Introduction

RARE PROFITS 43
where has remained ever since (Blindness having been replaced with
Stroke at the institute).
Noting his prior experience at Penn, the director put him to work
studying lipids (the insoluble fatty parts of cells) in the brain and nerves.
But within a few years Brady gravitated to the disorders caused by excess
lipid buildup in the body’s major organs. Many of the lysosomal storage
disorders had been discovered in the late nineteenth and early twentieth
centuries by scientists who gave them their eponymous names, but little
was known about their causes. Did the body create too much of a particular
lipid Was it failing to break it down properly when cells died and
were replaced Was there a genetic defect—these diseases were all
known to pass through families—causing them to make the wrong lipiddissolving
enzyme entirely Whatever the cause, the effects were disheartening
to see in the clinic. People with Gaucher disease, for instance,
often had distended bellies from their enlarged spleens and livers, where
an excess of a lipid called glucocerebroside wound up. It also wormed its
way into bone marrow, and symptoms included anemia, bone pain, and
a propensity to bleed uncontrollably and suffer bone fractures. Fabry
patients built up lipids in the walls of small blood vessels, which led to
unbearable pain in the feet and hands, kidney and heart failure, and
almost always early death. The average life expectancy for a Fabry disease
sufferer was forty-one years.
Brady spent his first two decades at NIH unraveling the mysteries of
these diseases. He eventually discovered that each disease was caused by
a missing enzyme, which broke down the lipids in normal people. Some
people were missing the enzymes due to either genetic inheritance or a
mutation at conception. The first breakthrough came in 1964 when
Brady and his team of scientists identified the missing enzyme for
Gaucher disease. “It was a biochemical Rosetta stone,” he said. “Once
we knew this was the basis of Gaucher disease, we had the key to all the
single lipid storage disorders.” By the early 1970s, Brady’s team had done
similar work on Niemann-Pick, Fabry, and Tay-Sachs diseases and other
lysosomal storage disorders. They also worked on mucopolysaccharide
diseases, where build-ups of jellylike sugars inhibit normal growth and
mental development. “There are about thirteen of them and it was the
same principle,” Brady said. “They don’t have enzymes to start the
breakdown.”
With much of the basic science under his belt, Brady turned to treatment.
“I started with a very simple concept. If this enzyme is not as
active as it should be, can you purify it from some source and put it into