22 
airflow, control of exhaust air and similar protective measures are 
mandated. Physical containment providing the highest possible 
safeguard is provided within the P4 facility. This type of facility 
builds on the preceding criteria and adds additionally stringent 
measures such as the use of special handling cabinets (under negative 
air pressure), filtering: of all air: through high-efficiency particulate 
air filters or filtering and incineration of air, careful sterilization pro- 
cedures, the use of chemical decontamination tanks, and a series of 
secondary safeguards such as air locks, clothing change and shower 
rooms, biowaste treatment facilities, and separate ventilation systems. 
Secondary Safeguards 
As pointed out by Dr. Barkley, the use of secondary safeguards is 
primarily an added safety factor not generally used in the typical 
microbiology laboratory even where pathogens are handled. However, 
in the opinion of the advisory groups which established the require- 
ments for DNA research, the additional use of secondary facility 
safeguards for experiments confined to P3 or P4 facilities will make 
any possible or potential hazard to the public from such research 
eyen more remote. 
Dr. Barkley then provided a summary of the history of accidental 
infections which had occurred in laboratories which had been handling 
extremely dangerous pathogens, such as in the research at Ft. Detrick 
op. biological warfare agents. According to his testimony, while acci- 
dents had occurred, the frequency of these accidents was quite low 
and there had never been any epidemic episode outside the laboratory 
and within the surrounding community. This knowledge, based upon 
experimental work under conditions less stringent than proposed at 
the P4 level, provides the designers of the physical facilities with a 
high degree of assurance that compliance with these requirements 
provides an extremely high degree of safety. Dr. Barkley, indicated 
that he was aware of 25 government, 4 university, and '5 industrial 
facilities which currently provide most of the primary and secondary 
safeguard requirements for a P4 facility (although these facilities are 
not yet certified as P4 facilities). All of these facilities would require 
additional work to be fully certified for P4 research. 
Dr. Barkley expressed his professional opinion that the combina- 
tion of the prescribed physical containment facilities with an appro- 
priate attitude, diligence, training, and proficiency on the part of the 
laboratory workers would provide the capability to protect the public 
from any potential risks postulated for this work. As also pointed 
out by Chairman Thornton, however, the fact that accidents had 
occurred was an indication that the. decision to incorporate the safety 
'precautions provided by the addition of biological containment 
requirements was wise. 
C. Biological Containment 
Dr. Curtiss 
Biological containment, as described by Roy Curtiss III, Depart- 
ment of Microbiology, University of Alabama Medical Center, in- 
volves the use of viral and plasmid cloning vectors (constructed into 
recombinant molecules as described by Dr. Singer) which have t>een 
[Appendix B — 71] 
