Here’s to the geneticist who helped map the first breast cancer gene

You probably don’t recognise the name Mary-Claire King, but I’m willing to bet you know this extraordinary woman’s work. King, a professor at the University of Washington, did her PhD with Allan Wilson in evolutionary genetics, and together they were the first to show that human and chimp are about 99 per cent identical at the DNA level.

In 1974, King took the evolutionary genetics insights she had learned during her PhD and applied them to a different problem. She started searching for genetic determinants of breast cancer. Next month, October 2014, is the 20th anniversary of the mapping of the first breast cancer gene.

Forty years ago, the landscape of genetics research was markedly different from today. There was not yet a single human genetic disease mapped. It was nine years before the first one, responsible for Huntington's Disease, was linked to a specific chromosome. There was no genome sequence to look up, not even an accurate idea of how many genes are in the human genome. Many scientists thought there were as many as 100,000 genes, but the true value is closer to a humbling 22,000.

Given these scientific challenges, the best approach available to King and her research team was to use a technique called “linkage mapping”.

Chromosomes

This takes advantage of the fact that as chromosomes are passed from parent to child, getting scrambled through the generations, genes that are physically close neighbours on a chromosome are more likely to stay together, unscrambled. Using this genetic insight, characteristics – in this case increased susceptibility to breast cancer – can be tested for proximity to known landmarks in the genome based on patterns of co-inheritance.

This work is slow and painstaking and, for about 16 years, King and her relatively small research team were working on this alone. By 1990 they had narrowed down the location of a breast cancer gene (dubbed BRCA1 by King) to a comparatively small region on chromosome 17.

To give an impression of what they had done, it was as if the total length of the genome was the road from Galway to Sligo, and King’s research had narrowed down the search to Tuam’s main street.

At this point, the goal was in sight. Others decided to join the search in competition with King. This was dubbed “the race” by many commentators. More than 100 researchers were working full tilt in about a dozen labs around the world.

In October 1994, 20 years after King had started work on this problem, the race ended with the mapping of BRCA1 and the discovery of this hitherto hypothetical gene. King didn’t win the race – instead the first ones to locate the gene were scientists working at Myriad Genetics. Because they were first, Myriad was allowed to patent this naturally occurring gene.

Everyone has two copies of the BRCA1 gene, one from each parent. However, anyone who inherits one faulty copy of the gene is at increased risk of developing breast or ovarian cancer during her lifetime. Last year Angelina Jolie revealed that she is a carrier of a faulty version BRCA1 and had had a double mastectomy in order to manage her risk.

King has argued that all young women should be screened for the known breast-cancer risk mutations. This would provide them with useful information that might inform their medical choices in the same way that Jolie’s medical choice was informed by her genetic status. However, for many years the cost of testing was high, due in part to the fees payable to the owners of the patents on these genes every time the test was carried out.

Last year, in a landmark case, the US supreme court invalidated the patents on the breast cancer genes BRCA1 and BRCA2 and stated in its ruling that naturally occurring genes should not be patented. The genetic status is only part of the story; other genes and other lifestyle factors contribute to risk.

However, this ruling opens up the possibility of more widespread testing for these and other genes as part of a public health initiative.

King is deserving of great recognition for her contributions to genetics and medicine. She has received multiple awards, including the 2010 Dawson Prize in Genetics from Trinity College. Just this month she was awarded the prestigious Lasker Prize, considered by some to be a predictor of even greater prizes to come. Aoife McLysaght is a professor in genetics in TCD, where she leads a research group focusing on identifying and interpreting the evolutionary patterns in animal genomes