November 22nd 2017
Eradicated in 1980, smallpox is listed as a category A bioterrorism agent and remains a focus for planning and preparedness globally. In most of the decades since eradication, security concerns have been primarily around theft of stockpiles of smallpox from the only known two repositories in the word in the United States and Russia. This changed in 2002, when scientists first created a virus synthetically in a lab. Since then, the theoretical possibility of smallpox being synthesized in a lab has been acknowledged, but dismissed as a difficult and unlikely feat. In 2017, this changed when Canadian scientists synthesized a closely related pox virus, hoursepox, using mail order DNA and just $100,000, proving the feasibility of creating smallpox in a lab. Compounding the changing risk landscape for smallpox re-emergence is the loss of experts who have living knowledge of smallpox treatment, prevention and eradication.
The world has recently lost two leading lights in the battle against smallpox - Dr Frank Fenner and Dr DA Henderson, who both shared the Japan prize for their work in smallpox eradication. Most doctors today have never seen a case of smallpox, and public health agencies have no experience in smallpox control. There are no clinical efficacy data on new second and third generation vaccines, nor on antiviral drugs such as cidofivir, developed after eradication, so many unknowns in preparing for the possibility of re-emergence of smallpox. One leader of the battle against smallpox is Dr Mike Lane, the former Director of the US CDC’s Smallpox Eradication Program, who worked alongside Fenner and Henderson in the eradication campaign. I first met Mike in 1991 when he was foundational director of the Australian Field Epidemiology Training program at ANU, the MAE. He opened my eyes to a completely new way of learning and transformed my career pathway, instilling in me a lifelong passion for epidemic response and field epidemiology. I have stayed in touch over the years and recently worked with him on modelling research on the impact of re-emergent smallpox in modern society. His knowledge and depth of understanding of smallpox, of the data which modellers accept and use without question, was incredible and it was a privilege to work with him on this research. Following this, I asked Dr Lane his thoughts on smallpox in the contemporary context.
Q: What were the biggest lessons you learned from smallpox eradication?
Mike Lane: I cannot stress enough that international cooperation is vital. It is critical to listen to locals, and be flexible to change. Engage local leaders of tribes, villages, religious groups. If they are on board they will make things easy. Another lesson is to collect and keep good data and use it well. Finally, money is less important than people. Recruit good people and they will find the resources. Contrast mass vaccination, surveillance and containment of smallpox with the attempted malaria eradication program's refusal to budge from spraying DDT on inside walls. So much can be learned from history.
Q: What are the main risks of smallpox today?
Mike Lane: Early in the post-eradication era there was paranoia and speculation about smallpox following the book, Biohazard, by former Deputy Director of the Soviet biowarfare program which claimed vast work on smallpox in the Soviet Union. Since the breakup of the Soviet Union no samples of the virus or former lab workers have been identified, but some people worry about stockpiles of smallpox in places like North Korea. Today, the biggest risk is synthetic biology, as it is now possible to recreate the virus in a lab, and this combined with the risk of terrorism is the main concern. The geopolitical landscape has changed, and so has enabling technology.
Q: What should be the focus of preparedness?
Mike Lane: There is too much emphasis on quick fixes, and not enough evaluation of public health impact. While vaccination is critical in containment, do we really need new vaccines, new antivirals, better labs tests? Is money spent on smallpox R&D better spent than on Ebola, antibiotic resistant microorganisms, etc? We need to evaluate risk, public health impact, cost-effectiveness and understand the best buys for impact.
Q: What are the main changes since eradication in1980?
a) synthetic biology - this is a game changer.
b) we now have two good antivirals and a fair stockpile of second and third generation vaccines.
c) lots of good training aids stockpiled and readily available.
d) The internet enables better surveillance, better contact tracing and better sharing of information, so we would expect to be able to act quickly if an outbreak of smallpox occurred.
Q: Was personal protective equipment routinely used in managing smallpox in the field?
Mike Lane: No. We believed in vaccination. No one went into the field unless they had a recent strong reaction (or "take") to vaccination . I remember when I went to Yugoslavia the physicians there were amazed that I would go in to examine patients without a mask, gloves, or indeed anything. Vaccination works!!
Q: Do you think the public health workforce today would have trouble using a bifurcated needle (used for smallpox vaccination)?
Mike Lane: We trained illiterate villagers in five minutes. Also used boy scouts, and a variety of volunteers. Today bifurcated needles have to be packaged like needles for injection, and discarded after one use. We always saved them and simply boiled them up in a bunch at the end of each day. I preferred using old ones, with slightly blunted points, which scarifies the skin without breaking through. The modern versions are so sharp that vaccinating infants must be done carefully... multiple pressure with the side of the needle rather than direct 90 degree light puncture.
Q: What is your advice to public health officials today?
Mike Lane: My advice is to keep funding the infrastructure, including good labs. Infectious diseases are not dead – you just have to look at HIV, Ebola, flu, antimicrobial resistance, SARS, many other zoonoses to see they remain a threat. Surveillance is vital, and needs improvement.
Planning for smallpox winds up also planning for Flu, SARS, Ebola, Marburg, MDRTB, so is never a wasted effort. We need to recruit good young people and train them to be prepared.
Dr J Michael Lane is Emeritus Professor of Preventive Medicine at Emory University School of Medicine, Atlanta, Georgia, USA. His research interests are smallpox, adverse events after smallpox vaccination, and smallpox vaccination policy. He was formerly Director of Smallpox Eradication at US CDC. He is also an alumnus of the US CDC’s Epidemic Intelligence Service and has extensive international public health and field epidemiology experience. He established the Australian Field Epidemiology Training Program in 1990, when he took up the position of inaugural Director of the program. This has now grown to boast more than 200 graduates, who have investigated over 300 outbreaks.
You can hear Dr Lane speak about smallpox at the workshop “New approaches to risk analysis in biosecurity” on Dec 10th in Arlington, VA.
Read some of Dr Lane’s many publications on smallpox:
- Remaining questions about clinical variola major.
- Myocarditis, pericarditis, and dilated cardiomyopathy after smallpoxvaccination among civilians in the United States, January-October 2003.
- Why not destroy the remaining smallpox virus stocks?