Gail and Edward Arnold
Rolling the Dice to Beat HIV
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PERSON-TO-PERSON |
WHERE THEY WORK
Gail Ferstandig Arnold is a Research Professor and Edward Arnold is a Professor at the Center for Advanced Biotechnology and Medicine and the Department of Chemistry, Rutgers University
KEY COLLABORATORS
Anqiang Zhang, Allen Smith, Dawn Resnick, Andrew Holmes, Sheila Geisler
WHERE THEY MET
As undergraduates at Cornell University
FAMILY LIFE
While they sometimes bring their work home with them and “talk shop” over the dinner table, their two young daughters don't resent their parents’ work at all. On the contrary, they say, “our daughters are fascinated by viruses.” |
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| Gail and Edward Arnold have happily married their careers and home life. |
In the everyday world, gambling can become a dangerous addiction. But in the laboratory that Gail and Edward Arnold run, a kind of biochemical gambling could someday lead to a vaccine against the deadly AIDS virus.
The Arnolds set up their lab in 1987, six years to the day after they were married. Gail is trained in biochemistry; Edward, in chemistry and the structure of viruses.
“It’s symbiotic,” Gail says. “We’re not stepping on each other’s toes, but instead really helping each other understand things beyond our normal limits.” Adds Edward, “Our different backgrounds and knowledge allow us to take diverse approaches to this kind of problem.”
This kind of problem is creating from scratch viruses whose external surfaces mimic the proteins of human immunodeficiency virus (HIV) that spark a human immune response. The goal is to develop a cocktail of these lab-made viruses to use as a vaccine that will prime the vaccine recipient’s immune system to ward off the live AIDS virus before it can take hold in the body.
Viruses infect a host through the actions of proteins on the surface of the cell; in the case of HIV, scientists have identified several surface proteins that enable the virus to take over some types of immune cells in an infected host.
The hope of other scientists developing a vaccine is to somehow create a harmless virus that displays HIV-specific surface proteins to the human’s immune system. The immune system will then create antibodies that will be ready to attack and eliminate any invasion by HIV.
Drawing on their respective backgrounds, and collaborating with other scientists, the Arnolds have developed and refined a method to generate millions of possible vaccine candidates. The method uses “
combinatorial chemistry ” that the Arnolds compare to gambling: rolling many many dice over and over again to increase the odds of winning the jackpot.
The dice-rolling approach involves two components:
First, make copies of the genes in HIV that provide the instructions for the surface proteins that stimulate the immune system — in other words, the virus’ immunogens.
Second, link random sequences of amino acids and other chemical building blocks to either side of the immunogen. Then insert the immunogens and links into a benign virus that infects humans, in this case,
rhinovirus. This benign virus will then “express” the HIV immunogens, hopefully in ways that precisely mimic how they are expressed by HIV itself, but without causing disease.
Keep rolling the dice thousands and thousands of times and the odds are that some of these chimeric viruses will work in stimulating an HIV-specific immune response.
Part of the beauty of this approach, the Arnolds say, is that it forgives our current lack of complete knowledge. “Even though we know dramatically more about protein structure and folding now than we did a decade ago, we still don’t know all the rules for protein engineering — for example, how to take a sequence from HIV and put it on a rhinovirus surface in a certain configuration.”
Since 1988, the Arnolds have created a massive library of
chimeric viruses, many of which hold promise for an AIDS vaccine. “With these libraries, we’re focusing only on the things that work,” Gail says. “We’re turning our backs on all the failures. We don’t need to worry about them, wondering why they didn’t work. We’re moving in a forward direction.”
