Lab Pitches Cancer Dream

Some time in the future, if you get cancer, Yale-New Haven Hospital may give part of your tumor to a bunch of mice. It may find a way to save your life in return, then save the lives of people like you.

“People like you” means people whose DNA matches yours remarkably closely—more closely than it used to be possible to determine.

Welcome to the futuristic world of how to cure disease with personalized medicines.

The Jackson Laboratory says it’s helping to bring that future to Connecticut. With state assistance, the Maine-based not-for-profit is building a 173,000-square-foot genomics research center in Farmington affiliated with the University of Connecticut. A center crawling with mice—mice it wants to inject with cancer to study what medicines work on people with specific genetic abnormalities.

The center is scheduled to open in 2014.

In recent weeks Jackson officials have toured the state trying to convince hospitals and university research institutions to team up on those experiments. That search has inevitably brought them to Yale, where the medical school and Yale-New Haven’s Smilow Cancer Hospital are at the forefront of cancer research and care.

It’s too early to ink any deals. But Yale officials are game. They, too, are mapping patients’ DNA in order to find them just the right medicines. They see Jackson Labs’ expertise with mice as “complementary” in that quest, according to genetics professor Richard Lifton.

“If we don’t have active collaborations with Jackson Labs in five years when they have their building up and running, we have really failed,” Thomas Lynch Jr., director of Yale’s cancer center and Smilow’s top doc, said Monday. “This should invigorate the state.”

Aunt Eunice’s Hospital Visit

Michael E. Hyde, Jackson Labs’ vice-president for advancement and external relations, has been making some of those New Haven visits with people like Lifton. During a stop Friday at the offices of the New Haven Independent and La Voz Hispana, he described how a collaboration with Yale might affect a hospital stay for an imaginary cancer patient named Aunt Eunice—and how that might change the way medicine works. (Click on the play arrow to the video at the top of this story to watch part of his description.)

Under the way medicine works now, doctors prescribe drugs for a specific kind of cancer (or virus or mental illness or heart problem) based on clinical trials. If trials show that, say, the drug seems to help 10 or 20 percent of people tested with that kind of cancer, and it doesn’t seem to harm the others, the doctor prescribes that drug. Maybe it’ll work. If it works on half the patients, Hyde said, that would be considered a lot.

Medicine works that way because, until recently, you couldn’t easily discover one of nature’s most important secrets: the detailed map of an individual’s DNA, basically the identify of every last gene.

Only in the last decade have researchers come up with maps of people’s genomes. And until very recently, it cost way too much to draw up a map, and it took years.

That’s rapidly changing. Researchers at places like Yale can now sequence all of a person’s genes within days, for as little as $5,000, according to Hyde.

So if Yale and Jackson Labs collaborates on studying a form of cancer ... and if Aunt Eunice has that cancer ... they will ask her if she wants to participate in the experiment.

If she does, they will start by slicing a piece of her tumor. They will study it to map all the genes. They may identify, say, 20 variations out of 21,000 genes that set her tumor apart.

Then Jackson Labs—which made its reputation in part by breeding specialized mice for medical experiments—will breed 10 or 20 mice with those variations.

Hyde called them “bubble mice.”

“Think of them like the bubble boy from Seinfield,” he said. “They’re mice with no immune system. They have to live in clean rooms because they are unable to reject foreign tissue.”

The research mice live in a Jackson Labs facility in Sacramento, California. Aunt Eunice’s tumor sample will be sent there. Researchers then will implant tiny fragments of the tumor into the mice. The researchers will test different drugs on the mice to see “which drug or which combination of drugs are most likely to work,” Hyde said.

They’ll then contact Aunt Eunice’s oncologist back at Smilow.

“According to our tests, we believe this combination of cancer drugs has the best chance of curing her,” they’ll say. If Eunice agrees, she will get that medicine. And hopefully feel better.

Meanwhile, Hyde said, the researchers will add the results of Eunice’s DNA sequencing and her drug treatment “together with hundreds and eventually thousands of other individual cases to build a very smart database that will be able to deliver more accurate predictions for future treatment much faster.”

So the next time someone comes to Yale-New Haven with a tumor similar to Aunt Eunice’s, and if her genes match Eunice’s, docs will have a good idea of what medicine will help her. A much better idea than doctors have now. And if her genes don’t match Eunice’s, eventually, one hopes, a better match will show up in the database.

“One might be able to show, for example, that lung cancers with mutations in genes ‘A’ ‘B’ and ‘C’ respond to one treatment, while those with mutations in genes ‘D’ ‘E’ and ‘F’ respond to another,” said Yale medical school’s Lifton.

That’s the optimistic vision of the new world of personalized medicine.

Tight Money, Vast Landscape

Yale has been pursuing that same vision, according to Lifton and Smilow’s Lynch. It has done extensive genetic sequencing. It has done work with mice, too (adhering to strict ethical-treatment standards, Lynch made a point of emphasizing).

“There is no doubt that cancer therapeutics is a major beneficiary of new capabilities in genetics and genomics. At Yale, we are currently performing clinical DNA sequencing of cancers from patients to determine which patients should receive particular drugs, and we are also doing DNA sequencing of large numbers of cancer samples from patients as part of research efforts to identify new genes that underlie each of the different types of cancer, which will pave the way for development of novel treatments,” Lifton wrote in an email message. “In this context, Jackson labs’ interests in transplanting human tumors into mice to determine response to different treatments can be complementary.” 

“I do believe [Hyde] is correct that the future of cancer therapy is this concept of personalized cancer medicine. I know it’s a big cliche at this point, but it’s true. We will go toward a day when [a patient] will have her tumor fully sequenced to look for all the genetic patterns” to locate the right medicine,” said Lynch.

The quest for that day remains “very much in the discovery mode,” he added. “The problem is we don’t know what to do with the vast number of abnormalities we’re finding [in genetic sequencing]. The challenge for the next generations of scientist to learn how to process the large amount of data we’re getting from the genomics screens.”

In other words, there’s lots of work to do. Yale or any other institution can’t do it alone, Lynch noted; it needs partners, the way medical and academic institutions work together in Massachusetts’ Route 128 corridor and in the Bay Area in California.

That need to collaborate has grown greater given federal research funding cutbacks, Lynch said. “The federal budget picture is so bleak ... We will have to find ways to be more efficient and be more collaborative.” Aunt Eunice’s fate may hang in the balance.

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