Biomarkers: What are they and why do we study them?

In my previous post, I stated that as part of the research of which I was involved, we took blood and urine samples from our subjects, i.e. the guys we were studying. These men are exposed to chemicals during the normal course of their workday. [I say men because the all the people in our study were men. We would have happily used women in our study, but the industry we were studying is dominated by male workers, and we did not find any females to participate or who even worked at that type of job.] While the men were exposed to numerous chemicals, we were interested in one specific chemical that is known to cause detrimental health effects. While the subject was working with this chemical, we had a personal air sampling device clipped to his clothing in the shoulder area. This gave us estimate of the amount of chemical that was in his breathing air space. It was important for us to measure the breathing air space to determine exposure because the worker was spraying this chemical, so the chemical concentration would not be uniform in the air around him. As an example, if you are standing in your house, you can presume the air around you is evenly mixed. However, if while standing there, you spray air freshener or something like that, then as you spray and right after you spray, there will be a very high concentration of the air freshener in front of the direction you sprayed it. There will be a lower, but still high concentration right behind the sprayer, presumably this would be where you are, as the spray mixes. The high concentration will quickly spread out, and the freshener will mix in the rest of the room. If the house’s ventilation system is operating at the time, the freshener will mix faster than if the ventilation is currently off. Thus, the air sample that was taken in the breathing air space gave us an estimate of what the worker would have breathed in had he not been wearing a respirator. All the workers wore respirators though. Some wore half-face filter type respirators (similar to what you buy at a hardware store), which generally reduce the chemical concentration in the air breathed in by a factor about ten or so, if they are worn properly. Some workers wore supplied-air respirators, like a firefighter only these were attached to a hose with an outside air supply. This type of respirators generally reduces the chemical concentration in air breathed in by a factor of 1000. Therefore, we got an estimate of what the worker was exposed to in the air but not of the amount that made it into the lungs.

After the subject worked with the chemical, we applied and quickly removed tape strips (medical tape) to his arms, wrists, hands, and neck to determine the amount of the chemical that made it onto his skin in those areas. The medical tape removed the very top layer of epidermis and any chemical that was in that layer. Basically it was like we applied and then removed a band-aid without the gauze section. Thus, the tape strip gave us an estimate of how much chemical made it on to his skin, but it couldn’t tell us how much of the chemical actually made it through the layers of the skin and into the blood stream. Previous research had indicated that it was possible for this chemical to be absorbed through the skin. Despite what some people might think, skin is not impervious to chemicals. If it was, the nicotine patch and the estrogen patch wouldn’t work.

To summarize, we could estimate what the worker was exposed to via inhalation and dermal exposure, but we didn’t know what he actually absorbed or what made it into his body. That is where biomarkers can be useful. Biomarkers are measurements of a chemical or some other tell-tale sign of exposure in some biological sample. They can be measured in the blood, urine, fecal matter, exhaled breath, and many other bodily fluids or materials. Some materials are used more frequently because they are a lot easier to get. It is much easier to get someone to agree to urinate in a cup then to let you do a spinal tap for spinal fluid. Which bodily material is used also depends on what the chemical of interest is. If you are looking for a volatile chemical, the exhaled breath might be used. To get the exhaled breath, the person simply exhales into a specially designed glass tube. Similarly, a suspected drunk driver who has just been pulled over by the police, may be asked to breath into a breathalyzer. The concentration of the alcohol, or chemical, in that air can then be measured. This is a biomarker. If the chemical or its metabolite is excreted quickly, then it would be more useful to study the urine than the blood because there would probably be higher concentrations in the urine than the blood. However, the concentration in the urine is generally more representative of short term exposure, while the blood is more representative of long-term exposure.

The metabolism of the chemical is very important because it indicates what chemical you are actually looking for in the body and also where to look for it. For example, when a person is exposed to lead, it does not change into another chemical because lead is an element. Thus, blood lead level is a biomarker used to indicate exposure to lead. A person’s intoxication level can be measured by exhaled breath as stated. A suspected intoxicated person can also have a blood sample withdrawn, and the amount of alcohol in the blood can be measured. It is called the blood alcohol content, and it a biomarker of alcohol exposure. The body metabolizes alcohol and uses it for fuel, so looking for it in the urine is not all that useful, or least not for the police. Alcohol in the urine is more indicative of consumption hours beforehand (i.e. it doesn’t tell the police how drunk the person is at that moment, crucial for legal reasons), and it is not completely accurate because the rate and amount that a person metabolizes alcohol differs from another person. Like alcohol, many other chemicals that people are exposed to, are metabolized or partially metabolized by the body. Unlike alcohol, if it is a chemical that the body does not need and can’t use for nutrition, then the body will generally try to get rid of it as quickly as possible, if it can. The chemical we were studying in our research was like this. The body has no use for it, so it is partially metabolized and excreted. Thus we looked for the metabolite, not the chemical itself, in the urine or blood. To what degree a chemical or metabolite can be found in the urine versus the blood versus some other bodily fluid or tissue depends on the physical and chemical properties of the chemical or its metabolite. The metabolism, storage, and excretion pathway in the body of different chemicals is the subject of fascinating research and possibly another blog post.

Shipping Human Specimens

This morning I read an article in the Chicago Sun-Times concerning 17 human heads that had been discovered at Chicago O’Hare Airport. The best part of the headline is that it said “no foul play suspected.” This article has now been updated to state that “‘They were properly preserved and tagged as human specimens,’ said Tony Brucci, chief investigator for the medical examiner’s office” and that according to U.S. Department of Homeland Security, “the specimens appear to be legitimate medical samples.” The original version of the article, which I can no longer find, did not have all these details. It just said 17 human heads had been discovered, transported to the medical examiner’s office, and no foul play was suspected. This of course, sent most people’s imaginations wild as to how 17 human heads could end up at an airport without foul play. Perhaps this is a new way to save on air fair, just send a head, not the whole body.

The shipment of human heads, legitimately or otherwise, made me think of my human specimen shipping adventures while in graduate school. The field work that my fellow graduate students and I performed included three one-month trips to Seattle. Everyday we would drive to a different location to sample at the type of workplace we were studying. Among the samples we collected were blood and urine. For the vast majority of blood analysis, including the ones we were doing, the blood has to be separated into the red blood cell fraction and plasma section before it can be frozen. We were actually isolating the white blood cells also. To separate blood into these fractions, the blood has to be separated within 24 hours of being drawn, in truth, the sooner the better. Therefore, every night after sampling, we would ship the samples overnight to the east coast where our university was located. This may surprise some people, but this is actually not that big of a deal. Another grad student and I became certified hazardous materials shippers to do everything properly. In the case of our biological samples, the blood and urine, they could be shipped as “exempt human specimens.” This is specific term for shipping that meant our samples were not infectious and only required certain precautions to ship. Unless a person has a urinary tract infection, urine is sterile. Blood of course can carry many infectious agents, but if a person can be reasonably believed to be healthy and free of a blood-borne infection, then the blood can also be assumed to be non-infectious, and the blood can be shipped as an exempt human specimen.

Therefore every night after sampling, we would put the blood and urine samples with ice packs in a styrofoam container that was within a cardboard box. The cardboard box was clearly labeled “EXEMPT HUMAN SPECIMENS” as per shipping rules. We would then ship via FedEx, or if we couldn’t make it to the FedEx drop off before the overnight cut off for east of the Rockies (FedEx had an hour later drop off for west of the Rockies, presumably those went to a different sorting center), then we would drive to SeaTac airport and ship via cargo on a passenger aircraft. Shipping cargo on a passenger aircraft was an adventure. This was post 9/11, and they had started to implement more security measures for cargo. I don’t fully know what the security measures were then or today, but let’s just say, I don’t have a lot of faith in the security of cargo. In any event, the first time I dropped a box off at the passenger airline, which I won’t be naming, after going through a whole lot of paperwork, the employee took the package which had already been sealed. He asked if he could open it to examine the contents for security reasons. As he had no gloves on, I said, of course you can examine it, but to avoid contamination of my samples and for your own safety, please put on latex or nitrile gloves. He stopped and stared at me and asked why. Another employee who was working on the paperwork stopped what he was doing, looked at the first employee, and then the second employee and I at about the same time, said because the package contains human specimens, as it states on the outside, and as all the paperwork states. The first employee then said “oh” and looked a little embarrassed and took the package to the back, hopefully to be x-rayed or something. I say hopefully because as someone who flies, I am hopeful but not confident all cargo gets x-rayed. The fact that the employee was going to open a package without reading or noticing the large letters on the outside that said “EXEMPT HUMAN SPECIMENS” made me rather wonder how much they check things they accept and how much their employees might endanger themselves by not paying attention. Things were much easier when we could make it to FedEx, and they ship thousands (millions?) of these types of packages everyday. [This is not a plug or advertisement for them.]

The packages’ return trip was also made me wonder how much people question or don’t question things. After our fellow grad students back at the lab had received a week’s worth of packages or so, they would put the thawed ice packs back in the styrofoam, close everything up, and ship them back to us via FedEx ground, so we could reuse the boxes. The first time they shipped boxes back, they didn’t bother to remove the taped labels that said “EXEMPT HUMAN SPECIMENS”. I thought I had told them to do this, or perhaps I just assumed they would. I don’t know if there is anything legally or technically wrong with shipping boxes labeled as exempt human specimens that don’t actually contain human specimens or anything else for that matter. However, as we were shipping them back via ground to save money, and it took five days to get from our university to Seattle, I would think it would be better to remove the labels so that no one at FedEx questioned why or what kind of specimens would not go bad over the course of five days. Because the label said “exempt”, it should not change the shipment method, but packages shouldn’t be labeled as something more dangerous than they are. There are some types of dangerous goods that can’t be shipped via ground because it takes too long or it would affect the route (think of all those freeways and roads that say “no hazardous cargo”). Conversely there are some dangerous goods that can’t go in an airplane. However, I guess I worry too much because the packages arrived at our hotel without any problems or questions from FedEx. I guess FedEx was not concerned with five day ground shipment of exempt human specimens, whatever they might be.

I’m not entirely sure what the hotel employees thought of us, but they must have wondered. We were there for an entire month, and the people at reception certainly knew me if only because we were rather unusual guests. We had a small freezer in our room to store our non-biological samples before shipping them back to the lab. We had stacks of empty boxes labeled “EXEMPT HUMAN SPECIMENS” and other boxes labeled for the chemicals we shipped. My room had boxes of urine and blood sample collection supplies. Another room had a bunch of charging personal air sample pumps and their calibration machine. No, we were not normal hotel guests. They knew me at reception because I was always picking up packages, including our returned “exempt human specimens” boxes. First time I came to pick up the returned packages, they had them stacked up in the front office. One employee timidly asked if I would mind telling him what was in the boxes. The boxes were about 18 inches wide by 12 inches deep by 18 inches or so. I explained that they were currently empty and what we were using them for. He started laughing and seemed relieved but almost disappointed. Evidently they had spent the day guessing what was in them. The winner had been human heads. I wasn’t sure how to respond to that. However they didn’t call the police or kick us out of the hotel, so I guess they thought we and our credit cards were trustworthy enough that what we were shipping was legitimate and safe. Still, it makes me wonder how much people pay attention to things and question what they see.