Of Mice and Men

Remarkable real-world advances in genomics in just the last decade have brought new medicines to market faster and at lower costs and are bringing us closer to a world of personalized medicine.

“We are in the midst of one of the most exciting yet tumultuous times in medicine and medical care,” says Dr. Edison Liu, president and CEO of the Jackson Laboratory, based in Bar Harbor, Maine. “We’ve never seen developments in biological sciences like we see today. It is not only that we know so much about medicine, but also about biology. And it is literally in the last 100 years.”

“The completion of a human genome [project] in 2000 took 10 years and cost $3 billion. Today we can sequence a genome in 10 days at a cost of $3,000. The increase in efficiency of discovery by six orders of magnitude has never been seen in the field of biology. Ever. Electronics has seen this. Computer sciences has seen this. Physics has seen this. But not biology. We’re just catching up to what you’ve seen in the physical sciences—explosive changes that took place in the 19th and 20th centuries.”

Liu is an international leader in cancer biology, genomics, human genetics and molecular epidemiology. He joined the Jackson Laboratory as president and CEO in 2012. An independent research institution, Jackson Lab has a history of innovative biomedical research. Its mission is to discover the genetic basis for preventing, treating and curing human disease, and to enable research and education for the global biomedical community.

It recently broke ground in Farmington, Conn., for a new laboratory for genomic medicine, which is leading the way in personalized, or individual, medicine.

The human body consists of about 20 trillion living cells. Each one contains about 23,000 genes and collectively is called the genome. While researchers are beginning to understand how the genome affects health, disease and response to drugs, technological advances make it possible to identify a person’s unique genome. Individual genomes may contain millions of variations, which affect susceptibility to disease and response to treatments.

Ultimately, a thorough knowledge of individual genomes will allow scientists and clinicians to begin to “personalize” medicine, tailoring treatment to each patient’s unique genome. Physicians will be able to prescribe the most effective drugs with the fewest side effects, based on the patient’s genome-driven response to those drugs.

Dr. David Levy, the global leader for healthcare at PwC, a global consulting company, says genomics is one of the hottest developments in global health and shows incredible promise.

“We talk a lot about personalized medicine and what that means with the genome being the last frontier for mass customization,” he says. “When we really know what’s going on in the human body, we have very highly specific therapeutics and diagnostics around it. I just believe we’re at the threshold of a mass explosion of really understanding genomics and understanding how the body works. I believe many of these chronic illnesses are going to be cured or effectively treated over the next 10 or 15 years.”

The Jackson Laboratory has three dozen research teams that study the genetic basis of human disease, including cancer, heart disease, Alzheimer’s, diabetes, osteoporosis and more, as well as how genes affect development, reproduction and aging. Additionally, investigators have dozens of research collaborations with leading biomedical and clinical researchers at institutions such as Stanford University, Harvard University, Dartmouth Medical School, Children’s Hospital of Boston, the University of North Carolina at Chapel Hill and many more.

• Over the years its researchers have made many significant discoveries:
• Leroy Stevens first described cells that can develop into different tissues, which today are known as stem cells.
• Elizabeth Russell performed the first bone marrow transplants in a mammal, leading to new treatments for blood and immunological diseases.
• Doug Coleman discovered an important controller of the body’s metabolism, now known as leptin, which is central to obesity and diabetes research.
• George Snell won a Nobel Prize in 1980 for providing an in-depth understanding of the immune system’s major histocompatibility complex, making organ transplants possible.

Founded in 1929, the Jackson Laboratory now has sites in Sacramento, Calif., and Farmington, Conn. It sprang from what had been considered a radical notion—that cancer is a genetic disorder and not an infectious disease.

Research Mice

Most of its research is conducted on laboratory mice because mice and humans share 95% of their genes and get most of the same diseases for the same genetic reason. This allows scientists to conduct tests on mice that they can’t perform on humans. A Jackson scientist successfully bred a strain of mice that can tolerate a variety of human cells, from blood cells to immune cells, making the mice ideal specimens for testing different therapies.

Using lab mice also drastically reduces the length of clinical trials for new therapies. While human trials are not eliminated, researchers can more quickly amass large amounts of data by testing mice with specific genetic characteristics than if they conducted only human trials. In this scenario, only the most promising therapies are tested on humans.

“You are looking at quickening and hastening and making more fast and cheap the R&D cycle, and I think that’s going to have deep implications for new drugs coming down the pike and new diagnostics in particular,” says Levy. “Research spending has a huge issue of spending tons of money and not getting what you want. A lot of it has to do with these enormous trials with the long tails because we don’t really know who has the disease we’re testing for. Genomics is going to solve that problem.”

The Jackson Lab also hosts the Mouse Genome Informatics database, the world’s premiere source for information on mouse genetics and biology, and offers more than 6,000 strains of lab mice to more than 20,000 scientists in at least 50 countries. Through its JAX Mice & Services, more than 3 million lab mice a year are distributed to researchers worldwide.

William Pavan, head of the Mouse Embryology Section and director of the National Human Genome Research Institute, says Jackson has played a key role in his research over the years.

“With its highly monitored population of mice that model human diseases, mice that exhibit a large amount of genetic diversity that mimics human populations, as well as curated biological information regarding biology and genomics, the Jackson Laboratory has been an instrumental component to advances my lab has made since its inception almost 20 years ago,” Pavan says.

Pavan isn’t alone.

“We joke around here that we’re the most important institution you’ve never heard of,” Dr. Edison Liu, head of Jackson Lab, says. “Our mice are in 95% of the laboratories in the U.S. that do any lab work. Somewhere along the way, some lab is touching our mice.”