The Lucky Years: How to Thrive in the Brave New World of Health (5 page)

In 2007, I was asked to be on Steve Jobs’s medical team to help with his care and serve as a sounding board for him to discuss all the specialists he had in his circle. He was trying to stay as many steps ahead of his cancer as possible. This particular cadre of specialists not only included a handful of doctors from Stanford, close to where Steve lived and worked, but also entailed collaborations with Johns Hopkins and the Broad Institute of MIT and Harvard, as well as the liver transplant program of the University of Tennessee. We took an aggressive, integrated approach that leveraged the best anticancer technology at our disposal. This meant sequencing his tumors’ genes so we could pick specific drugs that would target the defects in the cells that made them rogue. It was a revolutionary approach and totally different from conventional therapy, which generally attacks cell division in all of a body’s cells, striking healthy ones along with cancerous ones.

For us on his medical team, it was like playing chess. We’d make our move with a certain cocktail of drugs, some of which were novel and just in development, and then wait to see what the cancer would do next. When it mutated and found a crafty way to circumvent the impact of the drugs we were using, we’d find another combination to throw at the cancer in our next chess move. I’ll never forget the day we doctors huddled in a hotel room with Steve to go over the results of the genetic sequencing for his cancer.

This type of sequencing isn’t as black-and-white as you might think. Just as interpreting someone’s genetic profile can be subjective, so can the actual sequencing. Even the best gene sequencers from different institutions can find slightly different DNA portraits for the same exact patient, which is what happened with Steve’s screening. After Steve verbally criticized some of us for using Microsoft PowerPoint rather than Apple’s Keynote for our presentations, he learned that Harvard’s results from testing his tumor’s DNA didn’t line up exactly with those from Johns Hopkins. This made our strategizing all the more challenging
and demanded that we all get together to go over the molecular data and agree on a game plan.

I wish we could have saved him or turned his cancer into a chronic condition that could be controlled at the molecular level so he could go on to live a longer life and eventually die of something else. I have faith that one day cancer will be a manageable condition much in the way people can live with arthritis or type 1 diabetes for a long time before succumbing to, say, an age-related heart attack or stroke. Imagine being able to edit not only your own genes to live longer, but those of a cancer to keep it at bay, silence its copying power, and stop it in its tracks. From a rudimentary perspective, genes are your body’s instructions, encoded in DNA. And cancer involves genes with a defect or defects that enable the “bad” cells containing those genes to block their own death or to continually divide, creating more rogue cells that can then maim the body’s tissues and functionality. So with molecular anti-cancer therapies, it’ll be like fixing the typos and misspellings in your personal “document” to live as long as humanly possible. Cancer will become a manageable life sentence, not a death sentence.

One genetic editing tool already exists. It’s called CRISPR, which stands for Clustered Regularly Interspaced Short Palindromic Repeats. This genome editing tool is remarkably easy to use and effective, but it raises many concerns because of its ability to alter human DNA in a way that can be passed along to one’s children and future generations. On the one hand, it can be used to cure diseases inherited from birth or acquired in life. In a fantastic review of the technology for the
New England Journal of Medicine
, Dr. Eric Lander, director of MIT and Harvard’s Broad Institute, describes some of its utility:

Genome editing also holds great therapeutic promise. To treat human immunodeficiency virus (HIV) infection, physicians might edit a patient’s immune cells to delete the
CCR5
gene, conferring the resistance to HIV carried by the 1 percent of the US population lacking functional copies of this gene. To treat
progressive blindness caused by dominant forms of retinitis pigmentosa, they might inactivate the mutant allele in retinal cells. . . . Editing of blood stem cells might cure sickle cell anemia and hemophilia.
⁴

But where there’s a yin, there’s a yang. The other side of this story is that this incredibly powerful technology can be used to control qualities that were previously uncontrollable, such as intelligence, athleticism, and beauty. And we just don’t know what revising the human genome to create permanent genetic modifications might mean for future generations. What if you edit one part of the gene to reduce the risk of
X
but then inadvertently increase the risk of
Y
? As Lander notes, “For example, the
CCR5
mutations that protect against HIV also elevate the risk for West Nile virus, and multiple genes have variants with opposing effects on risk for type 1 diabetes and Crohn’s disease.” Indeed, our knowledge is incomplete, but we’ll be learning more as we move forward and try to deal with these possibilities—and challenges—on technical, logistical, moral, and ethical levels. I concur with Lander’s concluding statement: “It has been only about a decade since we first read the human genome. We should exercise great caution before we begin to rewrite it.”

Over the past few years, thousands of laboratories around the world have begun to use CRISPR technology in their research. In April 2015, Chinese scientists reported that, for the first time, they had edited the genomes of
human embryos
.
⁵
Wow! This was all made possible by a single discovery in 2012 by Jennifer A. Doudna, a biochemist at the University of California, Berkeley, who changed this field virtually overnight. Discoveries like this are now happening all the time around the world, and we need to be ready. It used to take a long time for new scientific knowledge or technologies published in the medical literature to enter mainstream medicine and fellow research labs, let alone the average doctor’s visit. While it’s been estimated that seventeen years usually passes before research evidence becomes part of clinical practice, that lag time will diminish quickly in the Lucky Years.
⁶
You’ll be able to
benefit from the findings of a new study or from a new technology in a matter of hours or days, not years or decades. But we’ll have to figure out what to do with technologies like CRISPR before we unleash those into a clinical setting.

Unlike Jobs’s binary world of computer programming, my field was a source of agony for him because I had to reconcile the hazy line between the science and art of medicine. He couldn’t understand why I couldn’t “debug” him like an Apple engineer.

But I learned again over those four years how important it is to tune in to your body. Steve had an admirable ability to listen to
himself
and know what his body wanted and needed. Although some will argue that he may have made some unwise choices early on in his fight against cancer—rejecting potentially life-saving surgery and turning to acupuncture, diet, and dietary supplements—that’s not the point. I’m a firm believer that each one of us should be able to make our own decisions when it comes to our health. No one can take away the fact Steve was always true to his wishes, values, and personal health decisions. That he may have lowered his chances of survival by taking an alternative route first is immaterial. It was part of his journey, and he wasn’t doing anything unethical. Steve was instrumental in choosing his therapy and his way of life from beginning to end. For him it was about how his choices made him
feel
. And he remained very much in tune with himself up to his last breath, letting that intuition guide his every action. I wish for that kind of mentality in not only myself, but in all my patients, friends, and loved ones.

Steve once said to me: “Health sounds like something I’m supposed to eat, but it tastes really bad.” He made sure I kept the word
health
out of the title of my first book. But I’m using it this time in the subtitle because health has a different context now. We live in an exciting time, a world that is increasingly affording us all the opportunity to thrive for as long as we choose.

At the end of the eighteenth century, the British scholar Thomas Robert Malthus wrote a controversial set of six books in which he meticulously calculated the end of the world based on the expanding population. At the time, the world housed 800 million people (to put that into perspective, that’s a little less than half the number of people who used Facebook in 2015). He predicted that once the world population hit 2 billion, there would be apocalyptic famine and war. The planet wouldn’t be able to sustain that number of people given its finite resources and arable land. Although Malthus’s computations were incredibly accurate, and many contemporary people would agree with one of Malthus’s assertions—“The power of population is indefinitely greater than the power in the earth to produce subsistence for man”—take a look around you. Obviously, we failed to elicit his predicted outcome, dubbed the Malthusian catastrophe.

In 2011, we surpassed the 7-billion mark, and we are headed to a whopping 8 billion by 2030, maybe sooner. Malthus could not have foreseen the impact that technological innovation would have. It has allowed us to thrive for millennia, and will continue to do so, but only if we prioritize it like never before. Yes, we need to fix global warming, develop plans for water security, solve poverty and pollution, end world hunger, prevent chronic disease, and discover new energy sources—and we can accomplish all of this through innovation in the Lucky Years.

The notion that experiments performed generations ago, like those of Wanda Lunsford, are relevant today should inspire great optimism. I only wonder how many other long-lost studies are holding the key to effective remedies and cures to our modern afflictions. And I also sometimes wonder if we have all the drugs we’d ever need to treat our ailments, but we just don’t know which ones to try on which diseases.

For another example of old ideas once considered crazy or unbelievable gaining a new life in twenty-first-century medicine, take the story of William B. Coley and his “Toxins.”

William Coley (center) in his surgeon’s jacket attending a Christmas party at the Hospital for the Ruptured and Crippled (now known as Hospital for Special Surgery) in New York City, 1892.
⁷

In 1891, while a surgeon at the New York Cancer Hospital (which later became Memorial Sloan Kettering Cancer Center), Coley reviewed the medical charts of patients with bone cancer and found the sarcoma story of patient Fred Stein. Stein’s cancer regressed after a high fever from an
erysipelas
(now known as the bacteria
Streptococcus pyogenes
) infection. The surgeon realized that this wasn’t the first reported case of cancer retreating after an
erysipelas
infection. Coley then deliberately injected cancer patients who had inoperable, malignant tumors with live bacteria first, then with dead bacteria. His thinking was that creating a bacterial infection would stimulate the immune system, which in turn would also attack the tumor. And it occasionally worked.
⁸
Some of the patients’ tumors vanished. For the next forty years, as head of the hospital’s Bone Tumor Service, Dr. Coley treated more than a thousand people with cancers of the bone and soft tissue using his unorthodox technique, dubbed immunotherapy—using the body’s own immune system to treat and sometimes cure a disease.

Coley’s bacterial elixirs became known as Coley’s Toxins, and they weren’t
without their detractors. Even though Coley and other doctors who used the toxins reported excellent results sometimes, Coley came under fire from colleagues who refused to believe them. The harsh criticism came at a time when radiation therapy and chemotherapy were developing, causing Coley’s Toxins to disappear gradually until modern science could show that his principles were correct and that some cancers are sensitive to an amplified immune system. Today Coley is revered as one of the fathers of immunotherapy.

The field of immunotherapy has exploded in the last decade, especially as a method of treating fatal forms of advanced kidney cancer, skin cancer, lymphoma, certain lung cancers, and a few other cancers. Though more patients are benefiting, immunotherapy doesn’t succeed in all cases. We need to learn much more if it will ever emerge as a safe, effective treatment for many different types of cancer. Currently, gains in survival can be seen in a patient where there are few to no effective treatment options and median overall survival is usually less than two years. In oncology-speak,
median survival
refers to the length of time from either the date of diagnosis or the start of treatment that half of the patients in a group of patients diagnosed with cancer are still alive.

Modern immunotherapy involves either infusing the body with a drug to unleash the body’s own immune system to attack the cancer or injecting a special type of immune system cell called a T cell that has been taken from the patient and then modified in a lab to directly target and attack the cancer cells. These altered T cells become known as CAR T cells, short for “chimeric antigen receptors,” which are proteins that allow the T cells to recognize and assault the specific protein on tumor cells, or antigen. These strategies share the same goal: harnessing the awesome power of the immune system to detect and attack cancer cells, which would otherwise flourish in the body undetected and unregulated.