New theory uncovers cancer's deep evolutionary roots

July 12, 2013

A new way to look at cancer – by tracing its deep evolutionary roots to the dawn of multicellularity more than a billion years ago – has been proposed by Paul Davies of Arizona State University’s Beyond Center for Fundamental Concepts in Science in collaboration with Charles Lineweaver of the Australian National University. If their theory is correct, it promises to transform the approach to cancer therapy, and to link the origin of cancer to the origin of life and the developmental processes of embryos.

Davies and Lineweaver are both theoretical physicists and cosmologists with experience in the field of astrobiology – the search for life beyond Earth. They turned to cancer research only recently, in part because of the creation at Arizona State University of the Center for the Convergence of Physical Science and Cancer Biology. The center is one of twelve established by the National Cancer Institute to encourage physical scientists to lend their insights into tackling cancer. portrait of Paul Davies in his office Download Full Image

The new theory challenges the orthodox view that cancer develops anew in each host by a series of chance mutational accidents. Davies and Lineweaver claim that cancer is actually an organized and systematic response to some sort of stress or physical challenge. It might be triggered by a random accident, they say, but thereafter it more or less predictably unfolds.

Their view of cancer is outlined in the article “Exposing cancer’s deep evolutionary roots,” written by Davies. It appears in a special July issue of Physics World devoted to the physics of cancer.

“We envisage cancer as the execution of an ancient program pre-loaded into the genomes of all cells,” says Davies, an Arizona State University Regents' Professor in ASU's College of Liberal Arts and Sciences. “It is rather like Windows defaulting to ‘safe mode’ after suffering an insult of some sort.” As such, he describes cancer as a throwback to an ancestral phenotype.

The new theory predicts that as cancer progresses through more and more malignant stages, it will express genes that are more deeply conserved among multicellular organisms, and so are in some sense more ancient. Davies and Lineweaver are currently testing this prediction by comparing gene expression data from cancer biopsies with phylogenetic trees going back 1.6 billion years, with the help of Luis Cisneros, a postdoctoral researcher with ASU's Beyond Center.

But if this is the case, then why hasn’t evolution eliminated the ancient cancer subroutine?

“Because it fulfills absolutely crucial functions during the early stages of embryo development,” Davies explains. “Genes that are active in the embryo and normally dormant thereafter are found to be switched back on in cancer. These same genes are the ‘ancient’ ones, deep in the tree of multicellular life.”

The link with embryo development has been known to cancer biologists for a long time, says Davies, but the significance of this fact is rarely appreciated. If the new theory is correct, researchers should find that the more malignant stages of cancer will re-express genes from the earliest stages of embryogenesis. Davies adds that there is already some evidence for this in several experimental studies, including recent research at Harvard University and the Albert Einstein College of Medicine in New York.

“As cancer progresses through its various stages within a single organism, it should be like running the evolutionary and developmental arrows of time backward at high speed,” says Davies.

This could provide clues to future treatments. For example, when life took the momentous step from single cells to multicellular assemblages, Earth had low levels of oxygen. Sure enough, cancer reverts to an ancient form of metabolism called fermentation, which can supply energy with little need for oxygen, although it requires lots of sugar.

Davies and Lineweaver predict that if cancer cells are saturated with oxygen but deprived of sugar, they will become more stressed than healthy cells, slowing them down or even killing them. ASU’s Center for the Convergence of Physical Science and Cancer Biology, of which Davies is principal investigator, is planning a workshop in November to examine the clinical evidence for this.

“It is clear that some radically new thinking is needed,” Davies states. “Like aging, cancer seems to be a deeply embedded part of the life process. Also like aging, cancer generally cannot be cured but its effects can certainly be mitigated, for example, by delaying onset and extending periods of dormancy. But we will learn to do this effectively only when we better understand cancer, including its place in the great sweep of evolutionary history.”

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Student makes the most of his Mayo-ASU adventure

July 15, 2013

Among the features of his degree program at Mayo Medical School that Layne Bettini likes best is that students are encouraged to seek academic enrichment opportunities at other universities.

Early in 2011, Bettini listened to presentations by faculty from other institutions visiting Mayo’s campus in Rochester, Minn. and he chose a collaborative field of study that suited him best: the law. Download Full Image

“When I was an undergraduate, I had the opportunity to be a congressional intern in Washington, D.C. and I got to see legislative hearings and work with health policy. That really piqued my interest in law. I want to practice medicine, but certainly, I hope to blend my passion for treating patients with a broader goal of helping shape health policy to provide people with maximum quality and access to health care.”

Bettini is enrolled in the M.D./J.D. program, an innovative partnership between Mayo and Arizona State University that enables students to earn medical and law degrees over the course of six years. Launched in 2005, the program has graduated eight students from ASU’s Sandra Day O’Connor College of Law, and four other medical students, including Bettini, are on track to obtain their Juris Doctor degrees in May 2014.

Bettini, who grew up in Taos, N.M., graduated in 2010 from the University of New Mexico with a bachelor's in biology and a bachelor's in languages, summa cum laude. While in high school, Bettini was drawn to science by the enthusiasm of his physics and calculus teacher who connected him to a general surgeon to shadow over the summer.

“All through college, I knew I wanted to go into medicine. I was very lucky to have the opportunity to interview at Mayo and at several other institutions, but Mayo really stuck out. I could tell they really cared about their students and had a great overall program.

“One of the great things about Mayo is they have a pass-fail curriculum, so we’re not competing against each other for the top spot. We’re all excellent students and that gives us time to work together – it’s not the cutthroat environment some people might think medical school is.”

Mayo gives its students hands-on experience with patients from the very beginning and encourages them to give back to the community. To that end, Bettini has mentored inner-city high school students in Rochester, Minn., served on a legislation committee of a local medical society, worked with Mayo physicians to provide health care to under-insured patients, visited Latin America to survey residents about their health care systems and worked at a student-run smoking cessation clinic.

Bettini also traveled to Honduras to work with Global Bridges, a student-led global health and sustainable development organization, bringing medications to small rural communities with limited health care. Such experiences will help Bettini narrow down the field of medicine to which he will devote his life.

“Having the chance to work with patients in Honduras really opened my eyes to global health and the general well-being of patients.”

Law school normally spans three years, but the M.D./J.D. is an accelerated program of two years, and includes two rigorous summer sessions in between. That appealed to Bettini.

“It’s a great chance to save on time. In medical school, there’s a natural break in the curriculum. The first two years are spent doing basic science work and the last two are in clinical in the hospital. That natural break is the perfect time to augment your education with another degree.”

In his first year of law school, Bettini took 14 classes – Contracts; Civil Procedure; Tort Law; Legal Method and Writing; Property; Legal Advocacy; Administrative Law; Criminal Law; Health Policy and Ethics; Constitutional Law I and II; Criminal Procedure; Professional Responsibility; and Evidence. Next year, in addition to coursework, he plans to join a research cluster in the College of Law’s Public Health Law and Policy Program, and is contemplating an externship in the Healthcare Entrepreneurship Program. He also is a scholar in the Center for Law, Science & Innovation.

“I’d have to say law school is a little more challenging than I anticipated. Of course, I’ve seen the movies about how scary law school can be, and it’s really a big commitment with a lot of reading and writing. But the best part is it’s all fascinating.”

Bettini said he would recommend the Mayo-ASU M.D./J.D. program to serious students because “It gives you a great opportunity to study two very interesting fields, and the chance to work at the forefront of law and medicine.”