New book by Robert Trivers, Deceit and Self-Deception

Few variables are as important in our lives as our perceived moral status. Even more than attractiveness and competence, degree of morality is a variable of considerable importance in determining our value to others—thus it is easily subject to deceit and self-deception. Moral hypocrisy is a deep part of our nature: the tendency to judge others more harshly for the same moral infraction than we judge ourselves—or to do so for members of other groups compared to members of our own group. For example, I am very forgiving where my own actions are concerned. I will forgive myself in a heartbeat—and toss in some compassionate humor in the bargain—for a crime that I would roast anybody else for….

In this foundational book, Robert Trivers seeks to answer one of the most provocative and consequential questions to face humanity: why do we lie to ourselves?

Deception is everywhere in nature. And nowhere more so than in our own species. We humans are especially good at telling others less — or more —than the truth. Why, however, would organisms both seek out information and then act to destroy it? In short, why practise self-deception? To biologists this has long been a mystery. Our sense organs have evolved to give us a marvellously detailed and accurate view of the outside world. So why should natural selection then lead us to systematically distort what we know?

After decades of research, Robert Trivers has at last provided the missing theory to answer these questions. What emerges is a picture of deceit and self-deception as, at root, different sides of the same coin. We deceive ourselves the better to deceive others, and thereby reap the advantages. From space and aviation disasters to warfare, politics and religion, and the anxieties of our everyday social lives, Deceit and Self-Deception explains what really underlies a whole host of human problems. But can we correct our own biases? Are we doomed to indulge in fantasies, inflate our egos, and show off? Is it even a good idea to battle self-deception?

With his characteristically wry and self-effacing wit, Trivers reveals how he finds self-deception everywhere in his own life, and shows us that while we may not always avoid it, we can now at least hope to understand it.

Syndicated from GMO Pundit aka David Tribe.

I like to think of myself as a skeptical blogger. I like to engage in critical thinking about scientific issues because this is an important aspect of my job as a graduate assistant. When I move into the workforce, I’ll still need some basic skills to parse evidence because this is my job as a scientist. Mythbusting is a great opportunity to do this, and I enjoy discussing things which may help people who read my posts whenever I can. Being an entomologist gives me some rather interesting opportunities to do this, which is leading me to discuss head lice of all things.

Pediculus humanus capitis by Gilles San Martin via Flickr.

In my last post, Do OTC Head Louse Treatments Work? Part 1: Mechanisms, I explained how the most commonly used FDA-approved treatments worked. In addition to those science-based products, there are many products that have no evidence of efficacy behind their claims, and that rely on fear to make a sale. What I’ve seen deeply concerns me not only as a scientist trying to make the world a better place, but as a parent trying to raise my daughter the best that I can. In this post, I’ve taken a few commonly sold products and listed some ways in which I think they play fast and loose with their claims.

A very brief review of how the nervous system works and how pesticides work in general can be found in the video below:

How do we know if treatments work?

Before getting down to the business of mythbusting, I think it’s appropriate to discuss how we know various products work. Treatments are assessed through clinical trails where infested volunteers subject themselves to putative treatments which are known as in vivo trials. In some cases, the lice are removed from the volunteers and exposed to the treatments in petri dishes which are known as in vitro treatments. In vitro treatments must be performed with the louse’s biology in mind because removing the louse from the host means that the louse is no longer in its natural environment. If the louse is not in it’s natural environment, the results gained from such a test may not be applicable to a real infestation. In vitro tests can disprove that a product works under ideal conditions, but proof of efficacy ultimately requires that the product be tested in real world conditions.

Clinical trials must have large numbers of people (and large numbers of lice) and untreated control groups. After all, insects are surprisingly fragile critters and even water or non-insecticidal shampoos may result in a small amount of mortality which is insignificant to treatment. Water or noninsecticidal shampoos can also temporarily clog the insect’s spiracles, resulting in immobile lice which could be interpreted as dead by a careless counter. Removal can physically injure the lice, which could cloud trial results if results are drawn from collected lice.

Another important aspect of clinical trials is blinding and randomization which make sure the person who is counting the lice isn’t aware of the treatment the person received. The human mind is a surprisingly bad tool for science because we tend to see patterns where none exist, and we may unintentionally superimpose patterns that don’t exist. Since everything in nature has some amount of variability (Anastasia is about six inches shorter than I am, Bug Girl is about a foot shorter than I am, and my boss is about a foot taller than I am for a quick example) we use statistics to tell us what the probability is that our results are due to random chance, eventually ending up with something known as a P-value. Followup observations are also required to show that the patient remained louse free, that is that there weren’t any hidden adults or unhatched eggs because the unhatched eggs can restart infestations.

Last week, I discussed some common OTC head louse treatments. While effective, there are some problems with resistance for some OTC treatments which results in failure of some treatments. This is a product of evolution where some lice are able to survive treatment because they have some random mutations which just so happen to be beneficial in a pesticide filled environment. The mechanisms of this resistance are actually similar to agricultural pests which have been treated with the same product.

One thing astute readers may have noticed is that I didn’t shy away from the use of the word ‘pesticide’ when discussing these treatments. One of my very first posts on Biofortified revolved around the definition of the word ‘pest’ which is completely anthropocentric. A pest is any critter which annoys us in the slightest, and a pesticide is a compound which kills a pest. Insecticides are used to kill insect pests and head louse treatments are referred to as ‘pediculicides’ because they kill lice. All pediculicides are insecticides (because they kill lice, which are insects), and many of the less toxic insecticides used in agriculture have been repurposed as pediculicides. Often times with head louse treatments, you hear companies claim with great pride that their products are pesticide free, are great at killing lice and that no resistance has evolved to their treatment.

Well… how do these claims stack up?

Uncomfortable Truths

Current packaging of products discussed in this article. Product images taken from the websites of their respective companies, used in accordance with the Fair Use Clause in US Copyright Law.

The use of agricultural insecticides to treat head lice is somewhat of an uncomfortable truth, and many companies have taken advantage of this to market head louse treatments. Despite what any label you read may say, any product which claims to kill lice is an insecticide by definition. It doesn’t matter if these are plant extracts, because pyrethrum falls straight into this category and it is classified as an insecticide. In fact, I would even go so far as to argue that a product is engaging in false advertising if it claims to kill headlice while being pesticide free. This, of course, doesn’t mean that all products must directly interfere with the inner workings of lice to be potential treatments.

Some compounds like mineral oil are used as insecticides in agriculture to kill aphids by suffocating them. The product marketed as ‘Lice MD‘ in the picture above claims to kill lice through a similar mechanism. The fact that these chemicals do not interfere with the neurological systems of insects does not mean that the product isn’t an insecticide. If the product claims to kill lice, as Lice MD does, it is claiming to be an insecticide.

A couple of examples of products that play fast and loose with advertising, in my opinion. Remember: natural products can be just as bad as synthetic products. Also, any product that claims to kill something is certainly not pesticide free. Both images taken from the websites of their respective companies, and used in accordance with the Fair Use Clause in US copyright law.

Uneasiness about insecticides has also given rise to many products which are derived from natural sources; these are popular because of a general assumption that natural products are safer than synthetic insecticides. The advantage of this from a company’s point of view is that these products don’t have to go through safety or efficacy testing, depending on how they’re marketed. The Dietary Supplement Health and Education Act of 1994 allows many products to go straight to market without testing under the guise of ‘supplements’ which allows them to make sometimes outlandish health-related claims. Homeopathic products are similarly exempt from safety and efficacy testing, which gives companies a great loophole to sell products which make medicinal claims.

This is a successful tactic because it plays on the unease parents have about treating their children with insecticides to kill lice. Unfortunately for these uneasy parents, the assumption that natural products are less harmful than synthetic products doesn’t always hold true. The LD50s for many synthetic pyrethroids are higher than their natural counterparts. Ricin and amantin are both incredibly powerful poisons derived from plants and fungi respectively. Eucalyptus oil, if used improperly as a head louse treatment, can have dire consequences including seizures and death. Many natural components can have chronic effects, too. Cyclopamine, derived from Vetratum californicum, causes some rather disturbing birth defects by inhibiting developmental pathways. Rotenone, a pesticide once used widely in organic agriculture, has been linked to Parkinson’s disease in workers exposed to sublethal doses of the toxin over the course of a very long time. Aflatoxins are powerful carcinogens produced by fungi which threaten food supplies all over the world. Even something as seemingly innocuous as a cockroach sex pheromone can be carcinogenic.

To be safe, it doesn’t matter if a chemical is derived from natural sources. Instead, safety depends on how the chemical interacts with the molecular machinery that keeps us alive. The safest way to make a new product is to construct it with chemicals where we know what everything does, as opposed to treating with soups of unknown composition. Unfortunately, this isn’t always possible because purifying and testing a compound for effects is extremely expensive and can take years of effort.

One of the components in the Quit Nits formula is a plant called Delphinium, a plant genus which is famed for its toxic alkaloids that poison cattle and make this plant genus a pest of cattle pastures. I’ll discuss this claim further in another paragraph, but the plant is in the formula at a concentration that is most likely too low to harm either lice or people. Other claims on this product are technically honest, but misleading. Some components of this product have been used in agriculture as insecticides. Lice consume a blood diet, and would probably have to eat these pesticides to see any effect. Components of the shampoo are toxic, but the concentrations these components are used in are harmless to people and are probably harmless to lice as well. As far as I can tell, most of these components haven’t been tested against lice in literature available to researchers. The statements made in the Quit Nits product comparison chart are misleading on multiple levels.

Misleading Statistics

Study methodology and results from the Lice Sheild website. This usage of the information from the company's website is in accordance with the Fair Use Clause of US copyright law.

Many products give misleading statistics that aim to trick parents into believing the product works. For example, let’s take a look at a product called Lice Sheild. They give a description of an experiment on their website that seems like a good test on the surface but is missing any information that actually allows you to draw any conclusions. For instance, they give P-values in their experimental setup, but do not give any information needed to verify their results. The P-values given imply statistical significance, but without any information on repetitions, sample sizes, means, or deviations the information is basically useless. There’s no way to check their math to see if the statistics were correctly performed. There are also no details on how many lice they used for the experiment. If they used two repetitions of five lice (the minimum required for 80% repellency with four lice moving between hair strands and away from the treatment), this would be a negligible result. If they used ten repetitions of 500 lice, the results would be a bit stronger. There simply isn’t enough information here to determine if the statistics were correctly performed.

Also lacking is a description of the experimental arena which is important because there are many ways in which you can test repellency that would potentially interfere with louse movement. If they placed the louse in a container in a patch of hair, one wouldn’t expect lice to move away from the hair at an appreciable rate. Many products are tested by placing the lice on a piece of filter paper and looking at the percentage of lice which move away from the product. While a test like this may appear to show some repellent activity, it’s not actually a very good measure of how good your product repels lice in real world conditions. Using in vitro tests means you’re trapping the lice in a place with the repellent and giving them essentially unlimited time to make their choice. This is a big problem because they’re using a timeframe that’s irrelevant to head louse transmission. Lice are mainly transmitted through hair to hair contact, and it’s rare for two people to be in hair to hair contact for this amount of time.

In short, showing 80% repellency is very different than saying that you have a 80% reduction in your chances of getting head lice. The company which makes Lice Shield uses questionable statistics to claim their product repels 80% of lice under conditions that don’t reflect the conditions where lice are transmitted, then turns around and claims in their FAQ this means that there is an 80% reduction in head louse transmission without any evidence for this claim. These two claims are quite different, because repellency doesn’t necessarily translate to a reduction of infestation.

Homeopathic Medicines are Marketed Differently than FDA Approved Drugs

Homeopathy is a system of beliefs which claim that serially diluting a ‘medicinal’ substance makes it stronger. These dilutions are pretty specific, for example the letter X denotes a 1:10 dilution. If a product is diluted 6X, it’s diluted to 10^-6 which is about one millionth of the original concentration. The idea that diluting a potential louse treatment makes it stronger is ridiculous because if the chemicals in any treatment interfere with insect biochemisty, they must be within a certain range to have an effect. Too much, the person gets poisoned (but the lice still die). Too little, and the lice survive and resistance can build up after the more susceptible individuals are culled from the population.

Homeopathy defies essentially every principle in science from biology to physics. Homeopaths claim that water has memory but, to paraphrase Tim Minchin, this ‘memory’ of water seems infinite when paired with some substances but water seems to have a case for amnesia when it comes to more harmful substances. Homeopathy has no a plausible mode of action.

The next paragraph of my post may get me into hot water with some of my skeptic friends. Many skeptical bloggers have taken on homeopathy. Let me restate: homeopathy has no plausible mode of action. I want to put this in writing to avoid the inevitable criticism from other skeptical bloggers. I also want to avoid the quote-mining from naturopaths who may want to say that I support homeopathy. I am not claiming the efficacy of homeopathy because there is no evidence that it works, and there is no plausible mechanism by which this practice could possibly work.

I am considering some homeopathic products as potentially effective. Why? Homeopathic formulas are exempt from safety and efficacy testing by the FDA which gives many products a free pass when it comes to clinical trials. Many products aren’t actually homeopathic because they contain ingredients in concentrations that could potentially have an effect. These products are often classified as homeopathic so they can make medicinal claims. A cold remedy product marketed under the name Zicam is a good example of this. Zicam was a solution of zinc which was marketed to treat the common cold after it was shown that zinc ions could interfere with viral replication in in vitro tests. The product was eventually recalled by the FDA because it was found to destroy the sense of smell. Another example of a product sold as a homeopathic remedy with potentially active components is sold under the name of Quit Nits.

Unlikely Modes of Introduction

Quit Nits bills itself as a homeopathic remedy and contains a bunch of plant extracts from several different species. As a result of intense selection by insect herbivory, all plants have some sort of anti-herbivore defense. Many plants have toxic components as a result of being under selective pressure to develop such components over the course of millions of years. Plants represent a wonderful treasure trove of different types of novel pesticide chemistries. After all, this is how we got pyrethrum. Despite the fact plant extracts are potentially plausible pesticides in and of themselves, we shouldn’t assume that any plant can kill any insect.

The first thing that raises a red flag for me in the Quit Nits formula is the mode of introduction of this pesticide. Some pesticides (see this RNAi post, for example) must be eaten to be toxic, and these are referred to as stomach poisons. Others can be absorbed, and are referred to as contact poisons. While this product does have toxic components, the fact these plants have natural toxins doesn’t automatically mean that they’ll be absorbed by the lice. Because the lice feed by inserting their mouthparts into the host, it seems very unlikely to me that they’d actually be able to pick up any pesticide by eating it unless the pesticide was in the blood of the host in appreciable amounts. Thus, any active ingredient would have to be absorbed through the exoskeleton.

A second thing that I am concerned about is the formulation. Spraying plant extracts on crops and lathering the same stuff into hair and then washing it off are very different modes of introduction. Pesticidal activity may not be preserved by the shampoo, even if the substance is downright toxic to bugs when dissolved in water. This stuff needs to be tested on lice in the formulation offered for sale before it can be said to have insecticidal activity. The mode of introduction and dosage play vital roles in the insecticidal activity. It’s possible the active ingredients wouldn’t retain their insecticidal activity in shampoo or that they wouldn’t be in contact with the lice long enough to be toxic. No pesticide kills every insect with equal efficacy in every situation. This is why the ultimate test of any pesticide is to test it on the pest in the situation you’re going to use it in, in the formulation in which it will be used.

Third, the mode of action of the two active ingredients means that they are unlikely to affect lice. Extract of the plant Delphinium and extract of a plant called Sabadilla (Schoenocaulon sp.) are listed as active ingredients at one part per million. There appears to be little work evaluating Delphinium for insecticidal activity, but Sabadilla and Delphinium both contain veratridine which acts as a stomach poison in insects. Because lice feed by inserting their mouthparts into the skin of the host and sucking blood from capillaries under the skin, I have a tough time believing they’d actually pick the insecticide up in appreciable amounts unless the toxins were absorbed directly into the bloodstream. Since the active ingredient is toxic to humans, there would probably be some major issues with the product if it made it’s way into the bloodstream. The mode of action here renders me skeptical that the lice would pick up a toxic dose of the pesticide in the first place.

Pesticides Used in Doses Unlikely to be Effective

The biggest problem with Quit Nits is the concentrations of the active ingredients. It’s the dose that makes the poison and if you look at the label of the product in question, there are two ingredients that are listed as parts per million and one component that’s in there at a 1:100 dilution.

Purified components of Sabadilla have been used as pesticides for high value orchards like oranges and mangoes. The lowest concentration for semi-purified Sabadilla alkaloids is about .1 g/l, or about one part in 10,000 if we’re going by weight. The extract of the plant seeds, of which the alkaloids are only a small part, is about a hundred times lower than this in the quit nits shampoo. The seeds of Schoenocaulon contain 2-4% insecticidal alkaloids by weight, which means the alkaloids from Sabadilla are present at one part in 25,000,000 in the shampoo.

Delphinium contains veratridine in appreciable amounts as well and has a large amount of other toxic alkaloids in addition to veratridine. It’s difficult to know what concentrations the insecticidal alkaloids are present in Delphinium because there are simply many potentially insecticidal alkaloids in these plants. However, we can make some educated guesses because researchers have purified alkaloids from Delphinium. The individual components are present in milligram amounts with all the alkaloids being present at about 6 grams per kilogram of plant tissue. If we assume the insecticidal alkaloids are present at a concentration of five grams per kilogram of plant material to make our math easy, this means that the insecticidal components comprise about one part in two hundred per unit weight. The concentration of plant in the shampoo is about two parts per million, which means the alkaloids are present at one two hundredth (1/200) this concentration. Given generous assumptions of grams per kilogram amounts, the active ingredients would be present part per hundred million concentrations if we assumed all of the alkaloids in the plants had insecticidal activity.

These plants combined are in about one part in 500,000 in the shampoo. This means that the concentrations of the insecticidal alkaloids is about one part in 4-6*10^-8 parts depending on the alkaloid concentrations of the plants used. Because the lowest concentration of this pesticide used in agriculture is one part in ten thousand, this comes out to a ballpark figure of somewhere around 1,000 times lower than the lowest dose used in agriculture. The dose the lice will be exposed to in the shampoo won’t be great, as there will only be a couple grams of the shampoo used on the entire scalp. To give you an idea of what the pesticidal concentrations are in other louse products, pyrethrum is generally in antilouse shampoos at one part per hundred (one percent). Malathion is generally present at one part in two hundred parts, or one-half percent. This means that the crude alkaloids from the plant extracts would be present at one one millionth the concentration of the active ingredients that have known insecticidal activity. The improbable mode of action combined with the low amounts of active ingredients in the plant means that I would assume these ingredients are essentially inert without proof that they kill lice at these concentrations.

These ingredients aren’t the main stuff in the Quit Nits treatment, though. The plant extracts listed above are in parts per million, but Quassia amara extract is present at a 1:100 dilution…about 10,000 times higher than Sabadilla and Delphinium. Furthermore, it’s in the ballpark of the Pyrethrum extract. So what about Quassia?

Ingredients with No Proof of Efficacy

Quassia amara is an interesting plant because it contains one of the most bitter substances in the world. These substances are called quassinoids, and have been examined for insecticidal and antifeedant activities against a wide range of pests. In many cases extracts and purified components from Quassia have been shown to have insecticidal and antifeedant activity, but it wasn’t always clear to me whether the antifeedant activity was so strong that it led to mortality. In other words, it was difficult to tell if the substance made the food taste so bad to the bug that they’d rather starve than eat. Either way, we’re interested in it’s activity against lice in particular.

There have only been two papers which have examined Quassia extracts against lice. One appears in a Dutch journal in 1978 and another in a Spanish journal in 1991. Since these papers are in rather obscure low impact journals, I was not able to access them directly through my library and instead had to rely on their descriptions in review articles. The review articles weren’t exactly favorable towards Quassia as a louse treatment. The Dutch paper claimed high efficacy, but the experiment was apparently ran as an un-controlled, un-randomized, un-blinded experiment and counts as nothing as far as proof goes. The Spanish paper claimed high efficacy, but the review states that the Spanish paper concluded that Quassia would only have repellent effects but didn’t mention whether the extract had a clinically relevant success rate. There have been no well performed tests of Quassia as a head louse treatment, and the few tests that have been performed have yielded conflicting results. There’s simply no proof that the “active” ingredients in Quit Nits work.

Quit Nits also sells a repellent spray that has undergone independent testing. One paper compared it’s repellent activity using a filter paper repellency test, incubating the lice with filter paper treated with repellent on one side and water on the other. The objective was to measure what percentage of the lice moved away from the treatment. At the earliest time point measured (two hours), Quit Nits performed about as well as water. At later time points, there was some non-significant repellent activity. Another paper looked at the repellency of Quit Nits under real world (or close to real world) conditions and looked at whether lice would transfer to hair under approximated hair-hair contact conditions, if the lice would move on the hair treated with Quit Nits repellent spray, or if the lice would feed on the forearm of one of the authors who performed the study. For the hair tests, KY jelly was used to simulate greasy hair and Quit Nits fared no better than this. For the skin tests, bare skin not receiving any treatment was used and the lice exposed to Quit Nits treated skin fed just as well as those on bare skin. Quit Nits repellent spray simply doesn’t repel lice, as far as the current experiments show.

Some Products Have no Plausible Mode of Action

The first example of a product with no mode of action is a product called X-pel. In fairness, I’ve only seen this at a few small grocery stores in Iowa, but the fact something like this is sold at all really worries me. The product is a shampoo which consists of ground up honeybees, phenol, and an uncommon species of Rhododendron at femptogram concentrations (15X), or one part in one quadrillion. On their website, they give a couple of vague descriptions of various tests. The tests contain very little methodology and give no statistical information about their results. They claim a few ‘major universities’ were involved in the testing of the product, but neglect to give any sort of contact information or any publications generated as I described in the Quit Nits treatment. They have a video on their website, below, where they show an in-vitro test that consists of them drowning a louse in the shampoo. Because lice can be inactive for a long time following immersion in water, there is no evidence given that the lice in this video were actually killed. They also show an uncontrolled, un-randomized, un-blinded test of a single subject without any apparent followup as proof that their product works. Phenol here is the most likely ingredient for insecticidal activity, as the concentration of the Rhododendron is far too low to do anything at all. Quite frankly, I’m not sure how honeybees are supposed to kill head lice unless we assume the venom glands were somehow involved, but I find this unlikely. The ingredients used in this product are only used in vanishingly small concentrations, and there’s really no way to justify using ground up honeybees to treat head lice.

Another product marketed under the name Licefreee! is little more than a concentrated sodium chloride solution. While it’s plausible the product could suffocate the lice, the data for suffocants in head lice treatment isn’t exactly convincing. Because lice are coated in a waxy layer that prevents dehydration, I find the claim that a 10% salt solution will kill lice suspect. As far as I can tell, there’s no evidence of this product works either because I’ve only seen this mentioned in passing under ‘folk treatment’ sections of review articles. I’ve seen no primary literature articles dealing with concentrated salt solutions as lice-killers.

Conclusion

Many of these companies use a variety of tactics to sell their products that have nothing to do with efficacy. Many use highly questionable advertising methods, like capitalizing on patient fears of synthetic medicines and pretending to identify with their customers to sell them products of uncertain effectiveness. Some of these products even go as far as to claim to be pesticide free while still claiming to kill lice. Many of these products claim to have been invented by parents, but as a parent myself I cannot imagine marketing a questionable head louse treatment and this is a big part of why I’ve written this post.

The science-based products currently on the market that I mentioned in Part 1 have been thoroughly studied and activity proven with the obvious exception for strains of lice that are resistant to some treatments. Even though there is a risk to any product you’re bound to use, the risks of these products have been investigated and have been taken into consideration when formulating treatment regimens. I can certainly understand anxiety about exposing kids to pesticides, but when looking at alternative treatments one needs to ask whether they’re safe and effective. Extraordinary claims require extraordinary evidence. If a product you spend money on makes any sort of claim, you should consider the claim extraordinary and ask for evidence behind the claim.

Burgess, I. (2009). Current treatments for pediculosis capitis Current Opinion in Infectious Diseases, 22 (2), 131-136 DOI: 10.1097/QCO.0b013e328322a019

Leone, P. (2007). Scabies and Pediculosis Pubis: An Update of Treatment Regimens and General Review Clinical Infectious Diseases, 44 (Supplement 3) DOI: 10.1086/511428

Canyon, D., & Speare, R. (2007). Do head lice spread in swimming pools? International Journal of Dermatology, 46 (11), 1211-1213 DOI: 10.1111/j.1365-4632.2007.03011.x

Heukelbach, J., Canyon, D., Olivera, F., Muller, R., & Speare, R. (2008). Efficacy of over-the-counter botanical pediculicides against the head louse based on a stringent standard for mortality assessment. Medical and Veterinary Entomology, 22 (3), 264-272 DOI: 10.1111/j.1365-2915.2008.00738.x

Lebwohl, M., Clark, L., & Levitt, J. (2007). Therapy for Head Lice Based on Life Cycle, Resistance, and Safety Considerations PEDIATRICS, 119 (5), 965-974 DOI: 10.1542/peds.2006-3087

Leone, P. (2007). Scabies and Pediculosis Pubis: An Update of Treatment Regimens and General Review Clinical Infectious Diseases, 44 (Supplement 3) DOI: 10.1086/511428

Greive KA, & Barnes TM (2011). In vitro comparison of four treatments which discourage infestation by head lice. Parasitology research PMID: 22030833

Canyon, D., & Speare, R. (2007). A comparison of botanical and synthetic substances commonly used to prevent head lice (Pediculus humanus var. capitis) infestation International Journal of Dermatology, 46 (4), 422-426 DOI: 10.1111/j.1365-4632.2007.03132.x

Rossini, C., Castillo, L., & González, A. (2007). Plant extracts and their components as potential control agents against human head lice Phytochemistry Reviews, 7 (1), 51-63 DOI: 10.1007/s11101-006-9026-0

When lice strike

"We all have lice" by Antonia Hayes via Flickr.

Head lice are something almost everyone has to deal with, and head lice treatments are something someone buys every once and awhile. These are big business in and of themselves. Because they’re big business, many firms have started popping up offering louse treatments with varying degrees of effectiveness.

A while back, I went through my own head louse ordeal with my daughter. Treatment was complicated by a family member who didn’t realize they were infested. We originally thought the lice were resistant to treatment, so I had to get a second treatment. Since then, I’ve become curious about what is for sale in stores for Over The Counter (OTC) head louse treatments and generally take a look at whatever treatments I can when I get the chance. Over the years, I’ve become surprised at how many dubious treatments are offered for sale (although perhaps I shouldn’t be) and how many of these use questionable advertising techniques mostly built upon fear rather than science. Many treatments offered for sale over the counter are either unproven, or have been proven not to work.

First, let’s discuss some headlouse biology. Then, let’s discuss how the treatments currently FDA approved work. In Do OTC Head Louse Treatments Work? Part 2: Questionable treatments, I’ll discuss the dubious treatments.

Disclaimer: I have worked in entry level positions at companies which sell these products. This, has not influenced my position. I should also mention that I’m not a medical professional and will not be discussing side-effects or risk-benefit analysis. I am an entomology graduate student who studies insect physiology and although I’ll mention the side effects of these products in passing I will not discuss them in detail. This post will discuss the science behind head louse therapies, how they work, and why some aren’t thought to work. I’ll also discuss the evidence that would be required to show that they work. This post deals with insect physiology and should not be mistaken for medical advice. Always consult a doctor if you think you may have health issues because blogs are notoriously bad places for medical advice*.

Lice biology

Male head louse, via Wikipedia.

Head lice are small hemimetabolous insects - basically booklice that have evolved to be parasitic. They start life as an egg or nit attached to hair, then go through a series of nymphal stages before maturing to an adult.  The adults and nymphs both feed, injecting saliva that causes small localized immune reactions which is why you itch. They’re very well adapted to hair and grasp it with clawlike legs. They can only grasp onto some kinds of hair which is why you don’t get pubic lice and head lice occurring on the same body parts. They spend all their lives on hair, even staying on the hair while they feed. Actually, off hair (or similar

fibrous material) human lice are nearly useless and have trouble getting around. They must feed every few hours, otherwise they quickly starve to death or die of dehydration off the host. Lice are transmitted mainly through direct hair to hair contact, with objects like combs and hats playing a potential minor role in transmission.

The nervous system of head lice is surprisingly similar to ours, with differences that are minor as far as we’re concerned. The nervous system is composed of several thousand cooperating neurons and is involved with every aspect of a louse’s life, movement, feeding and reproduction and many products target this system. When a nerve fires, sodium and potassium channels open which causes potassium to flow out of the cell and sodium to flow back in. Often, this process is touched off by the binding of another messenger such as acetylcholine which causes these channels to open. The charge changes from a negative charge to a positive charge, known as depolarization. The positive charge is very localized and moves down the nerve cell as a result of the sodium/potassium channels opening and closing in a very tightly regulated sequence that is essential to function. Other channels can prevent the nerves from firing such as GABA which binds to a receptor and causes the opening of chloride channels which prevent the nerve cell from firing by causing it to attain a very negative electrical charge. The pesticides used in headlouse treatments target all these systems, all of which can lead to a dysregulation of the nervous system and a collapse of nervous system function.

How do louse treatments work?

The safest products are sold over the counter and are used as commonly available first line treatments. Pyrethroids are generally considered to be the least toxic product, and are the most widely available. Lindane is a bit more toxic than either pyrethrum or malathion but most adverse reactions are still due to misuse. All three of these pesticides target different systems in the louse. Resistance has been documented in lindane and pyrethroid insecticides, but not malathion in the US. Pyrethroid based insecticides are used as a first line of attack with lindane and malathion being listed as a second and third route of attack respectively due to resistance of lindane and lack of resistance to malathion.

Pyrethroids are compounds similar to pyrethrum which is derived from the chrysanthemum plant.

Chemical structure of pyrethrum, the most commonly used pyrethroid derived from chrysanthemum plants.

Pyrethrum is a botanical product, while pyrethrins are artificial versions of this compound which have varying degrees of effectiveness on insects. In general, the artificial versions are more toxic to insects and less toxic to mammals based on LD50 values. Pyrethrum is the compound used in head lice treatments. Pyrethrum acts by propping open the sodium channels, allowing a sodium influx into the nerve cells. The nerve cells then become depolarized in unison, which results in the discoordination of the nervous system. The nervous system eventually shuts down, followed by the louse’s vital systems.

Resistance to this pesticide exists in two forms, knockdown resistance and cytochrome p450 degredation. Cytochrome p450s are enzymes which detoxify various compounds and catalyze a wide variety of breakdown reactions. These enzymes are present in humans as well, and also serve to detoxify the small amount of pyrethroids which are absorbed during treatment. In many resistant strains, the cytochrome p450s are upregulated, or overproduced. The overproduction of specific cytochrome p450 enzymes results in the increased breakdown of the pesticide. To combat this, a common additive called piperonyl butoxide is added as a cytp450 inhibitor. Knockdown resistance occurswith a change in the sodium channel that decreases the sensitivity to the pyrethrum, which is more difficult to combat. This is a wonderful example of evolution in action because it’s something which has evolved in direct response to usage of pyrethroids in headlouse treatment.

Chemical structure of lindane, courtesy of wikipedia commons. The molecule consists of a 6 membered ring decorated with chlorine atoms.

Lindane acts by binding to the GABA receptor and permanently inhibiting it. This results in the influx of chloride ions. With the GABA receptor stuck to the ‘on’ position, the nerves are unable to transmit any signals. This  mechanism is semi-complex mechanism but briefly the chloride ions reduce the charge in the cells, so much so that when the potassium flows out the nerve cell is still negatively charged and never fires. The nerves are unable to fire, and are in effect turned off. With the nervous system turned off, the louse becomes permanently paralyzed and dies as a result of not being able to feed. Resistance has been documented to lindane, but I’m not sure what the mechanism is. This product is one of the more toxic substances on the market for head louse treatment, and generally isn’t prescribed for children.

A third mechanism revolves around acetylcholinesterase, an enzyme not directly involved in the transmission of nerve signals. Acetylcholine Is used as a neurotransmitter, being sent between nerve cells to cause them to fire. When an action potential reaches the end of a nerve cell, the nerve cell releases acetylcholine which results in the nerve cell firing. Acetylcholine is degraded by an enzyme called acetylcholinesterase. Without acetylcholinesterase, the nerve remains permanently depolarized and the ion gradients collapse.

Chemical structure of malathion. The active portion of the molecule is the phosphate-like group on the far left which modifies the place in the enzyme responsible for catalyzing the reaction which shuts off nerve cells temporarily.

Even though acetylcholinesterase isn’t directly involved in the transmission of the signal, the enzyme is still important in ensuring the proper working of the nervous system. Organophosphates such as malathion knock the enzyme out, killing the insects. Malathion is an interesting molecule in and of itself. Toxicity requires degredation to another product, which happens better in insects than in mammals. Malathion is sold in a solution that contains isopropyl alcohol and tea tree oil which both synergize the effects of malathion by mechanisms which aren’t well understood. They work either by denaturing protiens in the lice as in isopropyl alcohol or by acting as a supplementary antiacetylcholinesterase as in tea tree oil.

Another method which has been used to cure head lice is what I refer to as the ‘nuclear option’ (or, to use a rare euphemism… landscaping for crab lice), and that’s simply removing the child’s hair. Without hair, the lice cannot hold onto their host and simply fall off. While side effects of the above treatments are relatively rare when the pesticide is used properly, this is by far the safest and most effective method of louse control. Unfortunately, this may not be acceptable for many people. When my daughter had head lice, she did not want to have her head shaved and this is the case for many little girls.

Are there treatment risks?

Although I’m keeping this post focused mainly on the mechanisms of these pesticides, remember that it’s the dose which makes the poison and any substance can be toxic when given in a high enough dose. Exposing yourself to a small amount of pesticide is OK so long as you allow it to break down and leave your system. Repeated exposure over a very long period isn’t a good thing because these products do inhibit neuronal function, leaving the door open for possible neurodevelopmental effects. Because of this, these products are not reccomended for long term use and treatment regimens are designed to last as short as possible. Head lice generally take about ten days to two weeks to mature into adults which is why retreatment is recommended within a week. Many products (except lindane) do not kill eggs, so any leftover eggs will hatch and eventually grow to reproductive adults if a followup treatment isn’t performed. The active ingredients have proven useful in a variety of contexts, including agriculture, but in this case the trick is to treat the patient with a dose high enough to kill most of the lice but low enough to not cause symptoms in the human.

Classifying these chemicals as pesticides sounds scary to many, and many companies have figured out how to take advantage of the unease many parents feel about treating their kids to sell products which have no evidence of efficacy. Next week, I’m going to expose many of these products and further explain the science behind clinical trials for these products.

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* One of my favorite fellow entomobloggers, Bug Girl, even has a page titled ‘I will not diagnose you’ and this applies to me as well. Do not contact me asking for any diagnosis because any E-mails of this character will be sent directly to my junk E-mail folder as it is outside of my duties as an entomologist to perform this sort of work and would be completely irresponsible.

As part of an Undergraduate Research Scholars program, I gathered research for Professor Jordan Rosenblum. He is interested in how the slow food and local food movements, as well as the biotechnology revolution relate to Kosher Laws. He is working on writing a book about ancient Jewish dietary practices, and the various arguments for or against it. He is a well-versed scholar on the subject of biblical and rabbinical literature. My role was to help him find modern arguments concerning Jewish dietary laws and culture, and how they are interpreted in the 21st century. I have read and analyzed over a dozen books, journal articles and web links to focus on two modern debates concerning Jewish dietary laws. I wanted to find out how Jewish beliefs influence their views on genetic engineering, and whether there was evidence for the modern argument that certain Kosher laws were based on health considerations.

The first topic that I researched was Jewish views on genetic engineering. I was surprised by what I found because I had assumptions going into it. I thought liberal Jews would be open to genetic engineering because of an “open mind” to modern biotechnology. On the other hand, I assumed conservative Jews would be against genetic engineering because I thought they would view it as a potential threat to their views on social and religious order. I was completely proven wrong.

Liberal Jews tend to be more cautious and reserved about food biotechnology. They employ a different set of ethics compared to their Conservative counterparts, like the use of secular, modern liberal ideology. They feel that not enough is known about its potential drawbacks and benefits to completely integrate its use into modern society. Some also feel, in a very general way, that an organism’s “soul” has been tampered with by manipulating its genome. There is one exception to these feelings of doubt and malaise concerning genetic engineering. This is the Jewish duty of pikuach nefesh – the solemn duty to save a human soul. If genetically engineered food can save lives, then it must be supported.

On the whole, conservative Jews are strongly in favor of biotechnology. There are a couple of reasons for this. First, there is no fear over “playing God.” They regard themselves as “co-creators” with God in improving the natural world. Psalm 115:6 reads ‘the heavens are the heavens of God’ yet ‘the earth he has given to the sons of man.’ Second, the Torah and the Talmud has nothing in it that directly or indirectly forbids genetic engineering. So conservative Jews who strictly follow the holy texts openly embrace genetic engineering and use it to their advantage. Interestingly enough, we also see Amish communities as deeply religious and resistant to modern technologies, yet there are Amish farmers who grow genetically engineered crops because they believe it supports their way of life and it is not directly forbidden in their Scriptures.

Frank and Jordan. Shalom! שָׁלוֹם

The second topic is about modern scientific claims surrounding the kosher laws. Our current understanding of food safety has imbued ancient religious discourses about food and dietary practices. For instance, there are many scholars who argue that ancient injunctions against consuming pork products were a way of avoiding being contaminated with trichinosis. The kosher laws were thought to have been enacted for religious purposes, intent upon purifying one’s soul of “unclean” food sources. The truth is, no scholar is certain as to the origin of the kosher laws. The modern analysis of kosher laws as health prescription is a wholly modern invention, with little Biblical or Talmudic justification. The application of modern scientific ideas to ancient food rules and practices is a way of rationalizing non-rational rituals.

There are various reasons given for the nature of the kosher laws, some are intellectual and others are hukum. Intellectual arguments in favor of kosher laws are laid out by rabbis in the Talmud. Hukum is a non-rational justification for following a rule. Basically, as a Jew, you are expected to follow the kosher laws because God said so. It is like being told to do something that seems irrational by a parent without a good explanation. The Kosher laws are also seen as a form of cohesion within the Jewish community. During ancient times and even today, they were a way of stating one’s unique Jewish heritage. Kosher food rules made it difficult to mingle with Gentiles or non-practicing Jews who did not keep kosher. This definitely solidified social bonds between Jews through food and ceremony. The fact that certain dietary laws may be healthy or sanitary is superfluous to its initial meaning.

My research on the kosher laws will be relevant to me as a trained sociologist and Registered Dietitian. This will be very useful for me as an aspiring dietitian to know the rationale behind religious food rituals. I would know what questions to ask and boundaries to respect concerning these food practices. Given the growing number of practicing Muslims and Jews in the United States alone makes this topic worth researching. Even after having completed my work with the Undergraduate Research Scholars, I plan to keep researching this topic. Food and sociology are two very relevant and important topics for me as an aspiring dietitian!

References:

1. Green, Ronald M. “The Jewish Perspective on GenEthics.” Ed. Pfleiderer, G., Brahier, G., Lindpainter, K. Genethics and Religion. Basel: Karger, 2010. 118-127.
   Hart, Mitchell B. The Healthy Jew. New York, Cambridge, 2007.
   Regenstein, Joe M. and Carrie E. “An Introduction to Kosher and Halal Food Laws.” Ed. Patricia A. Curtis.  Guide to Food Laws and Regulations Iowa: Blackwell, 2005. 163-201.
2. Reichman, Edward. “Why Is This Gene Different from All Other Genes? The Jewish Approach to Biotechnology.” Ed. Michael C. Brannigan. Cross-Cultural Biotechnology. Oxford: Rowman, 2004. 93-102.
3. Schlich, Thomas. “The Word of God and the Word of Science: Nutrition Science and the Jewish Dietary Laws in Germany, 1820-1920.” Ed. Harmke Kaminga and Andrew Cunningham. The Science and Culture of Nutrition, 1840-1940. Amsterdam: Atlanta, 1995. 97-120.
4. Sherwin, Byron L. Golems Among Us: How a Jewish Legend Can Help Us Navigate The Biotech Century. Chicago: Dee, 2004.
5. Tirosh-Samuelson, Hava. “Jewish Philosophy, Human Dignity, and  the New Genetics.” Ed. Sean D. Sutton. Biotechnology: Our Future as Human Beings and Citizens. New York: Albany, 2009. 81-112.
6. Zoloth, Laurie. “When You Plow the Field, Your Torah Is with You: Genetic Modification and GM Foods in the Jewish Tradition(s).” Ed. Conrad G. Brunk and Harold Coward. Acceptable Genes? Religious Traditions and Genetically Modified Foods. New York: Albany, 2009. 81-110.

Facepalm by Alex E. Proimos via Flickr.

On Twitter yesterday, @seekblunttruth shared a link with @franknfoode that I thought deserved greater scrutiny. The link is to an ISIS post* titled Bt Crops Failures & Hazards.

Others may spend some time criticizing ISIS itself, and that criticism may be worthy, but here I’d like to focus on the post. I’ll let you check out the post content  yourself, but I want to focus on the works cited list.

There are 29 citations. We find 11 sources that are by ISIS authors. It’s ok to refer to your previous work, we do it on Biofortified all the time, but having almost 40% of the citations be self-citations feels like an attempt to pad the citations list. Many of the rest of the sources are either by biased organizations or have been previously debunked either in the literature or in the blogosphere.

The following 6 sources are not peer-reviewed. Really, only one of these (the Bloomberg article) is a useful source (assuming that you feel that non-peer reviewed media is useful).

1. EPA memorandum saying they plan to review insect resistance – This is not really useful, maybe ISIS meant to cite something else?
2. Article in Bloomberg – Reasonably balanced and useful article about development of insect resistance to Bt.
3. ISAAA brief on global status of biotech crops – Source used for number of hectares planted in biotech crops. Reasonably useful information source for this particular piece of info, but take with a grain of salt because this is a self-described pro-biotech organization.
4. Report by Navdanya International – I’ll let you decide the seriousness of the report from the cover (hint – there’s no biotech traits in wheat).
5. “Compendium of Cotton Mealybugs” by India’s Central Institute for Cotton Research – I don’t know enough about this organization to judge (and I don’t have time to read the whole report at the moment).
6. Pesticide Action Network report – By a self-described anti-pesticide and also anti-biotech organization.

The following 12 sources are peer-reviewed (41%). Of these, 5 have been thoroughly thrashed elsewhere, and citing them without critique is dishonest, in my humble opinion. One (#4) reminds us that biotech isn’t a silver bullet. The rest don’t really say “Bt good” or “Bt bad”, they’re details to be examined.

1. Inter-laboratory comparison of Cry1Ab toxin quantification in MON 810 maize by enzyme-immunoassay 2011 in Food and Agricultural Immunity. Cited to show variability in Bt concentrations.
2. Temporal and intra-plant variability of Cry1Ac expression in Bt-cotton and its influence on the survival of the cotton bollworm 2005 in Current Science. Same as above, although examines expression differences by genotype. Genotypic differences in gene expression are not unique to biotech traits, and are expected by breeders, so this isn’t unexpected.
3. Seasonal expression profiles of insecticidal protein and control efficacy against Helicoverpa armigera for Bt cotton in the Yangtze River valley of China 2005 in Journal of Economic Entomology. Again, differences in expression, this time in different plant parts. Again, not an unexpected result.
4. Mirid bug outbreaks in multiple crops correlated with wide-scale adoption of Bt cotton in China 2010 in Science. This paper showed that when you stop spraying pesticides, pests come back. Unfortunate, but not an unexpected result. This paper is a great example of how biotech pest resistance needs to be paired with integrated pest management. There are no silver bullets.
5. Genetically modified crops safety assessments: present limits and possible improvements 2011 in Environmental Sciences Europe. This paper, by Séralini and Vendômois (and others) is based on a flawed paper that has been discussed elsewhere, including by the European Food Safety Authority.
6. Cry1Ac pro-toxin from Bacillus thuringiensis sp. kurstaki HD73 binds to surface proteins in the mouse small intestine 2010 in Biochemical Biophysical Research Communications. I have not seen previous analysis of this paper. Perhaps a Biofortified reader would like to discuss it further. One question I have is whether other proteins from plants and bacteria have similar reactions with proteins on the intestine. Another question is whether the proteins binding has any actual physiological effect.
7. Maternal and fetal exposure to pesticides associated to genetically modified foods in Eastern Townships of Quebec, Canada 2011 in Reproductive Toxicolology. This paper has been discussed elsewhere, including by Marcel Kuntz and Food Standards Australia New Zealand, then subsequently on Biofortified.
8. Reduced fitness of Daphnia magna fed a Bt-transgenic maize variety 2008 in Archives of Environmental Contamination and Toxicology. I have not seen previous analysis of this paper. Any Biofortified readers familiar with it?
9. Transgenic pollen harms monarch larvae 1999 in Nature. This famous paper by Losey (and others) has been extensively discussed elsewhere, including by Iowa State entomologist Hellmich.
10. Decline of monarch butterflies overwintering in Mexico: is the migratory phenomenon at risk? 2011 in Insect Conservation and Diversity. The hypothesis of this paper is pretty silly. It proposes that an increase in glyphosate resistant crops resulted in more milkweed being sprayed with glyphosate so less food for monarchs. Never mind increased deforestation and conversion of natural lands to cropland (resulting in less milkweed) in the same time frame. Never mind the fact that if glyphosate wasn’t being used, some other herbicide (that also kills milkweed) would be used. This is not an argument against glyphosate resistance, or against Bt, or against biotech traits. It may be an argument for careful land use, set-asides of land for natural habitat, and integrated pest management – all of which can just as easily be done with biotechnology as without.
11. Transgenic DNA introgressed into traditional maize landraces in Oaxaca, Mexico 2001 in Nature. As Mercer and Wainright point out, Quist’s results haven’t been replicated. I have written a post about gene flow that may be relevant to understanding the Quist paper.
12. Toxins in transgenic crop byproducts may affect headwater stream ecosystems 2007 in Proceedings of the National Academy of Sciences. This paper by Rosi-Marshall (and others) has been critiqued elsewhere (see the responses at the bottom of the article). I wrote about this paper back in 2008 (and in 2007).

The author of the ISIS post failed to do a proper literature search, so didn’t find any of the sources that showed anything but their preconceived notions of Bt. This is definitely worthy of a facepalm, if not a headdesk. If anyone has relevant points to add to this analysis, post a comment and I’ll update the post.

* They call it a report but if that is a report than most if not all of the posts on Biofortified are also reports.

However, the internet gives me some hope. Online science based communities such as this one, scienceblogs, freethought blogs and others are extremely popular and don’t show any sign of declining. Another site’s been a favorite of mine, a site on the immensely popular internet website Memebase called Dropping the Science. It’s chock-full of nerdy inside jokes and descriptions like the one below of how science *really* works. I even like the name, Dropping the Science. It’s defiant and confident… something you’d say when you’re about to unapologetically present a winning argument. Go check it out.

see more Dropping The Science

Tip ‘o the hat to ERV

The topic of the debate was “can organic agriculture solve food scarcity problems?”. The subjects were randomly chosen and don’t necessarily support the views of those engaged in the debate, so I will not speak for anybody but myself. I was on the con team, and we were charged with arguing that organic agriculture is an inferior method of food production. We were up against a very good team and all day folks were coming up to us and telling us how much they enjoyed our debate. Ultimately, we won the best overall debate team and took home an engraved trophy and left the meeting $125 richer after splitting a $500 prize between the four of us.

My role on the team was to look into the pesticides used in organic agriculture and their treatment regimes. To my surprise, I found that organic operations actually increase the amount of inputs put into the environment by requiring higher concentrations and more frequent applications of pesticides. The insecticides used in organic ag are often less effective, less selective, and can have greater non-target effects than synthetic insecticides. Some organic pesticides, like the biopesticide Beauveria bassiana, are assumed to have a very low environmental impact quotient (EIQ), but haven’t been tested for potential ecological side effects. My position (and position on the debate team) is that GMOs like Bt corn are better for the environment because they decrease the amount of pesticides that we must put on crops and that organic pesticides are worse for the environment because they must be constantly reapplied in very high concentrations.

This, however, wasn’t the idea that earned me my stripes during the debate. During the Q&A session, somebody asked us to clarify why we thought organic ag was able to innovate to a lesser extent than sustainable or conventional agriculture. My response was that we can modify pesticides to become less toxic, more easily degradeable and more difficult for insects to detoxify by producing insecticides synthetically and making it more or less difficult for the insecticides to degrade. While organic ag could certainly benefit from new chemistries, they reject them as soon as modifications such as these take place because the new pesticide is synthetic. In short, organic producers are unable to take advantage of novel chemistries. I used the example of adding carbon atoms or benzene rings in a specific place to keep beta-lactam antibiotics medically relevant during the debate, but there was a much better example I could have used but unfortunately neglected to discuss. But, hey… that’s what the blogosphere’s for isn’t it?

Very recently, the lab of Reddy Palli has figured out a way to genetically modify an organism to become a spray-on pesticide. To fully understand and appreciate what’s going on, there are a lot of things I need to explain. Fortunately, I’ve got about 12 hours of travel time ahead of me. Awesome, right?

A Colorado potato beetle. USDA photograph by Scott Bauer via Wikipedia.

First, let’s talk about the animal discussed in the paper. The Colorado Potato Beetle is what’s referred to as a ‘superpest’. It’s highly prolific, and essentially bulletproof. This insect specializes on solanaceous crops like potatoes and tomatoes, the crops most closely related to nightshade plants. These plants are famous for defending themselves by producing deadly secondary metabolites. By specializing on these plants, the Colorado Potato Beetle has evolved with some incredible detoxification mechanisms which shields it from our pesticides. As an unfortunate (for us) side effect, it manages to become resistant to every pesticide we throw at it very quickly. It can defoliate entire potato fields, and we can’t stop it very easily. We’re desperate for new chemistry to counteract this pest.

Next, let’s talk about a very basic part of insect physiology. Insects, like humans, are made from proteins encoded by DNA. When a protein needs to be made, an RNA polymerase translates DNA to RNA, and a ribosome transcribes the RNA molecule to protein. This is pretty constant throughout the kingdom of life plants, humans and insects all use a similar system and there is RNA in everything you consume. It can get a bit more complicated than this (see below), but there’s one thing I need to point out – mRNA is always single stranded in eukaryotic organisms. Some viruses use a double-stranded RNA (dsRNA) molecule. This is kind of like DNA, but it’s made out of slightly different stuff. Insect immune systems are good at picking up stuff that looks like it shouldn’t be there and dsRNA sticks out like a sore thumb.

The beetle has an immune system just like us. Ever get sick? Did you get better? That’s your immune system working. Beetles are exposed to pathogens just like we are every day. A good example of this is a cypovirus, which is kind of like an insect rotavirus. When the beetle gets a cypovirus, a series of enzymes pick the dsRNA it makes from the crowd of mRNA and selectively degrades it by using that dsRNA as a template to scan all the RNA in the insect and then degrade it. This is called RNA interference, or RNAi.

How can we use this to our advantage?

The experimental setup Palli's team used. Everything's labeled pretty well, and very self explanatory. The larvae eat the leaf, eat the dsRNA which causes their own body to shut down vital systems.

Unlike our antibody production system the RNAi system is kind of stupid and won’t distinguish self from nonself mRNA. The reason for this is that RNAi is also used to make sure the beetle doesn’t produce too much of a particular protein. If it wants to shut down certain specific proteins, it can make small interfering RNA (siRNA) and allow the RNAi system to destroy the RNA. It’s physiologically important for the beetle to be able to do this, but there’s no doublecheck system. The beetle can’t tell if it produced the RNA or if the dsRNA came from another source.

Reddy Palli’s lab did something ingenious with bacteria. They inserted several sequences into a bacterium that made double stranded RNA to a variety of important proteins. These included the muscle protein actin, sec23 which is a protein involved in the transport of newly produced proteins, and a couple ATPases which are responsible for producing the ATP energy currency of the cell. After killing the bacteria but preserving the RNA, they sprayed the bacteria onto potato plants which contained Colorado Potato Beetles. They also did this with just straight dsRNA. The beetles eat the plants, they eat the bacteria and a whole load of dsRNA.

What happened?

Here’s the cool part: it actually worked. To me this is mind blowing because RNA is incredibly unstable, thanks to an oxygen attached in a rather unfortunate place which allows it to break the backbone of the molecule. There are also nucleases which degrade RNA so the bacteria had to be modified so they wouldn’t produce these enzymes. Keeping the molecule double stranded helps by making it more difficult for either of these reactions to occur, so dsRNA is more stable than regular mRNA. But it’s still an incredible thing to me that this even worked.

If you want to show this works, you need to first show that the mRNA levels drop in response to the treatment. Turns out that they do for all the genes involved. Actin is the muscle protein, the ATPases produce energy and sec23 and CopB are involved in protein transport. The control was something which has relatively constant transcription that wasn't target by RNAi.

The beetles ate the killed bacteria, digested the outer wall and released the dsRNA. The cells take up the RNA, and the RNAi process occurs just as described above. The RNA coding for actin gets degraded, so that the beetles don’t make new actin or repair their existing actin polymers. In short, their muscles fall apart, their cells don’t divide. Even their sperm wouldn’t move…all these processes are dependent on actin.  As a direct result, the beetles stop eating, stop moving and die. Similar things happened with the other genes. When sec23 and COPB are silenced, their proteins don’t properly get transported and modified, resulting in a buildup of nonfunctional machinery. When the ATPases are silenced, ATP is no longer produced and the beetle can’t produce enough energy to maintain vital life functions. From this research, it would appear there are a great diversity of genes we could target which opens up a lot more avenues of attack when making pesticides.

Now, there are some neat implications to this research. This was a ‘proof of concept’ paper, which means that this works on a particular organism with a particular set of proteins under ideal lab conditions but doesn’t directly deal with the economics, field conditions or range of pests that could be targeted. It’s exciting and this technique has a lot of potential, but a lot more research needs to be done before we could use this in the field. That doesn’t mean there aren’t good reasons to be excited to see this further developed, though. Even though this may be a somewhat limited technique (see below), I could still see this being used to create very highly specific insecticides that quickly degrade in the environment.

In general, this would be the ideal pesticide for an environmentalist because RNA is all around you, as are nucleases. The Colorado Potato Beetle produces RNA and siRNA. We produce RNA and siRNA. Bacteria produce RNA, but I’m not sure if they produce siRNA. This is essentially all-natural, with the only difference being that we’re telling the beetle to degrade proteins at the wrong time and at a much higher rate than it normally would. RNA degrades by itself pretty easily and RNA degrading nucleases can be found almost anywhere you look. The bacteria can degrade in the environment and have no components which aren’t found in soil bacteria except foreign RNA sequences. There’s no reason to think there would be any issues with the bacteria staying around in the soil for an extended period such as we’d see with DDT.

Despite my enthusiasm for this clever technique, I also don’t want to give anybody the impression this is a ‘magic bullet’ for pest control. Some critters take up RNA better than others. RNAi was discovered in nematodes using this technique, so we could potentially use this on nematodes as well as beetles. Honeybees are able to ingest RNA and acheive silencing, so we might even be able to target sawflies. We could not use this on moth pests because lepidopterans are notoriously difficult to perform RNAi in, which has led to caterpillars being more of a biochemistry rather than genetic model organism. Since a lot of pests like aphids pierce the plant and suck the juices out, this would be useless against them because they’re not actually ingesting anything on the outside of the plant. There also may be better ways to introduce the dsRNA and for all we know using viral machinery may be a better way to introduce and replicate the dsRNA. There’s a lot more basic research which needs to be done on this before I’d be willing to say ‘we could use this’. With this paper, there are good reasons to think this would work.

The results from the experiment. This is a survival curve, with the percentage of the larvae surviving plotted on the Y axis and the time of survival plotted on the X axis. As you can see, the survival curves dropped far below the controls. A is the bacteria encapsulated dsRNA, while B is the dsRNA without bacteria. Both work, despite the limitations I explained earlier.

In addition to needing to pay attention to the pests this could work on, we need to pay attention to the kinds of beneficial insects and other animals this would potentially harm just as we would any other pesticide. Actin tends to be pretty similar in all organisms. The other genes are really important, and are probably very conserved in genetic sequence. I would think this could have some potential nontarget effects on other beetles, flies or wasps that I’d be pretty concerned about the potential for syrphid flies to eat aphids coated in dsRNA filled bacteria, for example. I think it’s unlikely that RNAi would be able to be done for humans in this manner because we’re coated in nucleases and to perform RNAi we must actually envelope dsRNA viral components in artificial cell walls to prevent degredation in the bloodstream if we inject RNA into the body as we would with medication used to treat ebola. I’ll go into more detail about this in the next paragraph but even if we found that we could potentially perform RNAi in humans by doing this I wouldn’t expect any big nontarget effects because we could choose the systems interfered with in the insects and avoid using systems humans and insects have in common. We aren’t able to do this with conventional insecticides as well as we could with dsRNA because they often target systems humans and insects have in common like sodium channels and acetylcholinesterase. We do OK by making pesticides less toxic to humans (synthetic pyrethroids have LD50s 10x less than natural pyrethrum for a quick example), but we could always do better.

I’m not sure how big of a problem resistance would be, but I can kind of sort of speculate on this. RNA is difficult for some organisms to take up, so I don’t think it’s impossible for the organism to change its ability to uptake RNA. As far as easily imaginable forms of resistance go, I think this would be the most problematic form of resistance. Increased nuclease activity in the digestive tract would be an issue from a resistance management standpoint, as well. The beauty of this technique is that we can put any sequence of RNA into the bacteria to perform this technique. If we were to target insect specific insulin-like peptides, we could kill the beetles by causing growth deformities or by putting the insect in a diabetic coma. If we found that we could silence some of the metabolic machinery in a species specific manner we could target this. We could target single genes, or groups of genes and thus custom-tailor our pesticides to the pest itself. If the sequence of the RNA changed in response to the management, we could just determine if a different RNA sequence would work. It’s very exciting stuff, and it uses chemistry that’s already existing all around (and even inside) you.

It’s a good example of how technology can be applied in novel ways. In this particular example, we are doing something very simple-genetically modifying bacteria-to accomplish the relatively simple goal of killing crop pests. If we were to develop this further and get it ready for field use, organic agriculture proponents would be sadly unable to take advantage of this technique because they ban both synthetic insecticides and genetically modified organisms. Organic agriculture rejects many tools which could help them further goals which are certainly admirable. Unfortunately organic agriculture proponents attempt to maintain a false dichotomy between synthetic insecticides, genetically modified organisms and environmental issues. A lot of this stems from simple chemophobia, the idea that synthetic things are inherently bad. This causes the field to reject many good tools like this based on little more than fear and misunderstanding. Unfortunately, as a result of this I reject organic agriculture and refuse to buy anything organically produced despite the fact I agree with their goals wholeheartedly. I sincerely hope the field moves in a direction which places an emphasis on environmentally friendly solutions rather than perceived naturalness of interventions. Unfortunately, from what I’ve seen I don’t expect that to happen anytime soon.

Zhu, F., Xu, J., Palli, R., Ferguson, J., & Palli, S. (2011). Ingested RNA interference for managing the populations of the Colorado potato beetle, Leptinotarsa decemlineata Pest Management Science, 67 (2), 175-182 DOI: 10.1002/ps.2048
Zehnder, G., Gurr, G., Kühne, S., Wade, M., Wratten, S., & Wyss, E. (2007). Arthropod Pest Management in Organic Crops Annual Review of Entomology, 52 (1), 57-80 DOI: 10.1146/annurev.ento.52.110405.091337

Bahlai, C., Xue, Y., McCreary, C., Schaafsma, A., & Hallett, R. (2010). Choosing Organic Pesticides over Synthetic Pesticides May Not Effectively Mitigate Environmental Risk in Soybeans PLoS ONE, 5 (6) DOI: 10.1371/journal.pone.0011250

Kovach, J., Petzoldt, C., Degni, J., & Tette, J. (1992). A Method to Measure the Environmental Impact of Pesticides New York’s Food and Life Sciences Bulletin

(see original blog post here)

European legislation in the field of genetic engineering is so narrow that it blocks the ability of researchers to take progress from publicly funded basic research on plants through to practical applications. We, 41 scientists who have received funding for basic research on plants from the Swedish Research Council, urge politicians and environmental groups to take the necessary steps to change the relevant legislation so that all available knowledge can be used to develop sustainable agricultural and forest industries.
One of the “Grand Challenges” facing mankind is to find ways to provide food, fuel and clean water to a burgeoning population using agricultural and forestry practices that are environmentally and economically sustainable. Research on plants has made tremendous progress and we now understand well how plants grow, how they protect themselves against disease and environmental stress and what factors limit production in agriculture and forestry. The prerequisite for progress has been basic research, especially studies of plant genes.

The application of this basic knowledge with the goal of making agriculture and forestry sustainable and environmentally friendly has been hindered by European gene technology legislation. These regulations impose very strict controls on the use of plant varieties developed by genetic engineering, while varieties developed via traditional breeding are released with no checks whatsoever. Some environmental groups leading opinion against GM plants criticise the use of genetic engineering by arguing that developments are linked to large multinational companies, that there is uncertainty about the risks, that they cannot be used in an agri-environment without increasing the use of chemicals and that only multinational companies benefit from GM plants. Let us examine these arguments.

Second: There is no scientific uncertainty on the issue of whether GM crops pose more risk to consumers or the environment than conventionally produced crops varieties. The legislation was formulated when there was not yet sufficient data on this but now we know better. 500 independent research groups have received 300 million € from the EU to study the risks. The conclusion in a summary of the results (“A decade of EU-funded GM research”) is that “GMOs are not per se more risky than conventional plant breeding technologies”. We are basic research scientists and we know that the changes produced by genetic engineering are easier to control than those produced in other ways. The legislation argues the opposite, and imposes controls only on GM plants. To put this in other terms; the logic of the current legislation would suggest that only drugs produced by genetic engineering should be evaluated for side effects.
One of the main arguments against GM crops has been that varieties providing for a more sustainable agricultural sector have not yet been launched. The problem is that this is unlikely to happen with the current legislation. While plants resistant to disease – developed in the traditional way – can be grown at once, it takes many years to get a GM variety with the same properties approved for cultivation. The process from basic research – through applied research – to the finished seed marketed by a company is not only time consuming but also very expensive for GM crops: it costs an estimated minimum of 100 million SEK. Publicly funded researchers or small businesses will never have such resources and thus cannot translate advances made in basic research into a product for consumers. Only a few multinational companies are able to take these costs and therefore give the impression of a monopoly.

The regulatory framework is contributing to the lack of competition and the appearance of monopolies; it is not simply patent rights or unsound business practices, as is often claimed.

The environmental movement’s opposition to genetically modified plants runs counter not only to a transition to sustainable agriculture but also, paradoxically, to their “fight against the major chemical companies.” The costs associated with the introduction of GM varieties give these companies a monopoly on a huge market; 10% of the world’s agricultural land is planted with GM crops today. In addition, companies that have as one part of their business the production of agrochemicals get “revenue insurance” from GM varieties because the use of GM crops often leads to a reduced demand for their agricultural chemicals.

Ultra-right religious groups in the U.S. are trying to raise a quasi-scientific version of creationism as an alternative to evolution. In Europe we look at this public debate with amazement, as if it went against the notion that the Earth is round. However, in Europe we have instead much quasi-scientific scaremongering about the risks of GMOs, and this is fuelled by some groups within the environmental movement. The Swedish environmental movement has a proud tradition of working from a sound scientific basis. For many of us, an early involvement in the non-profit environmental movement was an essential element in choosing our current careers; we wanted to contribute to a better world. The environmental movement should view it as a warning that many of us, with sadness, abandoned it when we felt we could no longer belong to organizations that sided with anti-science and populist forces – without subverting our scientific principles. We urge the Swedish environmental movement to unite with science and act as a rational, informed voice to influence their more vocal foreign counterparts.

Changing the genetic engineering legislation is not only a very important issue for Europe. Poorly funded plant breeding researchers and organisations in many third world countries are also being deprived of one of their best tools to provide better local crops because of the obvious risk of being excluded from the GM-hostile European market.

We therefore urge our politicians to change this outdated law. It should be the characteristics of a plant that determines whether it should be checked, not the technology used to produce it. We do not believe that all checks on the cultivation of GM plants should be removed. Varieties that are toxic or could cause allergies or environmental problems must be subjected to governmental control and independent evaluation – but these same controls should apply to ALL varieties, whether they are produced by genetic engineering or not.

Our desire is that the world’s farmers will be offered seeds that have been developed to provide the most energy-and water-efficient and chemical-free agriculture and forestry as possible, but current genetic engineering legislation prevents this.

Professor Nina Fedoroff of the Pennsylvania State University is the lead protest letter signatory.

The biotech crop regulation changes mooted by the EPA were announced March 2011 in the Federal Register here (pdf).

Scientist co-signatories on the Fedoroff Letter say that the EPA is going down a troublesome path that is not based on science, and which will frustrate and delay innovations needed to provide farmers with better cropping methods.  Because of the delays and unneeded extra cost burdens such a  policy shift would create, it would surely undermine global food security.

The text of Fedoroff Letter is provided below (see here for the full original letter).

Nina Fedoroff has (together with Robert Haselkorn,and Bruce M. Chassy) written a very readable  editorial about this issue in the FASEB biology journal:
“EPA’s Proposed Biotech Policy Turns a Deaf Ear to Science” (pdf). This great FASEB editorial fully explains the nature of the problem that is brewing with the current EPA policy direction.

Such expanded regulation would serve only to increase costs, hinder research, undermine the long-term viability of public university research programs, and limit product development from the private sector. The proposed actions would threaten our ability to produce high quality food at an affordable price and to feed a growing population.

They would also weaken the competitive advantage of U.S. public research programs in the global research arena, all with no increase in safety for consumers, farmers, or the environment — indeed, the contrary would be the case in many instances.

The academic community is committed to ensuring that the environmental and food safety benefits of biotechnology-derived plants continue to accrue, and it is essential that all agencies respect the scientific basis for regulation and division of regulatory responsibilities established by the Coordinated Framework. It is critical that regulations focus on scientifically demonstrated hazards, rather than being driven by issues of perception or political expediency. Therefore, we urge that the pending EPA regulatory actions be reconsidered and the rule-making proposal be limited to requirements for substances that have traditionally been regulated by the EPA, such as PIPs, and then only to those requirements that are fully justified on the basis of sound science.

Readers of Biofortified should start bending the ears of congressional representatives — and get the  EPA’s attention by every available communication channel — to make sure this potentially serious misadventure does not happen.

We, the undersigned members of the National Academy of Sciences, write today to voice our concern over the latest proposal from the U.S. Environmental Protection Agency (EPA) to further expand its regulatory coverage over transgenic crops in a way that cannot be justified on the basis of either scientific evidence or experience gained over the past several decades, both of which support the conclusion that molecular modification techniques are no more dangerous than any modification technique now in use. The increased regulatory burdens that would result from this expansion would impose steep barriers to scientific innovation and product development across all sectors of our economy and would not only fail to enhance safety, but would likely prolong reliance on less safe and obsolete practices.

Since then, extensive research, coupled with years of experience, led to the conclusion that there is no scientific basis to single out plants produced by transgene insertion for a special regulati•ry review, nor to distinguish these products from others on the basis of the process used to create them. There is now abundant evidence that the most appropriate regulatory approach would be to require review only of truly novel traits introduced into plants without regard to the methods used for their introduction. Yet the regulatory apparatus in the U.S. has increasingly moved in the opposite direction towards ever greater regulation and increased data requirements for transgenic plants, despite the abundant accumulation of data attesting to their safety.

The scientific community has a strong interest in keeping regulations science-based and Commensurate with the risk of the products at issue. This past March, EPA announced in the Federal Register a draft proposed rule to codify data requirements for plant incorporated protectants (PIPS). This draft was forwarded by EPA to the U.S. Department of Agriculture (USDA), Department of Health and Human Services and Congress for review in accordance with the Federal Insecticide, Fungicide, and Rodenticide Act.

Based on initial reviews of that draft proposal and recent EPA actions associated with biotechnology-derived crops, it is clear that the Agency is departing from a science-based regulatory process, walking down a path towards one based on the controversial European “precautionary principle” that goes beyond codifying data requirements for substances regulated as PIPs for the past 15 years.

We are particularly troubled by proposals to expand EPA’s current oversight into areas such as virus resistance and weediness that have been adequately addressed by USDA since 1986. Already, EPA has expanded its oversight into virus resistance, which previously had been the purview of USDA’s Animal and Plant Health Inspection Service (APHIS) and which EPA prudently proposed in 1994 to exempt from its regulations. With the draft proposed rules, EPA would further expand its regulations and data demands to other areas historically covered by USDA-APHIS without the slightest justification based on either data or experience.

It is most troubling that EPA is also proposing to increase its regulation to cover matters which are still not deemed to be threats even after years of study, such as potential gene transfer from plants to soil microorganisms. In other actions, EPA has expressed its right to regulate plants engineered for altered growth (e.g., by suppression of ethylene production), the same way it regulates synthetic plant growth regulators. The Agency does so based on a generous interpretation of the enabling legislation, despite the absence of any scientifically credible hazard.

Such an expansion in regulatory purview would reverse long established and highly successful policy under the Coordinated Framework. Such a shift would (1) create a duplicative regulatory system for very low risk products delivering substantial, demonstrated environmental benefits; (2) increase costs, reduce efficiency and prolong the review timelines thereby discouraging innovation; (3) dramatically increase the hurdles already facing academic institutions and companies attempting to improve so-called minor use or specialty crops through modern biotechnology; and (4) adversely impact trade in safe and wholesome commodities produced by U.S. growers because of the stigma attached to anything characterized as a “pesticide” — a regulatory label for DNA that is unique to the U.S. — and with no concomitant increase in product safety. In addition, any expansion in regulatory oversight not resulting from documented risk could have global ramifications, as policymakers in other countries routinely consider U.S. policymakers as leaders in the regulation of crops derived from biotechnology.

Indeed, it is astonishing that EPA would attempt such an expansion of its regulatory activity in this sphere. We now have more than 25 years of experience with biotechnology-derived crop plants. None of the hypothetical risks articulated at the dawn of this era has been realized and caused new environmental problems. On the contrary, billions upon billions of meals derived from these crops have been eaten by humans and livestock around the world with no ill effects. Moreover, environmental impacts of production agriculture and the carbon footprint of agriculture have been significantly reduced through the use of transgenic crops. At the same time, farmers have benefited economically, socially, and through improved health. These indisputable results make a compelling case that existing regulatory burdens should be reduced and refocused. There is absolutely no justification in either scientific data or experience for the regulatory expansion proposed by EPA.

Over the last two decades, advances in sequencing and genomic analysis have revealed that biotechnology is more precise and less disruptive to the genome than traditional plant breeding. In point of fact, recent genomic, proteomic and metabolomic comparisons of varieties bred through conventional and transgenic methods demonstrate that transgenic plants with incorporated novel traits more closely resemble the parental variety than do new varieties of the same plant produced by more traditional breeding or mutagenesis techniques. These findings confirm that transgene insertion is not inherently risky nor does it present new and greater hazards than conventional plant breeding.

In conclusion, recent EPA actions signal an intent to expand the Agency’s regulatory oversight into products regulated by USDA for over two decades and to products for which there has never been a justification for regulation. These actions are not only inconsistent with regulatory directives mandated by the current Administration, they also erode the integrity of the Coordinated Framework. Such expanded regulation would serve only to increase costs, hinder research, undermine the long-term viability of public university research programs, and limit product development from the private sector. The proposed actions would threaten our ability to produce high quality food at an affordable price and feed a growing population. They would also weaken the competitive advantage of U.S. public research programs in the global research arena, all with no increase in safety for consumers, farmers, or the environment — indeed, the contrary would be the case in many instances.

The academic community is committed to ensuring that the environmental and food safety benefits of biotechnology-derived plants continue to accrue, and it is essential that all agencies respect the scientific basis for regulation and division of regulatory responsibilities established by the Coordinated Framework. It is critical that regulations focus on scientifically demonstrated hazards, rather than being driven by issues of perception or political expediency. Therefore, Administrator Jackson, we urge you to reconsider the pending EPA regulatory actions and limit the rulemaking proposal to requirements for substances that have traditionally been regulated by EPA as PIPs, and then to only those requirements that are fully justified on the basis of safety and sound science.

I sign this letter on behalf of the more than 60 members of the U.S. National Academy of Sciences listed below. The list includes many of America’ most eminent biological scientists, including Nobel Laureates Dr. James Watson and Dr. Gunter Blobel.

Sincerely,
Dr. Nina V. Fedoroff
Member, National Academy of Sciences
2006 National Medal of Science Laureate
Science and Technology Adviser to the. Secretary of State and to the Administrator of USAID, 2007-10
Evan Pugh Professor, Pennsylvania State University
Huck institutes of the Life Sciences
211 Wartik
State College, PA 16801
nvflPpsu.edu

If you’re a graduate student like I am, PHD comics is an essential source of comfort. Emotionally and physically, graduate work is difficult. You’re working long hours with little pay and often (but not always), little gratitude. There are reasons for this, but to get the job in the first place you’ve got to be bright and have at least some modicum of passion to get through it.

There’s a lot to be said for obtaining an undergraduate degree. The course work can be really difficult and it’s often done at a time when you’ve got no real idea what you want to do with life. Aside from the *ahem* classical experimentation, you’re exposed to a lot of new ideas for the first time and for many, this is the first taste of independence. Personally, I spent my undergrad years living half an hour away from school while trying to figure out how to work two jobs that were a 20 minute commute from one another. I did this all while juggling classes, relationships and a kid.

I got accepted to a school halfway across the nation, and met up with a new set of challenges both personally and intellectually. I’d spent some time away from home as a teenager, so I was emotionally prepared to some degree. However, I’ve found it difficult to maintain a long-distance relationship with my child while having a really heavy workload. The lab I work in is also pretty heavy in biochemistry, but the last chemistry class I’d taken was in 2007 so I had to quickly re-learn some pretty basic skills.

When I say that being a graduate student is taxing, it may sound like I’m whining but I’m really not. Mentally, science can be very difficult. Many find the knowledge generated by their chosen field simply amazing, but the work required to generate that knowledge tiring and boring. I’ve met more than a handful of students who truly love their field, but absolutely hate their day to day work.

There are good reasons for this. My undergraduate work consisted of caring for bees, with the occasional PCR work. I had a good idea of how to generally read some data, but when it came down to reading some of the western blots I was generating there were a lot more subtleties than I realized.

These things are really quite normal as far as I can tell, and every student deals with them to some extent. There’s a lot of self doubt which comes along with the job because you’re learning to do things which are very precise for the first time. When you’re learning in undergraduate work, the experiments are pretty much pre-designed and almost always cookbook type labs which have a high probability of success. Mentally, it’s hard to prepare a student for a three month string of failed tests.

Undergraduate learning is mostly about learning whether you’re capable of understanding the generalities of the field. Proteins do this, this is how the organism makes them… that sort of thing. The answers are in books, and there’s a lot of wrote memorization but unless you land a research position there’s not a whole lot of real applied work. If you do land a research position in undergrad, it may or may not necessarily be similar to what you do in graduate school… and what I’m doing now can’t possibly be any more different than what I did while I was an undergrad.

Truth be told, I don’t know if I’m good at what I do. I think I am, or at least with a bit more experience I think I will be. I’m generating data and learning how to be more efficient at what I do. With every test, I’m learning more and more about how to pick out the subtleties of the tests despite the fact I still have a tendency to over-read my tests or occasionally overlook a relatively simple test which could answer a question I have about something or other. I’ve come a long way since I got here, but I’ve still got a hell of a way to go.

I’ve opined before that scientists are rarely treated as actual people. Science is hard work, and to make it in the field you’ve got to be good at what you do. Every one of us has their own personal backstory, some tragic, others not so much… but ultimately we’re all people who’ve got a passion for a certain subject and rack ourselves day in and day out to try to make the world a better place by making sense of the universe.

If this movie is anything like Cham’s comic (and the scenes in the trailer do correspond to Cham’s comics…I’ve read every single one) this movie is a must-see if you want to see what it’s like to be a scientist.