Looking Forward and Requests!

Due to some grant writing and general "ohmygod, lab work!" moments this past week, I haven't been able to put together a blog post.  I should be able to put up some new material this weekend, though.  Be excited!

In the mean time, I thought I'd let you know about some new posts that I have in the works.

  - Prions (think Mad Cow Disease!)
  - Unlearning fear - can our brains do it?
  - Same protein, two very different structures
  - A failed Australia expedition and the importance of beriberi
  - You say you "work with protein" - where do you get the protein?

I also brought my camera to work to finally do some posts about tissue culture!  I'm going to show you cells and how they grow.  I'm working on that this week!

I've also received some requests for posts about different diseases, including diabetes and sleeping sickness.  Feel free to throw more ideas at me!

My new blog, Dr. Amedeo, is still under construction.  I'm not entirely happy with the material yet.  Once I am, I will be advertising that, as well.

Finally, I'm beginning to add three sections to my Topics called "Subject: EASY," "Subject: INTERMEDIATE," and "Subject: DIFFICULT."  I'm going to rank my posts as easy, intermediate, or difficult so present readers and newcomers can gauge their own levels and pick their reading material accordingly.  Posts will now be grouped by subject in addition to difficulty of the material.

Talk to you soon!

Fugu for You?

              My husband’s birthday was a few weeks ago.  I told him we could go anywhere he wanted so he chose the most expensive place in the city.  Okay, sure.  It’s always a great meal and I get to eat well, too, so I’m definitely not complaining!  We went to the excellent restaurant Morimoto.  (And for you NYC readers, the Philly Morimoto came first.  So did the Philly Buddakan.  Stop stealing our restaurants.)

                Of course, being that Morimoto, which is owned by Iron Chef Masaharu Morimoto, is all Japanese food, we started the inevitable Japanese food conversation: Will we or won’t we try puffer fish when we travel to Japan.

                For anyone unfamiliar, puffer fish (or “fugu” in Japanese) is a meal prepared from one of several different kinds of fish (Figure 35.1) which have the poisonous tetrodotoxin within them.  Chefs must go through extensive training to learn how to prepare these fish (which includes removal of the most poisonous parts, such as the liver, ovary, skin, and intestine) and pass a comprehensive exam.  The regulations have to be this tight because tetrodotoxin has no known antidote.

         
               Obviously, a lot of deadly poisons exist in this world but they all don’t require the same amount of substance to kill you.  Sometimes you need 1 gram of your poison to kill but a different poison will only require 0.1 g.  Poisons are fun like that.  Scientists have developed a way to convey how poisonous something is with what is called an LD₅₀ or lethal dose, 50%.  I will explain what this means with the following example:

         

Let’s pretend you have ten people standing in a line 

that all weight 100 lbs, which is equal to 45 kg.

You start by feeding each of them 100 ug (microgram, 

see Slideshow Pictures – Microscopes and Photography post) 

of tetrodotoxin.   

Everyone is still standing there.

You then feed them another 100 ug, so everyone now has had 200 ug total of tetrodotoxin.   

One person dies but the other nine are still there.

Okay, good.

You then feed the remaining nine 250 ug of tetrodotoxin.   

Four more people die.

Here is where you stop and I asked you a question: 

How much tetrodotoxin must you feed a group of people in order to kill 50% of them?

The answer in this experiment was 450 ug (go back and count if you don’t believe me).   

Feeding 450 ug resulted in 5 out of 10 people dying.   

So, the LD₅₀ would be equal to 450 ug.

Since not everyone weighs the same thing, LD₅₀s are usually written as grams per unit weight.  In our example, everyone weighed 45 kg so it would be written as 450 ug/45 kg = 10 ug/kg.

The LD₅₀ for tetrodotoxin is 10 ug/kg or 0.00001 g/kg. Gosh, that’s a small amount!  Just for sake of comparison, the LD₅₀ for arsenic is 0.145 g/kg.  The LD₅₀ for botulism toxin is 0.000000003 g/kg.  (No LD₅₀ exists for iocane powder because… well, it doesn’t exist).

Let’s say you didn’t know any of this stuff and somehow came to catch a fugu and subsequently decide that you should definitely eat it.  What are you in for?  Well, dizziness, headache, nausea, difficulty breathing and exhaustion.  You will die from asphyxiation.  Tetrodotoxin, or TTX, is a neurotoxin that binds important sodium channels in our neurons (brain cells).  The structure of TTX can be seen in Figure 35.2.

Cells are enclosed by a plasma membrane (see CentralDogma post) in order to keep things out.  The plasma membrane is protecting the inside of the cell.  However, just as a with a walled-in city, some things still need to get inside!  Many molecules have helper proteins within the plasma membrane that facilitate their movement across the barrier.  These special proteins create tunnels in the membranes to allow things to pass.  In neurons, an important species that needs to pass is the sodium ion.  In response to certain stimuli in the brain, this action of sodium ions helps keep our brains working.  Sodium ions pass through proteins called voltage-gated sodium channels.

Unfortunately, if TTX is ingested, this small molecule will bind the voltage-gated sodium channels in our neurons and block them.  If sodium ions can’t pass through their channels, brain function stalls and we end up with all the lovely symptoms outlined above.  The voltage-gated ion channels in the pufferfish are slightly different than our own and, thus cannot bind TTX.  Their channels don’t become blocked - lucky ducks (err, fish).

Interestingly, TTX is not limited to pufferfish.  It is also found in salamanders, frogs, octopus, starfish, and a few types of crabs.  These animals do not make TTX, however.  Instead, it is the bacteria in their food supply which create the toxin.  It has been shown that if puffer fish are grown in an environment lacking these bacteria, then they will no longer have TTX in their system.

So, why would anyone eat this?  Why take the risk that the most poisonous parts may not have been removed before eating the fish?  Because those who have eaten it say it is wonderful.  Accordingly to Toshio Narahashi, “…puffer has long been regarded as one of the most delicious fish in Japan.”  My husband is all about trying it.  I am mostly all about trying it.  Whenever we do, I’ll gladly report back.

Microgram: 1 ug = 0.000001 g

REFERENCES

Narahashi, T. “Tetrodotoxin.” Proc. Jpn. Acad. Ser. B (2008) 84, pgs 147 – 154

Yu, F H and Catterall, W A. “Overview of the voltage-gated sodium channel family.” Genome Biology (2003) 4(3), pg 207

MSDS for Arsenic: http://www.sciencelab.com/msds.php?msdsId=9922970

LD₅₀ for Botulism: http://www.aahealth.org/physicianslink/bioterrorism_botulism_overview.asp

 

Photo for Japanese puffer fish: http://cmbi.bjmu.edu.cn/news/0110/109.htm

9 Years in Science

               I’m going to do something a little different this week.  I’m going to actually use a blog for what it was intended: a place to put thoughts and reflections.  This coming October marks my nine year voyage as a professional scientist (plus 4 years in college makes me 13 years in science!).  As I move into my tenth year, I realize that I don’t know everything about science (judging by my wide-eyed reaction to my boss’s recent words “Want to write a grant?”) but that I know far more than I’d ever give myself credit for (my list for potential blog posts is really long).  But, since readers come here every week to see what I’m talking about, I thought you’d like to know a little bit more about me and, perhaps, my experiences in science.

                I never intended to become a scientist.  At least, I don’t think so now that I’m looking back.  In college, when it came time to pick a major, I was faced with two normal choices: French or chemistry?  I was good at French and mediocre at chemistry.  However, I desperately wanted a major of which I could be proud.  I wanted to look at my diploma and think how awesome it was that I did it (imagine my horrible shock when, at graduation, my diploma did not have my major written on it).  More importantly, I wanted to feel that I got the absolute most out of my college education.  I’m not knocking French majors, here – I’m just saying that I personally felt I could do so much more.   And so, I chose chemistry.  I believe my parents were worried.

                I probably should have been, as well.  While I did just fine in Introductory Chemistry, Organic Chemistry was not my forte.  On my fifth exam when I amazingly wrote all the correct answers to a set of five reactions, my professor wrote on my paper “Congrats!!  You finally did it!”  Yeah.  Lab was also not my strong point (writing an abstract was truly mysterious) and I relied heavily on my lab mate (thank you, Jess!!) to help me through.  However, I loved Physical Chemistry and the higher level chemistry courses I had to take. My later college science years were much better than my earlier ones.

                It was also during college that I had my first run-in with what I like to call “The Old Boys Club of Science.”  I am not stupid.  Science was dominated by men for decades before my time.  Of course there are plenty of women who made important contributions (Roslind Franklin, who never gets any credit and Marie Curie, who gets a lot of credit, for example) but professors were predominantly older males.  Early on, I had thought about becoming a physics major.  Upon meeting with an older, male astronomy professor at my undergraduate university, I was promptly told I was too stupid to be a physics major. 

 Oh man.  Since I was only 18, I really didn’t know how to respond to this and took him at his word.  By my senior year, I knew (a little) better and took his class.  When I got an A, I promptly wrote a review of his teaching and explained that no one should be told they are too stupid to do anything.  

In truth, I don’t know if he said that because I was a woman or if he really thought my grades weren’t good enough.  I do, however, have strong evidence to the former.  Really, though, it doesn’t matter.  The attitude of “You aren’t good enough” should not pervade science (and I'll happily report that I rarely ran into this attitude in chemistry at my undergrad school or in the years since) no matter what the root of feeling is.  Unfortunately, I let this comment bother me for a very long time.

                When I finished college, I had no idea what I was doing.  I mean really – who does?  As with most things that have happened since May 2002, I fell ass-backwards into my next opportunity.  I was only qualified to do one thing: work in a lab (although I’ll debate with you about my level of “qualification” there).  Three months after graduation, I found myself working in a lab at a rather prestigious hospital for a rather prestigious university and mostly wondering how the hell I ended up there. 

                Two years later, I went to graduate school for the wrong reasons.  Everyone will tell you that you should go to graduate school because you have a career goal that a Ph.D. will help you achieve.  You shouldn’t go without thinking about your long term future.  Well, I went because I wondered if I could.  I wondered if my brain would work like all those professors who taught me and the scientists that worked with me after college.  I truly thought they were brilliant and that I was quite the peon.  

                Clearly, a lot of people knew something about me that I didn’t because my ultimate decision came down to: The Johns Hopkins University or the University of Pennsylvania?  (If you read the “About Me” tab, you’ll see where I chose.)  Classes baffled me a bit, but they only lasted one year.  After that, I worked in a lab every day for next five years.  I loved the lab.

I had my own projects, I ran my own experiments, I thought through all my problems and I troubleshooted everything I was working on.  I learned that I didn’t need Jess and it was okay that I didn’t pass Orgo with an A.  None of that mattered any more.  What did matter is that I could look at the problem, think critically about it and come to an answer that was supported by other research and my own experiences.

Graduate school wasn’t about learning science, it was about learning how to learn.  At that level, you are the expert on your projects and no one else knows what you know.  You have to trust yourself and know how to find the right answers because there is no book in which to look.  When I finally figured out the game, I was amazed.  It was so empowering when I understood that, even though my beginning was rough and I felt for sure I could never do it, I had the skills in me all along.  Not only that, but I really enjoyed my work and felt like I was doing rather well with it.

  By the end of my six year graduate school epic journey, I knew I was no different than all those professors that I had so revered in college.  I thought their brains were fundamentally different than mine and that I could only hope to be a little bit like them.  In the end, I was them.  

I tried to make note of these realizations on the dedication page of my thesis by writing:

Why, anybody can have a brain… Back where I come from, we have universities, seats of great learning, where men go to become great thinkers.  And when they come out, they think deep thoughts and with no more brains than you have.

Fleming, V. (1939) The Wizard of Oz

            Or… a more contemporary quote: “Anyone can cook!” – Chef Gusteau

Rosalind Franklin: in short, she provided the data to James Watson and Francis Crick that allowed them to determine that DNA was a double helix.  Her contribution tends to be overlooked.  There is some controversy surrounding Watson/Crick and Franklin and who really discovered what when.  Coinciding with the 50^th anniversary of publishing the structure of DNA, Brenda Maddox published “Rosalind Franklin: The Dark Lady of DNA,” which discussed Franklin’s life and work during those times.

Marie Curie: She loved radioactivity.  Okay, she was awarded two Nobel prizes for her work in physics and chemistry and was the University of Paris’s first female professor.

REFERENCES

Fleming C. (1939) The Wizard of Oz.

Bird, B and Pinkava, J. (2007) Ratatouille.

Me, myself, and I – which has absorbed a lot of knowledge in the past nine years and even before!

Hand Sanitizers vs. Soap + Water

I need to preface this post with two points:

One: This post is for Sarah.

Two: As a touchy and somewhat contentious subject, I am only going to present the facts.  Yes, I have an opinion and I will offer it at the end under the heading of “my opinion, “ but everything leading up to that will be fact.

                With the threat of swine and avian flu tumbling through our winter lives, I noticed an increase in Purell hand sanitizer stations.  They became pervasive in my last work establishment and probably had been a permanent fixture in my new workplace for several years.  I remember watching people religiously rubbing the gel all over their hands after touching door handles or their fellow workmates.   I’ve also noticed an increase in toilet seat covers, women leaving restrooms holding paper towels and pre-rolling paper towels from the machines before washing hands.  However, in sharp contrast, I also still see women putting a lot of soap on their hands, then turning on ice cold water and doing only a cursory wash job.  I still laugh at the complete juxtaposition of these two characterizations.  (I'm not trying to be down on women, by the way.  I'm a girl and, as such, hang out in women's bathrooms - that's all).

                Why is hand washing so important?

                The Center for Disease Control (CDC) urges everyone to wash their hands appropriately several times a day to help prevent the spread of disease.  The importance of hand washing has been well established, but I will elaborate this point with one particular example.

                Childbed fever, known in the medical world as puerperal fever, is a serious infection contracted by women following childbirth.  If left untreated, this bacterium will cause septicemia and eventual death.  In my mind, the most famous historical death due to puerperal fever was Jane Seymour, third wife of Henry VIII.  She died twelve days following the birth of Henry’s most cherished and longed for son, the future Edward VI.  

                In 1847, Dr. Ignac Semmelweis concluded that hand washing was integral to the spread of puerperal fever.  This was the era before antibiotics and where women commonly delivered at home.  One percent of women who delivered at home died of childbed fever; an astonishing 20% died in hospitals.  Why?  Dr. Semmelweis agonized over the differences and finally said it was hospital doctors spreading infection from patient to patient.  After demanding that each doctor and nurse extensively wash their hands with chlorine between patients, the maternal death rate dropped to 1% in his Vienna hospital.  (Honestly, the area of birth is quite interesting to me as is the medical profession in general.  I highly recommend the book “Complications” by Atul Gawande, as well as “Better” by Atul Gawande and “Birth” by Tina Cassidy.  Both “Better” and “Birth” detail the history of childbed fever.) 

                Currently, the world offers two choices for hand washing: soap + running water or hand sanitizers.  In my previous post Soap!, I discussed how soap works.  Bacteria and viruses use hydrophobic molecules to envelope their cytosols (The Central Dogma) and genetic material (DNA/RNA).  Soap, which has a hydrophic end, can work itself into those protective hydrophobic coats of bacteria and viruses to break them open.  Once opened, the soap molecules can then find their way to bacterial/viral proteins and start to disrupt their structures.  After the soap has done those two jobs, placing your hands under running water allows those broken viruses and bacteria to be washed down the drain.

                Hand sanitizers work similarly in that ethanol or isopropanol (the active ingredient in hand sanitizers, which must be in excess of 60%) will also disrupt bacterial membranes, break open the bacteria and destroy protein structures.  There is no running water in this case so hand sanitizers merely disinfect hands, but do not clean them.

                The CDC recommendations for hand washing can be found here: http://www.cdc.gov/handwashing/

                In short, they say this:

One: If you have clean running water available, use soap and the running water to wash your hands.

Two: if you have running water that isn’t necessarily clean, use soap and the available running water to wash your hands.

Three: If you have no running water, use hand sanitizers.  (Remember, hand sanitizers do not clean hands – they merely disinfect them.)

                I recently read a paper about hand sanitizers versus the human norovirus.  Noroviruses notoriously infect cruise ship passengers and well meaning people during winter to cause bouts of diarrhea and vomiting (my worst nightmare, folks).  Oddly, hand sanitizers are not effective against noroviruses or similarly nonenveloped enteric viruses.  Further work needs to be done to find hand sanitizers effective against these agents.

My Opinion

                Wash your hands with old fashioned soap and water.  It’s wonderful and effective.  The CDC even recommends hand washing in this fashion over hand sanitizers and – in my impression after reading - that hand sanitizers should really be used in conjunction with regular hand washing, not in place of.  I do believe that hand sanitizers have their place, but I will always defer to frequent soap and water.  

I realize that doctors and nurses, who quickly jump from patient to patient, do no share this luxury and a fast squirt from a Purell to disinfect is easiest and best for patients before moving on.

Yes, Purell will help coworkers minimize transfer of infection to each other when in a work place environment – absolutely.  But, if my experience in bathrooms is saying anything, people need to learn how to wash their hands properly, as well.  Read the CDC guidelines.  Washing your hands isn’t running them under water and isn’t just covering them with soap.  Spend 20 seconds really washing and massaging your hands, between fingers and under your nails.  Spend a few extra seconds really rinsing your hands under running water and using clean paper towels to dry off.  

Stay healthy!

Septicemia: presence of bacteria in the blood

Non-enveloped enteric viruses:  viruses that infect the intestines that do not have hydrophobic coats for protection

REFERENCES

http://www.cdc.gov/handwashing/

http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0002331/

Weir, Alison. "The Six Wives of Henry VIII."  (1991) The Bodley Head, London, England.

 

Liu et al. “Effectiveness of Liquid Soap and Hand Sanitizer against Norwalk Virus on Contaminated Hands.” (2010) Applied and Environmental Microbiology 76(2), pgs 394 – 399.

Gawande, Atul. “Better: A Surgeon’s Notes on Performance” (2007) Picador, New York, New York.

Cassidy, Tina. “Birth: The Surprising History of How We are Born.” (2006) Grove/Atantic Inc. New York, New York.