The Lucky Years: How to Thrive in the Brave New World of Health (3 page)

Indeed, despite the spectacular volume of information on how to live better available in the past two decades, we continue to suffer from chronic, debilitating, and largely preventable conditions that strike us at increasingly younger ages. And as a cancer doctor who watches people die weekly, I think this is categorically unacceptable. I’m excited about the opportunities that we all have today. But I’m also worried that many people won’t benefit from this medical revolution unless they have a certain knowledge base and the tools to take action. At the same time, we also need society to continually and speedily build the framework and allocate resources to enable further changes to occur. I hope this book will help us all do just that.

New technologies and constantly emerging data have produced the age of precision medicine, sometimes called personalized medicine. But precision medicine is still stuck in treatment mode—it’s being used primarily to learn how to treat your condition precisely once you have it. It hasn’t moved into the realm of prevention. However, it will, and it will shed the imperfections that distort the field today. For example, a major 2015 report published in the
New England Journal of Medicine
, one of the best, most respected medical journals in the world, warns that DNA testing results can be dramatically flawed.
¹⁴
These genetic analyses that profile your DNA are supposed to assess risk for numerous ailments including cancer, heart conditions, and Alzheimer’s disease.

You’d think these screenings would be straightforward and unequivocal, as if you’re reading a sentence that says, “You have a higher risk of breast cancer because you carry a defect on the BRCA gene.” But when
given the same test results, doctors interpret the data differently. Some say there’s a higher risk or lower risk of developing a disease based on the same genetic defect. Unfortunately, not all gene mutations—variations in human DNA, or variants—are equal.
Mutation
carries a connotation of negativity and harmfulness, but that’s not entirely accurate. Some mutations increase risk by a lot, while others barely nudge the risk meter or don’t do anything. And most variants are unresolved—we don’t know what they mean, which creates an even bigger dilemma for both doctors and patients. Complicating matters further, most variants are uncommon, so it becomes an even greater challenge to distinguish those that matter and determine by how much. Although the federal government helped create and finance ClinVar, a database for scientists around the world to collect anonymous gene findings, there’s no federal oversight on the actual execution of the technology to push for better standards and a universal understanding of how one should interpret results accurately.

In fact, the use of many new medical technologies lacks proper oversight, and this can make them harder to put into effect or more prone to errors and misuse. In the case of DNA screening, companies are testing for lots of gene variants, many of which haven’t been scientifically validated as to what they might mean in terms of risk factors for disease.

In the case of ClinVar, which became the basis for the review published in the
New England Journal of Medicine
, the project has documented more than 172,000 variants in nearly 23,000 genes.
¹⁵
This represents a mere fraction of the millions of variants known to exist, but at least they reflect some of the more common alterations. Nearly 120,000 of these variants can influence the risk for a disease. A few labs have analyzed a little more than 10 percent of these variants, allowing results to be compared. But they don’t agree on what the variants mean in all cases. Some identified variants that raise risk while others said those very same variants had either no effect or an unknown effect. Different interpretations are currently found in more than 400 gene variants—interpretations that could inform a medical decision, such as whether to get a defibrillator implanted in your chest to slash the risk
of sudden cardiac death, or to have healthy organs removed to lower the risk of certain cancers (e.g., breast and ovarian).

I’ve experienced the frustration of such fallibilities in my own family with a loved one who was tested for risk of Alzheimer’s disease. The results of her genetic screening showed a higher-than-normal risk. She lived with the psychological weight of this outcome for two years until she was tested again, and another variant was then discovered that
protects
her from that devastating affliction.

On a similar note, I had a fifty-year-old patient with metastatic lung cancer—cancer that had started in his lungs and traveled to other organs in his body. The odds of survival in cases such as this are typically low. When I ordered a test to sequence his tumor from the hospital that had done his initial lung surgery, it was determined that there were no gene variants to target with drugs. But then I had another lab perform the testing, and the results revealed a variant to target. This man is still alive today, four years later, thanks to finding that target and using drugs that slowed the progression of the cancer. I’ll be going into more detail about this kind of testing later in the book, as well as explaining more about what gene variants are and how they play into your fate. The point is, it’s sometimes better to do no test than the wrong test, and you should never underestimate the value of a second opinion. In the future, however, such testing will become more absolute and reliable, lessening the need for second opinions.

In the upcoming chapters, I’ll also be presenting some of the bigger issues we have to understand and face in the Lucky Years. What are the ethical considerations of many of these advances? Should there be regulation? Who should lead these efforts?

Let me give you a prime example of losing in the Lucky Years amid great revolutions. Over the next decade, millions of people will achieve better health with breakthrough new medicines. But at the same time, millions more will also become victims of counterfeit drugs. Upwards
of 40 percent of drugs in third world countries are fake, but even in the United States and Canada, doctors, pharmacies, and consumers have unknowingly purchased bad medicine due to weaknesses in the supply chain. It’s easier to counterfeit a drug than money; all you need is a pill presser, available today online for less than $1,000. The stakes are high when you look at human lives, and particularly so in areas of medicine where people are desperate. How many patients in Boston and Baton Rouge have died from counterfeit drugs? One of our most important anticancer drugs, bevacizumab (Avastin), was counterfeited in 2011 and sold to Americans who ended up losing several months of their lives.
¹⁶

We expend so much energy and brainpower to protect our bank accounts, credit cards, and other important things, yet we don’t do the same for drugs. We also lack proper safety measures in the production and distribution of food, hence the routine headlines about tainted meat and dairy, expensive recalls, and scary salmonella or listeria outbreaks that kill vulnerable people, young and old. We need to bring technology into the food and drug realms or we are going to be in trouble.

We also need health care to be above politics. For example, consider newborn screening with heel sticks, a tiny sampling of blood drawn by pricking the heel with a needle, which started in the 1960s and became standard and mandatory across the country. Every child is screened now for more than thirty rare and life-threatening diseases. In the past, research has been done on those blood samples to provide information that’s critical to improve the health of every child in this country. But in December of 2014, conservative lawmakers got their way when President Obama signed into law a bill requiring informed consent on every sample to be used for federally funded research. The new bill basically eliminated the research component to the blood draws because of the costs and difficulties involved with obtaining informed consent. Was anyone harmed by how the process worked for fifty years before that?

The answer is no, and thousands upon thousands of lives were saved with the information culled from those heel sticks, which not only alerted new parents as to their newborn’s chances of having a genetic
or metabolic disorder but also provided free, semi-anonymous data that fueled important research. (I say “semi” because individual names are redacted, but certain identifying features remain that are necessary for research, such as gender, age, and ethnicity.) One out of every 1,500 babies will develop a disorder detectable through newborn screening. Because most newborns tend to look normal, there is no way of knowing if a child has a problem until diagnosable, visible symptoms develop. By then, it may be too late to stop or reverse the effects.

Phenylketonuria, or PKU, is an example of one such inherited disorder that causes an amino acid called phenylalanine to build up in your blood. On soda cans you see labels warning people that the drinks contain phenylalanine, which individuals with PKU cannot metabolize properly. This is due to a defect in the gene that helps create the enzyme needed to break down the substance. If you don’t know that your child carries the mutation for the disorder upon birth, then you won’t know to avoid phenylalanine, commonly found in not just soda but many foods with protein. Serious developmental and intellectual challenges can result if a newborn with PKU isn’t screened and identified quickly after birth.

We know a lot more about inherited disorders like PKU today, thanks to these universal screenings and the research they have fueled. But in 2015, a study of about 400,000 newborns in California could not move forward due to the impasse the new law created when more than half of the participants didn’t sign the consent. So I ask: Do you want privacy above progress?

We allow people to drive their cars until they fail a portion of their test. If you’re older and have a problem, you lose your license. Clearly, our behaviors affect other people around us when we drive. By the same token, our health affects other people. When we are sick and in need of medical care, it strains family members, society, and the government to some degree. We all pay.

We need to think of health care in the same way. Driving is not a right; driving is a responsibility. Likewise, health care is not a right; it’s a responsibility. And step one in taking on that responsibility, both
personally and for the sake of a healthier society, requires an important tool that this book helps you gain: an understanding of your personal context.

When I have to tell patients and caregivers that I have nothing left to give them to treat a disease and that the end is surely near, I can’t help but think:
What could I have done differently? What could
they
have done differently? What could have changed the course of their fate? Was there a clinical trial that could have helped them? How could they have delayed this unfortunate, agonizing premature death when they deserved more fulfilling years of life?

And then I have to reconcile the fact that yes, there’s a lot we all could have done, but the clear changes could have been in their lifestyle choices and even in their
thinking processes
. Here’s what I mean by that: If you throw a lit match into a dewy wet forest, what happens? Nothing. But toss that same incendiary device into a parched landscape that hasn’t seen rain in a long time, and you’ll soon have a quickly moving fire on your hands. The difference between these two environments—one damp and saturated and another dry and thirsty—means everything in terms of how they respond to that spark.

I use this analogy frequently when I describe how one person can be diagnosed with cancer while another, perhaps even an identical twin, escapes such a condition. If I were to pluck at random one hundred people over the age of fifty from the streets of New York City and sequence their DNA, many of them will show mutations for genes that can trigger leukemia. But only a small fraction of them will ever develop it. What explains this? Again, go back to the image of the forest. One has an environment that effectively squelches the flame while the other has an environment that feeds it. In my world, in terms of the body, I call this “environment”
context
. Each one of us harbors a certain context we must honor in our health decisions. What’s good for me might not be good for you, depending on each of our individual contexts. If we
can know more about our personal contexts, we can make better decisions for ourselves.

An intriguing 2015 paper published in
Science
called attention to the fact that normal skin taken from people’s eyelids—a common place for cancer-causing UV exposure from the sun—is already chock-full of potential drivers, or mutations, for cancer.
¹⁷
So while the gene alterations pointing to cancer are already there, these people didn’t have skin cancers. Why not? Probably because the context wasn’t right despite these mutations. UV radiation causes so many mutations that we would all have skin cancer all the time if there were an absolute and linear path between these mutations and the development of skin cancer. But that doesn’t happen. Which points to the complexity of a disease like cancer and the complexity of its context—the human body. Quite simply, the DNA changes are necessary, but not sufficient for cancer to happen.

The concept of context cuts multiple ways. Your body today won’t be the same in five, ten, and twenty years. Similarly, your body goes through different contextual phases during every hour of the twenty-four-hour circadian cycle. When you woke up this morning, various hormone levels in your body were totally different from where they are now and where they will be when you climb into bed tonight. At the same time, your DNA—your inherited code of life—is probably behaving differently right this moment than it will tomorrow, next month, or a few years from now. When I was in medical school, the prevailing wisdom said that DNA was, for the most part, fixed. But today we know otherwise. Just as information is fluid and dynamic, so is the readout from your DNA. What we eat, how often we get off our butts and break a sweat, what we’re exposed to in our environment, how deeply we sleep, which drugs and supplements we take, and even the beliefs we keep in our minds all affect the expression of our genetic code. And this, too, plays into our context and risk for illness and disease.