The Industries of the Future

by Alec J. Ross

The last trillion-dollar industry was built on a code of 1s and 0s. The next will be built on our own genetic code.

But Wartman’s life is remarkable. He works on the cutting edge of genomic technology. From his lab at Washington University in St. Louis, the oncologist and medical researcher studies leukemia in mice, creating comprehensive genomic models of the disease. Even more remarkable, Wartman has battled acute lymphoblastic leukemia (ALL) and survived. Three times.

They decided to do something never done before: sequence both the deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) from Wartman’s cancer cells, then sequence DNA from Wartman’s skin sample as well, so they could compare the DNA between his healthy cells and leukemia cells.

Sequencing Wartman’s healthy genes, cancer genome, and RNA was a way of pinpointing where the breakdown had occurred. To do this, the Washington University team ran Wartman’s samples through the university’s 26 sequencing machines and a supercomputer.

Genome sequencing can be a vexing endeavor. Even when sequencing can pinpoint the offending genetic mutation, it’s often the case that the medical community does not yet have any drugs or treatments that are capable of targeting the problem, especially if the mutation is rare.

The pharmaceutical giant Pfizer had recently released a drug, Sutent, that could inhibit FLT3. Sutent was intended for treating kidney cancer, but because of his sequencing, Wartman would become the first person to use it for ALL. Within two weeks of taking the drug, Wartman was in remission. Soon after, he was in good enough shape to receive a bone marrow transplant to ensure that the cancer would not come back in a mutated form. Four years later, Lukas Wartman’s cancer has not returned.

Wartman says, he owes to intensive genetic sequencing. “I don’t have any doubt about that at all. In my case, sequencing really saved my life.” Lukas Wartman’s story is rare, but his treatment is just the beginning of the potential of genomics. Lukas’s story will someday be ordinary—someday soon.

GENOMICS: MELTING CANCER AWAY

As Lukas Wartman’s story hints, these advances may be dwarfed by the innovations yet to come. In the years ahead, we will live in a world where we’ll be able to target cancer cells with true precision, breathe air out of lungs transplanted from farm animals, and deliver medical treatment from the best hospitals in the world to the poorest, most remote corners of the earth.

Genomic research has been racing ahead ever since Gregor Mendel, a Czech monk, discovered the foundations of heredity in the mid-19th century. But the breakthrough that launched genomics on a collision course with medicine occurred in 1995, when the genome of a living organism—Haemophilus influenza, a bacterium that causes severe infections, typically in children—was sequenced for the first time.

If we could unravel the 3 billion base pairs that make up our DNA and decode who we are on a molecular level, one day Lukas Wartman’s doctors at Washington University would be able to understand why and how his cancer was growing.

The size of the genomics market was estimated at a little more than $11 billion in 2013 and is going to grow faster than anyone could imagine. Ronald W. Davis, director of the Stanford Genome Technology Center and professor of biochemistry and genetics at the Stanford School of Medicine, likens the state of genomics today to that of e-commerce in 1994, the year Amazon was founded and before the founders of Google had even begun working, as students, on Internet search. In addition to the falling cost of sequencing,

For the longest time I thought he was just a scraggly gym rat in his sixties. It turns out he is a Johns Hopkins oncology and pathology professor and an expert on cancer and genomics.

In the 1980s, Vogelstein and his colleagues effectively proved how DNA mutations turn into cancer. Since then, as a result of his work, more than 150 genes have been identified as key actors behind the development and spread of cancer. After proving the relationship between damaged DNA and cancer, Vogelstein began an intensive period of investigation into the meaning of this correlation, trying to figure out how to detect cancers earlier and earlier in their development so that they can be treated before becoming incurable.

His latest effort is what he calls a “liquid biopsy.” A blood sample is taken and tested for the presence of even the tiniest amounts of tumor DNA. A tumor detected by Vogelstein’s liquid biopsy can be detected at just 1 percent the size of what is necessary to be detected by an MRI, currently the most reliable tool for finding cancer.

The testing done to date by researchers at two dozen medical institutions shows that Vogelstein’s method found 47 percent of earliest-stage cancers. While there’s still room for improvement, even these early

The problem, Diaz says, is that most cancers are discovered in stages 3 and 4. Better genetic diagnostic testing will allow doctors to catch cancers in their earliest stages and treat them with much higher cure rates, and Vogelstein and Diaz are already well on their way to introducing tests that could save millions of lives.

So in 2009, Diaz and some Johns Hopkins colleagues launched Personal Genome Diagnostics, PGDx, for which Vogelstein serves as a “founding scientific advisor.” PGDx now offers cancer sequencing similar to what Lukas Wartman underwent, and it also has a research arm. PGDx’s offices sit on the waterfront in East Baltimore. Diaz and a dozen colleagues have been there for some time, yet the offices are surprisingly barren: everyone is too busy splicing tumors and crunching data to decorate the walls. They are on a mission, one that springs to life when Diaz thunders through the office.

And when the sequencing is done, your DNA’s output is hundreds of gigabytes of information—big data now—waiting to be analyzed. Any genomic sequencing company can do this kind of preparation. What sets PGDx apart is its proprietary computer program, developed at Hopkins, which functions as a high-speed detective. It parses out exactly where proteins are mutating. It makes sense of why your cancer is growing. It gives you more information about your tumor than any oncologist can.

“For years, we were studying one gene at a time. And then we could study ten genes at a time, and now we can study 20,000 genes at a time,” Diaz says. “For drugs, we develop one drug at a time. So there needs to be some revolution in drug development that will change that, so there will be more drugs than genes.” Today there is a complete mismatch between the drug development process and the speed and precision made possible by genomics.

“Too many people are still dying of cancer,” he says. “The success rate of our traditional chemotherapy has not been enough, so I think the key is to understand as much as you can about the disease. And we can do that if it is through a combination of these sequencing technologies. After we’ve done that, we’ll be able to tailor toward individual alterations in cancer cells.”

Wartman says that in the future, cancer treatment is going to be completely different. “Traditional chemotherapy will have a very limited role in the treatment of cancer. That’s what I hope. We will essentially be using targeted therapies. . . . I also don’t think it will take us two decades to get there. I really think that in the next ten years we’ll make substantial progress.”

designer drugs that will be able to melt the cancer away.

President Obama announced a $215 million investment by the US government in what could eventually be a decade-long, billion-dollar initiative involving a million volunteers to develop “precision medicines” tailored to a specific person’s genetics and the characteristics of their tumor. Developing drugs targeted to the genetics of an individual as opposed to just treating every cancer patient with chemotherapy is as unsubtle a change in the practice of medicine as the introduction of anesthesia in the 19th century.

Yet while every other body part is opening up to medical hacking, the human brain is still something of a mystery.

Scientists now want to break the brain’s code and begin to leverage genomics to diagnose and treat neurological and mental illnesses.

During my tenure at the State Department, I could see how big a toll mental health issues took on our soldiers and diplomats coming back from assignments in conflict zones.

“Seeking help is a sign of responsibility and it is not a threat to your security clearance,” Clinton wrote in an all-staff email encouraging those who needed help to seek it. The Pentagon followed suit. Defense Secretary Robert Gates announced that troops no longer had to disclose past mental health treatment when applying for security clearances. This had huge implications for the thousands of soldiers returning from Iraq and Afghanistan in need of treatment for mental health issues. They could finally admit to what they were experiencing.

If you were depressed in the early 1950s or before, your outlook was bleak. You were confined to a mental hospital, often given up on by your family and doctors.

Psychotherapy was the most common form of treatment, with occasional electroshock therapy, and efficacy rates were very bad.

Then antidepressants were discovered. These tricyclic drugs reached into the recesses of the brain, treating chemical imbalances. Suddenly there was a medicine that lifted the dark cloud of depression. For those who to...

Side effects ran the gamut from sedation to death if mixed with the wrong drugs.

Prozac, the first of these selective serotonin reuptake inhibitors (SSRIs), was pitched by pharmaceutical giant Eli Lilly as an easy-to-prescribe “one pill fits all” for those with depression.

Zoloft in 1991 and Paxil in 1992. By 2008, antidepressants were one of the most common drugs taken by Americans and the most prescribed drugs for Americans under age 60.

The post-SSRI opportunity for innovation in mental illness is through genomics. My uncle, Ray DePaulo, chairs the psychiatry department at Johns Hopkins. Uncle Ray and the Broad Institute’s Eric Lander are developing a strategy and program to comprehensively map the genes relevant to the field of psychiatry.

Dozens, possibly hundreds, of genetic risk factors are at play in mental disorders like depression. Because of the layers of the brain, it’s not as simple as unearthing a predisposition for cancer or testing a single gene for Huntington’s.

One interesting opportunity is in the area of suicide prevention. In the United States, 1.4 percent of all people die from suicide, and 4.6 percent of the population has attempted suicide. Uncle Ray’s colleagues at Johns Hopkins studied the DNA of 2,700 adults with bipolar disorder, 1,201 of whom had attempted suicide. They identified a gene, ACP1, that produces a protein that appears in excessive quantities in the brains of people who had attempted suicide.

Willour, says that “what’s promising are the implications of this work for learning more about the biology of suicide and the medications used to treat patients who may be at risk.”

What’s next is the development of a commercial product that can go to work on the small region in chromosome 2 with the biological pathway where there is too much ACP1.

One of the primary concerns, and one of Luis Diaz’s own worries, is that as genomics grows more sophisticated, it will begin a process of creating designer babies.

risk profiles will tell them, well, you’re predisposed to heart disease,” says Diaz. “It will tell you that you’re going to be five foot four. You’re going to weigh probably about 180 pounds. You are going to be one of the top-percent track runners in your class. You will play basketball. You have an aptitude for math.”

So, behaviors: alcoholism, gambling problems, people with a variety of different addictions. It’s going to unlock any genetic predispositions. And then it’s also going to be able to predict, well, you’re going to have curly hair, straight hair, blue eyes, brown eyes.

It is possible today to take a blood sample from a pregnant woman and reassemble the genome of the fetus. Fetal DNA tests have been used in the past to screen for Down syndrome. With advances in genomics, all the genetics of the fetus are now accessible and will force societies around the world to grapple with the issue of genetic selection.

As these tests become more common, one of the most crucial issues for us to grapple with, he says, “will be to educate people as well as physicians about the meaningfulness or meaninglessness of particular challenges they might find, and to do it in a fashion that doesn’t cause great anxiety or anxiety out of proportion to the risk.”

Vogelstein and Diaz’s concerns were brought to the surface recently by the genomic testing company 23andMe. Founded by Anne Wojcicki at age 32 in 2006, the company provides ancestry-related genetic reports and uninterpreted raw genetic data for its clients. You spit in a tube, send it to 23andMe’s lab, and for $99 they send you back your genetic information. It’s not a full sequencing of your genome, but a snapshot of the areas of your DNA that researchers know the most about, like genes that indicate a risk for Parkinson’s or how a person might react to certain blood thinners.

Wojcicki, 23andMe’s CEO, also happens to be Silicon Valley royalty: she married Google cofounder Sergey Brin; her father chaired the Stanford physics department; and her mother is a journalism teacher at Palo Alto High who rented out the family’s garage to graduate students Brin and Larry Page to incubate Google. It was through a 23andMe test that Brin learned he had a genetic mutation that increased his risk of getting Parkinson’s to somewhere between 30 and 75 percent, compared to the broader population’s ...

The difference is one of precision: there is still a vast difference between the quality of information produced by a $99 test and a test that costs several thousand dollars and takes days of processing through supercomputers. This difference has the potential to cause both false worry and false reassurance.

The FDA’s public letter to 23andMe said the FDA was “concerned about the public health consequences of inaccurate results.” Since the FDA came down on them, Wojcicki and her company have bowed to the pressure. Now their tests promise only ancestor information and a file with the raw data. An update on their website reads: “We intend to add some genetic-related health reports once we have a comprehensive product offering. At this time we do not know which health reports might be available or when they might be available.”

As people continue to pay $99 to 23andMe for ancestor information, they will be building a database that 23andMe can commercialize for drugmakers.

Rather than inspiring behavior change the way it did in Sergey, genetic testing may cause people who already feel disempowered to further reconcile themselves to unhealthy lifestyles.