Monthly Archives: February 2012

Of Pigs, Bugs, Drugs and Genomics: The Smoking Gun for Antibiotics on the Farm

This is a story that begins generations ago. Shortly after World War II, the makers of antibiotics realized that supplementing animal feed with antibiotic containing byproducts increased agricultural productivity.  Antibiotics were the miracle drugs of WW II, and at the time this seemed like yet another benefit.  However, by the 1970s, the emergence of resistant bacteria was becoming an increasing problem in medicine.  In seminal work, Levy showed that the introduction of antibiotic supplemented feed on a poultry farm led rapidly to changes in the gut bacteria of both the chickens and the workers on the farm, and to the emergence of bacterial strains resistant to the antibiotic in the feed.  Their article concludes:

“The present findings clearly demonstrate, however, that antibiotic-supplemented feed is a factor contributing to the selection of human resistant strains of bacteria. These data speak strongly against the unqualified and unlimited use of drug feeds in animal husbandry and speak for re-evaluation of this form of widespread treatment of animals.”

And that is how things sat for more than 40 years.  The agricultural industry argued that antibiotics were important in raising productivity, the drug companies sold literally tons of antibiotics in the agricultural market, shortly after each new generation of antibiotic was introduced in human medicine, they were distributed to the agricultural market, and shortly after that resistant strains emerged requiring the development of ever more potent (and expensive) new antibiotics.

If you think about it, feed supplements create nearly an ideal environment for the emergence of bacterial resistance.  The drugs are given at subtherapeutic doses to large populations of bacteria.  A few partially resistant variants gain selective advantage in this context, and as they proliferate and evolve greater resistance, they achieve even greater selective advantage until eventually they dominate the bacterial flora of the animals on the farm.

Unfortunately, farms are not research laboratories.  Workers are constantly and intimately exposed to waste products and aerosols as they care for animals, clean stalls and dispose of waste.  Thus it is not surprising that resistant strains could be passed from farm animals to human workers.  What is less obvious is that the farm animals might pick up bacteria from their human handlers.

Move the clock forward to 2012 and the era of modern genomics and inexpensive genome sequence analysis.  A multinational team showed that multiply resistant Staphylococcus aureus (MRSA; an important medical pathogen and public health threat) moved from humans to pigs, acquired additional antibiotic resistance, and moved back to humans.  They did this by sequencing the complete genomes of 88 bacterial isolates from multiple sources, a task that would have been unthinkable only a few years ago.  By sequencing the complete genomes, they were able to detect the minute genetic variations that all organisms acquire randomly from generation to generation (single nucleotide polymorphisms or SNPs).  By comparing the patterns of SNPs, they could determine which isolates were derived from which parental populations thus tracing the history of MRSA infection in pigs and its reintroduction in an even more resistant form back to humans.  This is the smoking gun that closes the loop and shows that not only does antibiotic use on the farm lead to resistant strains, but that it can directly lead to increased resistance in important human pathogens.

Finally, after 45 years, the FDA has issued rules beginning to govern antibiotic use on the farm.  Of course, MRSA did not exist back in 1974 when Levy et al. published their paper, and we now spend scarce resources tracking MRSA in the hospital and community.  And we are losing patients to untreatable infections.

Advertisements

The Case for a Calorie Tax

Americans, and increasingly peoples across the world, eat too much. We know we overeat. We complain about our fatness, we are constantly trying new diets and we blame the morbidly obese for their illnesses.  Over the past 20 years, we have done very little to change our eating habits.  In fact just the opposite, there has been an epidemic of obesity.

Perhaps it is time to take a lesson from other self-destructive habits like smoking and drinking. In both cases, the most effective method of control has been taxation. At $4/pack, most of the cost of a pack of cigarettes is the tax. By making cigarettes legally available but expensive, we have reduced both adult and childhood smoking and undoubtedly headed off many thousands of deaths due to cancer and emphysema.  Similarly, most of the cost of a bottle of liquor is tax, and the amount of alcohol we drink does depend on the price.

Alcohol consumption does increase cancer risk.  3.6% of all cancer cases and 3.5% of cancer deaths worldwide are attributable to consumption of alcohol.  Further, the risk of cancer increases with the amount of alcohol consumed.  Alcohol also increases blood pressure, risk for motor vehicle accidents and risk for work related injury.  By decreasing our alcohol consumption, alcoholic beverage taxes have prevented many thousands of cases of cancer, prevented hypertension and saved many lives.  As a public health program, the alcoholic beverage excise tax has been remarkably effective, and it even generates significant revenue.

What about food?  Excessive food consumption is clearly habit forming.  Ask anyone trying to lose weight.  The basic fact of obesity is that we are what we ate.  If a person is going to maintain an obese habitus (say 230 lbs for a 6′ tall male), they need to consume about 2740 calories.  This is about 300 calories more than than they would require to maintain an ideal body weight of 180 lbs.  If you reduce your caloric intake, you will lose weight.

How high would a tax have to be to make us alter our eating habits?  Let’s guess that making an unhealthy diet a few dollars a day more expensive than a healthy diet would be enough.  To use round numbers, a penny a calorie would make a 2740 cal obesity inducing diet about $3 per day more expensive than a healthy weight sustaining 2440 cal diet.  A 5′ 4″ female needs about 1800 calories to sustain an ideal body weight of 145 lbs and 2000 calories to maintain an obese weight of 175 lbs.  OK, so women get off a little easier.  On average the women would pay about $6 per day less than the men, about $2,000 over the course of a year.  This is still much less than the average wage disparity between men and women.  A little bit of justice in the world.   The same applies for height. Yes, tall people have a higher healthy body weight and need to consume more calories to sustain a healthy diet, but they also earn about $789 per year more for every additional inch of height, more than offsetting the increased calorie tax burden.  Growing children do need to eat more per body weight than do adults, but their overall caloric intake is still less than that of an adult.

How much revenue would a calorie tax generate?  The average American consumed about 2700 calories day in 2008 and the figure is increasing about 20 calories per year so we may now be closer to 2800 calories per day.  At a penny per calorie, the food consumption tax would be about $28 per day.   It would add $5.40 to the cost of a Big Mac, but only $2 to the cost of a chicken salad and only 31 cents to a serving of broccoli.  Multiplied by 311 million Americans and 365 days per year, the tax would generate about $3.2 trillion per year in revenue or about $10k per person per year at current rates of food consumption.  Yes, that would be a heavy and regressive tax, but it could easily be made less of a burden by reducing other taxes and issuing tax rebates that could be spent on either food or other items at the consumers choice.  Food stamps, could, of course be fully paid out of the food tax revenue.  On the other hand, a calorie tax would help to balance the federal deficit, and would help to cover the $179 billion per year in health care costs attributable to obesity.

Does a calorie tax have a chance of becoming law?  Well it does seem like a long shot given the prevailing anti-tax sentiment in DC today, and there are a number of well known politicians and pundits who might take it as a personal affront.   There are also large and politically active farming, food and restaurant industries that would undoubtedly oppose such a tax. Nevertheless, we have to start some place.  If Americans want to take meaningful steps to address the obesity epidemic, we should think seriously about the role of taxes.

The Broader Audience for Research Results

While libraries are an important component of research information dissemination, it is important to remember that there are many constituencies who lack access to libraries:

1)      Patients – in these days of cost containment and intrusion of insurers in care decisions, patients need to be, and are increasingly interested in being, their own advocates.  Most patients do not have ready access to a fully subscribed university library, but they need access to the literature to be effective advocates for their own care.  While many medical centers have patient resources centers that will provide a limited number of papers in hardcopy form, this is somewhat akin to the old days of inter-library loan and is not close to an effective substitute for direct electronic access to the relevant literature.

If we want community support for biomedical research, making the results of biomedical research accessible to patients is a critical step.

2)     Community health care providers – these physicians and nurse need to keep their own knowledgebase current and need to be effective advocates for their patients.  Again, most lack access to university libraries.  Yes, there are a large number of free “throw away journals” supported by advertising, but the editorial content of many of these journals reflects the sources of their advertising revenue.

If we want community health care providers to support biomedical research, making research results accessible is again a critical step.

3)     Small businesses and start-ups – while many start-ups may retain some personnel with some access to university libraries, this tends to be transient and unreliable.  Major pharmaceutical companies may be able to afford broad coverage subscriptions for their research staff, but this is not the case for most small to midsize businesses.  These small and midsize businesses are the real engines of economic growth and need to be considered in public policy.

This is getting repetitious, but business access to research results is an economic development issue as well as an issue for support of scientific research.

The current publication system, with expensive bundled subscriptions that only major research universities can afford, reinforces the ivory tower mentality on both sides.  Academics complain that business ignores them, but what do you expect if you publish in a journal not accessible to most businesses.  Conversely, businesses complain that academics are introspective and unconcerned about development and commercialization, but what do you expect when in many cases businesses are locked out of reading what is happening in academics.   The fact that universities are increasingly aggressive in pursuing intellectual property, and even suing their former faculty who have moved into commerce, does not help matters.

The old days when science in general and biomedical science in particular could depend on a few stalwart defenders in Congress are over.  Research funding is just another discretionary budget item in the eyes of many politicians.  Rebuilding ties with business and the community is critical to sustaining support for research funding, and the need for access to research results goes well beyond the academic community.

As has been pointed out, the high profit margin multinational publishers are struggling to find a sustainable business model in the era of electronic publishing.  I grew up in Rochester New York and Eastman Kodak was extremely generous to our community, but I am not going to argue that digital photography should have been suppressed until Kodak found a way to transition out of their film business.  The reality of modern business is that you innovate or die.  The publishers had a good run over the last 20 years, but if open access publishing is a better solution for the community, the publishers need to find their own future.