An Alternative Vision for the Boston University

National Emerging Infectious Diseases Laboratory

 

 

Summary Conclusions

 

Marginal value of Boston University’s present focus

 

There are two major shortcomings of the Boston University National Emerging Infectious Diseases Laboratory (NEIDL) plan, which focuses on emerging infectious disease and biodefense.  First, the bioweapons research proposed is redundant because of the large number of laboratories already engaged in this research. Second, the emerging disease research focus has minimal value compared to other infectious disease research. The NEIDL would better serve public health if it focused its research on prevalent natural infectious diseases, for which there are safe technologies, than on Biosafety Laboratory Level-4 (BSL4) research.

 

Although BU publicly downplays their intended biodefense-related research, they are obligated to carry out defense research at the bidding of their funder, the National Institutes of Health (NIH). Historically, Boston University has not been forthcoming or transparent about the pathogens that will be studied in its NEIDL facility, despite many requests for this information. Recently, however, the BU NEIDL website identified “some of the organisms that will be studied”: Five of the seven identified pathogens are Category A bioweapons agents.  This high percentage of bioweapons agents belies Boston University’s consistent claim in their literature and presentations that their focus is emerging infectious disease, not bioweapons agents. 

 

Regarding BU’s planned biodefense-related research, numerous laboratories are already researching and developing countermeasures for all the major bioweapons agents. As evidenced by the sheer number and large increase since 2002 in research publications on BSL4 agents, we question what the Boston University NEIDL can add at this late stage, and we challenge the utility of the BU BSL-4 laboratory. 

 

A second issue is the minimal value or utility of the “emerging infectious disease” research proposed by BU for the NEIDL laboratory. These diseases include those caused by the hemorrhagic fever viruses Ebola, Marburg and Lassa and require BSL4 biocontainment. The term “emerging infectious disease” is misleading as it implies an importance, in threat and risk to health, which these pathogens do not deserve. These are only minor public health threats in Africa, where they are exclusively found, and they represent no public health threat in the United States.  Only one on their list, Mycobacterium tuberculosis, is a public health threat in many parts of the world. These diseases should be rightfully classified as “rare,” not emerging, diseases.

 

In conclusion, research on BSL4 pathogens in the Boston University NEIDL has little public health or biodefense value.   An alternative focus and cost-effective strategy for NEIDL is clearly needed. Such a strategy, we maintain, should focus on development of new technologies and preventatives and cures for the infectious diseases of substantial public health concern. For example, an area of great public health need and substantial interest in infectious disease research is that of emerging antibiotic-resistant pathogens such as drug-resistant staph (MRSA). The World Health Organization has identified antibiotic resistance as one of the greatest threats to human health.[1]  BU NEIDL funding would be more wisely spent on countermeasures for truly emerging viruses such as West Nile and dengue viruses and infectious bacteria such as Staphylococcus aureus, Clostridium difficile, Streptococcus pneumoniae, Pseudomonas aeruginosa and Chlamydia trachomatis, where many strains are now resistant to multiple antibiotics.

 

An alternative vision

 

By refocusing most of its research and development to prevalent natural disease and adopting new, safe vaccine and antimicrobial technologies, Boston University can make a major contribution to public health without the hazards of working with dangerous pathogens that require BSL4 laboratories. With a focus on prevalent diseases, escape of pathogens from the lab would have less or little consequence, as they are already present in the community.

 

New vaccine technologies employ pathogen mimics or pathogen surface proteins that cannot cause infection or disease, so they pose no risk to laboratory workers or the communities surrounding the laboratory. Most research and development of vaccines using the new technologies may be carried out in BSL1 and BSL2 laboratories since special precautions are not needed. Furthermore, many of the new vaccine technologies are ideal for quick response to a newly encountered pathogen in a natural disease or biodefense setting. They can be formulated quickly and should be safe.

 

But vaccines are not the best approach for defense against a bioweapons attack. They have some unavoidable drawbacks such as questions about efficacy and short shelf life. In addition, vaccines against bioweapons agents and rare diseases are a “one bug, one drug” approach, as they target only one pathogen and sometimes only one strain of a pathogen. Witness the need for new vaccines each year for the annual flu.

 

In contrast, broad-spectrum antibiotics and antivirals developed to target prevalent natural diseases have immediate application to biodefense as well. The broad-spectrum approach is indeed a two-way street.  There is a pressing need for inexpensive new antivirals and antibiotics which are small-molecule, broad-spectrum, and orally available to counter both natural disease and biodefense. This urgent need is in part due to increasing microbial resistance to antibiotics and antivirals.

 

Currently the Boston University NEIDL seems to be focusing on and building staff in viruses and immunology, although they might consider bringing aboard expertise in bacterial pathogens.  If Boston University refocused some of its effort on new approaches to small-molecule drugs, it would need to bring in expertise to the NEIDL that they may not now have, in the areas of medicinal chemistry and rapid screening of target binding, in particular. A significant medicinal chemistry and screening capability would also serve the Boston-area infectious disease research community as well, as both are in short supply. BU should also consider making their Good Laboratory Practice, pilot manufacturing and clinical trial expertise available to academic labs and small biotechnology companies developing new infectious-disease drugs.

 

If vaccines must remain the focus

 

Biodefense vaccines appear to be a major focus of Boston University’s NIEDL, and the NEIDL already has considerable expertise in viral infection pathways and immunology. If BU focused, for example, on rapid vaccine development and manufacturing methodologies for seasonal influenza or prevalent urban diseases, this would assure that Boston University’s NEIDL is relevant to both our pressing public health needs and also to its required biodefense mission. From this perspective, the National Institutes of Allergy and Infectious Disease (NIAID) may be amenable to changing NEIDL’s mission to broad-spectrum approaches and away from “one bug, one drug” approaches, given NIAID is refocusing to broad-spectrum approaches itself.

 

Efficacy demonstrations for vaccines to prevalent pathogens would eventually require clinical trials in humans. In this regard, Boston University already has plans to carry vaccines and other countermeasures through phase I safety clinical trials, thus it will have in place the Good Laboratory Practice and small-scale manufacturing necessary for FDA approval of phase I trials. NEIDL might consider extending this expertise to managing Phase II and Phase III clinical trials.  This would provide a much needed service.  For new vaccines or drugs which are promising, special consideration should be given to residents of the surrounding communities to participate in clinical trials.

 

The full report to be released soon expands on and documents the ideas and assertions made in this summary.

 


[1] “Prospective antibacterial pipeline running dry,” by Talha Burki. The Lancet Infectious Diseases, Volume 9, Issue 11, November 2009, Page 661,