Is there anything that is completely non-toxic to humans at any dose?

Is there anything that is completely non-toxic to humans at any dose?

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Lately I have seen a number of unrelated "scientific" debates over whether certain substances should be outlawed because they are toxic to humans. My initial, informal reaction is usually to respond that anything is toxic to humans if you give them a sufficiently large dose.

However, formally I don't know if that's really true for everything a human being could ingest in some way. I started to wonder if there were some substances that our body could handle unlimited amounts of without any negative consequences.

As this question has been (correctly) identified as a bit vague, I'll try to explain what i'm looking for. For the purposes of this question, I'm willing to ignore the limitations of actually ingesting a given substance in "the usual way". For example, if you can't physically drink enough of some liquid fast enough to kill you without your stomach filling up and vomiting, but that same liquid injected intravenously could be lethal, I could consider that toxic. I also recognize that the body can only physically contain a certain volume of stuff, after which sheer pressure would cause it to fail; I'm more interested in "biochemical toxicity" as opposed to any physical damage (I just don't know the term for what I'm looking for.)

In other words, one of my goals is to learn if, under laboratory conditions, a properly motivated researcher could always find a dose that would be toxic, regardless of the impracticality of a real person ingesting that dose under normal circumstances.

So, with that qualification, my ultimate question is:

Is there any substance we know of that is completely non-toxic to humans at arbitrarily large doses ingested over an arbitrarily short period of time?

I'll answer this theoretically, since that's how it has been posed. And if we're ignoring practicalities, we may as well posit that the substance in question will be introduced directly into the bloodstream (This is, of course, simple to do in reality, but not how most people consume their non-toxic substances.) The easiest way to show that any unspecified substance can be toxic at an unlimited volume is to invoke the human body's mechanisms for volume homeostasis.

As mentioned in this answer, the human kidneys functioning optimally can produce up to ~ 25 L/day of urine.1 This would require complete suppression of ADH (anti-diuretic hormone, a.k.a. arginine vasopressin), which would occur only if the “toxin” load were markedly hypotonic (think water).2 There is therefore a theoretical maximum volume of any substance that can be dealt with by the body, which is something less than 25 L per day. (For any substance other than water, the maximum will be lower because ADH will not be as fully suppressed by a less hypotonic load.)

A volume of any substance introduced into the bloodstream (including a product precisely mimicking the constituents of the bloodstream itself!) will overwhelm the body's homeostatic mechanism. This will result in edema which is unpleasant and, in the case of pulmonary edema, certainly pathologic - a “toxidrome” in your scenario. In the case of hypotonic fluids, serum osmolality will also fall causing hyponatremia with all of its consequences.

Summary: No, the human body can not tolerate an unlimited volume of anything, therefore there is no substance that is non-toxic "at any dose."

1. Christopher Lote. (2012). Principles of Renal Physiology. Springer New York.

2. No, you may not drink 25 liters of water per day. For one thing, urine can not be made with a tonicity of 0 to balance this (more like 60 mOsm/kg minimum). Additionally, ADH can rarely be completely suppressed, yielding a somewhat more concentrated urine and therefore lower tolerance for hypotonic intake before serum osmolality is compromised.

It depends largely on the method of administration. If you are atomizing the substance and delivering it via water vapor, many, many substances have no known LDLo (lowest dose required to kill a member of the tested population). Almost any substance in existence has the potential to kill you if it is diluting your bloodstream via direct intravenous injection or oral consumption; however, when it comes to inhalants, many substances cannot kill you.

Since your question was specific to intoxicants, here's a couple of examples: There is no LDLo level of Tetrahydrocannabinol (the active ingredient in marijuana) when delivered via atomization. There is also no known LD50 (a similar, albeit somewhat less reliable, metric) for lysergic acid diethylamide (commonly referred to as LSD). For psilocybin (the active ingredient in "magic mushrooms"), the LD50 is high enough that an average person would need to ingest around 6 pounds before cause for concern.

Other far more dangerous substances that can kill with vastly lower amounts include anything that speeds or slows the heart rate: most specifically, cocaine (including crack), opiates (including morphine, heroin, and various pain pills), and any amphetamine, methamphetamine or derivative substance, or other stimulant (crystal meth, ADHD medication, and even caffeine or ephedrine). Of course, the most common killer categorically from a historical perspective is alcohol.

There is a problem with definition of toxicity - things that are dangerous in large amounts aren't usually called toxic. In spite of this, you're right: everything can be dangerous to a human in large enough amounts, or if delivered improperly.

For example, even water can be toxic if drank too much. Also, when it gets into the lungs, it may cause drowning.

On the other hand, air, while necessary in lungs, is dangerous if present as a gas in the bloodstream.

BTW, even botox (being one of the strongest poisons) is used in medicine in very small doses.

The inert gasses Helium and Neon are non-toxic when administered through inhalation, so long as the patient's oxygen supply is sufficient. They are also non-toxic when injected, so long as the injection is slow enough for them to be dissolved in the bloodstream.

You can be killed by them through various means (asphyxiation through oxygen displacement, rapid injection causing an air embolism, rapid decompression causing decompression sickness, and so on), but since the cause of death is unrelated to the chemical properties of the substance involved, it's not accurate to call this "toxicity" (unless you're XKCD).

Other inert gasses (Argon, Krypton, Xenon) may be toxic at high pressures: although I haven't found an LD50 for any of them, they can all induce nitrogen narcosis, and Xenon is usable as a general anesthetic.

not even AIR, because if you force too much you will explode it depends on how extreme is the "any dose" statement

water is also toxic in large Ingestible amounts

and since we go into theoretical application the answer would be dark matter

so the final answer is nothing , because the human body has evolved to exist in some equilibrium, so too much of one thing even if is harmless it itself ( like water, or proteins ) it causes an imbalance, and as a result it becomes "toxic"

Even simple water is "toxic in high amounts" as kidneys can remove 25 l per day at most. All other substances are probably even more "toxic".

Vitamin C won't kill you no matter how much you get into your body as long as it is enough to help prevent arterial wounds and atherosclerosis(This happens in people with scurvy or vitamin C deficiency because of how cholesterol is used to help repair the wounds and this can lead to a complete blockage of the artery and thus an infarction of all the tissue that artery supplies. So if you don't want to have an MI, one of the things you have to do is get vitamin C into your system.

Another example of this is chloride ions. While having high chloride ions might cause there to be a slower reaction time(since chloride acts as an inhibitor in neurons) it itself won't kill you. Yes it might affect the muscles by not having them contract as much as they are supposed to but this is naturally cured by urinating out more chloride and thus more sodium which can lead to a sodium deficiency which is bad because your body needs sodium in order to function. With a low amount of it it you wouldn't be able to think clearly or even have a normal heart rhythm which might lead to bradycardia from a higher pottasium concentration in the heart.

This is not really a substance, but anyway.


Neutrinos are ghostly particles that barely interact with any matter. Therefore, no sufficient amount of neutrino (that human can ever collect) can kill you. To have a lethal dose of neutrino radiation, you must stand inside the outer layout of a giant star that creates a supernova.

Source: XKCD, Lethal Neutrinos

Do We Have Free Will?

One of the oldest questions in psychology, and in other fields such as philosophy, is whether humans have free will. That is, are we able to choose what we will do with our lives?

Our choices feel free, don't they? I decided to be a psychologist because I felt called or inspired to understand what makes people tick. That was my choice, wasn't it?

The free will issue is especially thorny because it represents a collision between two opposing, yet equally valid, perspectives. From a purely metaphysical perspective, if we don't have free will, why are we here? What is the point of life if we cannot choose our own paths? Yet from a purely scientific perspective, how is it possible that anything can occur without having been caused by something else? If we really can choose, then these choices must be uncaused — something that cannot be explained within the model of science that many of us rely on.

There is no consensus within psychology as to whether we really do have free will — although much of our field seems to assume that we don't. Freud and Skinner didn't agree on very much, but one thing they did agree on was that human behavior was determined by influences within or outside the person. Freud talked about unconscious conflicts as causes of behavior, and Skinner talked about environmental contingencies, but either way, we were not free to decide.

New "threats" to the possibility of free will have come from fields such as neuroscience and genetics. Many neuroscientists, armed with functional magnetic resonance imaging (fMRI) and other brain scanning tools, argue that, now that we can peer into the brain, we can see that there is no "agent" there making choices. John Searle (1997) approaches consciousness from a biological perspective and argues that the brain is no more free than is the liver or the stomach. Geneticists are discovering that many psychological experiences are linked with gene-environment interactions, such that people with a specific gene are more likely to react in a certain way. For example, van Roekel et al. (2013) found that girls with a specific oxytocin receptor gene felt more lonely in the presence of judgmental friends than did girls without this gene. These results suggest that at least some of what we perceive as "free" responses are really determined by our biology, our environment, or both.

In a controversial set of experiments, neuroscientist Ben Libet (1985) scanned participants’ brains as he instructed them to move their arm. Libet found that brain activity increased even before participants were aware of their decision to move their arm. Libet interpreted this finding as meaning that the brain had somehow “decided” to make the movement, and that the person became consciously aware of this decision only after it had already been made. Many other neuroscientists have used Libet’s findings as evidence that human behavior is controlled by neurobiology, and that free will does not exist.

Further still, Harvard University psychologist Daniel Wegner and his colleagues (e.g., Pronin et al., 2006) have conducted studies suggesting that people claim control over events that are initiated by others. Fans try to "give good vibes" to a basketball player shooting critical free throws, or to a football quarterback trying to complete a pass. Yet common sense tells us that our “vibes” have nothing to with whether the player makes that free throw or completes that pass. Wegner argues that what we call "free will" is really just events whose causes we don't understand.

So is there any hope for free will? Are we really controlled by our biology and our environments?

Some psychological theories are actually based on an assumption of free will—or at least they are at first glance. Self-determination theory, for example, holds that volitional functioning—intentional, freely chosen behavior—is a basic human need (Deci & Ryan, 1985). Theories of personal identity, especially those rooted in Erikson’s (1950) ego psychology, state that adolescents and young adults must deliberately make sense of the world around them and of their place within that world (Côté & Levine, 2002 McAdams, 2013). Maslow’s (1968) humanistic theory regards self-actualization—identifying and living according to one’s highest potentials—as the ultimate goal of human existence.

This brings us to an inherent incompatibility. How can a person make self-determined choices, make sense of the world, and even self-actualize when neuroscientific evidence seems to indicate that our brains are making decisions before we even realize it? Are we claiming responsibility for events that have little or nothing to do with conscious intention? Are we really just automatons—creatures without the ability to choose? And if we are, what is the need for volitional functioning, making sense of the world, or self-actualization? An automaton would have no need for any of these things.

The free will issue has huge issues for many areas of our society, including our legal system. If a criminal defendant has no free will, then he cannot be held responsible for his crime, because he could not have chosen otherwise. A child who fails an exam cannot be punished, because that test score could not have been different. A parent who spoils her children is not doing anything “wrong”, because she did not make the choice to raise her children in any specific way.

Psychologists such as Roy Baumeister (2008) have attempted to develop a science of free will, but much of Baumeister’s argument focuses on the consequences of believing (or not believing) in free will—rather than on whether or not we actually have free will. Put differently, what matters is whether we think we are making choices, regardless of whether our behavior is really “uncaused”. For Baumeister, believing that we are free leads us to act as though we are, and he and his colleagues (Baumeister, Masicampo, & DeWall, 2009) have conducted experiments indicating that telling people that they have no free will leads them to behave in socially irresponsible ways such as cheating and refusing to help others.

So do we really have free will? Is this question even answerable? If we did not have free will, then a scientist who was able to measure all of the determinants of our behavior should be able to explain 100% of our behavior. If we did have free will, then even measuring all of the determinants would leave some of our behavior unexplained. Unfortunately, we don’t know all of the determinants of human behavior, and we may never understand all of these determinants—so the question of whether or not we have free will is likely to remain a philosophical quagmire.

But if Baumeister is correct, then does it really matter whether we actually have free will? Or does it matter only whether we believe that we do? And if the latter is true, and if Baumeister’s findings regarding how people behave when they think they don’t have free will are accurate, then should scientists be careful about making statements against free will? Are such statements encouraging people to behave as though they are not responsible for their behavior?

And perhaps psychology cannot speak to whether criminal defendants should be held accountable for their crimes. Libet’s experiments may have simply demonstrated that the brain is “gearing up” to initiate an action, which does not contraindicate free will. Gene-environment interactions generally explain very small percentages of variability in behavior, suggesting that there is a lot left over to be explained by other factors. The fact that we might overestimate the extent of our influence, as Wegner has found, does not necessarily mean that we have no influence at all.

So we are left pretty much where we started. Whether or not humans have free will is a question that philosophers have debated for centuries, and they will likely continue to do so. Psychology can provide some insights into how free will—or at least a belief in its existence—might work, but beyond that, we likely cannot verify or invalidate its existence. What is important, however, is that we treat each other (and ourselves) as self-determined beings whose thoughts and feelings are important. In that regard, Baumeister’s research has much to teach us. Maybe we should just follow the Golden Rule after all.

Baumeister, R. F. (2008). Free will in scientific psychology. Perspectives on Psychological Science, 3, 14-19.

Baumeister, R. F., Masicampo, E. J., & DeWall, C. N. (2009). Prosocial benefits of feeling free: Disbelief in free will increases aggression and reduces helpfulness. Personality and Social Psychology Bulletin, 35, 260-268.

Deci, E. L., & Ryan, R. M. (1985). Intrinsic motivation and self-determination in human behavior. New York: Plenum.

Erikson, E. H. (1950). Childhood and society. New York: Norton.

Libet, B. (1985). Unconscious cerebral initiative and the role of conscious will in voluntary action. Behavioral and Brain Sciences, 8, 529-566.

Maslow, A. H. (1968). The farther reaches of human nature. New York: Van Nostrand.

McAdams, D. P. (2013). Life authorship: A psychological challenge for emerging adulthood, as illustrated in two notable case studies. Emerging Adulthood, 1, 151-158.

Pronin, E., Wegner, D. M., McCarthy, K., & Rodriguez, S. (2006). Everyday magical powers: The role of apparent mental causation in the overestimation of personal influence. Journal of Personality and Social Psychology, 91, 218-231.

Searle, J. R. (1997). The mystery of consciousness. New York: New York Review of Books.

van Roekel, E., Verhagen, M., Scholte, R. H. J., Kleinjan, M., Goossens, L., & Engels, R. C. M. E. (2013). The oxytocin receptor gene (OXTR) in relation to state levels of loneliness in adolescence: Evidence for micro-level gene-environment interactions. PLoS One, 8(11), Article e77689.

Manmade or natural, tasty or toxic, they're all chemicals …

Chemicals are bad, right? Otherwise why would so many purveyors of all things healthy proudly proclaim their products to be "chemical-free" and why would phrases such as "it's chock full of chemicals" be so commonly used to imply something is unnatural and therefore inherently dangerous?

On one level these phrases are meaningless – after all, chemicals are everywhere, in everything. From the air that we breathe to the pills we pop, it's all chemicals. Conversely, many would argue (the Advertising Standards Agency included) that we all know perfectly well what "chemical-free" means and those who rail against the absurdity of the phrase are just being pedantic. Even the Oxford Dictionary defines a chemical as "a distinct compound or substance, especially one which has been artificially prepared or purified."

So "chemical-free" products are adhering to a recognised usage.

But pedantry and definition aren’t really the point. The point is that every time anti-chemical slogans are used people are being misinformed. The implication is always that the terms "chemical" and "poison" are interchangeable. This is a perception that permeates our subconscious to the extent that chemists themselves have been guilty of exactly the same lazy language.

As a result of this common usage of "chemicals" the whole subject has been tainted with unpleasant connotations. And while physics and biology have their celebrity scientists extolling the wonders of bosons, bugs and big bangs, chemists are left floundering in their wake or are left completely unrepresented in the mainstream media (where's the Guardian's chemistry blog?).

This is all despite the modern world having been built on the innovations of chemists. For example, most of the world's population is sustained by the innovations of one of them. Fritz Haber invented a means to turn the nitrogen in the air into useful agricultural fertiliser (40% of the nitrogen in you comes from Haber's reaction). Meanwhile the chemists who artificially prepared or purified antibiotics are responsible for a treatment that saves more lives than any other medical intervention.

All these arguments are trotted out by chemistry bloggers on a regular basis, but these writers are only preaching to the converted. The good news is that on Monday the campaign group Sense about Science joined the discussion with the publication of a guide entitled Making Sense of Chemical Stories. Sense about Science is a respected charitable organisation that "equips people to make sense of scientific and medical claims in public discussion". In short, it facilitates discussions between concerned/interested groups and relevant experts.

'A common misconception is that all manmade chemicals are harmful, and all natural chemicals are good for us. However, many natural chemicals are just as harmful to human health, if not more so.' Photograph: Compound Interest/Sense About Science Photograph: Compound Interest/Sense About Science

The aim of its guide is to bridge the disconnect between the lifestyle view (and popular definition) of chemicals and the realities of how chemistry is used to sustain the modern world. The guide does this by tackling common misconceptions about chemistry.

A key misconception is that natural chemicals are somehow safer than manmade ones. The wrongheadedness of this is nicely illustrated by a pair of infographics (above) created by Compound Interest that don’t shy away from admitting synthetic chemicals are often toxic, but also make it clear that whether a chemical is naturally occurring or manmade tells us precisely nothing about its toxicity.

Not only that, but where harmful chemicals do occur (be that in potatoes or lethal injections) the dose is the really important thing to consider.

BPA-Free Plastic Containers May Be Just as Hazardous

In 2012 the U.S. Food and Drug Administration banned the sale of baby bottles that contain bisphenol A (BPA), a compound frequently found in plastics. The ban came after manufacturers&rsquo responded to consumer concerns of BPA's safety after several studies found the chemical mimics estrogen and could harm brain and reproductive development in fetuses, infants and children.* Since then store shelves have been lined with BPA-free bottles for babies and adults alike. Yet, recent research reveals that a common BPA replacement, bisphenol S (BPS), may be just as harmful.

BPA is the starting material for making polycarbonate plastics. Any leftover BPA that is not consumed in the reaction used to make a plastic container can leach into its contents. From there it can enter the body. BPS was a favored replacement because it was thought to be more resistant to leaching. If people consumed less of the chemical, the idea went, it would not cause any or only minimal harm.

Yet BPS is getting out. Nearly 81 percent of Americans have detectable levels of BPS in their urine. And once it enters the body it can affect cells in ways that parallel BPA. A 2013 study by Cheryl Watson at The University of Texas Medical Branch at Galveston found that even picomolar concentrations (less than one part per trillion) of BPS can disrupt a cell&rsquos normal functioning, which could potentially lead to metabolic disorders such as diabetes and obesity, asthma, birth defects or even cancer. &ldquo[Manufacturers] put &lsquoBPA-free&rsquo on the label, which is true. The thing they neglected to tell you is that what they&rsquove substituted for BPA has not been tested for the same kinds of problems that BPA has been shown to cause. That&rsquos a little bit sneaky,&rdquo Watson says.

A 2011 study published in Environmental Health Perspectives found that almost all of the 455 commercially available plastics that were tested leached estrogenic chemicals. This study lead to a bitter legal battle between Eastman Chemical Co. and the study&rsquos author, George Bittner, professor of neurobiology at The University of Texas at Austin and founder of CertiChem and PlastiPure, two companies designed to test and discover nonestrogenic plastics.

Bittner claimed in the peer-reviewed report that Eastman&rsquos product Tritan, marketed to be completely free of estrogenic leaching, showed such activity. Eastman claimed otherwise and filed a suit. A federal jury ruled in favor of the latter, saying Bittner&rsquos testing methods were inadequate because the tests were done in vitro&mdashin a petri dish rather than in vivo, in a live animal.

Since this episode, independent scientists have focused their efforts on in vivo testing. Deborah Kurrasch, from the University of Calgary, turned to zebra fish to study the effects of BPS on embryo development. Brain development in zebra fish is similar to that in humans but much easier to track. When the fish were dosed with BPS in similar concentrations to that found in a nearby river, neuronal growth exploded, rising 170 percent for fish exposed to BPA and a whopping 240 percent for those exposed to BPS. As the fish aged they began zipping around their tank much faster and more erratically than the unexposed fish. The researchers concluded that increased neural growth likely lead to hyperactivity. &ldquoPart of the problem with endocrine disruptors is they usually have a U-shaped dose response profile,&rdquo Kurrasch says. &ldquoAt very low doses they have activity and then as you increase the dose it drops in activity. Then at higher doses it has activity again.&rdquo She found a very low dose&mdash1,000-fold lower than the daily recommended amount for humans&mdashcan affect neural growth in zebra fish.

In another study, Hong-Sheng Wang, an associate professor at the University of Cincinnati, found that both BPA and BPS cause heart arrhythmia in rats. He tested almost 50 rats, giving them the chemicals in doses akin to concentrations found in humans. Even at such low concentrations the rats&rsquo hearts began to race, but curiously only those of the females. They found that BPS blocked an estrogen receptor found only in female rats, which lead to the disruption of calcium channels&mdasha common cause of heart arrhythmia in humans.

These in vivo studies agree with in vitro studies claiming that BPS is a hazard. But the problem doesn&rsquot stop with removing bisphenol S from the market as was done for bisphenol A. The problem, according to Kurrasch, lies in the lack of industry regulation. Currently, no federal agency tests the toxicity of new materials before they are allowed on the market. &ldquoWe&rsquore paying a premium for a &lsquosafer&rsquo product that isn&rsquot even safer,&rdquo Kurrasch says. There are many types of bisphenols out there, so part of the public&rsquos responsibility &ldquois making sure [manufacturers] don&rsquot just go from BPA to BPS to BPF or whatever the next one is.&rdquo

*Clarification (8/12/14): This sentence was edited after posting to more precisely explain how the BPA ban came about.

AI Anxiety

Let's make the relevant question more personal: will machines replace me? I'm a mathematician my profession is often seen from the outside as a very complicated but ultimately purely mechanical game played with fixed rules, like checkers, chess, or Go. These are activities in which machines have already demonstrated superhuman ability.

But for me, math is different: it is a creative pursuit that calls on our intuition as much as our ability to compute. (To be fair, chess players probably feel the same way.) Henri Poincaré, the mathematician who re-envisioned the whole subject of geometry at the beginning of the 20 th century, insisted it would be hopeless

"to attempt to replace the mathematician's free initiative by a mechanical process of any kind. In order to obtain a result having any real value, it is not enough to grind out calculations, or to have a machine for putting things in order: it is not order only, but unexpected order, that has a value. A machine can take hold of the bare fact, but the soul of the fact will always escape it."

But machines can make deep changes in mathematical practice without shouldering humans aside. Peter Scholze, winner of a 2018 Fields Medal (sometimes called the "Nobel Prize of math") is deeply involved in an ambitious program at the frontiers of algebra and geometry called "condensed mathematics" — and no, there is no chance that I'm going to try to explain what that is in this space.

Human challenge: the people volunteering to be infected with Covid

I f Dominic Cummings is to be believed, Boris Johnson was so sceptical that Covid-19 was a threat early last year that he was willing to inject himself with the virus that causes the disease on television. But there are actual volunteers – young and healthy people – who elected to be infected with the virus, all in the name of science.

These volunteers lined up to participate in “human challenge trials”, which have long been successfully employed to develop vaccines for diseases from typhoid to cholera.

The world’s first such trial for Covid kicked off in the UK this March with scientists attempting to establish the minimum dose of the virus required to cause infection in volunteers aged 18 to 30.

However, Cummings, in his seven-hour appearance before a Commons inquiry hearing last week, suggested that the challenge trials should have been initiated much earlier. Had that been done, he said, the vaccination rollout could have kicked off in September 2020 instead of months later.

Alastair Fraser-Urquhart signed up “instantly” to be part of the challenge trial and serves as UK chapter manager of 1Day Sooner, a non-profit organisation advocating for human challenge study volunteers.

He said: “We got really, really lucky with … mRNA being a viable platform, but there was no guarantee of that whatsoever. And if it was completely useless, with a challenge trial you could have found that out in weeks rather than months.”

Fraser-Urquhart was one of the first few participants of the first phase of the challenge trial, in which pre-screened volunteers went into quarantine at the Royal Free hospital in London.

A few days in, the virus was administered nasally by a scientist wearing full personal protective equipment (PPE) as Fraser-Urquhart lay on the bed in a T-shirt and jeans. There were about six people in full PPE in his designated room: “One of them was like in the corner just counting down the seconds … like a rocket launch or something,” said Fraser-Urquhart.

The experience was in equal parts terrifying and amazing, he said. “Being in the room with a vast amount of extraordinarily pure [medical grade] virus … it just looked like water, but you don’t expect to see coronavirus like that.”

Jacob Hopkins: ‘We ended up high-fiving each other.’

After being dosed, subjects lie there for 10 minutes and then sit up and stay in that position for another 20 minutes, explained Jacob Hopkins, who was the first volunteer to be directly infected with the virus. “We actually ended up like … high-fiving each other. It was a really weird moment, where it’s like, yay, Covid?! And then the whole thing just began.”

After exposure, the participants were monitored 24 hours a day for at least 14 days, with blood samples and nose swabs taken every day. Both Fraser-Urquhart and Hopkins felt fine for the first few days after exposure but experienced a “rough” couple of days before bouncing back.

“Honestly, it wasn’t an easy thing to do but it was incredible, it’s one of the best things I’ve done in my life and maybe ever will do,” said Hopkins. “When you’re part of something that can do so much good … it’s really just an amazing feeling really to be involved.”

After being discharged, the participants will be followed up for a year so that researchers can monitor any long-lasting symptoms. Altogether, they will be compensated with roughly £4,500 for their involvement. Fraser-Urquhart has already donated the first tranche of his compensation to Gavi, the Vaccine Alliance, and plans to give away the rest to other charities.

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“It’s nice to be able to demonstrate that at least some challenge trial volunteers are motivated purely by altruism,” he said. “This compensation genuinely never came into my decision-making.”

Some scientists have expressed reservations about exposing volunteers to Sars-CoV-2 – the virus behind Covid-19 – for which there is no cure, although there are some treatments that have been shown to help.

Proponents argue that the risks posed by the coronavirus to young and healthy people are low and the benefits to society high. These benefits include potentially hastening the development of second-generation vaccines, as developing countries grapple with demand that far outstrips supply for the frontrunner jabs. They could also be used to compare multiple vaccine candidates, develop treatments and improve the scientific understanding of the virus.

Egnorance: The Egotistical Combination of Ignorance and Arrogance

Those who haven’t had the experience of reading Dr. Egnor’s contributions to the creation/evolution conflict will not know that he is a neurosurgeon at Stony Brook who has trumpeted his support for intelligent design and against evolution. Dr. Egnor has recently written an essay at the Ministry of Media Complaints of the Discovery Institute. Ever on-message, Dr. Egnor seems to think that doctors don’t need to know evolution because he objects to the Alliance for Science’s essay challenge. (Alliance for Science asked high schoolers to write an essay entitled and organized around the thesis, “Why would I want my doctor to have studied evolution.”)

Dr. Egnor has been the subject of multiple fiskings recently and this is a curiosity itself. I’m personally acquainted with at least four attending-level physicians who were creationists at the University of Kansas School of Medicine. Up at Minnesota, a chief resident in the department of surgery was a creationist. And now at Penn State, there’s at least one creationist. The Discovery Institute, fresh off their defeat from Dover, put a lot of effort into developing a five-page list of physicians who think evolution isn’t such a big deal - so why is Egnor getting all the infamy for his incredulity? I don’t have a good answer for that: maybe he’s just the DI “Flavor of the Month” or the only physician willing to write essays. What I can answer are Dr. Egnor’s claims that evolution is not needed in medical school.

And I’ll do it on the flipside.

Egnor’s Argument in Summary For those who can’t stomach Egnor’s essay, permit me to summarize:

Isn’t it “a funny question” whether we would want physicians to know evolution? There are basic sciences that are taught in medical school that must be “important to medicine” like anatomy and physiology. Doctors don’t “study evolution in medical school”, “there are no courses in medical school on evolution,” “there are no professors of evolution” in medical schools,” and “there are no departments of evolutionary biology in medical schools,” and “no evolutionary biologists” would provide useful information to a medical team in hospital. Therefore, evolution just isn’t important to the practice of medicine. I call upon my “20 years [of performing] over 4000 brain operations” to attest that I have never once used evolutionary biology in my work. How could I since evolution is random and doctors look for patterns, patterns that lie far afield from the randomness that is evolution? “I do use many” understandings provided by basic science in my work, such as population biology, “[but] evolutionary biology itself, as distinct from these scientific fields, contributes nothing to modern medicine.” “No Nobel prize in medicine has ever been awarded for work in evolutionary biology.” So I wouldn’t want my doctor to have studied evolution that answer wouldn’t win the “Alliance for Science” prize, but it would be the truth.

Man, there’s a lot of work fisking all that. I’ll leave the simple stuff (selection ain’t random and that’s why it’s called selection, dude) for others. Let me concentrate on the medical stuff, which I’ll deal with in separate sections.

Section 1: Evolution is a Vital Basic Science for Medicine I’ll start off my fisking by criticizing an aspect of medical practice and, to make sense of it, those who aren’t physicians need to know that there’s a great divide in the practice of medicine between the physicians who practice to simply the “standard of care,” (the kind of practice you’re expected to know for quizzes, tests, and boards and the level of care you need to meet to not get sued) and the physicians who know the basic science behind why the standards of care are what they are.

For example, when someone is having a heart attack (and daily after they have one), they need to be on aspirin because of the pathophysiology of heart attacks. (I review much of it that pathophysiology here.) Briefly, the aspirin irreversibly inhibits the platelet enzyme involved with forming clots. But you don’t have to know about the irreversible acetylation of cyclooxygenase that occurs in the presence of acetylsalycylic acid in platelets all you have to do is give people aspirins after heart attacks. The “divide” I refer to is between the physicians who know the biochemistry behind that reaction and the doctors who are content to know only that they should give aspirins after heart attacks. Make no mistake: one can be a great doctor and simply practice to the standard of care knowing not a whit of the basic science that provides that standard’s underpinnings. But if you can know the reasons why the standard of care is the way it is, why on Earth would you limit yourself by choosing to not know it?

The example I’ve given here is limited to a single therapeutic regimen in cardiology, but ideally there’s basic science that undergirds everything we do in medicine. There’s a reason why it’s no big deal if you’re not wearing lead in the radiology suite (thanks to the inverse-square law, as long as you’re three or four feet away from the radiation source, the dose you get is negligible). There’s a reason why diazepam - a drug we use to treat seizures - can cause seizures (much of the brain’s neurons are inhibitory and their suppression leads to increased seizure activity). There’s a reason why two different rheumatological diseases can require separate therapies (diseases involving deposition of immune complexes wouldn’t likely be amenable to an exchange of antibiodies as much as they would be to suppression of the immune system overall). Again, there are doctors who know or want to know the reasons behind the practice and there are doctors who don’t know and/or don’t want to know those reasons.

Doctor Egnor seems to like being in that latter category. More than that, he seems to recommend not knowing the basic science that undergirds the practice of medicine, to the extent that he perceives evolution might have had a hand in developing the state of the art. I see his perspectives as nothing more than ignorance advocacy for the basic sciences, writ large and not limited whatsoever to evolution.

I do use many kinds of science related to changes in organisms over time. Genetics is very important, as are population biology and microbiology. But evolutionary biology itself, as distinct from these scientific fields, contributes nothing to modern medicine.

as if to suggest that he has some interest in basic science, but I don’t buy it for a second. First, how is it possible to separate evolutionary biology from genetics and population biology? Post-Darwin, pre-Mendelian evolution, Egnor might have made a weak case that they might be separable fields. However, the entire modern synthesis of evolutionary biology dealt in its essence with merging genetics and selection. Today, they are so fused as to render Egnor’s phrase meaningless: the entity of population biology without evolution does not exist any more than water without wet exists.

Second (and this may be a bit snarky), Egnor quibbles at evolution being immaterial to the practice of medicine, but he says that he uses population biology. Man, don’t I know it. I just can’t get the vitals on patients referring to Hardy-Weinberg and Kimura at least once or twice per patient. Egnor knows as well as I do that if he isn’t going to find evolution in his daily rounds, he’s not going to find population biology, which leads me to suspect that his endorsement of it was a facile claim intended to stave off accusations that he’s an advocate of ignorance.

Well, I think he is an advocate of ignorance, despite the rhetoric he wrote about population biology and genetics.

Let’s move on to Egnor’s claims about evolution in medical school. First, he mentions anatomy and physiology - courses offered in the first two, or “pre-clinical,” years of medical school - and cites them as being important. But “Doctors never study [evolution] in medical school” so it’s therefore not important. I should also point out that calculus is also not studied in medical school. Neither was statistics. Neither was inorganic or organic chemistry, physics - hang on a second while I fish out my college transcript - composition and grammar, or biophysical chemistry. Med schools aren’t going to teach medical students how to write essays or how to add two and two. They also aren’t going to teach elementary chemistry or evolution. They’re going to assume that entering medical students have the barebones literacy to know certain things before they even get an offer to interview, let alone get enrolled.

Hmmm. Egnor might have a point though because that’s a pretty big assumption. I wonder if there were a way to tell whether a future physician would likely have the requisite understandings to succeed in medical school. If only there were a test, some sort of standardized test that admission committees could use evaluate how well medical school applicants had prepared for their medical careers! Can anyone think of such a test?

Of course I’m being facetious. Go here and do an in-PDF search for evolution. Dr. Egnor well knows that the MCAT is required to get into medical school and, according to the people who make the test, the MCAT in part tests one’s comprehension of evolution. And, unsurpringly, pre-medical committees across the nation have strongly recommended to kids that they know evolution. (There’s just something about a low med-school acceptance rates from pervasive failures to prepare students for the MCAT that makes a college or university unpalatable to parents.)

I tried to find something specific from the AAMC about evolution advocacy. Look what I found. (PZ may not have made much of Collins’ book, but the AAMC is an organization of medical schools to whom premed advisors and medical school hopefuls look for advice regarding career preparation for their students, and this interview of Collins appears on their website. I consider this a significant statement and wish they would be even more explicit about the “Look, guys, you need to know evolution” hint that they just haven’t brought themselves to say forthrightly.)

And I want to be the first to ruin the day of creationists when I say that you don’t stop having to know evolution once you get in. For those who don’t know, Step 1 (more formally known as the United States Medical Licensing Exam Step 1) is an exam you have to take after the second year of medical school in order to progress. And I can attest that, during my exam, a question that tested my ability to apply the central theory of population genetics - the Hardy-Weinberg Equilibrium - was asked, as was my knowledge of whence cometh the mitochondrion into eukaryotes.

That’s just getting into medical school. What about making sense of things once you are there? In the cardiovascular physiology block, we learned about the sympathetic and parasympathetic nervous systems. Whereas previous generations had to perform labs on dogs not intended to survive, we were spared this (so were the dogs) and instead watched a videodisk (it really was - this was before DVD-RW, I guess) of a dog being given various agents and seeing what affect it had on the blood pressure, heart rate, etc. I can’t imagine the befuddlement Dr. Egnor must have had, had he my experience in my medical school labs, when he perfectly understood what happened to the dog, but couldn’t allow himself to generalize the dog’s experience to the human.

Or consider my anatomy lab. So we’re learning the muscles of the back and having a dickens of a time trying to memorize their innervation. No problem, says my anatomy professor, and walks to the chalkboard. He draws a circle and puts in two perpendicular intersecting lines like crosshairs. Picking up the red chalk, he drew the musculature of the shark and with the yellow chalk he drew the nerves that innervate those muscles. Pretty primitive anatomy, really. Then he explained how, through phylogeny, the shark shape gets filleted down the middle, with the two inferior bits being the most lateral and the posterior being the medial, and there you’ve got the mammalian innervation. And the anatomy of it made perfect sense. There was no longer any memorization (past the damned names, that is) there was a theory that explained it all. And I can see Egnor refusing to admit the ease an evolutionary perspective of anatomy affords students, maybe to the point he would have refused the easy way of learning that material. His anatomy lessons must have been harsh, memorizing every muscle, compartment, bone and nerve, never once allowing himself to grasp the overall organizing patterns because he just knew that evolution was wrong.

Egnor reprised that theme often in his essay so let me make something clear here. Anytime you see comparative medicine, or comparative biochemistry, or comparative pharmacology, or anything comparative, that is evolutionary theory. We test drugs in rats and it’s not because we think rat pharmaceuticals are a lucrative industry. (Since 1938, non-toxicity must be demonstrated in animal models before a drug can come to market.) We don’t practice our surgical techniques on animals because we hate pigs. (Residents at SUNY Upstate have access to an animal surgery lab, in which they can hone their techniques on animals before they operate on humans.) Whenever you see stuff practiced or tested or homogenized or whatever on animals with the intention of applying those conclusions to humans or other species, that is evolution being used in practice. Without evolution, animal testing is just making drugs for rats and patting yourself on the back at the sheer (reproducible) dumb luck that the drug you’ve designed for the rat would likely do a decent job in humans as well. (Just a bit of intellectual integrity is needed to make the leap.)

Egnor thinks can say that evolution is unimportant to medicine when he points out that no course entitled “evolution” is generally to be found in medical school curricula. As I’ve shown, he’s dead wrong, and no medical school hopeful would be well served by avoiding an understanding of evolution. Word of advice to premed students: take the hint (which really ought not be a hint, ahem) from the AAMC and learn it if you want to do well.

What about making sense of things after you finish medical school? Has Dr. Egnor never obtained ATLS certification? I certainly don’t want to be the unfortunate patient needing a chest tube on whom Dr. Egnor discovers to my cost that a large amount of pressure but not too much is needed to introduce a trochar through the parietal pleura of the lung. I’d just as soon it be an anesthetized pig, like the one I learned on back in Wichita, KS.

In summary, evolution is indeed important to get into medical school, it is important to succeed during it, and it is important after you leave. Egnor’s perspectives are completely wrong.

Section 2: Professors of Evolution Do Teach in Medical Schools

There are no courses in medical school on evolution. There are no ‘professors of evolution’ in medical schools. There are no departments of evolutionary biology in medical schools.

This one is a simple claim to fisk. Andrea Bottaro, contributor to the Thumb is an associate professor of medicine at a medical school who has published explicitly evolutionary articles. Thanks for playing, Dr. Egnor.

But let’s run with this a bit because it’s so easy. Hans Thewissen, the dude who discovered Ambulocetus natans, is employed in the anatomy department of the Northeastern Ohio Universities Colleges of Medicine and Pharmacy. He appears to have a dual appointment, both to anatomy and also as the football program’s head coach. (Note to self: I am so getting one of these t-shirts.)

But he isn’t the only one. Nationwide (probably worldwide), there’s a push in medical schools to include specialists from non-medical disciplines in the basic sciences. It’s for this reason that Thewissen, a palentologist, teaches anatomy at a medical school.

Egnor teaches at SUNY Medical Center, right? Well, just check out their medical school’s website and look at their department faculty. Anatomy looks promising. Okay, we see that Sussman is interested in the “comparative morphology” of humans and apes, Stern is interested in “The evolution of postcranial adaptations in primates,” Rubin works on bones in animals and humans, … Those were just the last three - you guys look up the rest.

Want to be a graduate student at SUNY and get your doctorate in anatomy?

The program is concerned with the analysis and interpretation of gross vertebrate structure in relation to adaptation and systematics. Training and research focus on (a) an evolutionary perspective in the analysis of morphology, including the influences of function, structure, and phylogenetic history, and (b) the structural adaptations of bone as load-bearing tissue, including the physiologic mechanisms of osteogenesis and osteolysis.

And that’s just the anatomy department. And that’s just at SUNY.

The University of Chicago’s Department of Ecology and Evolution is part of an interdisciplinary medical program, the “Biological Sciences Division.” The dean of medical affairs is the dean of the division. Best still, they call their interdepartmental evolution program “Darwinian Sciences.”

No professors of evolution in medical schools? By any non-trivial parsing of that phrase, Egnor is dead wrong. Professors with evolution training and active research involving evolution are commonplace in medical schools and you’ll probably see more of that, not less, as time goes on because these people make the material so freaking easy.

Section 3: Nobel Prizes in Medicine Have Been Awarded for Work in Evolutionary Biology

No Nobel prize in medicine has ever been awarded for work in evolutionary biology.

Creationists evolve, rolling out new arguments and angles like automobile prototypes at a trade convention. The argument that no one has ever won a Nobel prize for work in evolution was apparently first trotted out by Steve Fuller at none other than the Kitzmiller trial:

And in a sense, one way you can see this is that, if you look at the Nobel prizes that have been awarded for physiology in medicine, which is the field, the biological field, essentially, you don’t find anyone ever getting the prize specifically for evolution.

Ideally, I could simply turn to the cross examination portion of the transcript, but Steve Fuller was scoring so many own-goals with his testimony that our lawyers let him off the hook without much of a fight. Yay for the Kizmiller trial, but now I have to do the work.

  • Insulin was first isolated in dogs and the research was subsequently applied to humans Macleod and Banting won the Nobel Prize for their discovery in 1923.
  • Neurophysiology was elucidated by studying squid, whose giant axons were large enough to pierce with the instruments of that day and the research was subsequently applied to humans Hodgkin and Huxley won the Nobel Prize for it in 1963.
  • Using an animal model of sea slugs, Eric Kandel deomnstrated how changes of synaptic function are central for learning and memory in 2000, he won the Nobel prize for his work.
  • The mechanism for olfaction and the genes giving rise to it were found Axel and Buck won the 2004 Nobel Prize for their discovery and their seminal paper described the evolution of the genes over lower vertebrates and invertebrates. (See this article for a great writeup on it.)

I’m certain there are others (and living Nobel laureates should please not feel slighted by my not listing their work here). Feel free to include any examples you can think of in the comments. By way of summary, Egnor is, again, completely wrong.

In fact, I think it’s safe to say that the only contribution evolution has made to modern medicine is to take it down the horrific road of eugenics, which brought forced sterilization and bodily harm to many thousands of Americans in the early 1900s. That’s a contribution which has brought shame—not advance—to the medical field.

So ‘Why would I want my doctor to have studied evolution?’ I wouldn’t. Evolutionary biology isn’t important to modern medicine. That answer won’t win the ‘Alliance for Science’ prize. It’s just the truth.

Dr. Egnor knows that he would be required to use glucocorticoids to prevent seizures in many situations in neurosurgery, but they were first tested in humans in 1948 - well after the FDA would have required the drugs to be proven non-toxic in animal models. Unless he isn’t giving medicines approved after the 1930s - and one doesn’t often find homeopathic surgeons - then he’s using evolution, even if he refuses to recognize it.

But that’s what his post is primarily about. It’s not that evolution is useless to medicine on the contrary, it is a non-controversial component of essential medical education and one needs to know it certainly to get into medical school these days, to say nothing of staying in and doing well afterwards, to say nothing of having any prayer of a chance of making sense of the science that others use to generate the “standards of care”.

What’s going on here is that Egnor dislikes evolution and is hoping to de-emphasize its importance. Why? It is possible that he earnestly and sincerely believes that evolution has not contributed to his art. It is possible that he earnestly and sincerely believes that recognizing the validity of evolution would render his life meaningless or without value. It is possible he is a cynical liar and he wants no readers of the Discovery Institute Ministry of Media Complaints who credit his perspectives to enter or do well in medical school. (Hey, if true, he wouldn’t be the first surgeon who knew better about evolution but still advocated for ID only to make a buck, gain a little influence, or exhibit some sort of other ulterior motive.) Whatever his motivations may be, readers should not credit his testimony: he is at least dead wrong.

Further, his perspectives are very difficult to distinguish from ignorance advocacy. Egnor first came to attention when a blogger at Time magazine criticized him for not being an expert in evolution. He has stated that he does not use evolution, but this is more an admission of a willful disregard for the evolution he does use and upon which his art is based. Taken together, along with his assurance that the only contribution evolution has made to medicine was eugenics*, his writings bespeak the dangerous combination of ignorance and arrogance, traits altogether common with creationists, but that shine in Dr. Egnor to such an extent that a neologism should bear his namesake.

Egnorance. (n) The egotistical combination of ignorance and arrogance.

*Recall please that Egnor endorsed population biology. I’m informed by my pal Reed Cartwright that the people to blame for eugenics were the early population geneticists. (D’oh!)

Effectiveness against other filarial diseases

Lymphatic Filariasis, also known as Elephantiasis, is another devastating, highly debilitating disease that threatens over 1 billion people in more than 80 countries. Over 120 million people are infected, 40 million of whom are seriously incapacitated and disfigured. The disease results from infection with filarial worms, Wuchereria bancrofti, Brugia malayi or B. timori. The parasites are transmitted to humans through the bite of an infected mosquito and develop into adult worms in the lymphatic vessels, causing severe damage and swelling (lymphoedema) (Fig. ​ (Fig.6 ). 6 ). Adult worms are responsible for the major disease manifestations, the most outwardly visible forms being painful, disfiguring swelling of the legs and genital organs (Fig. ​ (Fig.7 ). 7 ). The psychological and social stigma associated with the disease are immense, as are the economic and productivity losses it causes.

Life cycle of Wuchereria bancrofti.

Ghana: an old man co-infected with onchocerciasis and lymphatic filariasis. He is partially sighted, with a worm nodule on his right leg and leopard skin on his left leg. He also displays elephantiasis of the left leg and has a large hydrocele. Credit line: WHO/TDR/Crump.

With respect to the use of ivermectin for Lymphatic filariasis, again Merck took the initial lead, with TDR being involved in organising, expanding and broadening the research and clinical trials. In the mid-1980s, well before ivermectin was approved for human use to treat onchocerciasis, Merck were also undertaking trials of ivermectin to measure its impact against lymphatic filariasis and to find optimal treatment dosages. 36) Meanwhile, TDR was carrying out multi-centre field trials in Brazil, China, Haiti, India, Indonesia, Malaysia, Papua New Guinea, Sri Lanka and Tahiti to evaluate ivermectin, the existing treatment drug, DEC, and combinations of the two. The results showed that single-dose ivermectin and single-dose DEC worked as well as each other. The combination, even at low dose, proved even more effective, decreasing microfilarial density by 99% after one year and 96% after two years. 20,37�) DEC was also found to be effective in killing adult parasites.

Despite these findings, ivermectin remained unregistered for treatment of lymphatic filariasis for several years. Indeed it was not until 1998 that registration was forthcoming from the French authorities. Several years earlier another drug, albendazole, produced by SmithKlineBeecham (now GlaxoSmithKline – GSK) had also been shown to be effective in killing both immature and adult worms. Indeed, field trials had confirmed that once-yearly combinations of albendazole plus DEC or ivermectin were 99% effective in ridding the blood of microfilariae for at least a year after treatment. The primary goal of treating affected communities thus became elimination of microfilariae from the blood of infected individuals so that transmission of infection is interrupted. This opened up the prospect of actually eliminating the disease, something that was made eminently possible thanks to GSK agreeing to donate albendazole. In 1997, following advances in both diagnosis and treatment, WHO classified lymphatic filariasis as one of six 𠇎radicable” or “potentially eradicable” infectious diseases and requested Member States to initiate steps to eliminate lymphatic filariasis as a public health problem. 40) In late-1998, following registration of the drug for lymphatic filariasis, Merck extended its ivermectin donation programme to cover lymphatic filariasis in areas where it co-existed with Onchocerciasis. Subsequently, in 1999/2000, the WHO launched the Global Programme to Eliminate Lymphatic Filariasis (GPELF).

In summary, the vision of ivermectin as a potential drug for human onchocerciasis emanated from Merck’s research team. TDR facilitated the realisation of that vision though its initial recognition of the lack of an effective tool to identify potential anti-Onchocerca filaricides, its proactive engagement with pharmaceutical companies its creation of and funding for animal model and screening systems and by mobilizing and engaging its international network of researchers and institutions. TDR’s unique position as an international body with a mandate to coordinate research work and provide funds in tropical diseases facilitated and made possible the passage of Merck’s compound through to field use in Africa and elsewhere, allowing the foresight of Merck scientists and the enormous resources devoted by the company to result in immeasurable public health benefits.

How Your Immune System Works

Inside your body there is an amazing protectio­n mechanism called the immune system. It is designed to defend you against millions of bacteria, microbes, viruses, toxins and parasites that would love to invade your body. To understand the power of the immune system, all that you have to do is look at what happens to anything once it dies. That sounds gross, but it does show you something very important about your immune system.

When something dies, its immune system (along with everything else) shuts down. In a matter of hours, the body is invaded by all sorts of bacteria, microbes, parasites. None of these things are able to get in when your immune system is working, but the moment your immune system stops the door is wide open. Once you die it only takes a few weeks for these organisms to completely dismantle your body and carry it away, until all that's left is a skeleton. Obviously your immune system is doing something amazing to keep all of that dismantling from happening when you are alive.

The immune system is complex, intricate and interesting. And there are at least two good reasons for you to know more about it. First, it is just plain fascinating to understand where things like fevers, hives, inflammation, etc., come from when they happen inside your own body. You also hear a lot about the immune system in the news as new parts of it are understood and new drugs come on the market -- knowing about the immune system makes these news stories understandable. In this article, we will take a look at how your immune system works so that you can understand what it is doing for you each day, as well as what it is not.

Seeing Your Immune System

Your immune system works around the clock in thousands of different ways, but it does its work largely unnoticed. One thing that causes us to really notice our immune system is when it fails for some reason. We also notice it when it does something that has a side effect we can see or feel. Here are several examples:

  • When you get a cut, all sorts of bacteria and viruses enter your body through the break in the skin. When you get a splinter you also have the sliver of wood as a foreign object inside your body. Your immune system responds and eliminates the invaders while the skin heals itself and seals the puncture. In rare cases the immune system misses something and the cut gets infected. It gets inflamed and will often fill with pus. Inflammation and pus are both side-effects of the immune system doing its job.
  • When a mosquito bites you, you get a red, itchy bump. That too is a visible sign of your immune system at work.
  • Each day you inhale thousands of germs (bacteria and viruses) that are floating in the air. Your immune system deals with all of them without a problem. Occasionally a germ gets past the immune system and you catch a cold, get the flu or worse. A cold or flu is a visible sign that your immune system failed to stop the germ. The fact that you get over the cold or flu is a visible sign that your immune system was able to eliminate the invader after learning about it. If your immune system did nothing, you would never get over a cold or anything else.
  • Each day you also eat hundreds of germs, and again most of these die in the saliva or the acid of the stomach. Occasionally, however, one gets through and causes food poisoning. There is normally a very visible effect of this breach of the immune system: vomiting and diarrhea are two of the most common symptoms.
  • There are also all kinds of human ailments that are caused by the immune system working in unexpected or incorrect ways that cause problems. For example, some people have allergies. Allergies are really just the immune system overreacting to certain stimuli that other people don't react to at all. Some people have diabetes, which is caused by the immune system inappropriately attacking cells in the pancreas and destroying them. Some people have rheumatoid arthritis, which is caused by the immune system acting inappropriately in the joints. In many different diseases, the cause is actually an immune system error.
  • Finally, we sometimes see the immune system because it prevents us from doing things that would be otherwise beneficial. For example, organ transplants are much harder than they should be because the immune system often rejects the transplanted organ.

Basics of the Immune System

Let's start at the beginning. What does it mean when someone says "I feel sick today?" What is a disease? By understanding the different kinds of diseases it is possible to see what types of disease the immune system helps you handle.

When you "get sick", your body is not able to work properly or at its full potential. There are many different ways for you to get sick -- here are some of them:

  • Mechanical damage - If you break a bone or tear a ligament you will be "sick" (your body will not be able to perform at its full potential). The cause of the problem is something that is easy to understand and visible.
  • Vitamin or mineral deficiency - If you do not get enough vitamin D your body is not able to metabolize calcium properly and you get a disease known as rickets. People with rickets have weak bones (they break easily) and deformities because the bones do not grow properly. If you do not get enough vitamin C you get scurvy, which causes swollen and bleeding gums, swollen joints and bruising. If you do not get enough iron you get anemia, and so on.
  • Organ degradation - In some cases an organ is damaged or weakened. For example, one form of "heart disease" is caused by obstructions in the blood vessels leading to the heart muscle, so that the heart does not get enough blood. One form of "liver disease", known as Cirrhosis, is caused by damage to liver cells (drinking too much alcohol is one cause).
  • Genetic disease - A genetic disease is caused by a coding error in the DNA. The coding error causes too much or too little of certain proteins to be made, and that causes problems at the cellular level. For example, albinism is caused by a lack of an enzyme called tyrosinase. That missing enzyme means that the body cannot manufacture melanin, the natural pigment that causes hair color, eye color and tanning. Because of the lack of melanin, people with this genetic problem are extremely sensitive to the UV rays in sunlight.
  • Cancer - Occasionally a cell will change in a way that causes it to reproduce uncontrollably. For example, when cells in the skin called melanocytes are damaged by ultraviolet radiation in sunlight they change in a characteristic way into a cancerous form of cell. The visible cancer that appears as a tumor on the skin is called melanoma. (See How Sun Tans and Sunburns Work for more information.)

Viral or Bacterial Infection

When a virus or bacteria (also known generically as a germ) invades your body and reproduces, it normally causes problems. Generally the germ's presence produces some side effect that makes you sick. For example, the strep throat bacteria (Streptococcus) releases a toxin that causes inflammation in your throat. The polio virus releases toxins that destroy nerve cells (often leading to paralysis). Some bacteria are benign or beneficial (for example, we all have millions of bacteria in our intestines and they help digest food), but many are harmful once they get into the body or the bloodstream.

Viral and bacterial infections are by far the most common causes of illness for most people. They cause things like colds, influenza, measles, mumps, malaria, AIDS and so on.

The job of your immune system is to protect your body from these infections. The immune system protects you in three different ways:

  1. It creates a barrier that prevents bacteria and viruses from entering your body.
  2. If a bacteria or virus does get into the body, the immune system tries to detect and eliminate it before it can make itself at home and reproduce.
  3. If the virus or bacteria is able to reproduce and start causing problems, your immune system is in charge of eliminating it.

The immune system also has several other important jobs. For example, your immune system can detect cancer in early stages and eliminate it in many cases.

Your body is a multi-cellular organism made up of perhaps 100 trillion cells. The cells in your body are fairly complicated machines. Each one has a nucleus, energy production equipment, etc. Bacteria are single-celled organisms that are much simpler. For example, they have no nucleus. They are perhaps 1/100th the size of a human cell and might measure 1 micrometer long. Bacteria are completely independent organisms able to eat and reproduce - they are sort of like fish swimming in the ocean of your body. Under the right conditions bacteria reproduce very quickly: One bacteria divides into two separate bacteria perhaps once every 20 or 30 minutes. At that rate, one bacteria can become millions in just a few hours.

A virus is a different breed altogether. A virus is not really alive. A virus particle is nothing but a fragment of DNA in a protective coat. The virus comes in contact with a cell, attaches itself to the cell wall and injects its DNA (and perhaps a few enzymes) into the cell. The DNA uses the machinery inside the living cell to reproduce new virus particles. Eventually the hijacked cell dies and bursts, freeing the new virus particles or the viral particles may bud off of the cell so it remains alive. In either case, the cell is a factory for the virus.

Components of the Immune System

One of the funny things about the immune system is that it has been working inside your body your entire life but you probably know almost nothing about it. For example, you are probably aware that inside your chest you have an organ called a "heart". Who doesn't know that they have a heart? You have probably also heard about the fact that you have lungs and a liver and kidneys. But have you even heard about your thymus? There's a good chance you don't even know that you have a thymus, yet its there in your chest right next to your heart. There are many other parts of the immune system that are just as obscure, so let's start by learning about all of the parts.

The most obvious part of the immune system is what you can see. For example, skin is an important part of the immune system. It acts as a primary boundary between germs and your body. Part of your skin's job is to act as a barrier in much the same way we use plastic wrap to protect food. Skin is tough and generally impermeable to bacteria and viruses. The epidermis contains special cells called Langerhans cells (mixed in with the melanocytes in the basal layer) that are an important early-warning component in the immune system. The skin also secretes antibacterial substances. These substances explain why you don't wake up in the morning with a layer of mold growing on your skin -- most bacteria and spores that land on the skin die quickly.

Your nose, mouth and eyes are also obvious entry points for germs. Tears and mucus contain an enzyme (lysozyme) that breaks down the cell wall of many bacteria. Saliva is also anti-bacterial. Since the nasal passage and lungs are coated in mucus, many germs not killed immediately are trapped in the mucus and soon swallowed. Mast cells also line the nasal passages, throat, lungs and skin. Any bacteria or virus that wants to gain entry to your body must first make it past these defenses.

Once inside the body, a germ deals with the immune system at a different level. The major components of the immune system are:

  • Thymus
  • Spleen
  • Lymph system
  • Bone marrow
  • White blood cells
  • Antibodies
  • Complement system
  • Hormones

Let's look at each of these components in detail.

The lymph system is most familiar to people because doctors and mothers often check for "swollen lymph nodes" in the neck. It turns out that the lymph nodes are just one part of a system that extends throughout your body in much the same way your blood vessels do. The main difference between the blood flowing in the circulatory system and the lymph flowing in the lymph system is that blood is pressurized by the heart, while the lymph system is passive. There is no "lymph pump" like there is a "blood pump" (the heart). Instead, fluids ooze into the lymph system and get pushed by normal body and muscle motion to the lymph nodes. This is very much like the water and sewer systems in a community. Water is actively pressurized, while sewage is passive and flows by gravity.

Lymph is a clearish liquid that bathes the cells with water and nutrients. Lymph is blood plasma -- the liquid that makes up blood minus the red and white cells. Think about it -- each cell does not have its own private blood vessel feeding it, yet it has to get food, water, and oxygen to survive. Blood transfers these materials to the lymph through the capillary walls, and lymph carries it to the cells. The cells also produce proteins and waste products and the lymph absorbs these products and carries them away. Any random bacteria that enter the body also find their way into this inter-cell fluid. One job of the lymph system is to drain and filter these fluids to detect and remove the bacteria. Small lymph vessels collect the liquid and move it toward larger vessels so that the fluid finally arrives at the lymph nodes for processing.

Lymph nodes contain filtering tissue and a large number of lymph cells. When fighting certain bacterial infections, the lymph nodes swell with bacteria and the cells fighting the bacteria, to the point where you can actually feel them. Swollen lymph nodes are therefore a good indication that you have an infection of some sort.

Once lymph has been filtered through the lymph nodes it re-enters the bloodstream.

The thymus lives in your chest, between your breast bone and your heart. It is responsible for producing T-cells (see the next section), and is especially important in newborn babies - without a thymus a baby's immune system collapses and the baby will die. The thymus seems to be much less important in adults - for example, you can remove it and an adult will live because other parts of the immune system can handle the load. However, the thymus is important, especially to T cell maturation (as we will see in the section on white blood cells below).


The spleen filters the blood looking for foreign cells (the spleen is also looking for old red blood cells in need of replacement). A person missing their spleen gets sick much more often than someone with a spleen.

Bone marrow

Bone marrow produces new blood cells, both red and white. In the case of red blood cells the cells are fully formed in the marrow and then enter the bloodstream. In the case of some white blood cells, the cells mature elsewhere. The marrow produces all blood cells from stem cells. They are called "stem cells" because they can branch off and become many different types of cells - they are precursors to different cell types. Stem cells change into actual, specific types of white blood cells.

White blood cells

White blood cells are described in detail in the next section.

Antibodies (also referred to as immunoglobulins and gammaglobulins) are produced by white blood cells. They are Y-shaped proteins that each respond to a specific antigen (bacteria, virus or toxin). Each antibody has a special section (at the tips of the two branches of the Y) that is sensitive to a specific antigen and binds to it in some way. When an antibody binds to a toxin it is called an antitoxin (if the toxin comes from some form of venom, it is called an antivenin). The binding generally disables the chemical action of the toxin. When an antibody binds to the outer coat of a virus particle or the cell wall of a bacterium it can stop their movement through cell walls. Or a large number of antibodies can bind to an invader and signal to the complement system that the invader needs to be removed.

Antibodies come in five classes:

  • Immunoglobulin A (IgA)
  • Immunoglobulin D (IgD)
  • Immunoglobulin E (IgE)
  • Immunoglobulin G (IgG)
  • Immunoglobulin M (IgM)

Whenever you see an abbreviation like IgE in a medical document, you now know that what they are talking about is an antibody.

For additional information on antibodies see The Antibody Resource Page.

The complement system, like antibodies, is a series of proteins. There are millions of different antibodies in your blood stream, each sensitive to a specific antigen. There are only a handful of proteins in the complement system, and they are floating freely in your blood. Complements are manufactured in the liver. The complement proteins are activated by and work with (complement) the antibodies, hence the name. They cause lysing (bursting) of cells and signal to phagocytes that a cell needs to be removed.

For additional information on complements, see The Complement System.


There are several hormones generated by components of the immune system. These hormones are known generally as lymphokines. It is also known that certain hormones in the body suppress the immune system. Steroids and corticosteroids (components of adrenaline) suppress the immune system.

Tymosin (thought to be produced by the thymus) is a hormone that encourages lymphocyte production (a lymphocyte is a form of white blood cell - see below). Interleukins are another type of hormone generated by white blood cells. For example, Interleukin-1 is produced by macrophages after they eat a foreign cell. IL-1 has an interesting side-effect - when it reaches the hypothalamus it produces fever and fatigue. The raised temperature of a fever is known to kill some bacteria.

Tumor Necrosis Factor

Tumor Necrosis Factor (TNF) is also produced by macrophages. It is able to kill tumor cells, and it also promotes the creation of new blood vessels so it is important to healing.


Interferon interferes with viruses (hence the name) and is produced by most cells in the body. Interferons, like antibodies and complements, are proteins, and their job is to let cells signal to one another. When a cell detects interferon from other cells, it produces proteins that help prevent viral replication in the cell.

You are probably aware of the fact that you have "red blood cells" and "white blood cells" in your blood. The white blood cells are probably the most important part of your immune system. And it turns out that "white blood cells" are actually a whole collection of different cells that work together to destroy bacteria and viruses. Here are all of the different types, names and classifications of white blood cells working inside your body right now:

  • Leukocytes
  • Lymphocyte
  • Monocytes
  • Granulocytes
  • B-cells
  • Plasma cells
  • T-cells
  • Helper T-cells
  • Killer T-cells
  • Suppressor T-cells
  • Natural killer cells
  • Neutrophils
  • Eosinophils
  • Basophils
  • Phagocytes
  • Macrophages

Learning all of these different names and the function of each cell type takes a bit of effort, but you can understand scientific articles a lot better once you get it all figured out! Here's a quick summary to help you get all of the different cell types organized in your brain.

All white blood cells are known officially as leukocytes. White blood cells are not like normal cells in the body -- they actually act like independent, living single-cell organisms able to move and capture things on their own. White blood cells behave very much like amoeba in their movements and are able to engulf other cells and bacteria. Many white blood cells cannot divide and reproduce on their own, but instead have a factory somewhere in the body that produces them. That factory is the bone marrow.

Leukocytes are divided into three classes:

  • Granulocytes - Granulocytes make up 50% to 60% of all leukocytes. Granulocytes are themselves divided into three classes: neutrophils, eosinophils and basophils. Granulocytes get their name because they contain granules, and these granules contain different chemicals depending on the type of cell.
  • Lymphocyte - Lymphocytes make up 30% to 40% of all leukocytes. Lymphocytes come in two classes: B cells (those that mature in bone marrow) and T cells (those that mature in the thymus).
  • Monocyte - Monocytes make up 7% or so of all leukocytes. Monocytes evolve into macrophages.

All white blood cells start in bone marrow as stem cells. Stem cells are generic cells that can form into the many different types of leukocytes as they mature. For example, you can take a mouse, irradiate it to kill off its bone marrow's ability to produce new blood cells, and then inject stem cells into the mouse's blood stream. The stem cells will divide and differentiate into all different types of white blood cells. A "bone marrow transplant" is accomplished simply by injecting stem cells from a donor into the blood stream. The stem cells find their way, almost magically, into the marrow and make their home there.

Each of the different types of white blood cells have a special role in the immune system, and many are able to transform themselves in different ways. The following descriptions help to understand the roles of the different cells.

  • Neutrophils are by far the most common form of white blood cells that you have in your body. Your bone marrow produces trillions of them every day and releases them into the bloodstream, but their life span is short -- generally less than a day. Once in the bloodstream neutrophils can move through capillary walls into tissue. Neutorphils are attracted to foreign material, inflammation and bacteria. If you get a splinter or a cut, neutrophils will be attracted by a process called chemotaxis. Many single-celled organisms use this same process -- chemotaxis lets motile cells move toward higher concentrations of a chemical. Once a neutrophil finds a foreign particle or a bacteria it will engulf it, releasing enzymes, hydrogen peroxide and other chemicals from its granules to kill the bacteria. In a site of serious infection (where lots of bacteria have reproduced in the area), pus will form. Pus is simply dead neutrophils and other cellular debris.
  • Eosinophils and basophils are far less common than neutrophils. Eosinophils seem focused on parasites in the skin and the lungs, while Basophils carry histamine and therefore important (along with mast cells) to causing inflammation. From the immune system's standpoint inflammation is a good thing. It brings in more blood and it dilates capillary walls so that more immune system cells can get to the site of infection.
  • Of all blood cells, macrophages are the biggest (hence the name "macro"). Monocytes are released by the bone marrow, float in the bloodstream, enter tissue and turn into macrophages. Most boundary tissue has its own devoted macrophages. For example, alveolar macrophages live in the lungs and keep the lungs clean (by ingesting foreign particles like smoke and dust) and disease free (by ingesting bacteria and microbes). Macrophages are called langerhans cells when they live in the skin. Macrophages also swim freely. One of their jobs is to clean up dead neutrophils -- macropghages clean up pus, for example, as part of the healing process.
  • The lymphocytes handle most of the bacterial and viral infections that we get. Lymphocytes start in the bone marrow. Those destined to become B cells develop in the marrow before entering the bloodstream. T cells start in the marrow but migrate through the bloodstream to the thymus and mature there. T cells and B cells are often found in the bloodstream but tend to concentrate in lymph tissue such as the lymph nodes, the thymus and the spleen. There is also quite a bit of lymph tissue in the digestive system. B cells and T cells have different functions.
  • B cells, when stimulated, mature into plasma cells -- these are the cells that produce antibodies. A specific B cell is tuned to a specific germ, and when the germ is present in the body the B cell clones itself and produces millions of antibodies designed to eliminate the germ.
  • T cells, on the other hand, actually bump up against cells and kill them. T cells known as Killer T cells can detect cells in your body that are harboring viruses, and when it detects such a cell it kills it. Two other types of T cells, known as Helper and Suppressor T cells, help sensitize killer T cells and control the immune response.

Helper T cells are actually quite important and interesting. They are activated by Interleukin-1, produced by macrophages. Once activated, Helper T cells produce Interleukin-2, then interferon and other chemicals. These chemicals activate B cells so that they produce antibodies. The complexity and level of interaction between neutrophils, macrophages, T cells and B cells is really quite amazing.

Because white blood cells are so important to the immune system, they are used as a measure of immune system health. When you hear that someone has a "strong immune system" or a "suppressed immune system", one way it was determined was by counting different types of white blood cells in a blood sample. A normal white blood cell count is in the range of 4,000 to 11,000 cells per microliter of blood. 1.8 to 2.0 helper T-cells per suppressor T-cell is normal. A normal absolute neutrophil count (ANC) is in the range of 1,500 to 8,000 cells per microliter. An article like Introduction to Hematology can help you learn more about white blood cells in general and the different types of white blood cells found in your body.

One important question to ask about white blood cells (and several other parts of the immune system) is, "How does a white blood cell know what to attack and what to leave alone? Why doesn't a white blood cell attack every cell in the body?" There is a system built into all of the cells in your body called the Major Histocompatibility Complex (MHC) (also known as the Human Leukocyte Antigen (HLA)) that marks the cells in your body as "you". Anything that the immune system finds that does not have these markings (or that has the wrong markings) is definitely "not you" and is therefore fair game. Encyclopedia Britannica has this to say about the MHC:

"There are two major types of MHC protein molecules--class I and class II--that span the membrane of almost every cell in an organism. In humans these molecules are encoded by several genes all clustered in the same region on chromosome 6. Each gene has an unusual number of alleles (alternate forms of a gene). As a result, it is very rare for two individuals to have the same set of MHC molecules, which are collectively called a tissue type.

MHC molecules are important components of the immune response. They allow cells that have been invaded by an infectious organism to be detected by cells of the immune system called T lymphocytes, or T cells. The MHC molecules do this by presenting fragments of proteins (peptides) belonging to the invader on the surface of the cell. The T cell recognizes the foreign peptide attached to the MHC molecule and binds to it, an action that stimulates the T cell to either destroy or cure the infected cell. In uninfected healthy cells the MHC molecule presents peptides from its own cell (self peptides), to which T cells do not normally react. However, if the immune mechanism malfunctions and T cells react against self peptides, an autoimmune disease arises."

There are many diseases that, if you catch them once, you will never catch again. Measles is a good example, as is chicken pox. What happens with these diseases is that they make it into your body and start reproducing. The immune system gears up to eliminate them. In your body you already have B cells that can recognize the virus and produce antibodies for it. However, there are only a few of these cells for each antibody. Once a particlular disease is recognized by these few specific B cells, the B cells turn into plasma cells, clone themselves and start pumping out antibodies. This process takes time, but the disease runs it course and is eventually eliminated. However, while it is being eliminated, other B cells for the disease clone themselves but do not generate antibodies. This second set of B cells remains in your body for years, so if the disease reappears your body is able to eliminate it immediately before it can do anything to you.

A vaccine is a weakened form of a disease. It is either a killed form of the disease, or it is a similar but less virulent strain. Once inside your body your immune system mounts the same defense, but because the disease is different or weaker you get few or no symptoms of the disease. Now, when the real disease invades your body, your body is able to eliminate it immediately.

Vaccines exist for all sorts of diseases, both viral and bacterial: measles, mumps, whooping cough, tuberculosis, smallpox, polio, typhoid, etc.

Many diseases cannot be cured by vaccines, however. The common cold and Influenza are two good examples. These diseases either mutate so quickly or have so many different strains in the wild that it is impossible to inject all of them into your body. Each time you get the flu, for example, you are getting a different strain of the same disease.

AIDS (Acquired Immune Deficiency Syndrome) is a disease caused by HIV (the Human Immunodeficiency Virus). This is a particularly problematic disease for the immune system because the virus actually attacks immune system cells. In particular, it reproduces inside Helper T cells and kills them in the process. Without Helper T cells to orchestrate things, the immune system eventually collapses and the victim dies of some other infection that the immune system would normally be able to handle. See How AIDS Works as well as the links below for more information.

Sometimes your immune system is not able to activate itself quickly enough to outpace the reproductive rate of a certain bacteria, or the bacteria is producing a toxin so quickly that it will cause permanent damage before the immune system can eliminate the bacteria. In these cases it would be nice to help the immune system by killing the offending bacteria directly.

Antibiotics work on bacterial infections. Antibiotics are chemicals that kill the bacteria cells but do not affect the cells that make up your body. For example, many antibiotics interrupt the machinery inside bacterial cells that builds the cell wall. Human cells do not contain this machinery, so they are unaffected. Different antibiotics work on different parts of bacterial machinery, so each one is more or less effective on specific types of bacteria. You can see that, because a virus is not alive, antibiotics have no effect on a virus.

One problem with antibiotics is that they lose effectiveness over time. If you take an antibiotic it will normally kill all of the bacteria it targets over the course of a week or 10 days. You will feel better very quickly (in just a day or two) because the antibiotic kills the majority of the targeted bacteria very quickly. However, on occasion one of the bacterial offspring will contain a mutation that is able to survive the specific antibiotic. This bacteria will then reproduce and the whole disease mutates. Eventually the new strain is infecting everyone and the old antibiotic has no effect on it. This process has become more and more of a problem over time and has become a significant concern in the medical community.

Sometimes the immune system makes a mistake. One type of mistake is called autoimmunity: the immune system for some reason attacks your own body in the same way it would normally attack a germ. Two common diseases are caused by immune system mistakes. Juvenile-onset diabetes is caused by the immune system attacking and eliminating the cells in the pancreas that produce insulin. Rheumatoid arthritis is caused by the immune system attacking tissues inside the joints.

Allergies are another form of immune system error. For some reason, in people with allergies, the immune system strongly reacts to an allergen that should be ignored. The allergen might be a certain food, or a certain type of pollen, or a certain type of animal fur. For example, a person allergic to a certain pollen will get a runny nose, watery eyes, sneezing, etc. This reaction is caused primarily by mast cells in the nasal passages. In reaction to the pollen the mast cells release histamine. Histamine has the effect of causing inflammation, which allows fluid to flow from blood vessels. Histamine also causes itching. To eliminate these symptoms the drug of choice is, of course, an antihistamine.

The last example of an immune system mistake is the effect the immune system has on transplanted tissue. This really isn't a mistake, but it makes organ and tissue transplants nearly impossible. When the foreign tissue is placed inside your body, its cells do not contain the correct identification. Your immune system therefore attacks the tissue. The problem cannot be prevented, but can be diminished by carefully matching the tissue donor with the recipient and by using immunosuppressing drugs to try to prevent an immune system reaction. Of course, by suppressing the immune system these drugs open the patient to opportunistic infections.

For more information on the immune system and related topics, check out the links on the next page.

New Clues Found in Understanding Near-Death Experiences

Imagine a dream in which you sense an intense feeling of presence, the truest, most real experience in your life, as you float away from your body and look at your own face. You have a twinge of fear as memories of your life flash by, but then you pass a transcendent threshold and are overcome by a feeling of bliss. Although contemplating death elicits fear for many people, these positive features are reported in some of the near-death experiences (NDEs) undergone by those who reached the brink of death only to recover.

Accounts of NDEs are remarkably consistent in character and content. They include intensely vivid memories involving bodily sensations that give a strong impression of being real, more real even than memories of true events. The content of those experiences famously includes memories of one&rsquos life &ldquoflashing before the eyes,&rdquo and also the sensation of leaving the body, often seeing one&rsquos own face and body, blissfully traveling through a tunnel toward a light and feeling &ldquoat one&rdquo with something universal.

Not surprisingly, many have seized on NDEs as evidence of life after death, heaven and the existence of god. The descriptions of leaving the body and blissful unity with the universal seem almost scripted from religious beliefs about souls leaving the body at death and ascending toward heavenly bliss. But these experiences are shared across a broad range of cultures and religions so it&rsquos not likely that they are all reflections of specific religious expectations. Instead, that commonality suggests that NDEs might arise from something more fundamental than religious or cultural expectations. Perhaps NDEs reflect changes in how the brain functions as we approach death.

Many cultures employ drugs as part of religious practice to induce feelings of transcendence that have similarities to near-death experiences. If NDEs are based in brain biology, perhaps the action of those drugs that causes NDE-like experiences can teach us something about the NDE state. Of course, studying NDEs has significant technical hurdles. There is no way of examining the experience in animals, and rescuing a patient at death&rsquos door is far more important than interviewing them about their NDE. Moreover, many of the drugs used to induce religious states are illicit, which would complicate any efforts to study their effects.

Although it&rsquos impossible to directly examine what happens to the brain during NDEs, the stories collected from them provide a rich resource for linguistic analysis. In a fascinating new study, NDE stories were compared linguistically with anecdotes of drug experience in order to identify a drug that causes an experience most like a near-death experience. What is remarkable is how precise a tool this turned out to be. Even though the stories were open-ended subjective accounts often given many years after the fact, the linguistic analysis focused down not only to a specific class of drugs, but also to a specific drug as causing experiences very similar to NDEs.

This new study compared the stories of 625 individuals who reported NDEs with the stories of more than 15,000 individuals who had taken one of 165 different psychoactive drugs. When those stories were linguistically analyzed, similarities were found between recollections of near-death and drug experiences for those who had taken a specific class of drug. One drug in particular, ketamine, led to experiences very similar to NDE. This may mean that the near-death experience may reflect changes in the same chemical system in the brain that is targeted by drugs like ketamine.

The researchers drew on a large collection of NDE stories they had collected over many years. To compare NDEs with drug experiences, the researchers took advantage of a large collection of drug experience anecdotes found in the Erowid Experience Vaults, an open-source collection of accounts describing firsthand experiences with drugs and various substances.

In this study, the recollections of those who experienced NDEs and those who took drugs were compared linguistically. Their stories were broken down into individual words, and the words were sorted according to their meaning and counted. In this way, researchers were able to compare the number of times words having the same meaning were used in each story. They used this numerical analysis of story content to compare the content of drug-related and near-death experiences.

Each of the drugs included in these comparisons could be categorized by their ability to interact with a specific neurochemical system in the brain, and each drug fell into a specific category (antipsychotic, stimulant, psychedelic, depressant or sedative, deliriant, or hallucinogen). Few similarities were found when the accounts of one stimulant drug were compared with another within the same stimulant drug class, and few if any similarities were found between accounts of stimulant drug experience and NDEs. The same was true for depressants. The stories associated with hallucinogens, however, were very similar to one another, as were stories linked to antipsychotics and deliriants. When recollections of drug effects were compared with NDEs, stories about hallucinogens and psychedelics had the greatest similarities to NDEs, and the drug that scored the highest similarity to NDEs was the hallucinogen ketamine. The word most strongly represented in descriptions of both NDEs and ketamine experiences was &ldquoreality,&rdquo highlighting the sense of presence that accompanies NDEs. High among the list of words common to both experiences were those related to perception (saw, color, voice, vision), the body (face, arm, foot), emotion (fear) and transcendence (universe, understand, consciousness).

The researchers then sorted words into five large principal groups according to their common meaning. Those principal components dealt with perception and consciousness, drug dependency, negative sensations, drug preparation, and also a group that included disease state, religion and ceremony. NDEs reflected three of these components related to perception and consciousness, religion and ceremony, disease state, and drug preparation. The component related to perception and consciousness was labeled &ldquoLook/Self&rdquo and included terms such as color, vision, pattern, reality and face. The component &ldquoDisease/Religion&rdquo contained elements such as anxiety, ceremony, consciousness and self, whereas the component related to preparation &ldquoMake/Stuff&rdquo contained elements such as prepare, boil, smell and ceremony. Again, ketamine had the greatest overlap with NDEs in this type of analysis.

Other drugs that cause similar experiences to NDEs include LSD and N,N-Dimethyltryptamine (DMT). The famous hallucinogen LSD was as similar as ketamine to NDEs when the near-death event was caused by cardiac arrest. DMT is a hallucinogen found in South American plants and used in shamanistic rituals. It caused experiences like NDEs and is also made in the brain, leading to speculation that endogenous DMT may explain NDEs. It is not known, however, whether levels of DMT change in a meaningful way in the human brain near death, so its role in the phenomenon remain controversial.

This study has significant weaknesses because it is based on purely subjective reports&mdashsome taken decades after the event. Similarly, there is no way to substantiate the accounts in the Erowid collection as there is no way to prove that any individual took the drug they claimed or believed they were taking. This makes it all the more remarkable that a linguistic analysis of stories derived in this manner could discriminate among different drug classes in their similarities to NDEs.

Linking near-death experiences and the experience of taking ketamine is provocative yet it is far from conclusive that both are because of the same chemical events in the brain. The types of studies needed to demonstrate this hypothesis, such as measuring neurochemical changes in the critically ill, would be both technically and ethically challenging. The authors propose, however, a practical application of this relation. Because near-death experiences (NDEs) can be transformational and have profound and lasting effects on those who experience them, including a sense of fearlessness about death, the authors propose that ketamine could be used therapeutically to induce an NDE-like state in terminally ill patients as a &ldquopreview&rdquo of what they might experience, so as to relieve their anxieties about death. Those benefits need to be weighed against the risks of potential ketamine side effects, which include feelings of panic or extreme anxiety, effects that could defeat the purpose of the intervention.

More important, this study helps describe the psychological manifestations of dying. That knowledge may ultimately contribute more to alleviating fear of this inevitable transition than a dose of any drug.



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