Jackson Lab and its new CEO build a better mouse
photo/Leslie Bowman
Edison Liu is the first medical doctor to be named president and CEO of The Jackson Laboratory. Under his leadership, the lab has been perfecting a mouse for customized medical treatments.
photo/Leslie Bowman
Michael E. Hyde. vice president for advancement and external relations at Jackson Lab, says the lab is developing the ability to translate genomic information from a patient into information a doctor can use to treat that patient
photo/Courtesy Jackson LabS
Scientists at Jackson Lab's Avatar project in Sacramento Calif., work in the lab where researchers have created a mouse without an immune system that can accept diseased human tissue. The new test mouse is expected to advance treatments for diseases such as cancer.
The Jackson Laboratory isn't letting any moss grow under its planned $1.1 billion laboratory expansion in Farmington, Conn., announced last fall.
The groundbreaking for the 183,000-square-foot building at the University of Connecticut's health center is expected in early January, with occupation in late 2014, and plans already are afoot for the lab's first big project. Known as Avatar, it involves taking tumors from human patients and regrowing them in mice to test potential treatments using personalized medicine.
The project pulls together resources at all three of Jackson Lab's facilities: patients associated with the University of Connecticut health center, mice and basic biological research at Bar Harbor, and expertise to grow the tumors in mice at Jackson Lab-West in Sacramento, Calif.
Dr. Edison Liu, a physician who took over as president and CEO of Jackson Lab in January, says the Connecticut facility is part of the lab's plan to expand into translational science — applying basic research to human disease.
"There are geodemographic realities such as having a medical school, hospital and population center," he says of the location. "So that is a unique opportunity to expand without jeopardizing our functions here [in Bar Harbor]."
"This is a very fast-track thing," adds Michael E. Hyde, vice president for advancement and external relations at Jackson Lab and a key negotiator for the new Jackson Lab Genomic Medicine expansion in Connecticut. "Our target is to hire 27 people this year, and at the end of 10 years to have 300 employees." The new lab currently has 21 high-level scientists and administrators working in temporary quarters.
While Hyde says a couple scientists from Bar Harbor might go to Connecticut, moving a lab is expensive, and Jackson Lab expects to be able to tap a ready local supply of researchers. He notes there is a glut of researchers seeking jobs in the poor economy.
The Bar Harbor facility also has 32 open nonfaculty positions, as it has proven more difficult to attract talent to its more remote location. Only half of the Bar Harbor employees live on Mount Desert Island and the other half commute, many in lab-subsidized buses from Bangor and Cherryfield, notes lab spokesperson Joyce Peterson.
Liu says the expansion to Connecticut doesn't impact the lab's commitment to Maine.
"We are embedded here in Maine," he says. "We are very proud to be a contributor to the economic well-being of the state. We are tied for 10th-largest employer in Maine, and are the sixth-largest nonprofit."
With 65,000 mice shipped worldwide each week to 53 countries and 20,000 labs, and another 1 million mice at a time on campus, he calls the lab, "the L.L. Bean of mice." Mouse-breeding competitors include for-profit vendors such as Charles River Laboratory, Taconic Farms and Harlan Sprague Dawley. Some of those companies might ship more mice, he notes, but Jackson Lab is known for its wide variety of research mice.
Jackson Lab also plans a Maine expansion in Ellsworth, where it recently closed on the purchase of a 140,000-square-foot building formerly occupied by Lowe's. Peterson did not have an amount for the sale, and says the space-planning process hasn't started yet.
There is no estimate yet for the number of employees who will be based there. Earlier reports said the move may create 300 new jobs, 100 at first and 200 to be added over time, according to WCSH 6-Portland.
Mouse avatars
From humble origins in 1936, when Jackson Lab sold about $3,000 worth of mice to pay for its overhead, the research mouse and services business has grown to $160 million, or close to 75% of total revenue, with the rest of the institution's money coming from research grants ($56 million, primarily federal monies such as from the National Institutes of Health), endowments and philanthropists.
The lab now intends to use the latest genomic and other computational tools for discovering the genetic basis of disease, and to turn its basic research into human health treatments, Liu says, pointing to the Avatar project.
"By engineering the mouse as a model for human disease, you can have virtual clinical trials in the mouse," says Liu.
While mouse tumors and human tumors are different, the idea is to take a human tumor and transplant it onto a mouse, where it will continue to grow with the characteristics of a human tumor. The transplant between species is known as a xenograft and involves part of the tumor being inserted into a Jackson Lab-bred "humanized" mouse that has no immune system and is called the NOD scid gamma mouse. The result is that pieces of one patient's tumor can be xenografted into multiple mice, sometimes 100 mice or more.
"You can test whether your treatment works in multiple organisms," Liu says.
Another advantage is that in a typical human clinical trial, each patient has a different variation of a particular type of tumor, so it isn't clear whether one treatment will work on all patients.
"The average human response to cancer treatment is 20-30%," adds Hyde. With Avatar, it will be possible for a cancer patient to get a treatment and at the same time several other potential treatments can be tested on that patient's own tumor transplanted onto mice, he says.
The tumors also will be sequenced to learn more about their genetic makeup and to find more effective treatments. DNA extracted from the tumors can be compared to the DNA of other people with the same condition, as well as those who don't have it, to compare and contrast differences. Mathematical and statistical techniques can be applied, Hyde says, to construct a picture of people with a certain kind of cancer.
"You may see 20 genes distorted in a similar way in people with a certain condition," says Hyde. "Then you can ask, 'If this is a result, is that true?' We'd then turn to our genetic engineers in Bar Harbor and try to replicate the disturbed DNA pattern in mice to see if you have an analogous condition."
The goal is to get a tight hypothesis of which anomalies are associated with a particular disease, and then look for a new compound or an approved drug to treat it.
Hyde says Jackson Lab is talking with four Hartford-area hospitals to participate in the Avatar program, which is expected to start early next year. Funding remains to be determined, he says. The tumor biopsies will be taken from the patients and sent to the Sacramento lab to be xenografted.
"A couple months later you will have a cage of mice, each with a tumor identical to that of the patient, and those mice can be used to do a 'human' trial," he says. The technique holds promise for less costly clinical trials and for potentially getting new drug candidates to market more quickly, he notes.
"We want to develop the ability to do very accurate and high-speed cancer diagnoses and to be able to translate genomic information into information a doctor can use," Hyde says, adding that informatics data could become a revenue stream for Jackson Lab.
The lab also houses the mouse genome database, and has a history of doing database and repository work.
"The reuse of information is why this is so powerful," Liu says. The Jackson Laboratory, founded in 1929 as a cancer research facility, was designated as a Cancer Center by the National Cancer Institute since 1983 to conduct basic research.
Hyde expects that in about 18 years, the Connecticut operation will be bringing in $60 million a year from three main sources: grants, new sources and philanthropy.
Of mice and men
While Liu says there are other model systems that are better than mice, they are much more costly, so he believes work on the mouse model will continue to increase.
"The mouse is a fundamental tool to understand basic biology and physiology. We're now moving toward modeling for precise human disease," he says. And the more the mouse and human are studied together, the more is learned about their similarities and differences.
"Now that we can attack human diseases using strong tools such as metabolomics and genomics, the problem is having all this information and knowing how to parse it out," he says. "We need to take a systems approach, just like an aeronautical engineer doesn't just look at the wing."
He says computer-assisted design based on the collection of complex data from multiple sources can make a model to predict responses.
"The more we understand genotypes [the cell's genetic makeup], the more we can model, especially with mice. And by engineering the mouse as a model for human disease, we can then have virtual clinical trials in the mouse," he says. But no matter how good the mouse model is, potential treatments still need to be tried in patients, he adds.
Jackson Lab is working toward building a "tunable mouse" for any disease and mode that is needed to reflect the human condition, he says. His other goals are to accelerate the organization's use of genomics and computational tools, to do more genetic sequencing in-house, and to slowly move the business into emerging science countries in Southeast Asia, China, India and Korea.
"We have a global strategy, but we want to take it rationally and slowly," he says. "And at some point, we will increase our service offerings."
Although the Bar Harbor lab focuses on basic scientific research, it recently saw the second spin-off company in its 83-year history, led by cancer researcher Kevin Mills (see Mainebiz, Sept. 21, "New spinoff launched at The Jackson Laboratory"). The company, Cyteir Therapeutics Inc., is developing cancer therapies and autoimmune disease treatments, and initially is focused on a specific drug to treat chronic lymphocytic leukemia. Mills' lab discovered the drug candidate and found the pathway that could be an "Achilles heel" for leukemia and autoimmune diseases at the same time potentially decreasing side effects, according to Mills.
The first Jackson Lab spinoff, formed 10 years ago, was Bar Harbor BioTechnology Inc. of Trenton, which licensed proprietary gene analysis methods from the laboratory. Privately held, Bar Harbor BioTechnology has attracted nine individual and institutional investors, including New Hampshire-based Borealis Ventures, the company's lead investor.
Lori Valigra, a writer based in Harrison, can be reached ateditorial@mainebiz.biz.
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