Shortly after he joined the Biopreparat advisory council, Domaradsky became involved in plans to establish the genetic institute at Obolensk. He became deputy director of Obolensk in 1973, joining a small group of researchers in the newly built laboratory complex.
An atmosphere of improvisation charged their work. Originally a cluster of red and white brick buildings crisscrossed by dirt roads, Obolensk expanded each month as laboratory equipment was assembled from scientific institutes around Russia. The area around the compound was so sparsely settled that in wintertime elk wandering out of the woods would surprise scientists as they trudged from one snow-covered laboratory to another. The clandestine atmosphere surrounding the project gave it a certain appeal. The scientists saw themselves as pioneers.
Neighbors were told that the Institute of Applied Microbiology was involved in research into infectious diseases, but the high wire fence and heavy gates manned around the clock by troops from the Ministry of Internal Affairs ensured that there would be no casual visitors. Like other institutes, it was identified by a post office box number. Everyone knew that V-8724 meant Obolensk.
Domaradsky recruited a team of scientists from around the country to help him refine the techniques that would be used in Bonfire and Metol, a parallel project centered on the genetic alteration of bacteria to produce antibiotic-resistant strains. He never mentioned Bonfire or Metol in his memoirs, possibly fearing repercussions — both projects are still considered state secrets in Russia — but Obolensk was soon involved in genetic research into the diseases that had been Domaradsky's lifelong preoccupations. Foremost among them was plague.
There are two principal challenges in altering the genetic makeup of disease-producing bacteria. The first is to find the right mechanism for transporting genes into the DNA of another microorganism. The second is to achieve the transfer without reducing the bacteria's virulence.
Domaradsky turned to plasmids to meet the first challenge. Plasmids are strands of genetic material found in bacteria that carry the codes for such things as virulence and antibiotic resistance. They are used in genetic engineering because they can replicate without harming the organisms they come from and can be transferred intact to a new cell.
Domaradsky's scientists found a plasmid with the genes for resistance to tetracycline, one of the most potent and widely effective of all antibiotics. The plasmid was located in a strain of bacteria called
In a petri dish they mixed small quantities of B. thuringiensis with anthrax, cultivated the two strains together, and then placed them in a test tube with tetracycline, to see if the anthrax bacteria would survive. The process required endless repetition. It can take months, even years, using such procedures to isolate a strain with the hoped-for resistance. The antibiotic killed most of the anthrax bacilli, but a few cells survived. Most of these had incorporated the antibiotic-resistant genes from
The second challenge, that of maintaining the virulence of genetically altered material, was more problematic. Despite his talents, Domaradsky couldn't give the Ministry of Defense what it really wanted. The Soviet army wasn't satisfied with weapons resistant to one type of antibiotic. The treatments available for bacterial diseases offered doctors a broad range of choices. The only worthwhile genetically altered weapon, for military strategists, was one that could resist all possible treatments. In 1976, Domaradsky proposed a "triple-resistant" strain of tularemia. He struggled for nearly a decade at Obolensk but couldn't come up with a strain effective across the entire spectrum of antibiotics while retaining its degree of infectiousness.
The program's military chiefs didn't hide their disappointment. Domaradsky offered no apologies for his failure, arguing that science could not be run according to Five-Year Plans. He was reminded that he had first made the grandiose promise to develop a fully antibiotic resistant strain. This elicited his rejoinder that soldiers had no idea how to run a laboratory.