5 Costliest Microbes in Financial History

The field of synthetic biology is still in its infancy, with many of the most promising companies residing outside of public markets, but make no mistake: The bioeconomy is on its way. Just about everything and anything -- fuels, chemicals, oils, foods, pharmaceuticals, metals, and materials -- will one day be produced by hijacking large pieces of microbial genomes. In fact, there are hundreds of projects under way right now that will soon bring synthetic biology to your doorstep.

It is pretty amazing when you think about it: We are transforming bacteria, fungi, and viruses from massive financial and social burdens into economic tools used to advance society. This is a fascinating turnaround, especially when you consider that many of the deadliest plagues in history were spread along international trade routes (ironically, in the name of advancing society). Although exact economic numbers and even vague estimates are difficult to pin down, each major plague severely affected economic output and caused millions of deaths worldwide.

But plagues have also had positive impacts in shaping human history. By toying with human curiosity, several plagues advanced our understanding of biology and paved the way for modern biotechnology and synthetic biology. To remember how it all began, let's take a look back at the costliest microbes in human and financial history.

The greatest plagues in history

A scanning electron micrograph of Yersinia pestis -- the cause of bubonic plague -- doesn't look that scary, does it? Source: WikiCommons.

Numerous pandemics have wreaked social and financial ruin on human society in recorded history. You may be surprised to discover that hundreds of millions of deaths and perhaps billions of dollars of lost GDP can be attributed to just three microbes:

1. Yersinia pestis, the cause of bubonic plague

2. Vibrio cholera, the cause of cholera

3. Influenza, the cause of seasonal flu

Here is a brief summary of notable pandemics in recorded history.

Source: Harvard University Library, Brown University.

The list above isn't inclusive, but it demonstrates the major role that microbes have played in shaping human history. It is difficult to imagine how a major pandemic would affect the workforce of the world's largest economies. Written accounts also portray the difficulties of governments in collecting tax revenue during outbreaks (tough to generate funds for services when your populous is sick or dead). Historians don't have concrete numbers, but they do have an idea of how major pandemics have stressed economies.

The most famous bubonic plague, The Black Death, occurred at a time when peasants drove the European economy. But with entire towns essentially wiped out, serfs gained the unique competitive advantage of negotiation. Lords engaged in fierce competition for labor, which raised wages and the standard of living for peasants. Historians often credit The Black Death as a major driving force in ending feudalism.

Early cholera pandemics weren't as deadly as bubonic plague, but had a massive impact on the economy nonetheless. Ships were quarantined in ports for weeks or longer, stunting trade and leading to shortages of goods. As a result, layoffs and unemployment were rampant. These problems were exacerbated during outbreaks after the onset of the Industrial Revolution, when less workers were needed to produce the same amount of output.  

Despite occurring relatively recently, the economic toll of the Spanish Flu is unknown, although statistics paint a grim picture. A lethal strain of H1N1 infected 500 million people worldwide and killed 50-100 million people globally. It even reached remote Pacific islands and indigenous populations in the Arctic. In America, the strain killed 195,000 citizens in October 1918 alone and an estimated 675,000 people total. When public health officials talk of worst-case scenarios from avian influenza strains, the 20% lethality rate of the Spanish flu of 1918 is a good benchmark.  

We cannot stop here -- we are still two microbes short! So, what are the other two costliest microbes in financial history?

Genzyme contamination (Vesivirus 2117), 2009
Viruses aren't technically microbes, but they are still being engineered by humans (to deliver drug payloads into cancerous tumors, for instance) and can be quite deadly otherwise. In 2009, biotechnology trailblazer Genzyme, now a part of Sanofi (SNY 2.00%), demonstrated the worst-case scenario facing investors of today's biotechnology and industrial biotech companies: contamination.  

On June 16, 2009, the company announced that it had detected viral contamination at its Allston, Mass., biomanufacturing facility. The company's two best-selling products, Cerezyme and Fabrazyme, were manufactured at the facility. Shutdown caused severe shortages of each drug -- stockpiles eventually fell to just one-third of need -- forcing patients to ration inventory.

This viral contamination and later material contamination sent shares plummeting, cost the company well more than half a billion dollars in penalties and lost revenue, and resulted in several lawsuits from shareholders and patients. Genzyme has worked hard to put the episode behind it and just last year was granted regulatory approval for a new production facility for Fabrazyme. It was not the first time viruses made their way into the steel tanks of a major pharmaceutical company, and it surely won't be the last.

Antibiotic resistant bacteria (multiple), present

 

 

The petri dish on the left shows the effectiveness of antibiotics (white circles) in discouraging bacterial growth. The petri dish on the right, not so much. Source: WikiCommons.

Big Pharma hasn't been too excited to jump into the low-margin anti-infective market in recent years. Only GlaxoSmithKline (GSK 1.22%) and AstraZeneca (AZN 0.28%) have major antibiotic research arms. GlaxoSmithKline has three bacterial infection trials in early development, while AstraZeneca has two phase 3 trials and a healthy early- to mid-stage pipeline for the indication. Focusing resources on antibiotics is hardly the reason for their recent declines, but given the severity of the problem, could it become an unexpected boon for each?  

Companies have had success in the past. Johnson & Johnson (JNJ 1.49%) fielded a rare antibiotic blockbuster in Levaquin in the last decade, which recorded sales of $1.6 billion in 2007. The company still researches infectious medicine, but has enjoyed much more success in oncology and anti-inflammatory diseases. The field is heating up, though. Novo Nordisk (NVO -0.03%) bought anti-infective therapy developer Xellia for $700 million this week. Talk about enthusiasm for market prospects.  

Statistics also point to a huge opportunity. The World Health Organization estimates that there are 440,000 new cases of multidrug-resistant tuberculosis each year, which kills 150,000 people. That's a mortality rate of 33% -- much higher than the devastating Spanish Flu of 1918 -- and it is only one instance of a resistant microbe. One study pegs the additional cost of contracting an infection from a resistant bacterium at between $18,000 and $30,000. That works out to about $35 billion per year in the United States alone.

Should an infectious microbe become completely resistant to current drugs, the next international pandemic could follow.  

Foolish bottom line
Now that I've scared you, I know what you're thinking: "Should we fear the science-fiction scenario where an engineered microbe breaks out of its bioreactor, replicates uncontrollably in the environment, and wreaks unimaginable havoc on society?" It is a real possibility -- even if the details are exaggerated -- but, in many cases, engineered microbes are actually weaker than their wild-type predecessors. In fact, Dr. James Collins of Boston University has already developed a kill switch for microbes gone wild. The biologic self-destruct mechanism causes cells to burst when certain environmental conditions are met and will one day be incorporated into all engineered microbes.

Phew! You can sleep like a baby tonight.