Biomedical trade-offs

Summary: The biomedical world — that is, both the underlying biological systems and the medical community writ large that tries to fix problems — faces an untold number of trade-offs, some of which show up again and again. I’ve tried to take note of these trade-offs in my studies of biology and medicine over the past several years, since I find the study of trade-offs across all fields to be systematically under-discussed. Of course, whether or not this article is itself worthwhile for you to read involves a variety of trade-offs that likely only you, dear reader, will be able to answer for yourself. Also, I am not a doctor. First Published: 2/2/2016. Last Updated: 2/2/2016. Epistemic Status: I believe in all of these, although the way I describe some of them (~25%) are probably sometimes false dichotomies.


Molecular Biology

1) Antibodies: One key upside of antibodies to an infectious organism is that they protect against infection from that organism, while one key downside is that they can cause autoimmune disease if they happen to also bind to host tissue. A classic example of this is in antibodies to M protein, which provide defenses against the bacteria S. pyogenes, but often give rise to rhuematic fever, because the structure of the M protein is similar to that of cardiac tissue.

2) 2,3-DPG: The molecule 2,3-DPG binds to better to deoxygenated hemoglobin, and so it tends to shift the oxyhemoglobin dissociation curve to the right. The upside of this is that the body has an easier time unloading oxygen in the tissues, while the downside is that it is harder for the body to load pulmonary capillary blood with oxygen. The body makes more 2,3-DPG at high altitudes, presumably because unloading oxygen in the tissues is more of a pressing problem than loading oxygen in the pulmonary capillaries.

3) Surface Receptors: Without the CCR5 surface receptor on T-cells, individuals are resistant to HIV. But, they are also more susceptible to more severe clinical symptoms from West Nile virus infection, potentially because their immune response is altered.

4) Cancer & Autoimmunity: There appears to be a general trade-off between the immune system doing a good job of recognizing and killing cancer cells and accidentally killing normal cells. This is related to the more general sensitivity vs specificity trade-off in statistics — immune systems that do a better job of detecting cancer cells are more sensitive, but also less specific because they will target more host cells and cause autoimmune disease.

5) Carbs: In general, animals want to maintain a minimum level of blood glucose, because cells need energy, but they don’t want too much, because blood glucose is toxic at high levels (e.g., this is clearly the case in diabetic neuropathy).

Physiology

6) Watersheds: Some parts of the body (called watershed areas) receive dual blood supply from the distal branches of two arteries, rather than directly from a single artery. The upside of this is that it makes these areas more robust to a single acute blockage of that one blood vessel, while the downside is that it makes watershed areas among the most vulnerable to ischemia due to systemic hypoperfusion.

7) Adiposity: In general, a key upside of having more adipose tissue is that it allows animals to store energy and nutrients for later use (e.g., in case they can’t find food), while a key downside is that it decreases mobility (e.g., for predator/prey interactions).

8) Muscles: Compared to slow-twitch muscle, fast-twitch muscle tissue muscle is both faster to contract and contracts more powerfully. But, it is also more fatiguable.

9) Dopamine: As a gross oversimplification, higher levels of dopamine in the basal ganglia system can cause symptoms of psychosis, while lower levels of dopamine can cause parkinsonism. This can be seen, for example, in the use of high-potency neuroleptic drug such as haloperidol, which are effective antipsychotics, but they also have a common side of parkinsonism, such as muscle rigidity and motor restlessness. 

10) Bones: A very low bone turnover rate leads to poor microdamage repair, while a very fast one leads to decreased overall bone mass, which is why a high bone turnover rate in conditions such as hyperparathyroidism can be a risk factor for osteoporosis.

11) Expiration: Any given increase in expiratory effort that increases pressure in the alveoli will increase expiratory air flow, but it also increases pressure outside the airways that can cause them to collapse. The latter phenomenon is called dynamic compression of the airways

Medicine

12) Side effects: This is the most classic medical trade-off: treating patients with almost any drug or surgery is likely to have side effects. Sometimes the benefits are considered worth the upside, and sometimes they are not. In general, doctors and regulatory agencies are (or at least should be) more willing to tolerate side effects when the disease being treated has a high rate of morbidity and/or mortality.

13) End-of-life: At the end of people’s lives, there is sometimes a trade-off between expected quality and expected quantity of one’s remaining life, when considering different treatment options. For example, it is possible that aggressive chemotherapy would extend life, at the expense of having decreased quality of life during the chemotherapy treatment. It’s wrong to assume that a particular patient will prefer one or the other without helping them become an informed decision-maker (because, e.g., their values can sometimes differ from those of their surrogate decision-makers).

14) Live vaccines: In general, the upside of live viral vaccines, compared to killed viral vaccines, is that they induce more robust immunological responses (i.e., both humoral and cell-mediated), although the downside is that on rare occasions they are reported to have reverted to virulence. For example, this reversion happened in the case of a particular type of live polio vaccine. Sidenotevaccines do not cause autism.

15) Transplant immunity: In general, giving more immunosuppression to organ transplant patients decreases their risk of rejecting the transplanted organ, but it also increases their risk of infection and malignancy. 

16) Insight: In patients with mental disorders, insight varies, i.e., patients have more or less awareness of the fact that their thinking is disordered. For example, patients with Obsessive Compulsive Disorder often have insight that their behavior is often unreasonable. There is often a trade-off to having more or less insight in terms of the sequelae of the condition. For example, patients with Alzheimer’s disease with more insight are more likely to be depressed, while those with less insight are more likely to be psychotic.