Stephen Elledge was hooked on chemistry as a child, growing up in the rural town of Paris, Illinois, population 8,837. It was an interest that took hold of him well before his grandmother bought him a chemistry set when he was ten or so years old.
Stephen Elledge
He majored in chemistry as an undergraduate at the University of Illinois and went on to graduate school at MIT with the expectation of becoming an organic chemist.
But something happened along the way, causing him to cast those plans aside. He fell in love with DNA, which he calls “an amazing molecule.”
“The fact that you can take it apart and put it back together in different ways suggested possibilities that were virtually limitless,” says Elledge.
As a result of an infatuation with DNA that didn’t wear off, Elledge dashed his childhood dreams and became, instead, a geneticist who’s now based at Harvard Medical School with support from the Howard Hughes Medical Institute.
A Fortuitous Accident
As a postdoctoral researcher at Stanford in the late 1980s, Elledge and Ron Davis, his advisor at the time, made an accidental discovery: Working with yeast cells, which have many similarities to human cells, Elledge and Davis identified a family of genes called ribonucleotide reductases that become activated when DNA is damaged.
Elledge followed up on this work, after setting up his own laboratory, showing that the same response to DNA damage occurred in human cells.
“DNA has self-awareness,” says Elledge. “It can detect information about its integrity to make sure everything is intact and functional. When there’s a problem, it sends out signals, like calling an ambulance, and then decides what the problem is, and which proteins are needed to fix it.”
Elledge and his colleagues have mapped the entire DNA damage response pathway, which has contributed greatly to the understanding of various diseases, including cancer.
A Millionaire
For this and other accomplishments, Elledge was given a $3 million Breakthrough Prize in Life Sciences last night in a ceremony held in Silicon Valley. The citation for this prize also commended Elledge for “designing new technology tools, such as a test that reveals any human viruses an individual has [encountered] from a single drop of blood.”
The development of VirScan, as this particular tool is called, stands apart from his other research but is not wholly unrelated.
“DNA damage response has a role in cancer, which I’ve been studying to learn what causes the disease and how best to fight it,” Elledge explains.
One of the things that’s been lacking, he says, is a way to detect cancer earlier to better combat it. When tumor cells grow and die, they’re presented to the body’s immune system, which tries to kill them. Killing cells with mutations triggers an autoimmune response, which unleashes antibodies. Elledge is working on methods for recognizing autoimmune responses that could provide an early warning of a cancerous outbreak somewhere in the body.
Viral History
He then realized that this same approach, which was initially developed for detecting cancer, could also be used for determining which disease-causing pathogens people have been exposed to in the course of their lives. This notion led to the advent of VirScan, which Elledge first reported in the journal Science in June 2015.
“From just one drop of blood, we can create a permanent library of all the viruses you’ve been infected with,” he says.
VirScan exploits a basic feature of the immune system: When the body is invaded by a pathogen such as a virus, it produces antibodies from B (lymphocyte) cells, and some of those cells remain in the blood as so-called “memory” cells. When the same pathogen reappears, that memory cells kick into action, quickly producing antibodies to stave off infection.
VirScan takes a tiny bit of blood from a person, requiring just a fraction of a microliter, and mixes in traces of the 206 species of viruses known to infect humans. Antibodies present in the blood will find their viral targets and attach to them. Viruses that are not bound to antibodies get washed away. This tells researchers which viruses an individual has previously come in contact with.
Elledge and his colleagues are now using VirScan to figure out which human diseases are caused by viral infections.
“We could, for example, take an autoimmune disease like Type 1 diabetes and look at the blood from, say, 40 children to see if a particular virus seems to be correlated with those who get the disease,” he says. “The power of this method is that we can look at all viruses at the same time, and not have to check for them one by one.”
VirScan, according to Elledge, can detect the Zika virus, and that might eventually lead to a simple new blood test. With Ebola, he adds, “we thought everyone infected got really sick. But a whole bunch of people with antibodies to Ebola didn’t get seriously ill. VirScan might help us understand why.”
VirScan takes a tiny bit of blood from a person, requiring just a fraction of a microliter, and mixes in traces of the 206 species of viruses known to infect humans. Antibodies present in the blood will find their viral targets and attach to them. Viruses that are not bound to antibodies get washed away. The color of each cell in the heatmap indicates the relative number of virus “signatures” (rows) in each sample (columns). Science em Jun. 5, 2015: Vol. 348, Issue 6239,
DOI: 10.1126/science.aaa0698
As a VirScan analysis costs only about $25 per blood sample, there could be great advantages in making this part of a routine physical exam. One could regularly check for exposure to diseases like HIV or Hepatitis C and detect an infection earlier, thereby helping a patient’s chances for recovery. Periodic testing could also tell us at which age people are most susceptible to particular diseases, which could in turn help identify the best time for vaccinations throughout the population at large.
One limitation, Elledge acknowledges, is that “in the case of some diseases, we don’t have a treatment ready. But if we knew a certain virus was implicated with a given disease, we’d be in a better position to develop a new treatment, even if one was not yet available.”
Elledge is currently conducting basic research on many fronts, as well as developing new technologies like VirScan and continuing to improve it.
These efforts will surely be helped by the $3 million he just received for the Breakthrough Prize. But he has other plans for that money, including giving a lot of it away. He intends to set up a charitable foundation, which would promote education, help people go to college, and also support various social causes.
“That’s something I’ve always wanted to do,” says Elledge. “And I’m now in a position to do it.”