Hacking Darwin
Page 7
“Doctors have always recognized that every patient is unique,” U.S. president Barack Obama said in his 2015 State of the Union Address, “and doctors have always tried to tailor their treatments as best they can to individuals. You can match a blood transfusion to a blood type—that was an important discovery. What if matching a cancer cure to our genetic code was just as easy, just as standard? What if figuring out the right dose of medicine was as simple as taking our temperature?” Soon after, the Obama administration announced its Precision Medicine Initiative designed to “enable a new era of medicine through research, technology, and policies that empower patients, researchers, and providers to work together toward development of individualized care.”21
Progress toward this goal is being measured one initiative at a time. In 2018, Geisinger Health System (based in Danville, Pennsylvania) announced it was offering free genome sequencing to all patients as part of standard preventative care. Geisinger’s preliminary research found actionable findings in 3.5 percent of patients.22 For the patients, finding potential future dangers can be useful and potentially lifesaving. For the health system, sequencing patients potentially enables better care and could even lead to higher revenue from additional services provided in the short term and could provide savings down the line from preventing more serious conditions. On a societal level, identifying genetic abnormalities early has the potential to make the overall population healthier and reduce the downstream costs of care.*
Although the inefficiencies of health-care systems, the lack of genetics expertise among primary care doctors, and the generally conservative medical cultures around the world could slow the transition, millions then billions of people around the world will eventually have their genomes sequenced as part of the shift toward personalized medicine.23 Through this process, more and more of our species’ genetic, life, and health data will be placed in electronic records, allowing the industrial-scale analysis of our complex biologies.
As the number of people sequenced increases, the cost of sequencing continues to drop, and our computational power to do the necessary big-data analytics climbs, our understanding of complex genetic patterns will grow. Beyond better understanding the impact of an increasing number of single gene mutations, we will begin to grasp more complex genetic patterns that can lead to polygenic, or multiple gene, conditions like coronary heart disease, diabetes, and hypertension.
This process is already well underway. Researchers at the Broad Institute are building an algorithm and website designed to give people risk scores that assess their genetic predisposition to a range of complex diseases, including coronary artery disease, atrial fibrillation, type 2 diabetes, inflammatory bowel disease, and breast cancer. “[F]or a number of common diseases,” according to its letter in Nature Genetics in August 2018, “polygenic risk scores can now identify a substantially larger fraction of the population than is found by rare monogenic mutations, at comparable or greater disease risk.”24 Genomic Prediction, a start-up company founded in 2017 by Stephen Hsu, uses these kinds of advanced computer modeling techniques to score percentage risks of a given preimplanted embryo developing a range of complex genetic disorders, including intellectual disabilities, and traits.25 The company is an early example of the future of expanded PGT. This type of “polygenetic scoring” based on statistical probabilities will be the bridge connecting today’s high confidence of predicting many single-gene mutation disorders and our coming ability to predict far more complex disorders influenced by the minimal contribution of many hundreds or thousands of genes.
But there is no possibility that preventing or treating complex genetic disorders will be the endpoint of our genetic journey. It will, in fact, only be the beginning. Pairing assisted reproduction technologies with big-data analytics, machine learning, and AI will increasingly transform not just how we make babies but the nature of the babies we make.
In seeking to unlock the complex genetics of diseases, we will need to understand the bodily systems they impact. To grasp the genetics of cognitive decline, for example, we’ll need to understand the genetics of intelligence. To assess the genetics of premature aging, we’ll need to understand the broader genetic mechanisms of aging itself. To understand shortness, we’ll need to comprehend the biology of height. Seeking to understand genetic abnormalities and climbing the ladder of better understanding of our genetic complexity will, in other words, force us to understand the genetics of being.
And beginning to understand the genetic foundations of our most human characteristics will force us to recognize that the genetics revolution is about much more than our health care. It is about who and what we are today and in the future. Because in a series of incremental steps, it will alter our evolutionary trajectory as a species.
*Around 60 percent of genes connected with human diseases have correlates in flies. Researchers developed hundreds of strains of mice, our closer relatives, to give them all sorts of human diseases and help find cures. Model organism research is absolutely essential to finding cures to human diseases but can cause significant pain for the animals. That’s why we need to make sure both that animal experimentation continues and that it is overseen using strong ethical guidelines.
*We’ll talk more about data privacy later in the book, but I wanted to flag the issue here.
*All of this, of course, is set in the highly irrational U.S. health system, which creates many perverse incentives for everyone.
Chapter 3
Decoding Identity
Welcome back to the fertility clinic. The year is 2035.
When you were here ten years ago, you went through the IVF and embryo-screening process to make sure your beautiful daughter was not born with terrible single-gene-mutation diseases. That daughter is now ten and flourishing, giving you a lot of faith in the role embryo screening can play in enhancing a child’s health. Watching her and the other children stream out of school at the end of each day, you’ve also felt sorry for the kids born with genetic abnormalities that could have been avoided had the parents conceived in a lab rather than by selfishly indulging in the random and dangerous conception method of sex.
Raising your daughter over the past ten years, you’ve paid special attention to the growing stream of discoveries that identify the roles multiple genes play in an increasing number of disorders and traits.
You are back in the same fertility clinic you visited a decade ago, walking from the same waiting room into the same doctor’s office, but a lot feels different.
“Doctor,” you say, entering her office, “it’s nice to see you. I had such a great experience with IVF and embryo selection last time I’d like to do it again.” The office, like the waiting room you’ve just left, feels much more comfortable than a decade ago. The antiseptic white of the walls has been replaced by soft pastels of light blue and lavender. The chairs have gone from industrial to contemporary. The office smells faintly of roses.
The doctor rises to greet you with a warm smile. “That’s what everyone says. Can I offer you a cappuccino?”
The question startles you. Since when do they offer barista service at doctors’ offices? It seems assisted reproduction has become a competitive customer service business since you were last here. “Can you make it decaf?”
“This is going to be a relatively easy process,” the doctor says, then turns her head a moment to dictate your order to her coffee machine. “You were ahead of the game a decade ago when you decided to have us fertilize ten of your eggs.”
“I’ve been sleeping a little easier these past years because I knew the other nine embryos were still frozen. It’s hard to imagine I was ever even considering other options. I wasn’t sure I even wanted another child, but these past couple of years I haven’t been able to escape the feeling that having another is what I need to do.”
“And we’ll to do everything we can to help turn that feeling into a bubbly, angelic reality. Sugar?”
“Just a teaspoon, please.”
“Okay,” you reply. The doctor hasn’t lost the no-nonsense approach you remember from a decade ago.
“Then we’ll sequence those cells from each of those six embryos and let you know which of those potential children would be carriers of the single-gene diseases, just like last time.”
“Sure,” you say confidently, taking a sip of your coffee. It’s perfectly brewed. You’ve been through this process before so feel confident you know what to expect.
“But a lot has also changed since a decade ago,” the doctor continues. She leans toward you. “In those early days we could only screen for single-gene-mutation disorders and a few simple traits, like gender and hair and eye color. Now we’ve learned a lot more about the patterns of multiple genes that can lead to more complex genetic disorders, some of which may not show up until significantly later in life. Because these patterns vary from person to person, and because we still don’t fully understand the hugely complex whole genome, we can only see this kind of analysis as predictive. We’re no longer dealing with binary outcomes, the on-and-off switch for single gene mutation diseases and disorders we talked about a decade ago. We’ll just be able to make percentage predictions, like there’s about a 70 percent chance a child born from one embryo, for example, would get disease X before he or she is Y years old. It wouldn’t mean that the potential child would get that disease, just that someone with his or her genetics would have that chance of getting it. Of course, this wouldn’t account for environmental factors a child would experience after he or she was born. Does that make sense?”
“Yes,” you say, a little more cautiously. These are unchartered waters.
“But we are able to make these kinds of predictions for many of the most serious and painful diseases that are influenced by genetics—Alzheimer’s, heart disease, some cancers. You won’t be able to prevent all those diseases through embryo selection, but you certainly can improve the odds of your future child for delaying or avoiding them.”
“A lot really has changed,” you say.
“I’m required by law to ask if you want this predictive information. You obviously have the right to refuse it. If you’d like the information, you’ll need to sign the form on this tablet.”
You think for just a moment, pick up the stylus, and sign. Why wouldn’t you want that information? You have to implant one of the embryos anyway. Why not pick the one with the greatest chance to live a healthy life?
“The law also requires me to ask you specifically if you would like to know more about the likelihood that your embryos, if they are implanted and taken to term, would express other non-disease-related traits. It’s entirely up to you.”
You feel your spine inadvertently stiffen as you begin to comprehend the question. You sense you know the answer but ask anyway. “What types of traits?”
“Some of the most popular are the patterns of genes suggesting a greater chance to live a longer, healthier life.”
“That seems like a no-brainer,” you say, relieved. Isn’t living a long and healthy life what this process is all about, you ask yourself.
“That’s good. Some people get nervous the further we get from preventing disease. So many diseases are correlated with age, so if we want to fight disease we also need to defend our children against aging.”
“Some of those other people think doctors like you are playing god,” you say.
The doctor smiles wistfully at the suggestion. “Some people certainly feel that assisted reproduction is going too far, that we’re giving people choices that nature—or whatever deity they trust—didn’t want us humans to have. That’s why it’s so important to find out what each prospective parent is comfortable with. You tell us what works for you, so we can help you achieve it.”
“I would’ve had a lot more qualms when I came in a decade ago, but now I see not selecting the embryos with the greatest chance of a long and healthy life is like taking something away from my future child. It doesn’t feel like I’m adding healthy years to his or her life but preventing them from being taken away.” You lift the stylus to sign again.
The doctor gives a hand signal for you to wait. “Longevity is just one of the genetic screens. We can also very accurately predict height. Should I go on?”
“I read that tall people have higher incomes and tend to have more self-esteem than short people. Is that true?”
“Most of the studies suggest that.”
Do a couple of inches of height mean so much to you that you’d choose a different embryo to get it? But then all of these embryos are your potential natural children, so why not try to pick a taller one if all other things are equal. Picking a taller future child, you explain to yourself, is the same as not picking a shorter one. You take in a deep breath. “Why not? What’s the big deal? I’m already selecting for so many other things.” The stylus is feeling heavier, but you lift it again.
The doctor again raises her hand gently. “The next screen is IQ,” she says softly but with more gravitas. She clearly recognizes the implications of her words.
You’ve seen the news articles, but something still feels uncomfortable about choosing the potential IQ of your future child. “How accurate is the test?” you ask, stalling for time. “Can we really know something like that?”
“It’s all probabilities, but we’re getting better at making these kinds of predictions. IQ isn’t all about genetics. How you raise and educate your child still means a lot. But IQ is a mostly genetic characteristic, particularly as we age.”
“But will my child be happier if he or she has a higher IQ?”
“No one really knows,” the doctor says. “IQ is still controversial. Many people say it’s culturally biased. But society itself may be culturally biased, so I’m not sure where that leaves us. And there’s no denying the correlation between IQ and lots of other important life outcomes.”
You inhale again. Do you really want to be in the business of choosing your future child’s brain function, you ask yourself. If you don’t optimize your child for IQ, will she love you or hate you for it?
“Repeated studies from around the world have shown that people with higher IQs tend to live longer on average than people with lower IQs,” she adds.
“How do they know that?” you ask cautiously, a hint of humanist suspicion in your voice.
“Lots of ways. The Scottish government gave IQ tests to all eleven-year-olds in Scotland on a single day in the 1930s. Six decades later, researchers began correlating the IQs from the tests and those children’s life experiences. Even when they controlled for social class and lots of other factors, the outcome still showed that the higher IQ kids, on average, lived longer. Scores of additional studies have shown the same thing.”
“But IQ isn’t just one thing. How can they really know?” you ask, not wanting to reduce the identity of your future child to survey results.
“You’re right. IQ is a complicated concept many people reject. Some people even say a high IQ doesn’t even make you smart.”
“And if someone has a high IQ, does that make them a better artist, a more loyal friend, a more loving father or mother?” you ask.
“Those are all the right questions. The answer to all of them is no. There’s no evidence of any of that. But there’s a lot of statistical research suggesting that high IQs strongly correlates with success in school, career, wealth creation, and sociability.”
You feel yourself relenting in spite of yourself. You know IQ doesn’t measure everything and that a human is so much more than a simple IQ score. But are you prepared to reject the concept of IQ out of hand and leave it to your future child to suffer the consequences if you are wrong? That would also be a risk. If you don’t select the embryo with the highest IQ it’s not at all certain the
embryo you select will have a greater genetic predisposition to being a better artist or a more compassionate person. For all you know, those qualities might, like so much else, also be positively correlated with IQ.
But a twinge in your gut also tells you there’s something wrong—not about choosing an embryo with a relatively higher IQ than the others but about not choosing your higher IQ embryo. This is not the most politically correct thought you’ve ever had but now, you realize, is a moment for brutal honesty. You squeeze the stylus between your fingers and look up.
“There’s more,” the doctor continues, a grave look crossing her face. “I need to tell you about some of the latest research on personality styles.”
“Personality styles?” you repeat, a lump forming in your throat. What is left of the mystery of being human?
“I imagine you know people in your life who are more extroverted than others.”
“Oh yeah,” you say, thinking of your sister.
“And people who are more open or more neurotic?”
“I do.” Her husband and now, after only six months of puppyhood, their overfed and skittish dog.
“Or even people who are sadistic and cruel.”
Your mind shifts to your angry neighbor you saw yesterday kicking his malfunctioning sprinklerbot.
“Personality style has many foundations,” the doctor continues, “but genetics is probably the biggest.”
“Wait a second,” you say, feeling another tug at your humanity. “You’re telling me I can select which of these little embryos in your freezer is going to be the next Mother Theresa and which is the next Jeffrey Dahmer?”