Born: 5 May 1952, United States (assumed)
Died: NA
Country most active: United States
Also known as: NA
The following is excerpted from Infinite Women founder Allison Tyra’s book The View from the Hill: Women Who Made Their Mark After 40.
Helen Hobbs fundamentally changed the way we understand cholesterol, doing work that would save countless people from death and disability related to issues like heart disease and stroke. More than one out of every eight deaths in the world is attributable to heart disease, killing nine million people in 2021 alone.
Born in 1952, Hobbs initially studied art history in college before shifting her focus to medicine, which appealed to her passion for solving puzzles. During her residency, a mentor recognized this curiosity and encouraged her to pursue research rather than treating patients. She joined Michael Brown and Joseph Goldstein’s lab in 1983. Two years later, the two men would win the Nobel Prize in Physiology or Medicine for their work on the mechanisms that the body uses to control levels of cholesterol, which turns dangerous when it builds up in the arteries, creating blockages and chunks that can break off and cause other blood flow issues.
There are two basic types of cholesterol—high- and low-density lipoprotein, often referred to as “good” (HDL) and “bad” (LDL) cholesterol because higher levels of HDL are often beneficial while high levels of LDL are typically dangerous. Hobbs began investigating a genetic component to LDL levels, looking at the receptor that generally removes LDL from the bloodstream. Brown and Goldstein had identified a set of individuals who did not appear to have this receptor, but Hobbs discovered that they were missing the messenger RNA for the receptor and also noticed that a significant number of the group were French Canadian. The combination of RNA and shared ancestry led her to establish her own lab in 1987, publishing dozens of papers over the next 13 years. And then she had a second epiphany. When other researchers announced discovering a genetic link for a rare inherited condition connected to unusually small HDL levels, she realized that she should have been focusing on the movement of cholesterol in the body, not focusing on cells grown in culture dishes.
With this shift in perspective, she uncovered genetic aberrations that caused various diseases, as well as important discoveries on the mechanisms by which those disorders impact the body. She launched the Dallas Heart Study, collecting “an unprecedented amount of information” from more than 6,000 adults from 2000 to 2002. Identifying people with very high and low HDL and LDL levels, Hobbs and her team identified genetic anomalies in those with very low HDL, publishing the results in 2004. Their work contradicted common beliefs about the causes of disease, to the point that the first journal they submitted the paper to rejected it without even reviewing it. Their next major finding was related to a protein, PCSK9, associated with high LDL because too much PCSK9 removes LDL receptors from liver cells, meaning there are fewer receptors to pull LDL out of the bloodstream and so the LDL builds up in arteries. Flipping that, Hobbs reasoned that if too much PCSK9 meant high LDL, too little likely meant low LDL. Turning to the participants of the Dallas Heart Study with the lowest LDL rates, they found seven individuals who had PCSK9 genetic anomalies. Because the study was multi-ethnic (an unfortunate rarity), researchers were able to correlate this with the fact that all seven were African American, and determined that two percent of the African Americans in the study had one of two anomalies and significantly lower average LDL levels. Because they had had this condition their entire lives, it also created a longitudinal picture of the impact of low LDL on heart health over a lifetime. This work led to the development of drugs to deactivate PCSK9, which were subsequently approved in the U.S.