In 1968 two young physicians-in-training, Michael Brown and Joseph Goldstein, were called to treat a pair of siblings, ages 6 and 8, who were dying of recurrent heart attacks. The cause was a genetically elevated level of cholesterol-carrying low density lipo-protein (LDL) in blood. The children were born with blood cholesterol levels over 1000 mg/dl, and they began having heart attacks before age 5.

The children suffered from a rare genetic disorder called homozygous familial hypercholesterolemia (FH), which afflicts one in a million children. Doctors Brown and Goldstein determined to find the genetic cause of this defect, in part because they hoped that this understanding would provide insights into more subtle forms of hypercholesterolemia that are responsible for one-third of all deaths in the Western world.

Preparing for a Career in Medical Research
In preparation for research careers, the two young physicians sought training in basic science – Goldstein mastered the emerging field of molecular biology with Marshall Nirenberg, who received the Nobel Prize for cracking the genetic code, and he subsequently studied human genetics with Arno Motulsky, a pioneer in the field. Brown learned biochemistry with Earl Stadtman, a founder of the field of enzyme regulation and a recipient of the US National Medal of Science. In 1972 Brown and Goldstein were reunited as junior faculty members at UT Southwestern in Dallas and began the work that would eventually earn them the Nobel Prize in Medicine or Physiology in 1985 and the National Medal of Science in 1988.