It was 1945, and Oscar Whitaker was in a Louisville hospital, yet another of the Whitaker family struck with some kind of cancer. Stanley, who was 8 and was visiting, was already aware that this is what killed Whitakers.
It was what killed Stanley's grandfather when Stanley's dad was 3. It would kill Uncle Oscar, but not until 1965. Of Oscar's 10 kids, eight would develop cancers of the colon, uterus, stomach or pancreas.
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Stanley's sister Margaret died when she was 55 of colon and uterine cancer. His sister Marcella died after numerous cancer operations at 67, after her own son had died of colon cancer at 32.
And, sure enough, Stanley developed colon cancer in 1983 when he was 46.
So obvious was the plague on this family that a geneticist at the Cleveland Clinic, where some family members had been receiving treatment, helped them put together a family tree of sorts. What it revealed: In the latest generations, 38 members have been treated for cancer. In the earlier generations, those who died young from things as vague as "stomach ailments" — probably cancer — add up, too
A lot of the Whitakers die young which, says Stanley, is what made the thing unbearable.
In 2006, when yet another Whitaker cousin died from cancer in another Kentucky hospital, science, in the guise of a geneticist, asked family members whether they'd would be willing to take a few tests.
By then, a group of scientists had spent years combining genetic tests and genealogical digging to try to discover, and trace, the source of a gene mutation that causes Lynch syndrome, the cluster of cancers the Whitakers were dying of. The question before them in 2006 was how common the mutation was.
When Stanley Whitaker got the call from a nephew about the study, he became the relentless driving force behind getting 50 of his family members to the Cleveland Clinic, to the University of Kentucky and to Central Baptist Hospital for testing. Those tests, along with many other families' tests, were sent to Ohio State University, the institution heading up the study.
A second report on what is now being called the American Founder Mutation was issued last spring. It drew a startling conclusion: Of the 32,000 Americans who carry the gene, 8,000 are Kentuckians.
So prevalent is the syndrome in Kentucky and Ohio and so dire the cancers that it causes that OSU genetic researcher Heather Hampel says the situation has risen to the level of a serious public health concern.
It started with one big family
Most of the people who come to the Clinical Genetic Counseling Program at UK's Markey Cancer Center already have been identified by doctors as being very high risk for genetic abnormalities.
In her role as director of the center, Heather Hanson Pierce has referred patients to the Ohio State study, noting that most who agree to further testing "say they are doing it for their children."
Family can be both the blessing and the hurdle in handling diseases with a genetic component, she says. In the beginning, it was only hurdle.
"It all started with one large family," says Henry Lynch, now 80 and chair of medicine at Creighton University Medical School in Omaha, Neb. "It created a curiosity for me."
That was 50 years ago when Lynch was just a few years out of medical school. The young doctor had been asked to consult on the case of a man whose colon cancer was out of the ordinary because it didn't include polyps. After talking to the family, he decided to create a genetic chart.
A scientist deeply convinced of the need for statistical proof of anything, Lynch then set out into the wheat fields of Nebraska to research and document what he called "cancer family syndrome."
"Nobody used to talk about this kind of thing out loud," he says.
So Lynch took his own money, his wife, Jane, and his small son, Patrick, on the road. Along with him came social worker Anne Krush who believed, as he did, that family doctors in rural Nebraska probably knew a lot about the people they served. Together, the small group of ad hoc researchers would listen to family stories, look into family Bibles, construct careful family histories and try to create pictures of whole families that seemed plagued by early and recurring incidences of cancers.
"We went house to house, talked to virtually hundreds of families," he says. Applying for research grants so he might gather more family data, Lynch was refused by those most likely to say yes, such as the National Institutes of Health. Cancer was a disease of environmental causes, he was told. The discovery of the structure of DNA in 1953 was little more than 15 years old at the time of his first request.
Lynch would never change his position, pushing for family cancer centers long before the first cancer genes were identified in the 1990s. That was when his collection of family histories became important again.
Some of those histories were done on that first cancer he'd seen and worked with extensively in the 1960s, the hereditary disease grouping now known as Lynch syndrome.
Lynch always maintained that the control and management of cancer was his goal.
The missing piece
The discovery of the gene mutation that causes Lynch syndrome was independently achieved by researchers five years ago in the Netherlands collaborating with Lynch at Creighton and by researchers at Ohio State University, led by Albert de la Chapelle.
What they discovered is that those with Lynch syndrome are missing part of a gene. That missing part, in effect, disables their bodies from repairing genes when they begin to misreplicate, as in the replication of cancer cells. This has the effect of producing cancers of the colon, stomach, endometrium and pancreas, often in much younger adults than in the general population.
By proving the hereditary component and by explaining how it worked, Lynch was getting his wish — control and management of cancer. Patients as young as 25 could begin getting regular colonoscopies, mammograms and endometrial examinations. And insurance companies would begin to consider paying for those exams.
"Now my objective," says Lynch, "was to find those families once and for all who carry it."
Finding ground zero
Lynch's lifelong work began to pay off. His documentation of family cancers, combined with a nationwide Ohio State University search, yielded nine extended families with the mutation. The families offered to help investigators as they launched a genealogical study to trace their ancestry. Through the use of genealogical tools that rivaled archaeological digs, the Human Cancer Genetics Program and the Mathematical Biosciences Institute at OSU completed family histories going back 250 years.
Their conclusion, published in the Journal of the American Medical Association in February 2004, was that "the mutation was in either the husband or wife of a couple that had immigrated from Germany and settled in Pennsylvania in 1727."
This couple had 11 children. Painstakingly recreating their prodigious herd, the researchers created a family tree with 13 generations that could have received the defective gene. They had 566 individuals in nine families to test. Of those who underwent testing, 44.5 percent carried the mutation.
In three of the affected families, the researchers could definitively conclude that they were direct descendants of that one founder couple. In the genealogies compiled by the time the study was published, the remaining six families were showing that they, too, probably descended from the founder couple. That meant that 19,000 living Americans carried the mutation. But where were they?
Geographically pinpointing their whereabouts showed a pattern. It seemed to suggest that the German couple's children and grandchildren were typical Americans of their time, moving out across the United States, heading west and south, to Ohio, then to Texas.
A lot of them, however, seemed to stop in Kentucky and stay here.
Where the Whitakers fit in
The Whitakers of Kentucky were not included in the original study but, because of the preliminary Cleveland Clinic work, had roughly traced their family's own gene mutation. They discussed nothing else at family reunions.
Who they found, scientifically speaking, was Prudence Harvey Whitaker, born in 1775, whose people seem to have settled somewhere around Sinking Creek in Pulaski County. She had four sons but seems to have passed the gene to only one, James Harvey, who had nine children. One of those, Henry Frankfort, carried the gene and passed it along to his sons, John and Oscar, whose children were waiting in 2006 for some information to help stop the dying.
In the four years since the 2004 report, geneticists across the world had continued to be alert for potential Lynch syndrome families. When possible, family members provided family trees complete with birth and death date information. Professional genealogists would take over from there, supplementing with census data, cemetery records, wills, deeds, diaries and whatever else might provide clues on why family members died.
Everything was cross-verified.
In the process, OSU's lead genealogical researcher, Mark Baze, noted a problem with the original study. It put the identity of the founder couple in doubt. New work began in earnest.
In the meantime, a Creighton medical team released a study in 2006 that concluded that almost 2 percent of all newly diagnosed endometrial cancer patients have mutations for Lynch syndrome, which means they are at risk not only for endometrial cancer but for colon, ovarian and gastric cancer. And because it is hereditary, siblings and children also might be at risk. The stakes were getting higher.
So, too, the number of people who needed to know whether they were carrying the corrupted gene.
Kentucky's leading role
By last April, researchers from Ohio State, Creighton and the Netherlands plus those from the Mayo Clinic College of Medicine and the National Science Foundation had enough new families and enough new material to issue a correction of sorts.
The German couple probably were not the first to blame. In fact, new evidence derived from 32 families indicated the mutation was probably more like 500 years old and had arisen earlier in Europeans or in the native population of North America.
Further research continued to focus on Kentucky, Ohio and Texas, says Hampel, OSU's associate director of the division of human genetics.
More specifically, she says, "finding the mutation so common in Kentucky is telling us something about its introduction. ... You'd have thought it would have moved out more, but we couldn't find one in the Northeast for the longest time. We have one now. We have one in Michigan."
It looks now, says Hampel, that the mutation might have its beginnings near the Cumberland Gap. Some of the Kentucky cases congregate in southeast Kentucky.
"A few of the seven original families report Cherokee ancestry," says Hampel. The researchers have made no inroads into testing the Cherokee population, although that is an avenue they are interested in pursuing.
There are other areas of potential interest, such as Scotland. In the forays made so far, however, no evidence of the gene mutation has been found in Europe.
'We shouldn't be having kids'
The Whitaker family was always ahead of science on this one. They knew before anyone looked at their genes that they were not lucky in that department. Worry about impending cancer is something they all lived with.
Mary Louise Whitaker Phelps volunteered to be tested and was found to be just one of two of Stanley Whitaker's eight living siblings who does not carry the American Founder Mutation in her genes. She could not pass it to her three children, who cannot pass it to theirs. It is not what you'd call consolation.
Phelps is the family genealogist. In her diligence to help save her family, she has created an impressive family tree of 337 Whitakers and their relations.
Sister Willetta Whitis did not escape the family legacy but "what will be, will be," Whitis says. "We want to face this, and we old ones had to go first."
Stanley, however, was the one who told his children and his siblings' children that "it needs to be put a stop to."
He convinced a few who didn't want to have the test to have the test. He explained, cajoled and bullied.
"Until they get a cure for it," he told them quietly but firmly, "we shouldn't be having kids."
He has seen too many uncles and aunts and cousins and sisters die painful deaths to wish it on anyone else he loves or anyone else he ever would hope to.