How do you keep a medicine's effect isolated to a particular body tissue?

Question

In my world, a newly independent Mars established incentives to draw in scientists, engineers, and academics. Brilliant people flocked in from around the solar system, to fill high-paying but very selective jobs and gain instant citizenship as soon as they can land one. Rapidly increasing competition drove them to immigrate now, or wait a few years and potentially lose the opportunity forever. I don't mention IQ explicitly (it's a somewhat problematic measure), but imagine the average IQ on Mars is somewhere around 130, while real-world country averages top out at around 108.

The intelligence of the population has effects that deeply permeate the society. Combined with the fact that interplanetary trade is expensive, "globalized trade" tends to stop at the limits of the globe for anything but bulk materials that can be mined outside of a gravity well. So Mars has been able to reinvent itself with technology uniquely its own, unimpeded by real-world trade that keeps the technology of one country from far surpassing that of any other.

One such innovation, and the topic of this question, is a medical advance that among many others has allowed medicine to progress far beyond that of Earth. Real-world medicines are either directed to a specific tissue by topical application or injection, with topical application having limits on depth, and injection having limits on cost and convenience; or taken orally and distributed systemically via the bloodstream. Because most real-world medications are systemic, they have to be developed and tested using a complete organism, typically rodents, and then tested on complete humans, typically at great cost, both financial and temporal.

But the innovative people of Mars realized that if you could isolate the effect of a medication to a particular tissue, you could screen, test, and develop medications using small samples of lab-grown human tissue, bringing down the time to test a promising candidate medication from years to weeks, and replacing years of clinical trials with a single trial of several hundred volunteers, typically over a single year. The pace of medical innovation is staggering.

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How could this work? Some of my favorite works of fiction take particular care to ensure that their technologies are very realistic, and I'd like to do the same. I'm not a big fan of unobtainium or handwavium, so ideally the solution is explainable, just perhaps not to the degree that a given reader would care to understand, and we're looking for something only one medical leap away from current (2020s) technology. In other words, carefully-designed enzymes yes, nanotech no. How could you isolate the effects of a medication to a single tissue, and stop it from acting or potentially even spreading elsewhere?

One alternative I'm considering (but definitely not fixed on) that could allow for topical sprays to supplant pills in many cases: what if a medication can spread in the intracellular space, but is broken down by something in the bloodstream to keep it from spreading by blood? How do you chemically justify a medication being broken down by something in the bloodstream, and how do you guarantee the result is inert and doesn't bioaccumulate?

Note: I stopped short of using the hard-science tag because I don't think looking for references is a good use of your time, I'd rather hear your ideas and then confirm for myself that they're possible, but I am looking for an answer that a doctor would ideally say is "clever, but definitely possible". Think like the people of Mars!

Answer 1

There are four approaches I could suggest.

1. Affinity

Some substances have an affinity to specific organs, e.g. iodine with the thyroid. By utilizing this you can design a medication that only has the desired effect once it reaches a threshold concentration. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6314433/

2. Localised deposition.

Physically inserting the medication into the desired location. The medication would be fast-acting and difficult for the body to transport. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4632713/

3. Encapsulation

Encase the medication in an inactive molecular cage. The encased medication would be able to pass through the body without delivering the active ingredient unless the casing is broken. This could be done through focused sound, light, localized enzyme, or a specific chemical that has an affinty for a specific tissue. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3249419/

4. Gene editing

It is possible, and only more so in the future, to edit the genome to produce specific molecules within a cell. It in the future that we could have specific cells actually produce the medication that will be used locally. Failing that they could produce the enzyme to unlock encapsulated medication or be one half of the medication, the other half being introduced systematically.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5131771/#:~:text=The%20core%20technologies%20now%20most,)%2C%20and%20(4)%20homing

Answer 2

You can use the same approach certain virus use to attack only certain tissues: for example the rabies virus attacks brain cells, while the flu virus attacks only epithelial cells and so on.

It all depends on specific surface receptors expressed only by your target cells, which can be used as docking points.

If I remember correctly such an approach was actually proposed as a diagnostic/therapeutic approach some years ago, with the idea of attaching quantum dots to specific receptors, so that the target cells would embed the quantum dots which would then be either detected for diagnosis (e.g. fluorescence) or activated by an external energy source to destroy the cell (e.g. by heating it up from the inside).

Answer 3

mRNA vaccines.

This is amazing tech! It is now. Vaccines we are getting use it for only the crudest application - display of a nonfunctional foreign protein to produce an immune response. But it could do so much more.

https://www.cdc.gov/coronavirus/2019-ncov/vaccines/different-vaccines/mrna.html

A Closer Look at How COVID-19 mRNA Vaccines Work

COVID-19 mRNA vaccines give instructions for our cells to make a harmless piece of what is called the “spike protein.” The spike protein is found on the surface of the virus that causes COVID-19.

First, COVID-19 mRNA vaccines are given in the upper arm muscle. Once the instructions (mRNA) are inside the immune cells, the cells use them to make the protein piece.

After the protein piece is made, the cell breaks down the instructions and gets rid of them.

Next, the cell

displays the protein piece on its surface. Our immune systems recognize that the protein doesn’t belong there and begin building an immune response and making antibodies, like what happens in natural infection against COVID-19.

At the end of the process, our bodies have learned how to protect against future infection. The benefit of mRNA vaccines, like all vaccines, is those vaccinated gain this protection without ever having to risk the serious consequences of getting sick with COVID-19.

Suppose instead of a virus antigen, the vaccine caused production of functional proteins. Enzymes more efficient than the native protein to augment the cells. Enzymes to break down amyloid or toxins. Proteins from other species to allow our cells to do functions that they currently cannot.

One can selectively and reversibly modify cells without modifying the genome, introducing foreign organisms or shutting the door to future, different modifications. Really the possibilities are astounding. I think people who realize how amazing this tech is are keeping quiet to avoid scaring people who need to get the vaccine but are worried about Bill Gates selling their teeth to the United Nations.

The martians by virtue of their IQ are not so worried about their teeth. They freely use this tech to augment and modify their bodies. There are no infectious diseases. There is no cancer. Inherited predispositions to disease are countered.
Health issues are now all mental health issues.

Answer 4

Enhance the body's own defenses and healing mechanisms. (By way of a slight frame-challenge)

Most medicine in the west has focused on interventions - in the case of antibiotics, antivirals, anti-fungals - to kill the disease, or perform surgery to clear a blockage or remove troublesome growths. Indeed the majority of (non surgical) cancer treatments have served to irradiate, or poison the offending tissues.

Cancer:

A new approach, which is gaining some traction is to boost the body's own response to the cancer. Type (iv) chemotherapy, is designed to modulate the body's own response to the cancer cells, and has been shown to be of value in reducing tumors - specifically by the mechanism of getting the body's defenses to attack it. It's become known as immunotherapy.

An effective but cumbersome and expensive method involves removing some of the immune cells from the body of a patient, modifying them in a laboratory to specifically target cancer cells. Sipuleucel-T is the only currently approved version of this (US) and is used for prostate cancer only. Your culture's more advanced medicine might just involve a single pill or injection which stimulates this modification in the body itself.

Disease:

The same thing would go for diseases, coaxing the body to produce an appropriate immune response has been done crudely (and often too late to help everyone: vis-a-vis the current debacle) with pre-emptive immunization, ie. vaccines of a variety of types, all invariably developed after the disease has already made itself a problem. Immune boosters, perhaps a single pill before or shortly after contact with a pathogen, could give your culture the edge. (The science of that is in its infancy at the moment).

Wounds:

Wound healing has usually been accomplished by means of aseptic closure and leaving it to heal by itself (assuming adequate nutrition and general health of the subject). Since the nineteen sixties, LASER mediated healing (red/infrared) has been reported, but because of the rather spotty quality of the studies, has largely been dismissed by the mainstream as pseudoscience. A recent (2014) meta-study, analyzing over sixty previous studies with LASERs and LEDs:

Biological effects observed were reduction of inflammatory cells, increased fibroblast proliferation, collagen synthesis, stimulation of angiogenesis and granulation tissue formation ...

Presumably your culture can have refined this approach with a more specific and targeted set of light frequencies, and maybe a spray to increase the rate of granulation (1980's study on slightly successful approach with benzoyl peroxide) would increase the body's own ability to heal.

For broken bones, pulsed ultrasound has been found to have some effectiveness, again with refinement, and additional encouragement of the body to produce osteoblasts to build new bone tissue, the time to heal might be diminished considerably.

Brain damage:

Once considered impossible to repair, it seems the brain has some latent self-repair mechanisms of its own. When damaged, adult brain cells revert to a more primitive state, effectively closer to being stem-cells, they can then re-develop into adult cells and develop now connections to a certain extent. Enhancing this ability would potentially be able to repair damage completely. The memory engrams would need to be re-associated and integrated, but with a complete brain, that should be a lot easier than current therapies in say stroke patients can achieve.

Conclusion:

Viewing the body as a set of complex integrated systems, rather than as separate pieces bolted together, and holding in mind that evolution has conditioned our species with internal mechanisms which specifically enhance survival to reproduce - I'd see this is the key to understanding how an advanced treatment could work. Enhancing the pre-existing systems of repair, giving the individual's body greater resilience to take care of itself is the way to go (IMO).

Answer 5

While it sounds like I am tearing this question apart by making 3 seperate frame challenges, I should start by saying I actually really like it as a question. It contains many common pitfalls that that most people miss because they seem so far fetched or counter intuitive.

Frame Challenge #1: This Tech Already Exists

...nanotech no.

We have real nanobots today already designed with this exact purpose in mind. While Willk talks about one form of this nanotechnology in the form of the mRNA Covid vaccine, this is only one example. Even before Covid, it was already being applied to cancer treatment, selective organ targeting, gene modification, cellular level diagnostics, dental hygiene, etc.

Basically, what a nanobot is in context of the medical industry is a cellular sized, mass producible thing, typically made out of organic compounds, that is very similar to a virus but can be programed and/or controlled like a robot.

By the time the first colonist make it to Mars, this technology will already be old news.

https://utswmed.org/cancer/cancer-answers/nanotechnology-drug-delivery-genomic-medicines/

https://www.therobotreport.com/nanobots-promise-change-medical-treatment/

Frame Challenge #2: This Tech Would Not Replace Human Trials

We also already test a number of our medicines on grown human tissue as one of the early stages of many drug trials. That said, even with selective organ/tissue targeting, medicine still needs to go through whole human trials. The real reason is that you never actually know for a fact how the delivery mechanism, drug, and body will interact.

You may have a liver targeting nanobot with a liver medication that you tested on a test-tube liver, but when you put it in a whole body, the medicine may alter the nano-bot in an unexpected way that causes it to try implanting in other organs causing side-effects that you missed in your tissue trials.

For your Matians to skip human trials does not make them smart, it makes them reckless. Skipping human trials can accelerate medical research, but if your Martians are as smart as you say, they will be less tolerant of this practice than Earthlings because they could better understand the possible ways for it to go wrong.

Eventually, both Martians and Earthlings will consider the technology mature enough to stop human trials, but it would probably be the less risk-averse Earthlings that will stop human trials first.

Frame Challenge #3: Being Smart Is Not Enough

The pace of medical innovation is staggering.

This is a highly unlikely outcome even with a really smart population. The more our technology advances, the larger and larger infrastructure you need to be able to push it further forward. Your martians can have all the brains they want, but what they do not have is a global economy backing the development of the tools and machines they would require to put that intelligence to good use. Developing advanced sciences like medical research is not the work of a hand full of really smart people. It is the work of a small handful of really smart people backed by millions of consumers or tax payers funneling the fruits of their labor into one place for those smart people to use.

Also, people with an IQ of 130 or higher are typically great at handling details, but struggle with top-down thinking. In all likelihood, your colony will be surprisingly terrible at managing itself or finding common sense solutions to its daily problems because you've filled it up with a single type of intelligence instead of diversifying your levels of thinkers.

Despite higher average intelligence, the actual technology of your martian colony is likely to fall behind that of Earth, at least for the first few centuries until its population and diversity can rise to Earth like levels. At this point though, technology should be so future tech that the idea of a significant breakthrough in something we can already more or less do today would seem pretty anachronistic unless something were to happen on Earth in the very near future to cause Earthling technology to regress.

Answer 6

But the innovative people of Mars realized that if you could isolate the effect of a medication to a particular tissue

How could this work?

One possible way is to develop a "bacteriophage virus-like" vector, composed of a large capsid and a specific, targetable "mouth". There is an instructive video here.

The key factor here is that either the "mouth" of the virus or its "legs" need specific loci on the target cell, and those loci can be chosen so that they are tissue-specific. This way, a vector targeted on spleen cells will never attach itself to any other cell type, because it won't find suitable binding epitopes.

The main difficulties to overcome to be able to produce these structures is how to replicate them (viruses can hijack cells to do so; in this case, though, the capsid does not contain viral DNA but the medicine molecule), how to stabilize the molecule inside the capsid, and how to extract reliable epitopic "signatures" for the target tissues.

Possibly, a way of mass replacing viral DNA with a molecule of your choice once a suitable number of phages have been produced might be the martian breakthrough. They first let the virus run free in a culture medium, and when they have enough, they replace its DNA with the medicine - now they have a targeted cure which is no longer infectious (there being no longer any viral DNA).