This month, Sydney Spiesel explains and ventures an opinion about the latest in stem-cell research, parasite outbreaks, and cocaine consumption. He also updates some previously discussed topics. (Click here for the July and June roundups.)
Stem cells: New ways to make them, new ways to use them.
State of the Science: Like other mammals and most animals, humans begin as a single cell, the result of the fusion of egg and sperm. In the course of embryonic development, this first single cell divides and divides again and continues to divide. As time elapses, the dividing cells begin to take on individual characteristics: They acquire highly specific properties, and they lose some abilities, "differentiating" as they go on to become part of bone, brain, skin, and every other body part. The early undifferentiated cells are called "pluripotential" because they have the capacity to differentiate into every kind of cell in the body. Stem-cell therapy makes use of that capacity: In animal and some human experiments scientists have demonstrated that they can replace missing or misfiring differentiated adult cells and, in doing so, restore function to malfunctioning organs.
The politics: Stem-cell use is the most contentious issue in medicine these days—more contentious than really important concerns like cost and access to medical care and the impending risk of a worldwide influenza epidemic. Not all stem cells are derived from embryos. Until recently, however, the cells prepared from embryos were much more likely to work for research and therapy than the cells prepared from adult tissues. Using embryo cells raises religious objections; not using them raises objections about missed opportunities and waste.
Prognosis: The religious dilemma is here to stay. But this month, a report on stem-cell research using human umbilical-cord blood, by a team from Kingston University in Britain headed by Colin McGuckin, shed slightly more optimistic light on the possible use of stem-cell sources other than embryos. Until now, stem cells prepared from umbilical-cord blood were good as precursors only for the formation of blood cells, for example, in patients who can't make the blood cells because they're being treated for cancer. McGuckin's group for the first time used stem cells from umbilical-cord blood as precursors for tissue cells. Thus far, these results are limited to the liver; further research is needed to determine whether umbilical-cord blood can yield fully pluripotent stem cells.
Also promising: A report by Kevin Eggan of Harvard University describing a way to use embryonic stem cells to convert adult cells back into an undifferentiated state. This method could yield stem cells that are prepared from one's own tissues and thus less likely to be rejected by the body's normal defense mechanisms.
In terms of new treatments, Drs. Lee Ann Laurent-Applegate and Patrick Hohlfield and their collaborators report that they used human fetal cells to treat burns in children in Switzerland, with dramatic results. The treatment produced excellent cosmetic and functional results in all eight children on whom it was tested. * Also this month, some intriguing animal studies reinforced the hope that someday doctors will be able to use stem cells to repair damaged spinal cords and lungs.
Parasites: the not-so-innocent pleasures.
Outbreak: A summer romp in a Finger Lakes, N.Y., spray park during the brutal heat of August led to unexpected and mightily unpleasant illness for more than 3,000 people. The victims had stomach cramps, nausea, vomiting, and impressive diarrhea courtesy of a small parasite called cryptosporidium.
State of the Science: "Crypto" is probably the most common cause of waterborne disease in the United States and the world. The organism is extraordinarily hearty and easily survives even enthusiastic chlorination. It spreads from person to person via poop, as we pediatricians like to say. It's easy to transmit but hard to diagnose, treat, and eliminate. The Finger Lakes outbreak probably occurred because the spray park water is recycled, and the chlorination and filtration used to keep the water safe weren't up to the job.
The worst U.S. crypto epidemic occurred in 1993, when Milwaukee's water supply became contaminated and more than 400,000 people got sick. One American-population survey suggests that by the time you're 70, you have a 70 percent chance of having had this disease at some time in your life, perhaps without knowing it. Fortunately, crypto is pretty benign for people with normal immune systems: The cramps and runs generally last only two to four days. Young children can get sick for as long as four weeks, though, and the disease has long-term and sometimes life-threatening consequences for patients who are immunodeficient, especially those with AIDS.
Bug No. 2: Crypto is not the only generally mild and widely distributed bug to cause a U.S. outbreak this year. First identified in St. Louis in 1933, lymphocytic choriomeningitis virus, or LCM, causes fever, headache, muscle aches, nausea, and vomiting—pretty much the same as every viral illness described on TV. LCM is often harmless and often asymptomatic. As is the case with crypto, however, immunodeficient patients are at risk of serious or even lethal outcomes. We also now know that if women are infected early in pregnancy, LCM can cause severe illness or developmental defects in the fetus. LCM is carried by house mice and also pets, including sweet and cuddly hamsters and guinea pigs—yet another example of an innocent pleasure that sometimes isn't.
Prognosis: A new medication, nitazoxanide (Alinia), is effective in patients with normal immune systems. But it probably doesn't have much value because the disease generally resolves on its own before there is a chance for diagnosis. Unfortunately, it is not clear whether the new treatment works for the immunodeficient patients who need it most.
Preventive measures: How do you protect yourself and your children from these illnesses? People at special risk need to take special precautions, by avoiding contact with water in lakes and streams and staying away from spray parks and other places where they might be exposed to recycled water in which children have been playing. They should also avoid wild mice and their droppings and should not handle pet rodents or their cages and bedding material. Children should wash their hands after handling these pets (and, by the way, pet reptiles, which often carry salmonella, a germ that also causes severe diarrhea). Realistically, though, most children won't be so obliging. Which means we should be grateful that most of them won't become seriously ill if they catch crypto or LCM.
Cocaine: What goes in must come out.
State of the Science: The laboratory of Ettore Zuccato in the Mario Negri Institute in Milan, Italy, brings us a small and elegant study that introduces an audacious method for studying an old public-health problem: illicit drug use. Cocaine is an extremely potent and addictive drug, and there is a general sense that its use is increasing. But this impression is not based on reliable data. To assign resources and figure out what treatments work, it's important to know how much of the drug is being consumed in a community. But this is a problem that is very hard to study. Think about it: Who do you ask? How do you get to them? How truthfully do they respond?
To get at the question of daily cocaine consumption in four medium-sized Italian cities and the Po River basin, the Milanese researchers made use of a well-known property of the drug: the excretion of its breakdown products in urine. The researchers sampled the water of the Po and also wastewater entering treatment plants in the four cities. They used the results to estimate how much cocaine must have been consumed (and excreted) to achieve the measured concentrations.
Results: What they found is a little startling. In the sampled locations, the researchers estimated that an average of between two and seven doses per 1,000 people, or between nine and 26 doses per 1,000 young adults, had been consumed daily. The Po River water analysis showed that 4 kilograms a day—that is, more than 3,000 pounds a year, with a New York City street value of $150 million—are consumed in that region of Italy. This is perhaps three times as much as was previously thought to be the case, which obviously has huge economic and social implications. When a new methodology is introduced, it's always worthwhile to scrutinize the results to see if they are at least internally consistent. These data, however surprising, meet that test. The Po River was sampled at several locations and times, and the results were compared with wastewater samples for four small Italian cities. Similar results were found at all of the sampling sites.
Lesson: Surely cocaine isn't the only thing dumped overboard by the body that can be measured through excretions—how about medications? The same researchers, as well as several other labs around the world, have applied the excretion methodology to study medication consumption. Stay tuned—I'll come back to this research method in a future post about bacterial resistance to antibiotics.
In the meantime, here are some updates on topics that we've looked at before.
Health Canada's ban on Adderall XR as a treatment for attention-deficit disorder.
Under cover of darkness—or the closest thing to that an official agency has, the late-afternoon press release—Health Canada has rescinded its ban on Adderall XR. The Aug. 24 press release explained why only the XR form of the drug had been removed from the market rather than Adderall itself, an older drug with a slightly different rate of release. Contrary to my conspiracy-theory speculation, Health Canada neglected to ban the older version not because it was cheaper than Adderall XR, but because there was no need to: It hadn't ever been available in Canada. Why lift the ban on Adderall XR now? Naturally, Health Canada didn't admit any error and really didn't explain its earlier decision. The agency just said it had submitted the question to a small committee of experts who thought the original decision was the right one and then, after thinking about it, decided that rescinding it was also correct.
Rabies risk in underdeveloped countries.
The risk of rabies in countries too poor to afford a program of animal rabies control was underscored by another case reported this month. A 41-year-old man who sustained a dog bite on a visit to Haiti developed rabies after he returned to the United States. This case, which was not diagnosed until after the patient died, is one of nine lethal rabies cases since 1990 that developed after patients exposed in an underdeveloped country returned home. If you are bitten by any animal on a trip to a country where rabid animals are found, it is vital to seek immediate treatment, which is virtually 100 percent effective.
Avian flu and the risk of worldwide epidemic.
The news on the avian flu front ranges from very bad to moderately bad to slightly good.
The worst first: As this animated map shows, avian flu is marching inexorably westward across Russia toward Europe, wreaking havoc among poultry and occasionally infecting humans. Just to remind you, H5N1 influenza virus is highly virulent for chickens and for humans (infected chickens or humans have a substantial chance of dying), highly infectious for chickens (exposed birds usually become ill), but, so far, poorly infectious for humans (exposed people generally do not acquire the disease). However, if this strain of flu behaves like other strains—and there is no reason to expect otherwise—sooner or later it will acquire the ability to easily infect people; and if that happens, we may be at risk for the same fate as those tens of thousands of dead chickens in the poultry houses of Asia and Russia. The risk of the disease as it is carried west by migrating waterfowl is being taken so seriously in Europe that the Dutch government has ordered farmers to move all poultry indoors, and German farmers will likely shortly be similarly instructed.
The middling bad news: While H5N1 may be preventable by a vaccine, we don't have one yet that has been fully tested and shown to work. We have a candidate vaccine, and the federal government has contracted for 2 million doses of it (because if things get bad we might need to use it, fully tested or not). The federal agency sponsoring the vaccine's development, the National Institute of Allergy and Infectious Disease, trumpets it as strong and effective and anticipates that the only problem is whether we can produce enough. Others looking at the same data, however, are not sure the vaccine will work.
Sensing opportunity, some small startup American firms are aggressively trying to develop alternative vaccines based on totally different approaches that have ever been used before. There is no telling what people will do if widespread desperation sets in, but it seems to me very unlikely that any of these products can possibly be ready in time.
The minimally good news: The world is starting to take H5N1 seriously. For example, the British government just circulated a fine booklet about the virus. Probably more important, the Swiss drug maker Roche has donated 3,000,000 doses of the one remaining effective anti-viral drug (oseltamivir, sold as Tamiflu) to the World Health Organization's rapid-response stockpile, to be used in poor countries where the disease might emerge. I understand the U.S. government's need not to fan panic, but I hope it is privately addressing this problem in a more serious way than is readily apparent. If not, we are in big trouble.
Correction, Sept. 29, 2005: The article originally stated that the Switzerland study of burn treatments for children was conducted with human embryonic stem cells. In fact, the study was conducted with human fetal cells. (Thanks to Dr. John Gearhart, Armstrong professor of medicine at Johns Hopkins University, for pointing out the error.) (Return to the corrected sentence.)