As Clean As It Gets
On our fecund planet teeming with life, a School of Medicine facility holds biology at bay while creating specialized biomedical products.
Work done in the GMP facilitates medical treatments that cannot be done in any other part of the hospital.
Air at least a million times cleaner than the air we normally breathe rushes within the series of six interconnected labs. Massive air handlers with highly efficient HEPA filters maintain elevated air pressure to keep dirty air out. Gleaming metal surfaces are carefully wiped down and sterilized after use. Researchers and staff wear caps, masks, gowns, gloves and booties at all times to prevent contamination, and staff members perform weekly checks for any microbes on the walls, workbenches and floors. This is about as clean as it gets — on campus, on the planet. Why such obsessive housekeeping? It saves lives by preventing microbial contamination of specialized products made for patients.
NAMED FOR THE STRICT manufacturing regulations required by the Food and Drug Administration, the Good Manufacturing Practice facility (GMP) is a haven of high-tech environmental control. The superclean facility allows scientists to focus on translational research and to manipulate cells for use in a variety of medical treatments.
The GMP recently helped David Hamlyn, age 53, who suffered from myelodysplastic syndrome, a disorder of the bone marrow that disrupts the production of blood cells, including platelets, which are needed to form blood clots. His physician, Ravi Vij, MD, assistant professor of medicine in the division of oncology, knew this placed Hamlyn at risk for a potentially fatal hemorrhage at any moment.
Hamlyn's lack of platelets and his frequent infusions made it impossible to work. He had left his job in the paint department of a manufacturing company three years ago and was not able to return.
"I had severe headaches, and I'd bruise really easily," Hamlyn says. "If I got too close to something and skinned myself, I'd bleed and bleed. They told me if a blood vessel burst in my head, I'd be dead."
"After he came to Washington University and Barnes-Jewish Hospital, we followed him for close to a year and a half, treating him for what we thought was an immune system-based destruction of platelets," Vij says.
Several treatment attempts failed to restore Hamlyn's platelet levels, and his disease began to look incurable. But when Vij saw that Hamlyn's production of red and white cells was beginning to decline as well, he knew he was dealing with myelodysplastic syndrome. He recommended a bone marrow transplant, a risky procedure designed to wipe out Hamlyn's defective bone marrow and replace it with cells from a donor's bone marrow.
If all went well, stem cells from the donor marrow would move into Hamlyn's bones and develop to supply the blood components he was missing. Unfortunately, this transplant, performed in July 2005, wasn't effective.
"I still wasn't making any platelets," Hamlyn says. "Every other week I got two units of blood, and once a week I got a bag of platelets."
In addition, the bone marrow transplant left Hamlyn with graft vs. host disease, a complication caused when immune cells present in the donor marrow recognize the new host's cells as foreign and attack them. Because of this, Hamlyn needed to take drugs to suppress his immune system.
"He had the worst of both worlds," Vij says.
In December 2005, Vij considered the possibility of giving a second, booster infusion of bone marrow to restore Hamlyn's ability to make platelets. The problem with this plan was that a second infusion of whole marrow would bring a new wave of donor immune cells to attack Hamlyn's own cells.
"If we gave him more donor marrow, we would run the risk of worsening the graft vs. host," Vij says.
Vij decided that what Hamlyn needed was a concentrated infusion of stem cells minus the immune cells — and for that Vij needed the GMP.
Within an immaculate room of the facility, GMP staff used a magnetic cell selector to separate stem cells in the bone marrow donated for Hamlyn's procedure from the rest of the myriad of cells — including immune cells — that bone marrow possesses.
The technique required binding the stem cells to metallic beads coated with an antibody that attaches specifically to molecules on stem cells. The machine could then hold onto the bead-bound stem cells with its internal magnet while the rest of the cells in the marrow were washed away.
When the magnet was removed from the machine, the stem cells were pumped into a waiting IV bag, and the GMP sent the purified and concentrated stem cells to Vij and his patient. Three weeks after Vij infused Hamlyn with the cells, it was clear that this new transplant was working. Results showed that Hamlyn finally had a normal platelet count in his blood, and his life was no longer under threat.
"The air we breathe has billions of particles per cubic meter, including fungal spores, bacteria, viruses, pollen and dust," says Gerhard Bauer, designer and former director of the GMP. "If we made products like these stem cells in an ordinary lab, we could easily introduce a dangerous contaminant. In the GMP laboratories, the particle count is below a thousand particles per cubic meter so our products are very safe. We can facilitate medical treatments that can't be done in any other part of the hospital."
Around the time the GMP was preparing stem cells for Hamlyn, the facility also enabled production of artificial saliva for a study on taste in depressed patients and food oil with a tracer to determine if certain compounds in food are preferentially absorbed. The GMP also is involved in aiding physicians studying regenerative medical techniques to restore heart function after a heart attack, and to replace a defective gene in patients with Sly disease. Its ability to preserve tissue safely allows physicians to use the GMP as a bank for such needs as storing parathyroid tissue for thyroid cancer patients so that it can be reimplanted if needed.
"I've been designing ultra-clean laboratories for 15 years, but this is the best one I've worked on so far," Bauer says. "In the case of Dr. Vij's patient, we really saved a person's life because of the GMP and because quick approvals allowed the procedure to go forward."
Today, Hamlyn no longer needs infusions of platelets. While he still takes medications to control his graft vs. host reaction, it is not life-threatening. Looking back on his experience in trying to find the right treatment and undergoing sometimes difficult therapies, Hamlyn has no complaints.
"Everyone has treated me well, and they all worked really hard," Hamlyn says. "I don't know who the bone marrow donor was, but I appreciate what that person did. And I hope that what I had to go through and the treatments that I received will help someone else someday."