Will Nanotechnology Usher in a Post-Antibiotic Era?

Every week or so it seems there is a chilling report issued regarding an emerging or reemerging infectious disease or drug-resistant superbug.  These reports usually question whether there are sufficient new antibiotics in the pipeline or whether antibiotic resistance due to over-prescribing and exposure has rendered them ineffective when needed.

Is there really a global infectious disease crisis at hand?  The Infectious Disease Society of America (IDSA), the European Centre for Disease Prevention and Control (ECDC), the World Health Organization (WHO), and the U.S. Congress seem to think so.

For instance, in an April 15, 2010 issue of the Clinical Infectious Diseases, the IDSA challenged global leaders to develop 10 new antimicrobial drugs by 2020. This “10 x ’20” initiative is designed to address the lack of drugs designed to treat infections caused by the so-called “ESKAPE” pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species), which, according to an IDSA report and a joint report from the ECDC and the European Medicines Agency, effectively “escape” the effects of currently approved antibacterial drugs and cause the majority of hospital infections in the United States.

Congress also has clearly shown its concern by introducing bipartisan legislation known as the “Generating Antibiotic Incentives Now Act of 2011” (GAIN Act) (S. 1734).  The GAIN Act would streamline the FDA review process and incentivize antibiotic development by extending the exclusivity period for a new “qualified infectious disease product” by five years and another six months if the antibiotic manufacturer identifies a companion diagnostic test for the qualifying pathogen. A “qualifying pathogen” would include these ESKAPE pathogens, as well as multi-drug resistant tuberculosis, or any other infectious pathogen identified by the Secretary of HHS.

According to GAIN Act sponsor, Sen. Blumenthal (D-Conn.), “Antibiotic resistant ‘superbugs’ have been on the rise for the last decade, with the rate of antibiotic resistant Staph infections approaching 50 percent.” Blumenthal further states, “The issue increasingly affects troops returning from Iraq and Afghanistan, as many of them have been exposed to a new, highly-resistant and contagious strain of Acinetobacter bacteria – 89 percent of infections caused by mutant strains of Acinetobacter are resistant to at least three classes of antibiotics and 15 percent are resistant to all forms of treatment.”

As recently as March 23, 2011, Reuters Health Information, as reported by Medscape Today, stated that the WHO predicts more than 2 million people will contract a drug-resistant form of tuberculosis (TB) by 2015.

Finally, according to the Annual Epidemiological Report 2011 from the European Centre for Disease Prevention and Control (ECDC), TB remains a common infection in Europe, with nearly 80,000 cases annually. The ECDC also reports that:

  • Outbreaks and epidemics of measles are more frequent and widespread than previous generations;
  • HIV remains a major concern with ongoing transmission in all countries;
  • Microbial resistance is a major problem, as illustrated by the emergence of New Delhi metallo-beta-lactamase-1 (NDM-1) producing Enterobacteriaceae, from the Indian subcontinent, and its spread to the EU;
  • West Nile Virus is an epidemic in Southeast Europe;
  • Locally acquired cases of diseases previously considered to be only imported (malaria, dengue fever, and chikungunya) have been reported; and
  • Anthrax has emerged as a potential epidemic among intravenous drug users.

To sum up, some pretty smart people and prestigious organizations seem to think there is a global infectious disease problem.  But what are the drug manufacturers doing to fill the antibiotic pipeline?  For years we have heard that numerous drug manufacturers have left the field.  Why is this?  Is it due to the immense time and money required to gain FDA approval? – usually years and a billion dollars.  We know, of course, that treatment with antibiotics is merely “episodic,” and therefore not as profitable as daily maintenance drugs like those prescribed for high blood pressure and cholesterol.

And what if these efforts actually succeed and we get more drugs through the pipeline. Won’t doctors continue to over-prescribe antibiotics out of an abundance of caution or because their patients simply demand them? And won’t this practice just lead to further bacterial mutations and more antibacterial resistance? Won’t 10 new antibiotics just lead to the need for 10 more? After all, these bacteria are nefarious things.

Consider this possibility.  Perhaps antibiotic R&D is on the decline, in part, because the drug manufacturers know that a new technology is not just on the horizon, but is already here – nanotechology.  We know that nanotechnology allows scientists to work on the scale of molecular particles to manipulate the biological and material worlds measured in nanometers, which is one-billionth of a meter.  Will nanotechnology-in-medicine actually succeed in creating molecule-size nanomachines that will chew up the bacteria without allowing the bacteria to mutate and thereby resist the technology?

For some time, the Defense Advance Research Projects Agency (DARPA) and their partners have been trying to develop nanomachines that combat bacteria and all pathogens like viruses and other potential biological weapons. As reported by Steven Salzberg in Genomics, Evolution, and PsuedoScience, a group of scientists published results in The Lancet of their success in treating 4 rhesus monkeys infected with a dose of Ebola 30,000 times the normal fatal dose.

According to Salzberg, Thomas Geisbert of Boston University and scientists from Tekmira Pharmaceuticals and the U.S. Army Medical Research Institute for Infectious Diseases (USAMRIID) designed and synthesized “small interfering RNA” (siRNA) that would stick to the Ebola genes, but not human genes. The siRNAs were delivered by insertion into nanoparticles that were only 81-85 nanometers across. The siRNA treatments were injected 30 minutes after infecting the monkeys, and again each day for 6 days. All the monkeys survived without long-term effects.

The results of this study did not receive much coverage in the mainstream media until November 27, 2011, when Dr. Marc Seigel, associate professor of medicine at NYU Langone Medical Center, and Dr. David Samadi, Vice Chairman, Department of Urology and Chief of Robotics and Minimally Invasive Surgery at Mount Sinai School of Medicine in New York, reported the results on the Fox Sunday House Call segment.

Obviously, much must still be done before this Ebola treatment becomes an approved drug for humans. After all, the FDA is involved.  But isn’t it interesting that, once again, the military has had a hand in this breakthrough?  After all, didn’t they facilitate the first mass production of penicillin during WWII?

So maybe we have gone full circle on antibiotics. And perhaps we are about to enter a post-antibiotic nanotechnology-in-medicine era.  But with all the dire predictions of superbugs and epidemics, the question is – will this new era arrive in time?  Tick tock, tick tock…