Boston scientists have developed a technique that can trace a cancer cell back to the tissue where it started, raising hope for one day improving treatment for mysterious cancers of unknown origin.
Using the same data set, a team in Cambridge discovered, to their surprise, that immune cells — and not brain cells involved in learning and memory — appear to be at the genetic root of Alzheimer’s disease.
The findings were included in a series of papers published Wednesday in the journal Nature that shed light on the genomic circuits that cells activate in order to become a lung cell or a liver cell.
Researchers said the findings on Alzheimer’s and cancer are only the first fruits of the application of this new knowledge to understanding human disease and biology.
“It’s breathtaking. The Human Genome Project was the static picture of human genetic information — the snapshot,” said Eric Lander, a leader of the genome project and founding director of the Broad Institute, a genomic research center in Cambridge. “This is now ‘Human Genome: The Movie,’ because what it does is it shows how the static information that’s the same in every cell is getting read out differently in each type of cell.”
The research was one major piece of a $240 million National Institutes of Health program that funded 88 grants over 10 years. A team with several leading Boston-area researchers meticulously mapped the “epigenome” of 111 types of human cells, from the gut to the brain over seven years.
Every cell in the body carries the same copy of the genome: 3 billion letters of DNA that are often called the blueprint of a human being. Since every cell carries the same instruction book, the epigenome is critical — like stage cues in a play, telling each cell which lines of DNA it should read in order to come into character, whether they are liver cells or lung cells.
In order to do the work, scientists at institutions across the country carried out 2,800 experiments to map the spots where chemicals were attached to the genome. This map of chemical modifications is the epigenome. It’s the kind of “big data” experiment that boggles the mind, creating so much information that researchers at the Massachusetts Institute of Technology had to develop a special kind of artificial intelligence to make sense of it all.
But it is also the kind of expensive research project that has raised significant skepticism from scientists who question whether these types of high-profile projects are overhyped and ask whether they provide a valuable communal resource worth the investment.
Lior Pachter, a professor of mathematics and molecular and cellular biology at the University of California Berkeley, said he does think epigenome information will be valuable. But he noted that many large-scale projects, including this one, are launched at a time when the technology costs are plummeting, meaning they could be accomplished with a fraction of the expense in the next few years.
“What was discovered here that is really significant? A lot of data has been generated, and I’m sure some of it will be useful,” Pachter said. “It’s not clear to me this is the best use of limited resources in genomics.”
Proponents of the research argue that the database will be helpful in understanding major questions in biomedical research.
A team led by Shamil Sunyaev, a geneticist at Brigham and Women’s Hospital, started out intending to use the database to better understand why, how, and where mutations arise in cancer cells. But his group discovered accidentally that they could predict the type of tissue where cancer cells originated with about 90 percent accuracy.
“Every year, there are thousands of patients that show up in oncology clinics with metastatic cancers where we do not know what the primary site is,” said Dr. John Stamatoyannopoulos, associate professor of genome sciences and medicine at the University of Washington in Seattle and a coauthor of the paper. “Most of the time the patients are treated empirically; the oncologist tries to make a guess as to what the cancer might be but typically those patients have very bad outcomes.”
The late mayor Thomas M. Menino, for example, had a cancer of unknown origin. Knowing more about where cancer started could guide treatment.
“I think that this paper highlights the kind of clinical payout we might get in the future,” said Dr. Raghu Kalluri, chairman of the department of cancer biology at the University of Texas MD Anderson Cancer Center.
The insight into Alzheimer’s disease comes from studying a mouse version of the disease. Counter to expectations, the genetic predisposition to Alzheimer’s was rooted in immune cells.
“If somebody asks you, ‘What is the basis of Alzheimer’s disease?’ you’d say something about the brain,” said Manolis Kellis, a professor of computer science at MIT who led the research. “This map seems to disagree. . . . The reason why you get Alzheimer’s is that you are unlucky in your immune system, not unlucky in your neurons.”
The hope is that these papers are just the first step, and the resource will open up many corners of human disease and biology as researchers are able to use it as a reference book to help guide and understand their experiments.