The virus outbreak forced Plum Island to renew its commitment to biological safety — but this transformation took years to effect. Brushing off a reporter's question about the virus outbreak that truly occurred and the decision to continue research, one of the lab chiefs replied matter-of-factly, "Rift Valley fever is transmitted only by mosquito. For our security to break down, a mosquito would have to get into the lab, bite an infected animal, get out through our intricate security system, and bite a susceptible man or animal. We think that possibility is extremely unlikely."
The documented holes in the roof of the "intricate security system" of the USDA-described "World's Safest Lab" shifts this glib assessment from "extremely unlikely" to frighteningly possible. It is easy to see how a second outbreak could have occurred on Plum Island, one of unimaginable ramifications.
In the meantime, the deadly Rift Valley fever virus research charged ahead.
Fortunately, they got away with it.
9
Crossing the Rubicon
A potential for agent escape is still present….It istime to reconsider Plum Island Animal Disease Center's future.
To Dr. Jerry Callis's disappointment, the virus outbreak and the Rift Valley fever debacle overshadowed Plum Island's positive contributions, including an achievement that would change the future of science. While attention focused elsewhere, Callis's chief scientist, the unassuming Dr. Howard Bachrach, was quietly achieving scientific miracles deep inside Laboratory 101.
Working for Nobel laureate Wendell Meredith Stanley after the war, Dr. Bachrach was the first to isolate the polio virus. He was also the first to photograph polio with the lab's primitive electron microscope — though Stanley, according to scientific traditions, received credit for both as lead researcher. These accomplishments led to the development of Jonas Salk's polio vaccine and the end of the virus as a menace. Soon after, the promising young biochemist accepted Doc Shahan's generous offer to come to Plum Island. The parallel paths of Jerry Callis and Howard Bachrach represent two threads running through Plum Island's history. Both Callis, the youngest of ten siblings on a rural Georgia farm, and Bachrach, whose father owned a boys' haberdashery in Minnesota, were drafted by the USDA to learn hands-on science in Europe while America prepared to research exotic animal germs for the first time. While the outgoing Dr. Callis was a tall, officious administrator type, one who relished giving authoritative speeches about scientific research, the bespectacled Bachrach was a gnome-sized scientist who preferred tinkering on the workbench in the window-less lab fortress. When Callis was elevated to director in the early 1960s, Bachrach was named chief scientist. "Callis was very supportive of Howard," says Dr. Robert Shope.
Dr. Bachrach had been using chemicals in the mid-1970s to fractionate viruses, or break them up into component protein pieces. He theorized that one or more of a virus's proteins might provide enough of a "signature" to fool an immune system into creating a response, triggering immune memory cells and thus providing protection from being subsequently infected by the real germ. Vaccines, traditionally killed or weakened viruses that provided immunity, always left open the danger of reverting to virulence and causing disease to the host. But if an inanimate viral subunit vaccine could be designed, not only would it never revert to a virulence, but it would eliminate vaccine contaminants that sometimes caused harmful side effects. He discovered that the foot-and-mouth disease virus's capsid, or shell, was made up of four distinct proteins that latched on to healthy cells to infiltrate and infect them. After many years of trial and error, in 1975 Bachrach found his subunit protein: VP3. When he injected this third capsid protein into pigs, it protected them from a later challenge with the virus.
This was a bittersweet discovery, however, because extracting and producing VP3 in large quantities was too complicated to be practical.
That is, until genetic engineering came into the picture.
Scientists figured out how to manipulate DNA, molecule chains coded in specific patterns that instruct cells how to build proteins. By snipping portions of DNA that made insulin and splicing those portions into cells, they caused the cells to manufacture large amounts of synthetic insulin. Insulin, traditionally extracted from animals, was at last widely available to diabetics, helping them lead normal everyday lives. Scientists called the technique gene splicing or recombinant DNA, and it promised to advance microbiology to infinite heights. In the world of disease prevention it held even greater promise. This new technology, thought Bachrach, could produce VP3 en masse! Dr. Callis agreed with the chief scientist. He presented Bachrach's proposed work to a special committee at the National Institutes of Health to obtain their approval. The NIH liked the idea of using an animal virus as opposed to a human virus — the stakes were lower, and there was less of a chance that an accident or an unexpected new resultant germ would attack human populations.
In 1981, aided by three assistants on loan from the brand-new San Francisco-based biotechnology company Genentech, Bachrach entered the air lock, donned his white lab coat, and went to work in Lab 101.[28] The infective part of the foot-and-mouth disease virus (called the virion) consists of eight thousand nucleotide building blocks, housed inside the capsid. These blocks code the information for the virus's proteins. Dr. Bachrach knew that VP3 was made up of protein numbers 8 through 211. Using special enzymes, he pasted the DNA building blocks that coded for the VP3 proteins into a plasmid. A plasmid is a small ring of DNA that acts as a transporter, or magic carpet. The plasmid was then spliced into an E. coli bacterium, a benign microbe found in the human digestive tract. Lodged inside the bacterium, the plasmid directed the E. coli to assemble VP3 protein molecules; it essentially taught a living germ how to cobble together a foreign protein. When the E. coli replicated, the DNA instructions to make VP3 also replicated with it. Bachrach grew the modified bacteria — now an entirely new life form — in large kettles, and the newfangled bacteria grew easily in unlimited amounts as unmodified E. coli normally would. Each new E. coli produced an astonishing two million VP3 proteins.
Seven weeks into the project, they extracted the synthesized VP3 from the vats of slurry. Healthy cows and pigs were vaccinated with it, then held in animal rooms with disease-carrying swine infected with a highly virulent virus strain. of the thirty-three animal species that can transmit foot-and-mouth disease, pigs are the worst offenders, spewing virus everywhere in their vicinity. on the tenth day of exposure, the scientists walked into the animal rooms and cheered — not one of the vaccinated animals had caught the disease. Bachrach and his team were thrilled with the results of the experiment. They created the first genetically engineered vaccine in history. And they did it on Plum Island in 1981.
"We believe this to be the first production through gene splicing of an effective vaccine against any disease in animals or humans," Secretary of Agriculture John R. Block proudly announced. With Bachrach's ingenious recombinant DNA vaccine, disease control would be safer and far less expensive. Genetically engineered vaccines for this and other viruses could be produced anywhere in complete safety, because modified E. coli with VP3, and not the offending virus itself, would be produced. There was zero chance of VP3 becoming virulent on its own. And unlike traditional vaccines, genetically engineered vaccines didn't require refrigeration, no small benefit given the prevalence of disease in the developing world.
28
Genentech was founded by scientist Herbert Boyer, the co-inventor of recombinant DNA in 1973. The company spawned the biotech business, an industry valued at over $430 billion today.