Alnylam succeeds in sickening subjects so it can test drug
The Cambridge biotechnology company Alnylam Pharmaceuticals Inc. made a big splash this month by inking one of the largest-ever deals in its industry, a partnership with drug giant Roche that could eventually be worth $1 billion.
Overshadowed by the deal, however, was a curious success in the scientific realm: Last winter, Alnylam's researchers successfully made 26 people sick. If that seems like a small achievement to build a billion-dollar company on -- well, of such small steps is medical progress made.
Alnylam wants to develop a new drug to fight a pesky lung infection called respiratory syncytial virus, or RSV. It's normally not serious but can be dangerous when it attacks infants and older people.
In healthy adults, RSV looks so much like a cold that it's almost impossible to distinguish the two. So before Alnylam can test its drug, it needs a pool of guaranteed sick people -- which means it needs to create them.
So, earlier this year, the company undertook an unusual human study. Using doctors at different universities and hospitals, it recruited 36 volunteers and gave them a shot of the virus. When the results of the test were presented at a medical conference last spring, the company declared victory: 26 people were infected. There were no serious problems.
Alnylam executives, through a spokeswoman, declined to discuss the study in more detail, but a scientific summary explained how exactly to give a new virus to a cohort of people. Researchers harvested the virus from a baby with a confirmed case of the disease. It was purified, grown in a dish of monkey cells, tested for other diseases that might have hitchhiked into the sample, and bottled in sterile vials.
The 36 patients had the virus sprayed into their noses in increasingly large doses, and the measurements began. They reported how they felt. They were assessed by a doctor. They had their noses rinsed out twice a day and the virus levels analyzed. Their used tissues were weighed. The results were charted, each person's illness growing in a broad arc across a graph.
Dr. John DeVincenzo, the University of Tennessee pediatrician who helped Alnylam design the trial and analyze the results, said the test removes a "huge impediment" to the treatment of RSV by giving researchers a way to measure the disease and whether a drug actually works against it.
"I see kids die all the time from RSV," DeVincenzo said. "It's not a benign disease."
Such tests are unusual in medicine, but not unprecedented. In academic research, patients are sometimes infected with diseases as serious as malaria or cholera so that cures or vaccines can be tested reliably.
In Alnylam's case, it has now launched a second trial in which people will be first sickened with the virus then treated with an experimental drug to make them better. The company has already performed early safety tests on the drug, which appears to work in mice.
If it works, the treatment will be only a small part of Alnylam's future. The company has attracted attention in the drug industry for using a new kind of biology called RNA interference, or RNAi, a way to interrupt the workings of genes.
Nobody has ever made an RNAi-based drug, partly because the technique is new and partly because the drug molecules are difficult to deliver to the body.
Alnylam believes one way to deliver an RNAi drug is through inhalation. An inhalable drug directly hits the lungs, where it could fight RSV and other respiratory viruses. It could also fight a lung disease such as cystic fibrosis, and the company has received $1.5 million from the Cystic Fibrosis Foundation to test that possibility. In its labs, Alnylam is trying to develop drugs for a wide range of diseases, including Ebola, influenza, cancer, Huntington's disease, and neuropathic pain, although the RSV drug is the first to reach human tests.
Stephen Heuser can be reached at sheuser@globe.com. 
