Friday, April 1, 2011
Tuesday, March 29, 2011
At the time, radioactive elements were just discovered and businessmen were quick to find ways to utilize them. One property that made radium so intriguing was its otherworldly glow, an eerie blue green shimmer. While today we take for granted our digital watches with luminescent faces, in the early 20th century there was no such technology. And one popular application of these wondrous new elements was self-luminescent paint, used to make the dials and numbers of watches and other interments visible in the dark. Of course these details had to be painted on by hand, where workers had to craft a fine tip to their brush with their lips between strokes…
“The painters were teen-aged girls and young women who became friendly during the hours together and entertained themselves during by breaks by playing with the paint. They sprinkled the luminous liquid in their hair to make their curls twinkle in the dark. They brightened their fingernails with it. One girl covered her teeth to give herself a Cheshire cat smile when she went home at night. None of them considered this risky behavior. Why would they when doctors were using the same material to cure people, when wealthy spa residents were paying good money to soak in the stuff, when the popular tonic Radithor was promoted by neighboring company? No one – certainly not the dial painters themselves – saw anything to worry about it.
Until, one by one, the dial painters began, mysteriously, to fall ill. Their teeth fell out, their mouths filled with sores, their jaws rotted, they wasted away, weakened by an apparently unstoppable anemia. By 1924, nine of the dial painters were dead. They were all young women in their 20s, formerly healthy, with little in common except for those hours they spent, sitting at their iron-and-wood desks at the factory, painting tiny bright numbers on delicate instruments.”
It was not known at the time but radium is treated by the body as calcium and is incorporated into the bones. The girls’ severe anemia was caused by a degradation of their bone marrow from the radiation. And with each breath they took, they poisoned themselves further. As radium decays, it breaks down to radon, a gas which is also radioactive. With a constant inhale and exhale of lethal air, the girls withered away as their eventual legal fight ensued.
“Katherine Schaub’s jaws were starting to break apart; as she told her lawyers, she hoped the money – they were asking $250,000 each – would pay for her funeral. “If I won my $250,000, mightn’t I have lots of roses?””
The whole story is recounted by Blum brilliantly in this three part series (Part I // Part II // Part III) which is also found in her book, The Poisoner's Handbook: Murder and the Birth of Forensic Medicine in Jazz Age New York. I encourage everyone it up as it is easily the best popular science book I have come across. It is especially interesting to me, as it shows the birth of my whole field, toxicology, something that I had not realized was such a recent branch of science. The book details the work of the two most steadfast scientists, Charles Norris and Alexander Gettler, transforming not only the reputation of the notorious New York Medical Examiner’s Office but also building the foundations of an entirely new field of science. Thorough their endless experimentation and the constant battle against sheer bloody-mindedness of political corruption at the time, Norris and Gettler were unmatched in their novel thinking and perseverance. It was actually quite inspirational to read the lengths and sacrifices these two went through to convince the scientific, legal and political communities that toxicology was a field on its own and worthy of respect. The most amazing part of the book is Blum’s engrossing storytelling as you can glean from the excerpt above. The whole book reads like fiction but it is entirely factual.
So after the next apocalyptic scenario you hear about Japan's radiation reaching American, think back on the Radium Girls and a time when radioactivity was so poorly understood.
Saturday, March 19, 2011
Friday, March 18, 2011
They have both been in the news recently but not for the reasons you may think.
Companies like Wal-Mart and McDonalds were forced to recall thousands of items, such as Miley Cyrus jewelry and Shrek promotional glasses, because of the presence of cadmium. And it’s not too uncommon now that you hear on the news of some product made in China tainted with a toxic heavy metal like lead and cadmium. The most common culprit? Cheap jewelry, specifically, children’s jewelry. But is the cadmium present in these items bioavailable? Meaning, what is the risk to the consumer and just how much cadmium in these products can be potentially taken up by the user’s body? Researchers asked just that.
Cadmium (Cd) has broad industrial applications so it is a common environmental contaminant that is studied. Chronic cadmium exposure in humans can lead to kidney damage as well as osteotoxicity, where the bones become soft and less dense leading to increased fractures as well as general pain and weakness. Chronic exposure at any level is likely unsafe because it is not readily removed from the body and bioaccumilates, persisting in the body for a very, very long time. For example, the half-life of cadmium concentration in the kidneys is between 10 to 30 years. Yikes!
Certain cohorts tend to be more sensitive to cadmium as well. Smokers for example directly absorb cadmium from the inhalation of cigarette smoke, leading to a much more direct route of exposure. The group of most concern through is children. Children have been shown to have increased gut absorption of cadmium compared to adults, especially females (anyone know the reason for this? I’d be interested to know). However current guidelines for safe levels of cadmium exposure do not exist for children, so using the recommendation for adults (0.1 µg/kg bw/day) is likely an overestimate of safe levels for a child. In addition, there are no regulatory limits for cadmium levels in jewelry products.
To test whether there is a risk of cadmium exposure from children’s jewelry, in a coming issue of EHP, researchers went out and bought a bunch of cheap bracelets, charms and pendants. No more than $12 an item, most under $10 and many of the items manufactured in China. In order to determine the risk associated with these items, researchers had to simulate the most common pathways a child would be exposed to the cadmium found in these products and determine whether or not the metal is bioavailable. To simulate a child mouthing or sucking on their jewelry, the items were placed in saline for 6hrs. And to simulate the swallowing of one of these items, the jewelry was placed in HCl for on average 24hrs. The US Consumer Product Safety Commission (CPSC) recommends a maximum cadmium level of 18 µg/6hr saline extraction and 200 µg for the acid extraction.
Of the 612 pieces of jewelry purchased for this experiment, more than 270 contained more than 10,000 ppm (1%) cadmium, with 70 of those containing more than 10% cadmium. There did not seem to be any correlation between the amount of cadmium present in the items and the amount of cadmium extracted from the above methods. This is likely due to the different manufacturing of each item (different items made of different alloys, different coatings etc.) which also lead to a high variability between items. But none the less, both extraction methods yielded very high amounts of cadmium. In the mouthing scenario, up to 2200 µg Cd was leached into saline, and 10 of the 48 items tested were above the 18 µg CPSC recommended threshold.
The HCl extraction yielded even more interesting results because the amount leached into the acid increased linearly over time, tested up to 96hrs. A third of the jewelry tested leached more than the 200 µg recommended amount after just 24 hrs and the highest content measured at 20,000 µg. In addition, some jewelry that was damaged with 1-2mm cutss to simulate normal wear yielded 30 times more cadmium than undamaged replicates. But the differences in damaged versus undamaged jewelry were item specific in both the saline and acid extractions which just highlights the difficulty and complexity of trying to simulate and ultimately regulate the risk associated with cadmium tainted jewelry.
The authors raise an interesting point about whether the time points which are recommended are representative enough of actual ingestion exposure. In another study of children swallowing foreign objects, the “transit time through the digestive tract” (read: poop) was 6 days, but varied from 1 to 46 days (eewww). So maybe 6 or 24hrs time points are not long enough to replicate potential absorption. It would appear to me that the acid digestion utilized in this study would only account for cadmium leached while in the stomach and may not take account any enhanced absorption while passing through the intestines. But there are limitations on any simulation.
Overall though, this study really shows how difficult it is to calculate bioavailability of cadmium when the application and usage is so diverse, even when dealing with a specific subset of products like cheap children’s jewelry. But still, researchers were able purchase items that were both really high in cadmium content but also leached about to 100 times the recommended amount. So the danger is out there on the store shelves right now. As if the dreadful pop music and animated movies weren’t enough reason to avoid Miley Cyrus and Shrek, exposure to toxic cadmium can now be added to the list.
The longer my tenure as a grad student, the more and more I realize that it is a total learning experience. It is not enough for me to only learn the intricacies of select HIV/SIV proteins or the phylogenetic trees of viruses, humans and, non-human primates. I must also figure out what type of scientist I am and what type of project is best for me.
As I mentioned in my last post, thesis project #2 died in late August. As with thesis project #1, it was well thought out and based on good data and better ideas. However, things simply did not pan out, think of it as a “miscarriage of science.” The real question is what did I learn?
Sure I increased my depth of literature read, I learned and got close to mastering some techniques in lab. However, the true value of what I learned is that a project has to have a little bit of your personality in it. If the project is not a good fit how can you possibly be motivated to work hard on it, especially since a good project that is a good fit will test a student’s resolve at times.
Some scientists have amazingly good technique. You can say that they pipette excellence every time they change tips. The lab slang for these prodigies is that they have “very good hands.” Someone with hands of gold can get away with smaller more elegant experiments or using very technical assays to create beautiful data. A scientific paper tries to tell a story, it makes life a lot easier when you have beautiful figures to convince the reader your are right. Unfortunately for me my hands are average at best. Admittedly, had either project panned out I would have had to do some technically challenging assays that would have been hard for me to do well.
So, at the end of August I had to ask myself, what then are my strengths? If I don’t have great hands how can I ever hope to graduate? It was at this point that I had to step back and remember what had gotten me this far, the brute force approach. Whether it was my running or studying in college or basically any other aspect of my life I have always tried to outwork or do more then my “competitors.” Why then would grad school be any different?
The new project has a lot of my personality in it. I am a competitive person and we jumped into a competitive area with this one. I see the project as a race against the other groups. Just like running a race, with science there is no prize for second place. I try to work in lab with that in mind. We are also trying to answer a very complicated question; it does not lend itself to very elegant targeted experiments. Instead it requires me to approach question with a sledgehammer and learn all I can from the pieces. What this means on a daily basis is that I need to generate as many mutant viruses as I possible can as quickly as I can.
I have to say I am very happy with this approach and importantly it keeps me motivated in lab. Will success follow, I am not sure, but so far it has been one hell of a ride so far.