Tag Archives: science

Science Fiction and Science Fact

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Brooke picked up “The Immortal Life of Henrietta Lacks” in e-format from the library a few weeks ago, and as it’s a book I’d heard of and had some interest in, I joined her in reading it. Overall, it was a fascinating tale of how a black woman named Henrietta Lacks in the American South of the early-1950s died of cervical cancer, but samples of her cancerous cells survived in a dish (now known as HeLa cells), paving the way for not only the modern technique of cell culture, but also the discoveries that would develop the polio vaccine, new cancer treatments, and unlock many secrets of genetics.

While the book covers the science in a comprehensive, yet very readable manner, it also tells the reader of what happened to Henrietta’s family in the aftermath of her death, and the fact that they not only had no knowledge of the fact that Henrietta’s cells were being used in research, but they also received no compensation whatsoever for the discoveries that came from it.  When the family eventually discovered what had been happening with HeLa cells over the previous 20 years (seriously…20 years after her death, the family found out…), they didn’t understand what was going on, partially because researchers didn’t take the time to explain it to them, but also because many of them never completed high school, let alone took a single biology class.

This passage jumped out at me:

Deborah realized these movies were fiction, but for her the line between sci-fi and reality had blurred years earlier, when her father got that first call saying Henrietta’s cells were still alive.  Deborah knew her mother’s cells had grown like the Blob until there were so many of them they could wrap around the Earth several times.  It sounded crazy, but it was true.

“You just never know,” Deborah said, fishing two more articles from the pile and handing them to me.  One was called HUMAN, PLANT CELLS FUSED: WALKING CARROTS NEXT?  The other was MAN-ANIMAL CELLS BRED IN LAB.  Both were about her mother’s cells, and neither was science fiction.

“I don’t know what they did,” Deborah said, “but it all sound like ‘Jurassic Park’ to me.”

This conversation took place in the early-2000s, though Deborah, Henrietta’s youngest daughter, had been reading articles like the ones mentioned for decades, especially in the early years before the media and society really could grasp the power and utility of cell culture.  Sure, researchers were making “hybrids,” but what exactly did that mean?  The articles were sensationalistic, rarely providing enough background information to explain the meaning behind what researchers were doing (i.e. not making “man-animals”…).

But a lot of it goes back to the lack of education.  The Lacks family simply could not understand what was happening with Henrietta’s cells because they barely had a concept of what a ‘cell’ was, let along the technologies and diseases HeLa cells could (or did) help cure.  Heck, I remember trying to explain my graduate work to my 90+ year old grandmother (who possibly never took a biology class, and even if she did, it was in the early-1930s…), and that was extremely difficult.  It’s not that she wasn’t intelligent: she just didn’t have the background knowledge to understand much of what I was telling her.

As scientists, I think many of us expect that society, as a whole, has a basic understanding of how the world around them functions, but I have to wonder if society understands less than we think.  We expect that people over the age of 50 have taken a biology class before, but forget that biology has come a long way since they took those classes in the 1970s (when cell culture was still in its infancy).  We further don’t recognize that many of our aging population (i.e. people older than 60) haven’t had a biology class since the 1960s or earlier, if they took a ‘biology class’ at all.  And these are the people that we’re marketing countless drugs to during the commercial breaks from the evening news.

We need to get better at recognizing that “science” moves faster than society’s understanding of it. Perhaps this is why researchers have a tough time getting the concepts of “global climate change,” “evolution” and “childhood vaccination” across to certain segments of the population.  If they had the scientific background (or the will to learn more on the subject from primary literature, rather than silly blogs like this one), perhaps our society could move forward on many fronts, whether environmental, sociological or spiritual.

Though it’s important for scientists to communicate more effectively, it’s also incumbent upon society to start listening.  Otherwise, we are all doomed to repeat the failures presented in the book.  It’s definitely worth a read.

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Neuroscience 2012

A shot from inside the conference hall, looking toward the poster boards.

Yeah, yeah, I know this happened almost a month ago now, but I’ve been meaning to post something about my trip to New Orleans and just haven’t had a ton of spare time to get it done.  Better late than never, eh?

It’s been almost three years since I last attended the annual Society for Neuroscience meeting.  On previous occasions, I’d gone to San Diego (2007), Washington, D.C. (2008), and then my last one in Chicago (2009).  Ever since starting grad school at SLU, I’d heard stories about “the last one in New Orleans” (that will go undescribed here…), but unfortunately, due to Hurricane Katrina, the SfN meeting couldn’t return on schedule.

That is, until 2012, when, coincidentally, I had my next chance to go.

Taking a step back, the reason why this conference is held in a few specific cities is that there are only a few specific cities capable of hosting about 28,500 conference attendees.  New Orleans was one such city, and taking it out of the rotation meant that Chicago had to be substituted, as it had a conference center large enough, and also enough hotels within a reasonable distance to hold all those people.  Unfortunately, Chicago’s conference center just isn’t in a very good location and its overall configuration isn’t ideal for this particular convention (the locations of stair cases, the number of floors, etc).  The logistics of handling 28,500 people can be handled much easier in New Orleans, San Diego, and D.C., at least so far as I’ve seen.

Regardless, I flew down on Friday, October 12th and returned on Wednesday, October 17th.  I presented a poster during the very first session, Saturday afternoon, and had a bit more traffic than I expected to have, as most attendees are arriving on Saturday and/or Sunday and could easily miss my poster.  Still, it was nice to get it out of the way early, freeing up additional time for the rest of the week.  Overall, I attended some good talks, wrote plenty of notes, and got a few ideas on new experiments to run.

Crescent City Blues and BBQ Festival

 Of course, this is New Orleans, after all, so the meeting wasn’t where all the fun was had.  I was splitting time between lab members from here at Wash U, and others from SLU.  Mostly, that split depended on what time of the evening it was: if it was early, it was the Wash U crowd, and if it was late, it was the SLU crowd.  One important exception was Friday night, after watching the Cardinals win Game 5 of the Wild Card Series against the Washington Nationals, we stayed out a bit late.  That weekend, there was a BBQ & Blues Festival going on, so we stopped by for some good food and tunes on Friday and Saturday evening for dinner.  They had it set up with a series of tents hosting a variety of different wares, and then a live stage with different musicians taking their turns.

I should remind you that Brooke and I took a trip to New Orleans in 2005, just after we got married and before Katrina rolled through, so I had already done much of the “touristy” things you’re supposed to do on a visit to the area.  This time was more focused on the food and night life (and science, of course… :-)).   I still stopped by Central Grocery for a muffuletta, had some Pasta Jambalaya at Crescent City Brewhouse, and had Po’ Boys from a few different vendors.  Needless to say, the food was spectacular.

I tried an oyster, though.  That was, perhaps, the absolute worst thing I have ever ingested.  Never.  Again.

Bourbon Street...er...late at night...

Again, last time around, Brooke was still falling asleep around 9:00 pm (well, she still does, to a degree, but she can stay up later now than she used to…), so we didn’t really stay out late.  This time, however, I was hanging out with night owls, so we hit up a variety of different establishments up and down Bourbon Street and, believe you me, I was genuinely surprised at the number of people out at 2:00 am on a Sunday night in mid-October.  I can’t imagine what it would be like during Mardi Gras.  The number of folks we saw in Soulard for a single day for Mardi Gras in February was probably approaching what I was seeing on a given weekend in October in New Orleans, and I don’t think the number of people was directly related to the number of geeky scientists that also happened to be in town.

Regardless, I had a really fun time down in New Orleans.  The city seemed a bit nicer than it was in 2005, the populace seemed genuinely happy to have us all there (28,500 people bring in a lot of sales tax revenue), and I think the conference, as a whole, was glad to go someplace warm, instead of Chicago.  It was great to hang out with good friends in a different setting, learn some new stuff at a large science conference, and “get away for awhile” (though, Brooke did a good job potty training Meg in my absence!!).  I hope I get the opportunity to go back sometime!

Empiricism vs Rationalism

As part of the grant I’m on at work, I am expected to attend “continuing ethics training” each year.  Last Wednesday was the first of two sessions, each a little over an hour long, and I ended up presenting a case study to the other folks in the room regarding the way science is conducted and how it is perceived by the general public.  This past Wednesday, however, we had a guest speaker in the form of Stephen Lefrak, a pulmonary physician that also has research interests in medical ethics.

He covered a range of subjects, but he specifically highlighted a series of studies he was involved with over 10 years ago, studies published in the New England Journal of Medicine, among other high profile journals.  Studies funded by the NIH and carried out by the National Emphysema Treatment Trial Research Group (NETT).  These studies involved a surgical procedure for patients with emphysema, where portions of the lung with damaged tissue would be removed, and the rest of the lung (presumably healthy tissue) would be restructured to form a better-functioning respiratory organ.  Lefrak and his colleague here at Wash U were involved early on with the trial, but left after they had serious ethical concerns, one of which centered on the idea of a “randomized controlled trial (RCT).”

For the sake of simplicity, an RCT is essentially the idea that you apply one of two (or more) potential treatments to a given individual, and that individual is selected at random from a given group.  In this case, the treatment was the surgical removal of lung tissue (presumably damaged) in order to refashion a healthier lung, and the group was emphysema patients.  However, and importantly, it was known at the time that you can’t just do this to someone that has lung damage spread throughout the lung: it only works if there is healthy tissue still in there to salvage.

Lefrak knew it wouldn’t work if the trials were carried out at random (i.e. paying no attention to the quality of the patients lungs, or whether they had healthy lung tissue remaining, or whether they had a “homogeneous” mix of damaged and undamaged tissue).  However, when this concern was raised in the pages of NEJM, he was essentially told that he couldn’t “know” it because an RCT had not been done to prove it.

As a result, almost 50% of the patients it was tried on ended up dying, for the very reason Lefrak and colleagues warned them about.

Which brings us to the title of this post: empiricism vs rationalism.  “Empiricism” is what drives the belief that an RCT is essential to making the claim that this kind of lung surgery is “dangerous” to a subset of individuals.  “Rationalism” is behind the idea that we actually know things about how the body works and can make an informed inference as to what the outcome would be without having to do the RCT to “prove” it.

The example Lefrak gave is that an RCT to prove that you need a parachute to jump out of a plane would be silly.  We already know the answer.

As Lefrak talked about his experience, it got me thinking about where our knowledge comes from and how we build upon it.  Whether I concern myself, personally, with “evidence” more than I should, without thinking rationally about a particular subject in order to come to a conclusion.  I’d consider myself to be a “rational” person, but perhaps not.  Then again, as he described what the surgery was seeking to do, my physiology training assured me that I would have been on his side from the beginning, rather than advocating the continuation of the NETT work.

It’s just something we, as scientists, ought to consider more often than we typically do, I guess.

Primer: Electrophysiology

These posts, tagged “Primer,” are posted for two reasons: 1). to help me get better at teaching non-scientists about science-related topics; and 2). to help non-scientists learn more about things they otherwise would not.  So, while I realize most people won’t read these, I’m going to write them anyway, partially for my own benefit, but mostly for yours.

It’s been awhile since I posted one of these, but as I’m working on radically different science than I have in years past, and people ask me “what I do,” I figured I should take the time to explain, to some degree.

Wikipedia defines “electrophysiology” in the following way:

Electrophysiology (from Greek ἥλεκτρον, ēlektron, “amber” [see the etymology of "electron"]; φύσις, physis, “nature, origin”; and -λογία, -logia) is the study of the electrical properties of biological cells and tissues. It involves measurements of voltage change or electric current on a wide variety of scales from single ion channel proteins to whole organs like the heart. In neuroscience, it includes measurements of the electrical activity of neurons, and particularly action potential activity.

So, in the most general sense, I’m “listening to neurons talk to each other,” and occasionally, “interrupting their ‘conversations’” in various ways.  When I talk about “conversations,” I’m referring to the act of neurotransmission, whereby one neuron sends a chemical signal across a synapse to another neuron, resulting in the propagation of that signal (an action potential), or sometimes the inhibition of another signal.

As I talked about in a previous primer, in order for an action potential to occur, various ion channels in the membrane of a neuron must open, allowing sodium (Na+) from outside the cell to come in, and potassium (K+) to go out.  Other ions will play roles as well, including chloride (Cl-) and calcium (Ca2+).

Using electrophysiology, it is possible to measure the movement of these ions across a cell membrane using relatively simple principles of physics.  Specifically, [V=IR], or [voltage = current X resistance].  If you hold two of the terms of this equation constant, it is possible to determine the third term.  Effectively, we do this using a “patch pipette,” a small, sharp, glass tube that has a wire electrode running through it.  If you know the resistance of the pipette, and you hold the electrode at a constant voltage, you can measure the current across the membrane of a cell (i.e. the flow of ions).

In short, this diagram describes the actual process of making this measurement, using a technique called “patch clamp“:

Looking through a microscope (like the one pictured above), you move one of these glass electrode pipettes to be just touching the membrane of a cell.  You have to be very careful so you don’t puncture the cell, thus damaging the cell membrane to the point where you can’t make accurate measurements.  You then apply a small amount of suction using a syringe to actually suck some of the cell membrane inside the pipette.  Once you have a strong seal formed (typically termed a “gigaseal”), you can apply a brief, large amount of suction with your syringe to rupture the membrane of the cell, where now, the inside of the cell is being exchanged with whatever you put on the inside of the pipette.  The internal solution of a pipette is usually something like potassium, basically trying to recreate what the inside of a cell would be, aside from all the organelles, however you can add compounds or drugs to manipulate the actions of channels you are trying to study.  Typically, though, you apply drugs to the outside of the cell, as well.

So, a real-world example of how this technique is used would be in my study of NMDA channels.  The NMDA receptor is a sodium channel and is very important in neurotransmission, but especially in memory.  When I have a cell “patched” like in the diagram above, I can apply the drug, NMDA, to the cell and see a large sodium current on my computer screen, kinda like this one.

So, over time, when a drug like NMDA or this “Blocker” is applied, you can see a change in the current (measured in “picoamps”) across the membrane of the cell.  In this case, we would read these data such that NMDA opens its channel and sodium ions flood inward, then that current is reduced by the “Blocker” that was applied for a few seconds, and then once the application of the “Blocker” was stopped and NMDA alone was applied to the cell, the inward sodium current increased again.

These traces allow you to get information about how channels are opening, what ions are flowing in what direction, and to what degree drugs like this “Blocker” are affecting channels.  It is work like this, for example, that led to characterization of benzodiazepines and barbiturates, drugs that interact with the GABA receptor, a chloride channel.  Without these techniques, it is difficult to know how a drug is affecting a channel at the cellular level.  Just about every cell in your body has channels of some kind, as they are very important for maintaining the function of that cell.  Neurons are just highly specialized to require ions more than some other cells do, though heart cells are also studied in this way, among others.

Effectively, these techniques allow you to determine how a cell works.

Fred Flintstone Wants To Kill You

I’m slowly catching up on podcasts from the last few weeks when I wasn’t really in Podcast Listening Mode, and recently, I listened to On Point’s discussion on recent research on vitamins.  Much of the discussion focused on recent reports suggesting that over-dosing on vitamins for years could do more harm than good.  Specifically, they discussed a recent study called the Selenium and Vitamin E Cancer Prevention Trial (SELECT) where men took the daily recommended dose of Vitamin E and were found to be 17% more likely to develop prostate cancer over the 7 years they were followed.  This news comes after another recent study from the Archives of Internal Medicine suggesting that multivitamins, folic acid, and iron and copper supplements may increase mortality in older women.

This all reminds me of what Dr. Shaffer told us in psychopharmacology class back at Truman: you don’t need vitamins if you eat a healthy diet.  Human physiology is set up to absorb the nutrients you need and get rid of the ones you don’t, provided you eat the diet your body needs to survive.  This includes vegetable, dairy, grain and meat sources.  If you start removing any of those sources of food, you either a). replace those nutrients with something like a multivitamin, or b). die sooner.  Apparently, however, new data like those referred to above suggest that even with the replacement of nutrients, your body still may not be very happy with you.

Brooke and I talked about this a few days ago and we both had a question about Folic Acid (Vitamin B9) intake, as this is one of those vitamins pregnant women are instructed to take to limit the risk of congenital malformations of children, including spina bifida and cleft palate.  The recommended daily allotment of Folic Acid is between 400 and 800 ug for a pregnant woman per day, though your doctor may prescribe more if there’s a history of problems in your family.  Bear in mind, however, that it’s important that women of child-bearing years have Folic Acid in their diet or take supplements before they are pregnant, as it’s more important in the early stages, before many women even know they’re pregnant.

Speaking of which, what are the ways to get Folic Acid in your diet, aside from a pill?  Spinach, peas, beans, egg yolks, sunflower seeds, white rice, fortified grain products (e.g. pastas, cereals), livers and kidneys, among others.  Now, I ask you: How many women between the ages of 18-25 are eating anything from that list on a daily basis?  I’d guess not very many.  They’re probably going to get most of it from breads and cereals, though the recommended daily allotment of folate is added to the product: it’s not endemic to wheat.

(Side-note: The U.S. government, on their Women’s Health fact sheet, says that vitamins are still essential to ensure you are getting the daily allotment of folate every day, and that it’s possible to do so by diet alone, yet difficult.  Anyone reading this should go by what their doctor tells them.  I’m only using folic acid as an example.  I am, by no means, a medical professional.  :-))

I guess my larger point is that vitamins are alright, but trying to rely on them in order to avoid eating foods that we as Homo sapiens have evolved to require over millenia is unwise.  It’s more important that we get proper dietary sources of vitamins and minerals that our stomachs have “learned” to take advantage of for generations.  This isn’t to say you should only eat organic food, or only eat food that you grow yourself.  Sure, organic sources can be healthy, but I’d argue that it’s better you eat your broccoli every day regardless of whether it’s organic or not.  Women of child-bearing years should be eating food from the outlined sources above anyway.  Men at risk of prostate cancer should be eating grapes, leafy green vegetables, and avoid trans fats anyway.  Heck, regardless of whether you’re “at risk” of prostate cancer or “at risk” of becoming pregnant, these are things you should be eating anyway.

So yeah, I don’t really think that vitamins are that bad for you.  But what is bad for you is trying to rely on them, or other supplements, as a substitute for a healthy diet.

(Final Note: An actual medical professional posted this article up on Huffington Post to help assure people that they shouldn’t necessarily stop taking all their vitamins and that there are some flaws in the conclusions being drawn from these studies.  As with anything in science, more studies are needed to come to any real conclusions on this matter)