20% of its energy. It's a real hog. Anything that causes people's brains to be less active will reduce metabolic energy expenditure (think sedatives, barbiturates, etc.).

Batteries Already Included

In general, you don't need to take a pill to run on fewer calories: the body is already designed to respond to whatever level of calorie consumption is available, and has both short-term and long-term responses to starvation. For instance, people who survived World War I and II have epigenetic markers of starvation on their DNA, which has been passed down through multiple generations. The human genome is literally programmed to cope with inter-generational food shortages, and will typically respond by making people smaller and weaker (and probably more dimwitted, too).

Customized Starvation

What you might want to do is tailor the body's response to insufficient calories. Some folks might want to specialize in martial prowess and are willing to give up some gray matter in exchange for retained muscle mass. To give you an idea how much variability we have, consider that humans and chimps descended from a common ancestor not that long ago, but chimp muscles are about 2x as efficient as human muscles, pound for pound. That's why chimps can be less than a quarter our size and still beat the crap out of untrained humans.

Other folks may want more brainpower at the expense of muscle mass, and are walking twig eggheads. It would be like a parody of high school cliques, but for a scientifically driven reason. Except that you wouldn't have the good-looking, muscle-bound smarter-than-you-expected quarterback prom king, unless he was also getting twice as many calories as everyone else.

Some folks may prefer endurance to strength, and sacrifice fast-twitch for slow-twitch muscles. This can be done to some extent purely through physical training; but training just activates gene networks, so a sufficiently advanced technology should be able to shortcut the effect with a drug.

No Free Lunch

If you want hard science, you can't cheat thermodynamics and conservation of energy. Biological bodies are already pretty darned energy-efficient (except when they have a massive glut of energy, of course; c.f. obesity). The best you can do is reduce the energy demands via different sacrifices. Note that indigenous people are typically short and lightweight compared to well-fed folks in developed countries. Going from subsistence hunting/farming to factory farming can add a good 4-6" of height to the population average. Obviously, you can go the other direction, too.

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