Getting sick for science (and money)

I went to medical school at a time when it was still affordable. Even though it was a private Ivy League university, tuition was only $1200/yr at the start and I had a half scholarship. Room was $33/month. Still, it was a long time ago and that was still real money for some of us, so I ate dinner in the cafeteria and often made lunch by heating up a 19 cent can of Spaghetti-O's on a hot plate in my room across from the hospital. Medical school classes didn't allow much time for part time jobs, so I supplemented my income working as a guinea pig and blood donor. Whenever open heart surgery was scheduled they paid $20 for a pint of fresh blood the morning of the surgery (blood type specific, of course) and I subjected myself to a variety of experimental protocols for money. Once I allowed them to infuse me intravenously with alcohol while they measured the response of my retina via a contact lens-like affair. This experiment gave me one of the worst hangovers of my life, but with the proceeds I was able to buy a nice Christmas present for my girlfriend (Larousse Gastronomique, in case you are interested).

But there were some things I wouldn't do, even for money. Things like this:

Noroviruses are the most common cause of viral gastroenteritis in the United States. To determine the magnitude and duration of virus shedding in feces, we evaluated persons who had been experimentally infected with Norwalk virus. Of 16 persons, clinical gastroenteritis (watery diarrhea and/or vomiting) developed in 11; symptomatic illness lasted 1-2 days. Virus shedding was first detected by reverse transcription-PCR (RT-PCR) â19.5 hours after participant inoculation and lasted a median of 28 days after inoculation (range 13-56 days). (Atmar RL, Opekun AR, Gilger MA, Estes MK, Crawford SE, Neill FH, et al. Norwalk virus shedding after experimental human infection. Emerg Infect Dis. 2008 Oct; [Epub ahead of print])

Norwalk virus is the leading cause of epidemic gatroenteritis in the US. It's the virus that causes cruise ship outbreaks. It's the kind of food poisoning or stomach flu where first you're afraid you're going to die and then you're afraid you're not going to die. So why deliberately infect people? The simple answer is that the only source of good information we have about this common and costly acute illness comes either from experimentally infecting human volunteers or trying to collect information from outbreaks. There is no animal model and only recently has a culture method been described. So we are reduced to giving people the virus and then measuring the result. In this case the source was derived from the liquid feces of a previous volunteer after clarification, centrifugation and then serial filtration with smaller and smaller pore size. Eventually the researchers, from Baylor College of Medicine, had an experimental inoculum with only norovirus left. They packaged it and froze it.

They then recruited 16 volunteers, ages 18 to 50, and gave each varying doses of this highly infectious agent. There is no mention of how much they paid each of them, but my guess is that it was substantial, probably better than $1000 apiece. At the outset they were admitted to Bayloar's General Clinical Research Center and given varying doses or a placebo. All of them remained in the hospital for at least four days, some longer if they remained sick. They were released only if they had no watery diarrhea or vomiting for at least 18 hours. That should tell you something.

The goal was to describe the course of illness and determine how long virus was shed in the feces, so after discharge they were asked to keep collecting feces for daily for 21 days and then weekly for up to 5 more weeks. The logistics of feces collection weren't described in the paper but in other experiments I'm familiar with, 24 hour fecal collection was done by evacuating into a wide mouth picnic thermos jug and delivered to the laboratory within one day (now you know a second reason why the volunteers have to be paid a lot). I was once at a meeting, about ten years ago, where one of these volunteer experiments with cryptosporidium was presented and on the slide it showed samples were collected from 82 out of 83 participants. Someone asked what happened to the lone volunteer whose fecal sample was missing. The answer was that this volunteer lived about two hours from the lab and took a bus to get there. He had his thermos next to him on the seat and he fell asleep. When he woke up he discovered someone had stolen it.

Back to norovirus:

A total of 16 persons inoculated with Norwalk virus met the criteria for having Norwalk virus infection. Of these, 11 (69%) met the predefined definition for viral gastroenteritis. The 5 who did not meet this predefined definition had >3 symptoms that did not include vomiting or >200 g of watery diarrhea. All 11 participants with viral gastroenteritis had abdominal cramps, nausea, and vomiting; 5 of these participants also had >200 g of watery diarrhea, and 1 had 37.6oC (n = 4), and chills (n = 3). The 5 participants who did not fulfill the criteria for gastroenteritis had nausea (n = 5), anorexia (n = 5), malaise (n = 4), abdominal cramps (n = 3), myalgia (n = 3), headache (n = 3), temperature >37.6oC (n = 2), chills (n = 2), and watery diarrhea

To summarize: Almost everyone got sick, although five didn't meet the full definition for full blown infection. Illness lasted between 10 hours and 60 hours (two and half days!) but for half it was over in 24 hours -- the 24 hour stomach bug. The surprise, though, was that all volunteers continued to shed virus for a long period, how long depended on how it was measured. Half of the volunteers were still shedding detectable virus 4 weeks later, and the peak of shedding occurred after the end of symptoms, that is, when the patient was recovered. Some were still shedding 8 weeks later. This is a possible explanation for how apparently well food handlers might still be a source of infection.

However there is a major unknown concerning these viral shedding data. Just because viral genetic material is still detectable 4 or 8 weeks later using a sensitive test like RT-PCR doesn't mean there is intact virus capable of infecting someone. That's yet another step in figuring out what is going on with this common viral infection.

Meanwhile, hats off to these volunteers. Sure they were paid. But there are some things I wouldn't do for money and I think this is one of them. I hope it was worth it.

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Am I wrong to find the entire article interesting (and enlightening, as an amateur cook)but find the bit about the stolen thermos of fecal sample hilarious?

I summarized it for my husband between howls of laughter and said, "I can't help thinking in this case karma is swift and sure."

By Alexandra Lynch (not verified) on 03 Oct 2008 #permalink

Some things are more important than money. I would rather have a Larousse Gastronomique than a $1,000. and a thermos-type container full of warm fecal material any day. Like you, I really hope that they were able to get something extraordinary out of being guinee pigs for this test.

Didn't a college football team just cancel their game this weekend due to almost the whole team coming down with this stuff? I thought I saw something on the ESPN ticker at the bottom of the page, but I was cheering for the Dodgers (sorry Cub fans, including late mum). I told hubby the team was smart to do so, considering how truly godawful you feel with this junk.

By G in INdiana (not verified) on 03 Oct 2008 #permalink

"There is no mention of how much they paid each of them, but my guess is that it was substantial, probably better than $1000 apiece."

You would definitely know more than I about typical compensation for medical studies, but I would be surprised if the compensation was substantial. I remember back in grad school when discussing ethics and participant compensation, we always mentioned the fine line between offering enough to entice the person to participate, yet not so much that the person would not be able to say no (which would be unethical).

But, then again, these days, who can say how far even $1000 will go...

You would definitely know more than I about typical compensation for medical studies, but I would be surprised if the compensation was substantial.

When I was a freshman in college, I signed up to participate in a flu vaccine study, with some possibility of getting ill. The participants were housed in a hotel for a week and observed, and received $3000 apiece (in 1997 dollars). So $1000+ seems unsurprising considering the time involved here, and the near-certainty of illness.

(Incidentally, I had flu antibodies present and was thus rejected for that study.)

I'm not sure I would do it, but I'm not entirely sure I wouldn't, either. I mean, you can get norovirus in the wild with nobody paying you anything. And the cramping and watery diarrhea sounds like colonoscopy prep, when you have to pay them. ;)

The study I mentioned on crypto from ten years ago I think paid $900, so my estimate is probably low, considering Davis's comment. Remember the discomfort, four days in the hospital and the shkeeve factor.

I've been injected with the new Anthrax vaccine in a one and a half year study. It's not the sketchy attenuated version but a recombinant, and I go in for antibody tests in a few weeks. The pay totals $700.

From a public health standpoint, someone needs to pounce on that item about shedding virus for 4 weeks. Unfortunately this will probably call for another study with volunteers getting shot up with fecal extract taken from each week's samples, to figure out where the demarcation is for "no longer infectious." I'm going to guess the mean value turns out to be 2 weeks, and a fairly flat curve, meaning some people are still infectious at 4 weeks.

This goes a long way toward explaining why these outbreaks are so damn hard to contain. "Oh, I was sick two weeks ago but now I'm fiiiiine!"

What we really need is mandatory sick leave from work for the entire duration of the contagious phase of anything worse than a simple cold.

That and train people to wash their hands every time they use the bathroom, which might take a while in a culture where 1/3 of the population believes the Earth is 6,000 years old.

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I had this little nastie or something similar, twice, in college, and was inpatient both times. The first time included a high fever and an interesting experience: one morning I told the nurse of a dream I'd had the preceding night, of a naval ship going down in a sea battle. She got a shocked look on her face and told me that that particular day was the anniversary of the death of a close family member who was in the Navy and whose ship had gone down in a sea battle. Thinking that I might have heard her talking about it while I was asleep, I asked her if she had mentioned it to anyone while she was at the clinic, and she said she had not.

The second time, I decided that if a third time occurred and there had happened to be a gun on the bedside table, I'd use it to put myself out of my misery. Mentioning that to a nurse won me a visit from the school psychologist "just in case." To this day, despite my support of 2nd Amendment rights and my belief that everyone should practice their constitutional rights regularly, I don't own firearms because I realized that that specific case was an indicator of a risk I'd sooner not take.

Word to the wise: Do Not self-medicate this with opiates, as that can be fatal. Narcotic analgesics may be seen as the anti-diarrheal medications of last resort, because they slow intestinal transport and thereby also shut down the cramps as well. However, slowing intestinal transport just gives whatever-it-is a greater degree of contact time to be absorbed into your bloodstream, and in some cases that can kill you. The best medications for this are the conventional anti-diarrheal bulking agents. Also, to avoid dehydration and the resulting high fever and cognitive symptoms, without triggering another vomiting spell, take water by the teaspoon full, small sips at regular intervals.

So far as I know there is no medication that will safely alleviate the pure horrific misery of this kind of bug. The ideal case would be: you're rendered basically unconscious and propped up in a leaning-forward position (so you don't drown on your puke) with a tube connected to your rear end, and wake up a couple of days later after it's all over. Heh, some day....

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As for the stolen thermos story: Heh, the bastard deserved it. "Oh boy, hot coffee..." Owing to the cognitive dissonance over the idea of "poo in a thermos," even if he sniffed at it he may not have recognized it, but instead thought it was something else, like maybe soup from the deli or whatever. And then taken a sip to try to figure out what it was. And then another sip due to the uncertainty of the first one. And then come down with the bug himself.

I heard a story about someone who had to pee while on the road, and only had an empty scotch bottle from a party the night before. So he did his business, screwed the cap back on the bottle, and left the bottle on the passenger seat pending proper disposal. Later that day someone broke into the car and stole the bottle. Here's to hoping that cretin didn't bother to check further before taking a great big swig.

g336: "That and train (sic) people to wash their hands every time they use the bathroom, which might take a while in a culture where 1/3 of the population believes the Earth is 6,000 years old.

Initially I was offended at your gratuitous swipe at people of religious belief (of whatever religion), who, because of their literal interpretation of the Bible, they must all have unenlightened and unsanitary habits of hygiene.

Unless you too, were a cretin (the term you use elsewhere in your post), I couldn't imagine this to have been your serious attempt at inductive reasoning: i.e., because they have a belief system that doesn't conform to yours, they must be unaware of the necessity of hand washing after using the toilet. (I love how so many scientists familiar with modern theories of physics, concerning the elasticity and relativity of time, cannot imagine that "6,000 years" might represent something beyond their narrowed and literal Newtonian concept of time).

But then witnessing the rest of your discursive prolixity, I was reassured that your faulty reasoning was not of malicious intent; its endlessness confirming your own unfortunate cretinism.

Paul: I know your remarks were directed at g336 and not me, but I must call your reposte into question. It assumes that any belief system is as good as any other and that people who believe the earth is only 6000 years old on the basis of a book of dubious authorship don't really believe it. The second of these points is condescending to the believers (a condescension which they deserve but which you only condemn in others), not to mention the belief systems you criticize and abhor but which by your reasoning are worthy of respect (I won't go there but you know what I mean). And why not apply it to your own condemnation of g336's beliefs? Because your tolerance is hypocritical and only applies to your own beliefs, not those of others. Regarding science and time, your remarks have nothing to do with the science amd time nor do they exhibit any understanding of the issue in relativity theory or classical mechanics. They are just your own little rhetorical swipe, like g336's (and mine).

Whether someone who believes the world is 6000 years old or not washes their hands at an appropriate time is an open question, but they point that someone who has so little regard for scientific fact might have a major risk factor for not believing some other scientific fact seems to me at least plausible.

Revere, I will start with a concession: I understood your very last sentence, and could follow the logic of your hypothesis: that if people were uninformed about certain accepted scientific facts, they might also be uninformed about the need to wash their hands. And quite honestly, that did help me make the connection that I missed with g336's statement.

However, to me, this is again the same issue I've raised with you personally, in my last two comments at this blog. g336 is using the same reductio ad incommodum that you resorted to twice. I know you understand this concept, but for those who might not, it is discrediting the position of the opposition in an argument or debate, by citing an extreme (implausible and usually incriminating or derogatory) as being perfectly analogous to the legitimate point that the opposition has posited. This bit of sophistry is commonly employed when no more valid response can be summoned. This is not quite the same as reductio ad absurdum, though the two are often used interchangeably.

The last example of your use of this fallacious debating technique was your conflating my position on the need to use any means to defend one's country, first, with "torture," and later adding "atrocity." You were trying to demonstrate that my defense of the defense of a nation-state by any means equates all such means with the "barbarity" of the most unsavory means you could conjure.

As an aside, an atrocity is an unquantifiable and subjective description of some action, which by its very definition, means unacceptably or monstrously inhumane. So it is really little more than name-calling. You might declare "torture," as an atrocity in any context. I do not. Were I interrogating a terrorist who likely had information as to where and when a nuclear device was going to destroy some American city, I would not only use every conceivable application of pain, i.e., "torture," to secure that information from this atrocity of a human being, but I would not hesitate to engage the services of the most infamous sadist to add to my repertoire of persuasive measures. To paraphrase your rather humorous statement, I would take this piece of shit beyond his fear of dying, to his fear of not dying.

Now, let me address your next three accusations.

(1) Your claim: I am demonstrating condescension to those who believe that which is recorded in the Bible. Comparison of my direct quote to your paraphrase of it, not only bears no resemblance to my statement, but your added description of the Bible as âa book of dubious authorshipâ (which can be found nowhere in my statement) represents a classic example of the psychological phenomenon of projection.

My second paragraph: âInitially, I was offended at your (g336âs) gratuitous swipe at people of religious beliefâ¦who, because of their literal interpretation of the Bible, they must all have unenlightened and unsanitary habits of hygiene.â

This is a straightforward defense of people of religion against g336âs reductio comparison of their belief in the Bibleâs contents with unsanitary habits. I capitalized the word, Bible (as I do every time I write its title). Where is the condescension? Where do you see the words âa book of dubious authorship?â Those are YOUR WORDS, revere, and are consistent with your allusions to this Book in countless other of your posts.

You have projected your disrespect for the Bible by hallucinating words you would use to defame this Book as being present in my statement. *EXAMINE AGAIN, IF YOU WOULD, the quote of my statement. WHERE DO YOU SEE THAT DEFAMATORY DESCRIPTION? Those are YOUR words.

You present a blatantly fabricated misquote to substantiate your accusation of my being condescending to the very people whom I am obviously defending, without there being any HINT in my second paragraph of insincerity, sarcasm, or condescension.

As I HAVE cited your many past ridicules of people of faith as being condescending, you then take your twisted paraphrasing a step further by labeling my âcondescension,â which you have pathetically failed to demonstrate, as being âHYPOCRITICAL.â

Donât get me wrong, revere. I donât believe you purposely made such a transparent attempt to falsify what I actually said, so that you could accuse me of hypocritical inconsistency. That would not become you. However, and perhaps more unsettling, you are clearly demonstrating the mechanism of projection to a pathological degree. I dare not say more.

(2) ââ¦not to mention the belief systems you criticize and abhor but which by your reasoning are worthy of respect (I won't go there but you know what I mean). And why not apply it to your own condemnation of g336's beliefs? Because your tolerance is hypocritical and only applies to your own beliefs, not those of others.â

â(I wonât go there but you know what I mean).â

I havenât the foggiest clue of what you mean. In fact, you have often used this concluding obscurity to avoid listing the specific instances, my previous statements, or whatever it is to which you are supposedly referring. Perhaps, you have a clear memory of these past postings, but please, do me the favor of specifying whatever it is that only YOU KNOW WHAT YOU MEAN. Without doing so, the above quote is not only indecipherable in its style, but also lacks any substance, since you have stated nothing other than your erroneous assumption that I can divine what you are unwilling to explicitly state.

(3) âRegarding science and time, your remarks have nothing to do with the science and time nor do they exhibit any understanding of the issue in relativity theory or classical mechanics. They are just your own little rhetorical swipe, like g336's (and mine).â

Sir that is nothing more than an empty attempt at a put-down. How could you possibly make such sweeping assumptions about my knowledge of all the fields to which you glibly refer. On what possible basis can you discern my lack of understanding of the elasticity of time and the Special and General Theories of Relativity?

There is more substance in my parenthetical statement than your entire disparagement. Let me simplify my statement for your benefit.

If one believes that a Creator created what exists, and there is a specific reference to the time He took to do so, (wherever that reference might be found), and also considering that the Theory of Relativity has demonstrated (to those familiar with the theory) that time may not be as absolute a measurement as men once thought it to be prior to Einstein, but in fact may appear, and does indeed, have different parameters, depending on the context in which it is measured, then 6,000 years might not be the same measure of time as is usually understood in our daily more pedestrian perception of this dimension.

If you asked an eagle what time is it, his quizzical response would be, âWhat time is it? Itâs now.â (Credit to Eckhart Tolle).

Were the volunteers lawyers?

"He had his thermos next to him on the seat and he fell asleep. When he woke up he discovered someone had stolen it."

Today I will tell everybody in our lab that story. Thank you.

By antipodean (not verified) on 23 Aug 2009 #permalink

wow. Thanks for the informative post, I liked it anyhow. More fascinating almost was the back and forth in the comments. Thanks folks for making me appreciate my tendencies and such even more today. I needed that. The arguing on semantic points is fine and logical and all that, yet still strikes even me as a bit odd. Congrats on that. =) And don't bother to try to rip me up, as I likely won't see it, and with my IQ, I don't really care what you think of my thinking. (oh that makes me giggle too) Ciao! Thanks again Revere!