Is Free Will a Thing?

I’d like to call the following a neurophysiosophical rant, i.e. philosophical rant grounded in neurophysiology. You can use it.

If any of you have studied for the GRE (Graduate Records Examination) within the past several years, chances are you’ve run across a reading passage describing the findings of Benjamin Libet, a neurophysiologist from UC, San Francisco. When I think about it, I’ve actually learned a lot of interesting things from GRE reading passages. But this one in particular has stuck with me, because ever since I read it I’ve been skeptical about the idea of free will.

There is a lengthy (understatement!) Wikipedia page dedicated to this historical debate, but if you aren’t particularly in the mood to tackle an 8,920 word scientific discourse (that’s equivalent to 10% of a full-length novel), this post should suffice (however, if you are, you should seriously read it–it’s pretty cool). Here’s the meat:

Two scientists name Lüder Deecke and Hans Helmut Kornhuber discovered something called readiness potential (RP) in 1964. RP quantifies the ramping up of electrical activity in the motor cortex and supplementary motor area of the brain that precedes a voluntary muscle movement. Benjamin Libet’s contribution in the 1980s was to show through experimentation that this RP signal precedes  the conscious will to move. Of course, his methods were a bit ghetto: RP was measured with an electroencephalogram (EEG), movement was detected with  an electromyograph (EMG), and first awareness of will to move was noted by the test subject using a fancy oscilloscope timer–as you can imagine, the time of this first will to move would be impossible to record exactly due to the amount of time between urge to act and ability to note the location of the dot on the oscilloscope. Furthermore, if the subject follows Libet’s direct instructions to note when “s/he was first aware of the wish or urge to act,” s/he would not in fact be willfully deciding to move. In this case, perhaps the “urge” felt by the subjects is the RP.

I wouldn’t hang my hat on the results of this study. But a more recent study (2008) repeated the experiment with some modifications and extensions, including the use of fMRI machine learning through multivariate pattern analysis to predict which button, left or right, a test subject would choose to press. The authors write, “We found that the outcome of a decision can be encoded in brain activity of prefrontal and parietal cortex up to 10 seconds before it enters awareness.” However, the accuracy rate was only 60%. Moreover, this experiment still relied on the test subjects noting the time of first awareness of urge to move. In my opinion, the result is therefore more intuitive than the alternative. I would be much more surprised if a person felt an “urge” to move and it was not the result of an electrical signal in the brain. On the other hand–is it even possible to experience will to move in the absence of an urge of any kind? The neural motor default is inhibition, not excitation.

The issue of finding proper controls for a scientific experiment is pervasive and fascinating. This scientific question regarding free will is particularly troublesome because there are so many unanswered questions whose predicted answers necessarily contribute to the premise upon which the experiment is based. Such questions include: How might free will be observed if it does exist? If asked to exercise free will, does this conscious determination to make certain decisions at “random” intervals preclude the ability to act in a truly autonomous manner? (I hypothesize yes.) Under the right circumstances, can RP actually start after conscious will to move (and then, what are these circumstances)? Do different kinds of actions require different kinds of free will? What is free will, anyway?

To the last question, I present the Merriam-Webster definition: “Freedom of humans to make choices that are not determined by prior causes or by divine intervention.” Great–now what do these “prior causes” entail? Where philosophy meets science, the rabbit hole runs deep.

Okay, so here is one sub-question which some scientists, including Libet, have endeavored to answer: Once started, can RP and/or the progression toward movement be stopped? Libet did observe that RP could be initiated without being followed by actual movement, implying that the subconscious decision to move was vetoed. Michael Egnor of Science News thinks that the buck, while perhaps not stopping, brakes to a school-zone appropriate speed here, and Benjamin Libet would agree. According to Egnor, Libet wrote, “This kind of role for free will is actually in accord with religious and ethical strictures. These commonly advocate that you ‘control yourself.’ Most of the Ten Commandments are ‘do not’ orders.” Interestingly, he firmly believed in free will (or at least free won’t), maintaining that the ‘veto’ need not be neurophysiologically predetermined–in his words: “We would not need to view ourselves as machines that act in a manner completely controlled by the known physical laws.” But in my opinion, it’s very likely that there is a separate brain signal that competes with the readiness potential and overrides it. In fact, how could there not be? Our sensory neurons are constantly competing with each other to dominate our awareness, so why should the process of decision-making be any different? I don’t think anyone would argue that consciousness is an entity wholly distinct from the physical wiring of the brain. Thus, the question that I think becomes most pertinent in this debate is: Does the competing “veto” signal exist physically, and if so, where and how does it arise?

Scientists Simone Kühn and Marcel Brass were of the mind that the veto probably also arises subconsciously. In 2009, they sought to answer this question. The premise: If in fact the decision to veto is an act of consciousness, test subjects should be able to  distinguish the true permission of movement from mere impulse (as in failure to make a decision at all either way). I won’t go into the methods (read their paper if you’re interested), but the results showed that the volunteers could not make this critical distinction. Thus, the evidence more strongly supports a model in which decision to veto an action also arises subconsciously.

One of the most compelling experiments on this subject for me is a 1990 study by Ammon and Gandevia in which the scientists were able to manipulate test subjects’ perception of their control over decisions. Summary: any given right-handed volunteer would normally choose to move his right hand 60% of the time; however, when the right hemisphere of the brain was stimulated using magnets, he would choose to move his left hand 80% of the time. The incredible part: despite external influence, subjects still believed that their choices regarding which hand to move had been made freely.

After reading all this literature, if I had to say which side I’m leaning to, it’s definitely the one in which all our decisions result from an optimization calculation in the brain. It makes so much sense to me that we would integrate all our nature and nurture–observations, information, training and genetic tendencies–as parameters for some extremely complex multivariate nonlinear regression, in order to make the best possible decision. I mean, I can understand situations in which even suicide might be computed by the brain to be the least negative/painful option.

Am I okay with the idea that I may be no more than a biotic cyborg? I guess so, yea. But there’s still a strong sense of personal responsibility. It’s more important than ever to stay as informed as I possibly can about all issues (moral and otherwise) that might directly affect my life, so that when the need to decide presents itself, my neural networks will make the best decision for me and for those around me.

Discussion Topic: What do you think? Is free will a thing?

Don’t Worry–You DO Make New Brain Cells

So, you know how your mom always told you to wear a helmet when riding your bike because if you hit your head, you’ll lose brain cells that you can never get back? Well, back in the 90s, researchers discovered that adult neuronal stem cells (NSCs, cells which can become new neurons) do in fact exist, and what’s more, the brain never stops developing and incorporating new neurons! However, these NSCs have remained shrouded in mystery for some time. The big questions have included:

  • “How are adult stem cells maintained in the adult?” and
  • “What are the factors that control adult stem cell proliferation and differentiation?”

The first question was answered by Duke researchers in 2011 when they discovered the cells that keep the brain’s stem cells neurogenic, or able to form new neurons. When NSCs are harvested for culture in a dish, they don’t form new neurons; instead they form a type of cell called astrocytes, which if permitted to proliferate unchecked, can lead to brain tumor formation. This has been a major impediment to cultivating neurons for replacement therapies to treat brain injuries. But in their Neuron journal article, the researchers explain that neighboring cells called ependymal cells produce proteins involved in a pathway that is required for neurogenesis. When these genes were deleted from the ependyma, there was a dramatic depletion of neurogenesis. What’s special about these proteins? They instruct the ependymal cells to cluster around NSCs and morph into pinwheel-like architecture, providing what seems to be critical structural support. The study’s senior author, one Dr. Chay Kuo said, “We believe these findings will have important implications for human therapy,” and how could they not? With this new knowledge, cultivating neurons in a lab dish to implant in a damaged brain is much more feasible. Woo hoo!

The second question was answered at least in part by…the same Duke researchers. In an advance online publication released on June 1, 2014 (that’s like two weeks ago, guys!) they describe the discovery of an entirely new kind of brain cell called a ChAT+ neuron within the subventricular zone (SVZ) of the brain, an area where neurogenesis occurs. This region is hot stuff right now. A recent Medical Xpress article speaks of experiments in rodents with stroke injury which demonstrate migration of SVZ cells into the neighboring striatum (just a subcortical part of the forebrain that helps coordinate motivation with motor activity–don’t freak out), apparently aiding in the healing process. Additionally, a recent Cell paper identifies the striatum as a destination for new interneurons (connector brain cells) from this area. What’s more, the researchers write that “postnatally generated striatal neurons are preferentially depleted in patients with Huntington’s disease.” If only we could figure out how fix this! Now, thanks to the Duke scientists, we’re starting to put the puzzle together. The previously mentioned ChAT+ neurons were discovered to direct NSC differentiation–they use the neurotransmitter acetlycholine (ACh) to tell the stem cells to become neurons! When the ChAT+ neurons were stimulated by the researchers, there was an increase in nueroblast (dividing cells that will become neurons) formation. When they were inhibited, formation of neuroblasts was also inhibited. ChAT+ neurons are now a major target for medical research because the ability to stimulate new neuron formation will be invaluable in the treatment of traumatic brain injuries. The next step is to figure out what’s telling the ChAT+ cells to tell the stem cells to differentiate. What a beautiful and complex molecular bureaucracy!

Dr. Chay Kuo is on the ball lately, because he’s also behind some amazing recent discoveries about the brain’s response to injury. But first, some statistics. The CDC reports that in 2010, 2.5 million people suffered from a traumatic brain injury in the U.S. Additionally, 795,000 people a year suffer a stroke, the leading cause of death in the United States (it kills nearly 130,000 Americans each year). So it’s really exciting to be able to peek into the brain’s self-healing process, because the better we understand that, the better we can aid the process medically.

800px-Human_astrocyteWhat Kuo and colleagues discovered in this 2013 study was surprising, given the scientific understanding at the time. Besides neurons, neural stem cells can differentiate into several different types of brain cells, including astrocytes (see pic at right), as mentioned previously. When astrogenesis occurs prolifically, it often leads to malignant astrocytic gliomas (e.g. glioblastoma), which are the most invasive, aggressive and lethal type of intracranial tumor, especially due to their resistance to most current therapeutic approaches (read about this kind of brain cancer here). So it was pretty crazy when the Duke researchers found that instead of producing new neurons to replace the damaged ones, the brain’s initial response after severe trauma is to up-regulate production of a certain kind of astrocyte that will migrate to the injured area in order to make a scar to stop the bleeding, which allows the tissue to start recovering. Importantly, when the scientists experimentally prevented mouse neural stem cells from differentiating into these astrocytes after a brain injury, it resulted in hemorrhaging and failure of the region to heal. But in fact, while this was an unexpected finding, it’s by no means counter-intuitive. Why would the brain produce new neurons to replace the dead ones when the brain is still bleeding? They wouldn’t have a chance.

So now we better understand the brain’s internal equivalent of a band-aid or scab, and we can use this knowledge to better treat brain traumas. According to this Medical Xpress article, the lead investigator Kuo commented, “We are very excited about this innate flexibility in neural stem cell behavior to know just what to do to help the brain after injury. Since bleeding in the brain after injury is a common and serious problem for patients, further research into this area may lead to effective therapies for accelerated brain recovery after injury.” And in the Nature letter itself the authors write, “We believe these results will have important implications for therapeutic interventions using transplanted and/or endogenous NSCs after brain injury28,29, as well as astrocytic tumors that can arise from the SVZ niche30.” Considering how many people are affected by brain trauma each year, this is a pretty big deal.

Of course, having said all that, you should still wear a helmet when you ride your bike.

Discussion Topic: What are some other things you thought were true ten years ago that you now know are completely false?

Gene Editing Update: Genetically Modified Primates Are Here!

Incredible progress in the world of gene editing:

  1. Researchers have successfully generated genetically-modified monkey babies!Image
    If you recall, in an earlier post I mentioned a few types of “molecular cursors” whose job it is to find the right place in the DNA out of the whole genome (using a guide RNA to bring it to the right spot) in order to add or delete certain pieces of DNA. Well, using the newest cursor,  CRISPR/Cas9, collaborators from at Nanjing University, the Yunnan Key Laboratory of Primate Biomedical Research and Kunming Biomed International succeeded in making not one but two different precise genetic mutations at once, and what’s more, they confirmed the absence of off-site mutations at other locations where the single guide RNAs (sgRNAs) could feasibly (albeit poorly) bind, which has been a concern with this particular editing system. The mutated embryos were then implanted into the uterus of a surrogate monkey mother and carried to term. See highly technical “graphical abstract” at right (can’t you just picture an undergrad shrinking, copying and pasting those monkeys?), and pic of the babies below.This is the first time that GM primates have been made–which means that we’re closer than ever (although still very far off, for ethical reasons) to creation of genetically modified humans. But the truly revolutionary thing about this achievement is that now we can study human genetic diseases way more effectively, since humans are obviously more closely related to other primates than to rodents such as mice. And the fact that CRISPR/Cas9 successfully made simultaneous mutations at different genes is particularly exciting, because many human genetic diseases result from a combination of genetic mutations, rather than a single one. Read an article on this paper here, or read the actual paper here.
  2. Fine-tuning of the editing process: A Nature Biotechnology paper was just published on May 18, 2014 (two weeks ago!) that analyzed and improved the accuracy of the CRISPR/Cas9 gene editing system. Many scientists (like the ones performing the monkey gene editing above) predict where Cas9 will bind based on where else the guide RNAs might hybridize with the organism’s DNA, and then test each possible off-site target for mutations one-by-freakin’-one. In contrast, the University of Virginia School of Medicine researchers in this study performed a genome-wide analysis of Cas9 binding using a technique called ChIP-Seq, or Chromatin Immunoprecipitation followed by high-throughput DNA sequencing. This accurately and without bias identified all the locations where Cas9 was binding, because it didn’t depend on the sequence of the sgRNA.Dr. Mazhar Adli and team were able to identify several factors that influence Cas9 binding (read the abstract if you’re interested to know what these factors are), which are already helping scientists everywhere design more effective and precise gene editing experiments. In addition, these researchers found that a certain variant of the Cas9 enzyme, while more difficult to use, is much more accurate and introduces far fewer unintended mutations than the wild type enzyme does. Go science!

Read more than you ever cared to know about CRISPR/Cas9 here.

ImageDiscussion Topic: Dr. Adli from University of Virginia found that ChIP-Seq is highly effective at identifying all genomic locations that Cas9 binds during a given gene editing process. I can imagine this method one day being applied to IVF gene editing treatments–any cultured embryos that show presence of undesired mutations would not be selected for transfer to the mother’s uterus. Such a reliable screening process makes gene editing way safer and more practical. Someday it will be inevitably proven safe and effective in all organisms, even humans, but that’s not to say it will ever be permitted. Does the good of gene editing outweigh the evil? What laws could we put in place to make sure that it does?

 

 

Natural and Unnatural Highs

If you think about it, it’s so interesting that your brain’s neurons talk with each other via small molecules. This was a pretty outside of the box theory prior to the 1920s. A more intuitive hypothesis was that synaptic transmission (direct communication between neurons) was just a flow of electrons from one neuron to the next. These electrical synapses actually do exist, but there are also chemical synapses, as proven by one Otto Loewi in 1921.

Basically, Otto woke up in the middle of the night to a grand epiphany, wrote it down, and then promptly fell back asleep. The next morning, he couldn’t read his own writing. This has happened to the best of us. He wrote of that day, “That Sunday was the most desperate day in my whole scientific life.” However, the next night at 3:00 am, he woke again and remembered the idea. Instead of trusting his clearly terrible penmanship, he got up immediately and went to his lab to perform the experiment his subconscious had conceived, which was this:
1. Electrically stimulate the vagus nerve of a frog (which results in slowing of the frog’s heartbeat).
2. Take the “solution that bathed the heart” and apply it to a new frog heart.
3. Observe.

The idea that there would be sufficient chemical messengers released into the fluid around the heart during electrical stimulation that the fluid would elicit the same response in the second heart as the electrical stimulation did in the first was borderline insane, even to Otto. He said afterwards that “careful consideration in daytime would undoubtedly have rejected the kind of experiment I performed.” I totally get this. I can’t describe how many good ideas I’ve woken up with, only to discover seconds later in the cruel light of lucid reasoning that my idea makes absolutely zero sense and probably involves colors outside of the visible spectrum. But Otto’s idea did work–the fluid from the first heart indeed slowed the second heart’s rate–and now we know that neurotransmitters are a thing.

In order to have any effect when released from a neuron, there must be a type of “receptor” at the neurotransmitter’s destination that it can bind to. And you know what else can bind to these receptors? Drugs. It makes sense that in order for drugs to have any effect on your brain, they must have to somehow affect communication between neurons. Many drugs are counterfeit neurotransmitters, or “agonists,” which can bind to and activate a subset of their endogenous counterparts’ receptors. Other drugs can induce release of certain transmitters or prevent their re-uptake (removal) from the synapse. Here I present an incomplete list of drugs, their corresponding or affected transmitters, and related effects:

NorepinephrineDopamineSerotonin

I. Cannabinoidergic
A. Endocannabinoids: Stimulate hunger. A certain variety found in the developing brain and in breast milk are shown to actually control oral motor function so babies will make the suckling motion in order to feed.

  • THC from marijuana: munchies.

II. Cholinergic
A. Acetylcholine: Attention, learning, arousal, reward, muscle contraction, slowing and speeding of heart rate, etc.

  • Nicotine: activates reward system, increases concentration, increases heart rate.
  • Muscarine: stimulates intestinal muscles, slows heart rate.

III. Catecholaminergic
For a natural high: sex, thinking about your crush, trying something new
A. Dopamine: Alertness, euphoria, and decrease of appetite.

  • Cocaine: increases dopamine, serotonin and norepinephrine levels.
  • Amphetamines: More dramatically increases the same neurotransmitter levels.

B. Norepinephrine: increases heart rate, alertness, and happiness; decreases blood circulation and pain.

  • Cocaine
  • Amphetamines

IV. Serotonergic 
For a natural high: exercise, sex, confidence-boosting activities
A. Serotonin: increases happiness, fullness, feeling of satisfaction; decreases pain. Interestingly, too much (for example from excessive exercise) can cause mental fatigue.

  • Ecstasy (MDMA): increases dopamine, norepinephrine, and causes an extremely dramatic increase in serotonin levels.
  • Amphetamines
  • Cocaine

V. Opioidergic
For a natural high: sex, exercise, listening to music, laughing (this is incidentally why laughter is the best medicine)
A. Endorphins, enkephalins, and dynorphins: euphoria, pain relief, calmness, relaxation, sleepiness, appetite suppression.

  • Morphine & heroin: activate all opioid receptors, so effects are the same as above.

VI. Oxytocinergic:
For a natural high: sex, cuddling, thinking about your loved ones. Click here to read a hilarious article on how to trick yourself into feeling in love, i.e. to increase your oxytocin levels.
A. Oxytocin: increases happiness, feelings of attachment, trust, heart rate, and social skills; increases strength of bad and good social memories; induces labor; helps prevent obesity, relieves stress, speeds the healing process, and decreases pain. Read more here.

  • Pitocin: induces labor
  • Apomorphine: increases oxytocin and dopamine levels

As you can see, sex and love have similar effects as many drugs and they are very addictive. When you’re deprived of the related neurotransmitters, you will experience legitimate withdrawal. Also, like with any prolonged exposure to drugs, you eventually build up a desensitization, or “tolerance”–the amount of neurotransmitters involved in the neural reward system that are released during the same stimulus (i.e. thinking about your significant other) decrease.

Discussion Topic: If you had to get a tattoo of a neurotransmitter (or an item of neurotransmitter jewelry), which one would you choose?

Modern-Day Human Evolution

I love Mental Floss. I love the gadgets they advertise in the back of the magazine, and the awesome gifts that will make happy the nerdiest birthday-girl in your life. A few highlights: Te (Tellurium) and A (Admantium) teacup coasters, Be (Beryllium) and Er (Erbium) beer coasters, a Darwin tote bag, hilarious bookends, a glass pie pan with pi etched into it (my birthday is in September, guys), typewriter key cuff-links, and a pencil case with the words “Choose your weapon.”

I also love how, every question I have, they have already covered in a user-friendly numbered list. For example, they have an itemized article on signs that humans are still evolving. I’ll summarize them briefly here:

  1. As heartthrob Calvin & Hobbes author Bill Watterson once wrote in his strip, “The more you think about things, the weirder they seem. Take milk for example. Why do we drink COW milk? Who was the guy who first looked at a cow and said. I think I’ll drink whatever comes out of these things when I squeeze ‘em!” As it turns out, this is a really valid point. Before cows, goats, etc. were domesticated, humans lost the ability to metabolism lactose (milk sugar) after they were weaned off their mother’s breast milk. But the added nutritional benefits we got from drinking other animals’ milk proved to be selectively advantageous. Though lactose intolerance was the norm around 3,000 years ago, the mutations that allows us to digest lactose our whole lives are now known to be carried by approximately 95% of Northern European descendants!
  2. Have you had your wisdom teeth removed? If so, you’re in the majority, according to this NY Times article that estimates the number of Americans with jaws too small to accommodate them to be around 70%. While our ancestors needed them in order to masticate foodstuff of hunter-gatherer variety, we with our fancy forks, knives, and food processors don’t have a use for a third set of molars. Because of this, people born without wisdom teeth (especially common among Inuits) have no disadvantage that prevents them from passing on their genes. And oral surgery makes it possible for those of us born with painfully impacted wisdom teeth to remove them, so we can pass on our small jaws to our babies.
  3. Mutations that make people more resistant to malaria, tuberculosis, leprosy and HIV are becoming more and more common. Incidentally, it’s nothing other than the sickle cell gene that gives an increasing population of Africans resistance to malaria. When people have one allele with the sickle-cell mutation and the other without, they have a much smaller chance of dying from Plasmodium falciparum infection of their blood cells. Also, since they still have one good copy of normal hemoglobin, they do not suffer from sickle cell anemia (SCA). As a result, Africans with this heterozygous mutation do not die of either disease, and therefore live to pass on their genes. Of course, as a result of this selection, it is also more common for people living in places at a high risk for malaria transmission to be homozygous for the sickle cell gene (having it in both alleles), and thus to die of SCA.
  4. Our brains are getting smaller. Fossil records show that the human brain has gone from 1,500 cubic centimeters to 1,350 cubic cm over the last 30,000 years. Why would a smaller brain be advantageous? The theory I like says that our brains are becoming more efficient. We also may be getting less aggressive and more tolerant, which affords us a social advantage. 
  5. Blue eyes–what’s up with that? Scientists think that prior to 10,000 years ago, our ancestors only had brown eyes. Around that time, genetic mutations popped up in people near the Black Sea that gave them blue eyes. Because blue eyes are recessive, two blue-eyed partners can only have blue-eyed children (unless a very unlucky mutation occurs in the parents’ germ cells). This helps ensure fidelity, because if a blue-eyed man’s blue-eyed partner has a brown-eyed baby, he’s not likely to make any more babies with this partner. Interestingly, this is proven to play a significant subconscious role in mate-selection by blue-eyed males. This study by researchers in Norway showed that, while brown-eyed males show no bias toward women of a certain eye-color, blue-eyed males do rate blue-eyed women as more attractive.

Now, I think there’s one more item that should be added to the list: the evolution of the hymen. Unfortunately, there are no hard statistics on the hymens of the past, as tissues are obviously not preserved in the fossil record. But we can make some compelling deductions from our current numbers if we factor in the importance of the hymen in some ancient cultures, and in more conservative cultures today.

Theories about how the hymen originally arose in primates generally converge on: it protects against microbial infection of the vagina and womb, preserving reproductive viability right up to the moment reproduction first occurs. After it showed up, it began to play a role in sexual selection; i.e. males might preferentially choose to mate with a virgin to ensure that the first offspring is his.

It’s now common knowledge that the presence of an unbroken hymen isn’t always an accurate way to determine whether a girl is a virgin or not. The hymen can break during activities like bike-riding, horse-back riding, tampon insertion, etc. Interestingly, the opposite is also true: a 2004 study found that 52% of adolescent girl subjects who admitted to previous intercourse still had an intact, non-disrupted hymen. This is not extremely surprising, as only 1 in 2,000 females are born with imperforated hymens (having no opening whatsoever).

I imagine that in cultures where women were/are punished for failing to bleed during consummation of marriage, an ideal hymen would evolve that does not break easily, but which reliably does break during first coitus. Take a moment to read Deuteronomy 22:13-21:

“If any man takes a wife and goes in to her and then turns against her, and charges her with shameful deeds and publicly defames her, and says, ‘I took this woman, but when I came near her, I did not find her a virgin,’ then the girl’s father and her mother shall take and bring out the evidence of the girl’s virginity [i.e. the sheets from the marriage consummation] to the elders of the city at the gate. And the girl’s father shall say to the elders, ‘I gave my daughter to this man for a wife, but he turned against her; and behold, he has charged her with shameful deeds, saying, “I did not find your daughter a virgin.” But this is the evidence of my daughter’s virginity.’ And they shall spread the garment before the elders of the city. So the elders of that city shall take the man and chastise him, and they shall fine him a hundred shekels of silver and give it to the girl’s father, because he publicly defamed a virgin of Israel. And she shall remain his wife; he cannot divorce her all his days.
But if this charge is true, that the girl was not found a virgin, then they shall bring out the girl to the doorway of her father’s house, and the men of her city shall stone her to death because she has committed an act of folly in Israel, by playing the harlot in her father’s house; thus you shall purge the evil from among you.”

Clearly, the women who had hymens weak enough to break prior to marriage or perhaps flexible enough to remain intact during intercourse would often not survive long enough to reproduce and pass on their genes. Several world cultures, including the Yungar people of Australia, starved, tortured or even killed girls found to be lacking an intact hymen prior to marriage, according to a 1990 textbook cited by this article–and this was the 20th century! But in present-day cultures where it’s socially standard to be sexually active out of legal covenant (largely due to invention of reliable birth control), there is no sexual selective pressure on the preservation of the hymen. Women who don’t bleed on their wedding nights are not stoned to death, and thus are free to pass on their loser hymen genes to progeny. Additionally, if in fact it’s true that the hymen protects the womb from infection that eliminates reproductive viability, then only in untreatable cases will the hymen provide a selective advantage. This doesn’t necessarily mean that the hymen is being phased out–polymorphisms can occur that make it weaker or stronger, and neither will affect the female’s ability to survive and reproduce.

Even in cultures where virginity is still highly valued and impurity is punished, it doesn’t matter whether women would naturally have an intact hymen on her wedding night, because she can undergo hymenoplasty. In Marjane Satrapi’s (Iranian author of Persepolis) graphic novel Embroideries–highly recommend!-she mentions that sometimes Iranian women undergo this surgical procedure in which the remnants of a torn hymen are stretched and stitched to the vaginal orifice, in order to fake their virginity and avoid divorce or other consequences. Actually, the word “embroidery” is the euphemism for this procedure. It allows women to be as sexually active as men, while still having the selective advantage of a virgin. And thus, even in these countries, women can pass on whatever hymen genes they have to give.

Discussion Topic: We’re still evolving! What are some other human traits that you predict are changing or increasing in variability due to medical/technological breakthroughs?

Real Life Love Potion Coming Soon

“Poetry it is not. Nor is it particularly romantic. But reducing love to its component parts helps us to understand human sexuality, and may lead to drugs that enhance or diminish our love for another.” Dr. Larry Young of the Emory University School of Medicine isn’t talking about aphrodisiacs–substances that can increase libido. He’s talking about drugs that can affect our desire to spend the rest of our lives with someone. That’s crazy talk, right? Well, guess what. There’s already a proven love potion for voles, and scientists are working to develop one for humans, too.  

1. How to make a certain person be attracted to you:

Several products claim to increase your appeal to the opposite sex. In fact, here’s a link to five that you can already buy. However, as the author of that list acknowledges, there’s no way to separate the effects of the substances from the effects of the extra confidence the substance users feel. More importantly, even if effective, these products merely increase someone’s sexual attraction to you–they don’t presume to be able to help you find your mate.

More compelling are the custom “biologically effective perfumes” that link preference in body odor to one’s own genetic variants of the MHC (major histocompatibility complex) immune system genes. The guys behind this idea are thinking something along the lines of a custom perfume that mimics your own body odor, allowing potential mates to smell you better and thus allowing you to more effectively attract the ones you would naturally attract anyway (in fact, researchers have already shown that this works). Of course, one can also envision a world in which you inconspicuously swab your crush’s pits and send the sample to a custom synthesis lab to get a perfume scent you know he’d be attracted to. Unethical? Yes. Unsustainable? Yes. But at least when he bails you’ll have an answer to that inevitable question, “Why doesn’t he love me anymore?” It’s because you stopped wearing your veil of lies.

On a side note, a woman’s odor preferences can actually change when she uses oral contraceptives, according to this study. Scary that messing with hormones can [theoretically] mess with your choice of a life partner.

2. How to make someone be emotionally available:

Let’s talk about voles.

The prairie vole is as highly social and monogamous or more than any other known mammal. My Neuroscience textbook by Bear, Connors & Paradiso describes these voles as having an “intense period of initial matings,” after which the male and female live together in one nest pretty much forever. These males fiercely defend home and mate, and even participate in child rearing.

Meadow voles, on the other hand, are sluts. Each has a private crib where guests are entertained on a one-night-only basis. Males take no part in parenting, and even the females kick the kids out as soon as they have a nonzero probability of dying immediately.

So what sets these species apart? They are physically and genetically very similar, with one noticeable exception: their brain maps of vasopressin and oxytocin receptors differ significantly. Interestingly, after a meadow vole gives birth, her receptor maps briefly resemble that of a prairie vole, presumably so she can [want to] feed her babies.

If you know what molecular receptors are, skip this paragraph. Receptors are big molecules with specific pockets that small signaling molecules (drugs or natural neurotransmitters) can fit in and bind to. I’ll be doing a post on drugs and their natural analogues soon, but for now, all you need to know is that when these signal molecules bind their receptors, the neuron attached to the receptor responds and can pass on the signal to other cells. Stuff just doesn’t get done without sufficient receptors in the proper places, even if you dump a boatload of extra neurotransmitters there.

Vasopressin and oxytocin are peptide hormones that serve as neurotransmitters (chemical signals) in the brain. The former stimulates pair bonding, competitive aggression and paternal activities in males; the latter stimulates maternal instincts, lactation, uterine contractions during birth, and feelings of attachment toward offspring and mate in females. Oxytocin interacts with the reward and reinforcement system driven by the neurotransmitter dopamine. This happens to be the same circuitry that’s affected by nicotine, cocaine and heroin to produce euphoria and addiction.

During the deed, levels of vasopressin in male prairie voles and oxytocin in females increase sharply. However, even the clingy male prairie vole will hit it and quit it if he’s given vasopressin antagonists (which prevent binding of vasopressin to the receptors) prior to copulation. Obversely, if gene therapy is used to put more vasopressin receptors in the brain of the promiscuous male meadow vole, he’ll put a ring on it like any born and bred prairie vole.

Another interesting experiment was this: when vasopressin was given to a male prairie vole while he was exposed to a new female, he quickly became attached to her even though they hadn’t done it yet. Similarly, a female prairie vole whose brain is infused with oxytocin will rapidly form a preference for the nearest male. 

This is crazy. This is chemical manipulation of love.

“Psh,” you might say, “but voles don’t feel what I feel for my partner.” While I’m sure there is some truth to this, there are many similarities between vole pair-bonds and those of humans. When a mother looks at pictures of her child, the dopamine-related regions of her brain lights up. This also occurs when people look at photographs of their lovers. And you can’t ignore this fact: For both humans and voles, polymorphisms in the AVPR1A gene are directly responsible for the amount of vasopressin receptors expressed in the brain. The likelihood that a male vole will bond with a female can be accurately predicted from the layout of his avpr1a regulatory region, and differences in human AVPR1A are associated with variations in pair bonding and relationship quality. In fact, Dr. Young’s Nature article describes a recent study showing that “men with a particular AVPR1A variant are twice as likely as men without it to remain unmarried, or when married, twice as likely to report a recent crisis in their marriage.” 

We’re moving toward a world in which failure to commit and fear of intimacy are legitimate, treatable genetic disorders. I can hear Beyoncé now: “If you want it then you should’ve got a vasopressin booster.”

What on earth could compel scientists to develop a real love potion? Well, for starters, studies are ongoing in Australia to determine the feasibility of an oxytocin spray as an aid in couples therapy. But marital troubles aren’t the only things that call for chemical intervention. For instance, Japan is currently struggling with an asexual epidemic that has already dramatically reduced its population, and a recent study predicts that its population will decrease another third by 2060. According to a member of the Japan Family Planning Association, the severe lack of dating and sex could result in the “extinction” of the Japanese people. All I’m sayin’ is, I wouldn’t be surprised if the love potion were introduced as a way to save an entire human race. Drastic times call for drastic measures.

So how close are we to developing an effective love potion? Experiments have shown that a nasal squirt of oxytocin makes men more attracted to their partner than to a stranger of the same attractiveness, but take it with a grain of salt because there was a pretty small difference between results from the placebo and oxytocin. I think that in order to have a significant and lasting effect, a “love potion” would have to increase the expression of vasopressin and oxytocin receptors in the brain. This would require gene therapy of the kind that uses viruses to carry the genes to target cells, so it’s still a bit risky. That’s not to say harmless viruses aren’t an appropriate vector for this, and in fact if you’ve read my gene editing post, you know that this technology has been successfully used in humans before to treat several serious diseases. It’s only that, unlike deafness or Bubble-boy disease, “fear of intimacy” is not necessarily worth the risks associated with this therapy right now. Having said that, we’ve got to remember that biotechnology is advancing at a mind-blowing rate and it’s not too far-fetched to predict that someone might start clinical trials for an actual love treatment in the near future. Ethical impediments aside.

Should you freak out? Fortunately, I don’t foresee this kind of treatment ever coming in a DIY kit, so unless you’re dating the Overly Attached Girlfriend, you’re probably safe from being chemically manipulated into falling in love.

If you or a loved one are experiencing fear of intimacy, talk to your doctor to see if the Vasopressin Booster is right for you. Side effects may include: feelings for people, and cancer.

Discussion Topic: How would you feel about dating someone with chemically enhanced emotional availability?

Scientist Humor: Funny Gene Names

After the research-heavy posts of the last few weeks, I thought it would be fun to do a less Scicrazy definition 1 and more definition 6 type of post. Enjoy!

Human genes tend to follow a strict “license plate” nomenclature: letters and numbers. This helps ensure consistency and organization, but it also serves the purpose of preventing scenarios in which doctors have to tell patients they have a mutation in their fear of intimacy gene, for example. Of course, fly physicians are not so fortunate. It’s something of a tradition for Drosophila genes to be named after the mutant phenotype–in other words, named for the main characteristics of a fly lacking a functional copy of that gene. That’s why you get genes like tinman (mutant doesn’t develop a heart), casanova (is born with two hearts), ken and barbie (mutant improperly develops genitals–male and female genitalia often remain inside the body). I’m a particular fan of the indy gene, where mutants have drastically lengthened lifespans. It’s an acronym for “I’m not dead yet,” referring to that one scene in Monty Python and the Holy Grail. There’s a whole set of genes called the “Halloween Genes,” which are essential for proper exoskeleton development. These include spookspookierphantomdisembodied, and shadow, among others. Mental Floss did a great piece on 18 famous gene names and their etymology, not limited to flies (a few they list are spock, Callipyge (apparently Greek for “beautiful buttocks”), and my other favorite, cheap date).

Even though scientists have recognized the need for a more professional naming system in mammals, sometimes punny genes still slip through. For example, a gene that causes mammals to develop extras nipples is called Scaramanga, after the James Bond villain known as “the man with the golden gun” [and a third nipple]. In 2005, UK scientists discovered that this gene can also “trigger” the development of breasts, making it a new target of study for breast cancer research. A smart aleck article breaking this news was titled, “Scientists discover scaramanga gene’s bond with breast cancer.” Heh heh, “bond.” I’m honestly really surprised that this gene’s name hasn’t been changed yet.

More frequently, scientists get around this usually strict professionalism in human gene nomenclature by giving a pair of genes a hidden meaning. One good example of this are the AHR (aryl hydrocarbon receptor) and ARNT (AHR nuclear translocator) genes. A 2012 paper called “High-resolution genome-wide mapping of AHR and ARNT binding sites” makes me think that if the researchers could have, they would rather have titled it something like, “Where AHR and ARNT are and aren’t bound.”

The initial inspiration behind this blog post came while I was doing literature review on an imprinted gene locus that I’m studying right now in mice. One of the genes at this locus is called Meg3–pretty straight-forward, the acronym makes sense (maternally expressed gene #3), and not something that an immature uncle would chuckle at while the doctor explains your copy isn’t working right. But then I found another gene just downstream of Meg3 called RNA Imprinted and Accumulated in Nucleus…or “Rian.” Meg3 and Rian, in that order. I wonder if Meg Ryan knows about this?

But back to Drosophila. While many names are well-known, there are a lot of hidden gems. By scrolling through my Drosophila genome annotation, I found several I hadn’t heard of before but love. Here are a five of my favorite not-as-famous-but-still-oh-so-clever Drosophila gene names (unless otherwise stated, descriptions are taken from The Interactive Fly website):

  • nervous wreck: related to excessive growth of larval neuromuscular junctions. So literally the mutant’s nerves are a wreck.
  • happyhour: mutations in this gene allow flies to drink a lot more alcohol than wild-type controls before succumbing to its sedating effects (Corl et al., 2009). This is the opposite of what a mutation in cheap date does.
  • slimfast: its downregulation, specifically within the fat body, causes a global growth defect similar to that seen in Drosophila raised under poor nutritional conditions. 
  • Thor: expression of a certain transcript from this gene increases during infection, so it was named after the Nordic demi-god in charge of protecting mankind (Rodriguez et al., 1996).
  • scarface: mutants have what appears to be “scarring” around the mouthparts (Bonin and Mann, 2004).

A few other great names are chico, krakensplit ends, kismet, dreadlocks, mind the gap, not enough muscle, pickled eggs, pickpocket, roadkill, rolling pebbles (not to be confused with rolling stones), screw, slow as molasses, trailer hitch, transformer, zelda, bag of marbles, charlatan, dachshund, and double parked.

There still remain new genes to be discovered, even in Drosophila. In fact, one of the research studies I’m currently working on has great potential to reveal novel genes–and who knows, maybe I’ll get to help name them.

Discussion Topic: Would you make a good Drosophila scientist? Come up with a fictional gene and an associated name based on its mutant phenotype. Also, please let me know what your favorite gene names are!