Annotation Tuesday! Antonio Regalado and liquid biopsies

In August 2014 Antonio Regalado introduced an almost heretical approach to cancer treatment to the wider world in a feature he wrote for MIT Technology Review. Regalado, the senior biomedicine editor for the magazine, suggested we were going about cancer treatment all wrong. Rather than pouring billions into trying to stop advanced stages of the disease, we should try to detect cancer before it could do any harm.

In “Spotting Cancer in a Vial of Blood” Regalado profiled an iconoclastic group of researchers with a “Plan B” for cancer: a “liquid biopsy” technique that could detect the disease long before symptoms arise. The work was led by one of the world’s leading cancer researchers, Bert Vogelstein, whose younger brother had died of skin cancer. Regalado himself had lost his father to cancer, giving the story a particular meaning for him. Regalado had talked with Vogelstein before, for a piece on an unrelated topic, and Vogelstein had told him then about his research on early cancer diagnosis techniques. When he was asked by his editors to come up with a feature, Vogelstein immediately came to mind.

Regalado came to journalism after studying physics as an undergraduate. He’s worked as a science writer at the Wall Street Journal and as a contributing correspondent for Science magazine, and has written for National Geographic.  

This interview was conducted by phone and has been condensed and edited.

My questions are in red, his responses in blue. To read the story without annotations first, click the ‘Hide all annotations’ button below the byline, up and to the right.

Spotting Cancer in a Vial of Blood

He watched his brother die from a cancer no drug could cure. Now one of the world’s most renowned cancer researchers says it’s time for Plan B. Originally published in MIT Technology Review, August 11, 2014

The answers Bert Vogelstein needed and feared were in the blood sample.

Vogelstein is among the most highly cited scientists in the world. He was described, in the 1980s, as having broken into “the cockpit of cancer” after he and coworkers at Johns Hopkins University showed for the first time exactly how a series of DNA mutations, adding up silently over decades, turn cells cancerous. Damaged DNA, he helped prove, is the cause of cancer.

Now imagine you could see these mutations—see cancer itself—in a vial of blood. Nearly every type of cancer sheds DNA into the bloodstream, and Vogelstein’s laboratory at Johns ­Hopkins has developed a technique, called a “liquid biopsy,” that can find the telltale genetic material.

The technology is made possible by instruments that speedily sequence DNA in a blood sample so researchers can spot tumor DNA even when it’s present in trace amounts. The ­Hopkins scientists, working alongside doctors who treat patients in Baltimore’s largest oncology center, have now studied blood from more than a thousand people. They say liquid biopsies can find cancer long before symptoms of the disease arise.

This particular blood sample, though, was personal. It was from Vogelstein’s brother, an orthopedic surgeon one year younger. He was fighting skin cancer, and the disease was already spreading. There was hope he’d respond to a new type of drug, but the treatment causes swelling, and it’s difficult to tell from an x-ray or CT scan whether the cancer is melting away or not. So Vogelstein used his lab’s new technology. If the cancer DNA had disappeared from the blood, they might celebrate. If it was still there, maybe he could steer his brother to some last-ditch drug.

“We tried to guide the treatment. That was the hope, anyway,” says Vogelstein. His voice tightens. He doesn’t say what happened next.

The obituary of Barry Vogelstein, born in Baltimore, appeared on July 3, 2013.

Tell me more about your lead subject, Bert Vogelstein. Vogelstein was the first or among the first to show how a series of genetic mutations builds up over time to cause cancer, the famous “Vogelgram.” I went to Hopkins and met with Victor Velculescu and Vogelstein’s protégé, Luis Diaz, but I actually never met Vogelstein in person. I talked to him on the phone. I wasn’t able to reach him the day I was at Hopkins. I think he wanted to let credit flow to the other people in the group and not have it be about him. For any of these stories about a new treatment or a new test, you often want the patient story. It’s almost necessary, you have to see the patient getting the test or experiencing the consequences of a new treatment to hear the human side of the situation. Because the test was still experimental, it wasn’t easy to find someone. It had to be someone in a clinical trial, and a bunch of the trials they were doing were actually on banked tissue. Lastly, some cancer centers will kind of trip over themselves to help you get a patient, and others just won’t help, they don’t care, they are there to treat patients. Hopkins is just one of these serious places. I was after Diaz for days, weeks, my deadline was rapidly approaching and there was no patient. I was having another phone conversation with Vogelstein and I asked him if he had used the liquid biopsy test on himself. It’s so frequent in science that the scientists are using themselves as guinea pigs. He said, “No, but I did the test on my brother.” It just kind of fell out of the sky there, a little bit, this sad story about his brother’s death. It brought this patient story I was looking for much closer to the subject; the brother of the principal scientist of the lab. From a storytelling point of view it kind of fell into place.

We’re not winning the war on cancer, and the death of ­Vogelstein’s brother shows why. Too many cancers are caught when they have become incurable. Each year, $91 billion is spent on cancer drugs worldwide, but most of those medicines are given to patients when it’s too late. The newest treatments, created at staggering expense, cost $10,000 a month and often extend life by only a few weeks. Pharmaceutical firms develop and test more drugs for late-stage cancer than for any other kind of disease.

“We as the public and as scientists have been entranced by this idea of curing advanced cancers,” says Vogelstein. “That is society’s Plan A. I don’t think that has to be the case.” There are other ways to reduce cancer deaths: wearing sunscreen, not smoking, and getting screened to catch cancer early. To ­Vogelstein, all these preventive steps represent “Plan B” because they receive so much less attention and funding. Yet when prevention works, it has better results than any drug. In the United States, the chance of dying from colorectal cancer is 40 percent lower than it was in 1975, a decrease mostly due to colonoscopy screening. Melanoma skin cancer, too, is treatable with surgery if caught early. “We think Plan B needs to be Plan A,” says Vogelstein.

The new blood tests could make that possible. For the first time, Hopkins researchers say, they are within reach of a general screening tool that could be used to scan broadly—perhaps at an annual physical—for molecular traces of cancer in people with no symptoms. “We think we’ve solved early detection,” says Victor Velculescu, a Hopkins researcher who runs a lab in the building next to Vogelstein’s.

“Solved” is a pretty strong statement when talking about something as intractable as cancer. You go on to qualify this in the next paragraph. Is this something you had to constantly watch, how you and your sources described the promise of early detection without overselling it?  Since this was a new idea for me and for readers, at the outset you have to kind of dramatize in some fashion the potential of the technology, why we are even talking about it and why you are going to read a story about it. The reason is, if you detected cancer early, potentially, you could be curing it. In that section where Victor Velculescu says we’ve solved early detection, I think he was speaking mostly to the technical question of whether you could find this DNA in the blood very early in the course of someone’s cancer. Technically, it had been very hard to do. They had to invent at least two new technologies to allow them to detect these DNA fragments. So when he’s talking about solving early detection he means the technical solution for being able to detect that DNA if it’s there. I don’t think he was speaking about solving the medical or social issues of applying the test. This story spent a lot of words, a lot of inches, talking about the potential limitations and the problems. The ending is pretty much focused on [the idea that] even if this test works, you may never be able to use it or may not be useful to you. Lately there have been a lot of commercial efforts to develop liquid biopsy tests and news stories about it. Vogelstein has emailed me out of the blue a couple of times to thank me for what he seems to think was a fairly skeptical take.

Making such screening a routine practice in medicine will be challenging. One difficulty is that while the test may detect the presence of cancer DNA in the body, physicians might not know where the tumor is, how dangerous it is, or even whether it is worth treating. “We have to be cautious about how we talk about that,” says Daniel Haber, director of the Massachusetts General Hospital Cancer Center. He believes the DNA blood tests are “far from ready” and says very large studies will be needed to prove that they are useful. “There is a huge bar to get over,” he says.

You introduce Haber, a skeptic, early on. Is this because the stakes are so high with cancer that you don’t want to overhype it? Do you introduce him to balance out a big claim and keep the narrative tension before you dive into the research?    Dan Haber is one of the proponents of a competing technology, single cell detection, an approach that tries to capture individual cancer cells from the blood stream and analyze them. When I originally filed this to my editor, David Rotman, there was an even stronger quote, something like “People better watch out what they say. They better watch out even talking about this. This is a dangerous thing to talk about, and people could get knocked down.” My editor cut that part out. It may have been that I had two quotes saying the same thing. It may have been that it was so strong that it would have disoriented the reader. Like the reader is expecting to hear about a new technology but then, very early on, if you have someone come in and say it can’t be true, or to just have a very strongly worded quote in opposition to the technology, that can create a narrative difficulty. So what remains is a compromise. This other researcher will take the stage and say something but it won’t be so strong as to turn the story in a different direction that we didn’t want it to go, a controversy between two groups of researchers with different ideas about how to do things. On the other hand, we did want this skepticism high, partly just as insurance, because what if this technology doesn’t work, what if the skeptics are right? I did my best to understand it and to judge it, but you can also buy a little bit of insurance by giving a critic a nice place in the front row.

Despite such skepticism, the technology is gaining attention. Tony Dickherber, head of the Innovative Molecular Analysis Technologies Program at the National Cancer Institute, says the idea of scanning blood for tumor DNA was “fringe at best” only three years ago. But now labs and companies from California to London are jumping in, producing a stream of improvements to the blood screening technology and new data supporting it. “People are starting to think that [Vogelstein] is right—this could be the best way to do early diagnosis,” he says. “[It] could be done much more widely than other screening technology we have, and you could screen for an incredible range of cancers.”

In February, doctors from Hopkins and 23 other institutions provided the largest survey yet of their findings. They studied the tumors of 846 patients with 15 different types of cancer. They found tumor DNA in the blood of more than 80 percent of patients with advanced cancers, the kind that have spread, and about 47 percent of those whose cancer was still localized and at the earliest stage. In advanced colorectal cancer, the DNA was always seen.

The results might not at first appear impressive. A test that misses half the time? The benefit is that the tests are “exquisitely specific,” according to Velculescu. If you do have tumor DNA, it appears, so far, that you also have cancer. That could give DNA screening the edge over current tests for prostate and breast cancer, which frequently produce false positives. “It’s normal to have circulating DNA in the blood; it is not normal to have circulating DNA that matches a tumor,” says Stefanie Jeffrey, chief of surgical oncology research at Stanford University.

To Vogelstein, the blood tests mean it may be possible to catch more than half of cancers early on, and potentially cure them with surgery. “If there were a drug that cured half of cancer you’d have a ticker-tape parade in New York City,” he says.

You navigate some difficult terrain, describing false positives in a way that doesn’t bog down. Did you have to wrestle with this section to keep it from going too deep into the weeds? It’s always a struggle to get the right mix of information. I’m not a fast writer. I don’t just sit down and it all comes flying out. Probably like most writers, I feel very tortured about the writing and it takes a long time. With this particular story, it is more or less a triptych, many of our stories at Technology Review have three parts. The first part kind of wrote itself, but then the second part, I had to pause and start again telling this new section. I can definitely remember getting bogged down and there are probably still vestiges of that swamp of writing that weren’t totally removed. It didn’t seem at all swampy to me. That is the battle. The writer and editor are trying to pump out swamps, trying to make sure that when readers come to story it’s smooth and nothing stops them from reading to the end and getting the information.

Early Days

President Nixon’s War on Cancer was launched in 1971, when Vogelstein was in medical school. Years of frustration followed as drugs failed to make much of a dent in cancer deaths. What has changed is that now we know what causes cancer. Vogelstein’s work in the 1980s, carried out with colleague Kenneth Kinzler, helped demonstrate the crucial role of mutated genes in the disease. And scientists have now assembled a list of more than 150 genes that appear to be the key drivers. Even though cancer’s genetic landscape is complex, all the DNA mutations do one thing: they allow some cells to keep multiplying when normal cells would die. The resulting imbalance is cancer.

For pharmaceutical companies, this insight and the gene list have been the launching point for billion-dollar efforts to develop new drugs for advanced cancers. But to Vogelstein, the knowledge that DNA mutations cause cancer has always also meant something different: that it should be possible to spot the telltale changes early on, well before the disease is usually diagnosed. And in oncology, it’s a truism: the sooner you detect cancer, the better your chances.

Consider colorectal cancer, the type Vogelstein has studied most closely. It begins with a single mutation to a gene called APC. Yet it takes on average 30 years from that point for the cells to acquire several other DNA mutations they need in order to spread and kill. About 600,000 people die from colorectal cancer each year. “Nearly all of them will die only because their cancer was not detected in the first 27 years of the tumor’s existence,” Vogelstein says. “That is a huge window to intervene in this process.”

The problem has been that until the blood tests, there was no very easy way to look for these mutations. Vogelstein has been working on early-detection schemes since the 1990s, when he began looking for tumor DNA in urine and stool, using the laborious methods available at that time.

He believes prevention and screening still receive too little attention, putting him, even now, in an “absolute minority” of researchers. He estimates that 100 times as many research dollars go toward drugs as toward these strategies.

Why is he in such a minority on this? it seems like such an obvious spot to focus on. Detecting cancer is hard. How do they do it? They might do it with an MRI machine, but think about the technology of the MRI machine, it’s expensive to develop. Developing a diagnostic test for cancer costs just as much as developing a new drug, maybe more. There are a bunch of liquid biopsy companies out there now. To get their tests to market the average one of them spends $100 million. And nobody wants to pay for a test. The commercial marketplace does not value tests. Nobody has any problem paying $10,000 a month for a drug, but when it comes to a test they want to pay $1.99.

This may explain why, despite his preëminence, Vogelstein seems to have a chip on his shoulder. The Hopkins research group, which includes several other well-known researchers, is quick to publish new ideas, but it often makes the effort to shoot down scientific concepts that are trendy elsewhere. Any young scientist who want to work there, according to the lab’s traditions, must first present his or her earlier scientific work while wearing a Burger King crown.

I love this anecdote. Tell me more about this crown and why you chose to include it?  What the crown says to me is that this lab is very iconoclastic. They spend a lot of time punching holes in other people’s ideas. Some of their best papers are oriented towards taking down or punching holes in the conventional wisdom around cancer. The Burger King crown was sort of an instance, where if you wanted to join this group, it was a hazing. You have to talk about your earlier work and you are wearing this silly crown; you have to go through the looking glass, and be in a new environment.

The lab’s work on the blood tests has been led by Luis Diaz, an oncologist who has become Vogelstein’s protégé. He hit on the idea of testing blood for cancer DNA in 2005, while researching whether a flesh-eating bacterium could be used to eradicate tumors. The work involved transplanting human cancers into mice, and Diaz recalls that he “needed a way to monitor the tumors in the mouse without killing it.” He and a colleague decided that they might be able to do that with a blood test. Soon they saw the level of human DNA bouncing down and up as the treatment worked or failed. If they could monitor DNA from a human tumor in mice, wouldn’t it work in humans, too?

The idea wasn’t entirely new. It’s been known since 1948 that free-floating DNA circulates in our veins and arteries. It’s normally a waste product of dead cells. But tumors also shed DNA into the blood. The portion of DNA in the blood that comes from tumors can be as high as 87 percent in a person dying from cancer, but often the amount is vanishingly small.

When Diaz began looking at the question, all this was not yet fact but muddy possibility. To develop the liquid biopsy, the Hopkins scientists first had to invent ways to pick out the tumor DNA from an overwhelming background of normal DNA. Working with blood donated by patients with colorectal cancer whom Diaz was treating in Baltimore, the researchers initially tracked only four cancer genes. Yet they could see that the tumor DNA in the blood would disappear quickly—even within a day—after these patients had surgery or drug treatments. Healthy control subjects never tested positive. “We realized this test can ask and answer the question ‘Do I have cancer?’” says Diaz.

Hopkins believes its test may be more sensitive than any tool doctors have now—at least for cancers that are too small to be seen with an imaging machine. Vogelstein estimates that a tumor has to contain at least 10 million cells, making it about as big as the head of a pin, to shed a detectable amount of DNA. To be visible on an MRI, by contrast, a tumor needs to be about 100 times that size, containing at least one billion cells.

The Hopkins physicians have begun using the DNA tests in an effort to determine whether malignant cells remain behind in patients whose tumors have been surgically removed. Working with Peter Gibbs, an Australian oncologist, they have scanned blood samples from 250 patients who have been operated on for early-stage colon cancer. Most of these people will turn out to be cured, but up to 30 percent are expected to suffer a relapse because not all the tumor cells were removed. The problem is that doctors don’t know which patients will relapse. “The surgeon will say, ‘Don’t worry—we got it all,’” says Diaz. “It’s frustrating to me, because then I have to tell the patient, ‘We don’t really know if you are cured.’” Survivors can get caught in a state of limbo, uncertain whether their disease is coming back, possibly in a more dangerous form. And the situation can drag on for years.

Seems like a study Diaz and Vogelstein would want to do at Hopkins. Did they have to go all the way to Australia to partner with someone to do this test? I think in general each cancer center has a limited number of people coming through. If they want to run a clinical trial, they often have to partner up and they will partner with their colleagues or scientist friends. So this guy from Australia was probably in the lab at some point or associated with the lab. Interestingly enough, Vice President Joe Biden with his cancer moonshot announced in the President’s State of the Union, the main thing that Biden has been saying is he wants to break down silos in cancer research and put an end to cancer politics. There is quite a lot of politics in cancer research. Could Hopkins have collaborated with Memorial Sloan Kettering or with Daniel Haber at Mass General? Possibly, but those are competing groups. Maybe the safe person to collaborate with is on other side of the world.

The patients in Australia are checked for tumor DNA in their blood six weeks after surgery. So far, the researchers say, they have correctly identified about half the people who later relapsed. In the future, says Vogelstein, these patients could be flagged to receive chemotherapy, probably saving at least a third of them. Yet the limits of the test are also apparent, since it still missed half the patients whose cancer later reappeared.

Diaz says this may be because whatever cancer cells remain aren’t giving off enough DNA to detect. “We may have hit the biological limits,” he says. However, the cancer DNA could rise to detectable levels over time, and retesting patients periodically could pick that up. Even though Hopkins’s testing remains experimental, Diaz says he has enough confidence in it to tell some patients they are still sick and others that they are probably healed. “Six to eight weeks later, we can tell them if they are cured,” he says. “It’s very satisfying.”

Mass Screening

Vogelstein says his ultimate goal is to turn the blood tests into a way to routinely screen everyone for cancer. The Hopkins researchers believe they have a version of the test that can do that. Instead of tracking a few key cancer genes, they sequence a person’s entire genome using DNA from the blood sample. This lets them count how often chunks of genetic material are misplaced or appear scrambled. A large amount of rearranged DNA is a molecular side effect seen only on the chromosomes of cancer cells—a tip-off that cancer is present. But a full genome sequence is still expensive. “If a person has cancer, you don’t mind spending $5,000 on a DNA test. But you can’t have a test that costs $1,000 that you can do at an annual physical,” says Vogelstein. “The goal is to get the technology cheap enough to use in screening.”

That could take time. The cost of DNA sequencing has been falling very rapidly, yet a $100 genome—the price that might be low enough for a general screening test—could be 10 years away. In the meantime, Hopkins has begun several studies, mostly on individuals predisposed to cancer, to determine whether the techniques can catch tumors early in healthy people. One involves 800 people at risk for pancreatic cancer. In these unusual cases, people have cysts on the pancreas that sometimes turn into cancer but sometimes don’t. The clinical trial began following patients in 2012, and the researchers will get their first look at the results late this year.

Pancreatic cancer is a good test case for early screening. It’s not a very common cancer, but it’s the fourth-highest cause of cancer deaths in the United States, because it’s cured only 4 percent of the time. If detected very early, before it spreads, the survival rate rises to about 25 percent. (Apple founder Steve Jobs died of a different type of pancreatic cancer, called a neuroendocrine tumor, at age 56.)

But extending the DNA tests to everyone is an enormous leap. Haber, the Mass. General oncologist, says the technology, as currently conceived, might tell a doctor if cancer is present. But unlike an imaging scan or a biopsy, it could leave you guessing where in the body it is. Patients would be frightened, doctors uncertain how to act. “The idea of screening healthy people and telling them ‘Oh, look, there is cancer somewhere but we don’t know where it is’—well, that would be the death of the whole [idea],” Haber says.

Medicine has a precedent of handling predictive tests poorly. Consider the PSA test, which detects a protein linked to prostate cancer. Not only does the test produce false positives a majority of the time, but some of the tumors it actually detects are so slow-growing that they aren’t worth treating. Millions of men have ended up getting treated for cancers that ultimately wouldn’t have affected them. By one estimate, for every 47 men who had their prostates removed, a single cancer death was avoided. Studies by researchers at Dartmouth College suggest that mammography also leads to overdiagnosis and overtreatment. About 25 percent of breast cancers discovered, and treated, would not have caused any symptoms. “You test everyone and end up treating people for diseases that would never have mattered, either because they wouldn’t have progressed or because people die of something else,” says Jonathan Skinner, a health economist at Dartmouth. “The downside of early screening can be very high.”

At Hopkins, however, Velculescu says he’s hopeful that mass DNA screening for cancer will become a reality. “If you can’t make a difference, then maybe you would want to remain ignorant,” he says.

“But I can’t imagine that knowing about cancer wouldn’t help patients. Maybe we won’t dramatically act on every piece of information. Maybe we don’t do anything. But with these tests, it would be so easy to keep doing them and say to the patient, ‘Let’s see how it develops.’”

So far, companies aren’t talking loudly about broad screening for cancer in seemingly healthy patients. For now, Personal Genome Diagnostics, a diagnostic testing startup that Diaz and Velculescu founded, and several competitors, like Boreal Genomics and Guardant Health, offer liquid biopsies only to patients who are fighting late-stage cancer. For those patients, the tests might reveal whether a treatment is working in time to try something else if it’s not. Another valuable use of the technology is to track the specific DNA mutations driving a patient’s tumors. Since many new cancer medications are “targeted”—they block specific molecular processes—patients get them only if their tumor is the kind expected to respond. Doctors can already use DNA tests on chunks of tumor obtained through tissue biopsies. But the noninvasive blood tests could be easier and safer, allowing patients to be evaluated more frequently. Since cancer DNA is constantly mutating, that could help patients switch drugs when appropriate.

To Helmy Eltoukhy, the CEO of Guardant, liquid biopsies are “a huge idea” with many applications. For commercial and medical reasons, his company so far is marketing the tests only to people who have cancer. But he says early screening tests are on his company’s road map. “It’s obviously the Holy Grail,” he says. “Imagine the applications, and that is what we are working on.”

It seems liquid biopsy had a couple of niche markets when you wrote this in 2014. What has happened since? Since we published the story the concept has absolutely exploded. The story was vindicated in a way. Our timing was good, propitious. Probably the biggest single thing that has happened recently is that Illumina, which is the big company that makes the DNA sequencers and is sort of the 800-pound gorilla of DNA sequencing, launched a subsidiary with $100 million in funding to develop these early detection tests. They called the subsidiary Grail, [as in] “Holy Grail,” the name says it all. There are very big companies getting involved, a ton of money, lots of startups, everybody is excited, nobody is talking about this other technology, the single cells, so I’m glad we didn’t focus on that. But the tests themselves, whether they will help patients or not, that all hasn’t been proven.

I asked both Vogelstein, who is 65, and Velculescu, who is 44, if they had ever tested themselves. Both said no.

Did they say why not? Was there some ethical or moral dilemma that prevented them from testing themselves? I think it hadn’t occurred to them, at least it hadn’t occurred to Velculescu, he is the younger of the two, he’s maybe in his late 40s. When I asked him he seemed surprised, you know, “Why would he test himself?” I don’t think it was so much the ethical issue; scientists are pretty willing to make themselves into guinea pigs, all it takes is a blood draw. I think there is a kind of question mark there, that maybe they didn’t really want to know. A lot of people don’t want to know if they have cancer or not. Even people who are suffering from terrible symptoms of cancer sometimes don’t want to know. I remember my father was diagnosed with prostate cancer and I was with him in the doctor’s office, and there was a question of whether the cancer had metastasized to different places, was it worse than the initial diagnosis? My father was cracking jokes, he was changing the subject, I could tell he was reluctant to know. So when my father left the room I asked the doctor, ‘If people don’t want to know do you tell them?’ The doctor said, “No, I don’t tell them.” People don’t necessarily want to know about their health. Steve Jobs died of a form of pancreatic cancer and he was kind of in denial about it. That is one of the reasons it killed him. It’s the ultimate question. Do you really want to know whether you have some incipient cancer that is just going to raise all kinds of uncertainties in your life that you wouldn’t otherwise have to face? Did what you experienced with your father get you more interested in writing about cancer and did it lead to you finding this story?    It may have. Maybe I had a kind of mental substitution and put Vogelstein as a kind of father figure. I am always seeking out father figures, generally, mentors. Vogelstein kind of reminded me of my own father. He’s a very senior researcher, the kind of person that you approach with lots of kowtowing, not that you have to, but you do. My father was an academic, different field. This is a strange comment, but I think science journalists, when they are dealing with researchers that are senior and older than them, there is a power dynamic that has the father aspect to it. My own father died [of cancer]. Maybe I was looking for a story to explain it, some way to fill that gap.

Yet overall, men in the United States have a 40 percent chance of developing cancer sometime, and the odds rise with age. If these researchers haven’t sought the screening, it seems questionable that the broader public will be eager to do it either. For a screening test to be performed widely as a public health measure, the entire medical community will have to participate, and that will take a great deal of time.

Vogelstein isn’t naïve. We’ll still need new drugs to treat people who develop cancer anyway. But he remains convinced that the best way to beat late-stage cancer is to prevent it from happening. When I offered my condolences to Vogelstein on the death of his brother, he waved them aside.

“This is why we do the work,” he says. “A hundred years from now, when cancer and death from cancer is a lot less common, a lot of that is going to be due to early detection, not because we can cure a body riddled with tumors.”

How did you deal with this subject? I ended up working with pretty limited information. I never felt comfortable pressing Vogelstein to learn the blow by blow of his brother’s case. When reporters look for “patient stories” they almost invariably talk to the patient him/herself, because the patient has the autonomy to share their story and whatever details they wish. Not everyone is ready to speak publicly about their disease – thus, the challenge of finding patients. An when you aren’t the patient, it’s hard to say very much at all. There are privacy issues. Even people who have passed away have a right to be remembered in a certain way. So I felt a sense of relief when, after the article, Vogelstein wrote me: “My brother was my biggest supporter, and there is no question he would have loved your article.”

This story was updated on August 13 to clarify that Steve Jobs did not have the kind of pancreatic cancer that Hopkins researchers are trying to detect in the trial of 800 patients.