Human face of genetics - The Irish Times - Tue, Apr 20, 2010

The death of a friend from cancer started Prof Mary-Claire King on a path that would lead to a groundbreaking discovery in medicine, writes CLAIRE O'CONNELL

ON THE FACE of it, genetic research can seem cold and clinical. Isolating DNA, working out the sequence of its “letters” to see what information it contains and figuring out what particular genes do in the body sounds abstract.

But Prof Mary-Claire King has spent much of her career putting a far more human face on genetics.

Her landmark studies include a comparison of human and chimp DNA in the 1970s, she uses DNA profiling to identify victims of human rights abuses and she is working on the genetics of deafness, HIV and schizophrenia.

But her most high-profile contribution to the field of medicine was the groundbreaking discovery in 1990 of the inherited breast cancer gene, Brca1.

Even her route into that area of research has a poignantly human slant: her childhood friend died of cancer when they were both aged 16, recalls King, who is now American Cancer Research Professor at the University of Washington, Seattle.

“I was so angry when that happened to her, and I thought if there’s anything I can do to make cancer a thing of the past I am going to try to do it,” she says after a recent public lecture at Trinity College Dublin organised by the Smurfit Institute of Genetics and Women in Technology and Science.

“Of course, it takes decades for this kind of thing to percolate, but I thought it could be a good niche for me.”

Within that niche King trawled through several extended families – including some Irish branches – and worked out that carrying damaging mutations in a gene on chromosome 17 bumped up the risk of developing breast or ovarian cancer at an early age.

After nearly two decades of looking, she presented the results in late 1990.

“The audience went from scepticism and disinterest to, ‘Oh, we knew it all along’, in about 20 minutes. So you really had to enjoy that 20 minutes,” she says.

But that 20 minutes quickly changed the mindset on cancer genetics and has since helped to usher in more personalised approaches to treatment and a better understanding of how cancer can arise when protective genes such as Brca1 don’t function properly.

King has subsequently worked on another gene, Brca2, where mutations can also increase the breast or ovarian cancer risk.

Not everyone who carries mutations in these Brca genes will develop breast or ovarian cancer, notes King. But Brca1 accounts for about 5 per cent of all female breast cancers, and for some people opting to have breast tissue or ovaries surgically removed, it can dramatically reduce the cancer risk.

Still, the key is knowing whether you have it. “We want to make screening faster, cheaper and more efficient so women don’t find out after the cancer has been diagnosed,” she says.

And even 20 years after its discovery, Brca1 is still hitting the headlines. Last month a US judge upheld a challenge to the patent held on the gene by the company Myriad Genetics, which markets a genetic screening test for Brca1 mutations.

While the issue is not yet resolved, it throws open the issue of gene patenting, which King argues is a different landscape to taking out a protective patent on a new pharmaceutical drug that takes many years and millions of dollars to bring to market.

“We are not talking about medications here, we are talking about resequencing a gene so the person can know whether they have a mutation or not,” she says.

“All does is constrain the competition on the best and most efficient ways of doing the test, and in this case it has meant that the most modern technology has not been applied. I think that the patient is most at benefit if there is an open competition in the market for genetic testing, and this is a step in that direction.”

Meanwhile, she sees more rewards for patients as the field of personalised medicine develops further. “I think more and more genes from more and more complex traits will be reduced to this kind of analysis. So it’s going to become both broader in terms of the traits we can identify in this way and deeper in terms of the number of people we can help.”

DNA PROFILING: PIONEERING WORK THAT CHANGED LIVES


Almost three decades ago, Prof Mary-Claire King got a request that was to change the lives of many.

A group in Argentina called the Abuelas (Grandmothers of the Plaza de Mayo) contacted the geneticist and asked for help in finding their grandchildren who had gone missing after the children’s own parents had been “disappeared”.

“They wanted to identify the ancestry of children who were showing up all over the place – in orphanages, families, on the street and in kindergarten,” says King.

“They heard of me through friends of friends. I was the age of their daughters, I spoke Spanish and they wanted me to do this.”

While DNA profiling is commonplace today, back then it was pioneering work, and King developed an approach to analyse the “mitochondrial” DNA that passes down the maternal line. The project has now identified more than 100 children and helped reunite them with their biological families.

“I thought it would be a one-shot thing, but here we are years later – and that ain’t bad,” says King, who knew she had to do the job when asked.

“The grandmothers demanded it, and you don’t say ‘no’ to a grandmother.”

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Human face of genetics - The Irish Times - Tue, Apr 20, 2010