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70 Scientific American, April 2019

W


orking behind the scenes, calculus is an unsung hero of modern life.
By harnessing the forecasting powers of differential equations—the sooth­
sayers of calculus—humans have used an arcane branch of mathematics
to change the world. Consider, for instance, the supporting role that calcu lus
played in the fight against HIV, the human immunodeficiency virus.

In the 1980s a mysterious disease began killing tens of thousands of people a year in the U.S. and hundreds of thousands world­
wide. No one knew what it was, where it came from or what was causing it, but its effects were clear—it weakened patients’ immune
systems so severely that they became vulnerable to rare kinds of cancer, pneumonia and opportunistic infections. Death from the
disease was slow, painful and disfiguring. Doctors named it acquired immunodeficiency syndrome (AIDS). No cure was in sight.
Basic research demonstrated that a retrovirus was the culprit. Its mechanism was insidious: The virus attacked and infected
white blood cells called helper T  cells, a key component of the immune system. Once inside, the virus hijacked the cell’s genetic
machinery and co­opted it into making more viruses. Those new virus particles then escaped from the cell, hitched a ride in the
bloodstream and other bodily fluids, and looked for more T  cells to infect. The body’s immune system responded to this invasion
by trying to flush out the virus particles from the blood and kill as many infected T  cells as it could find. In so doing, the immune
system was killing an important part of itself.
The first antiretroviral drug approved to treat HIV appeared in 1987. It slowed the virus down by interfering with the hijacking
process, but it was not as effective as hoped, and HIV often became resistant to it. A different class of drugs called protease inhibi­
tors appeared in 1994. They thwarted HIV by interfering with the newly produced virus particles,
keeping them from maturing and rendering them noninfectious. Though also not a cure, prote­
ase inhibitors were a godsend.
Soon after protease inhibitors became available, a team of researchers led by David Ho (a for­
mer physics major at the California Institute of Technology and so, presumably, someone comfort­
able with calculus) and a mathematical immunologist named Alan Perelson collaborated on a
study that changed how doctors thought about HIV and revolutionized how they treated it. Before
the work of Ho and Perelson, it was known that untreated HIV infection typically progressed
through three stages: an acute primary stage of a few weeks, a chronic and paradoxically asymp­

M ATHEM ATIC S

OUTSMARTING A


VIRUS WITH MATH


How calculus helped to drive the fight against HIV


By Steven Strogatz


Excerpted from Infinite Powers:
How Calculus Reveals the Secrets
of the Universe, by Steven Strogatz,
to be published by Houghton Mifflin
Harcourt on April 2, 2019. Copyright
© 2019 by Steven Strogatz. Used
by permission. All rights reserved.

© 2019 Scientific American © 2019 Scientific American
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