7
THE GENIE IS OUT OF THE BOTTLE

SO, WHERE ARE WE? In the previous six chapters, you have seen how the development and application of modern science over the last 400 years have led to an understanding of everything from planetary motion to the innermost workings of the cells in your body. You have learned about many of the bits and pieces that you’re made of, what they do, and how you can measure them, resulting in the “molecular you.” We have seen how the advent of the digital age allows us to store all this information electronically, and how analysis of the “digital you” embodied by this massive data cloud can identify biomarkers that provide an incredibly accurate picture of your state of health and disease. Remote-sensing devices can now analyze every breath you take and every beat of your heart and alert you well before you pass your best before, or rest in peace, date. Through social media, you will soon be able to share these intimate details with sympathetic listeners suffering from disorders just like yours, compare your digital selves to find the most effective therapies that should work for you, and locate where these are available. Taken together, these advances are driving massive changes in the practice of medicine as we know it today. But that’s only the beginning of the potential disruptions molecular medicine may cause.

Let’s explore the near future first. Chapter 6 described what might happen during the next ten years, and it seems pretty exciting. Ten years from now, cancer will be managed much better than it is today. Detection of causative “driver” genes in your cancer genome should allow for a personalized cocktail of drugs to be administered to you to cure or control the particular cancer you have. Blood tests to detect pre-cancerous conditions and very early manifestations of cancer should be routine, allowing for effective treatment before cancers metastasize to other parts of the body. Increasingly sophisticated imaging techniques will detect the extent of your cancers more readily, leading to more complete removal of cancer cells during surgery. Today’s anticancer drugs will be augmented by “smart” nanomedicines that are specifically designed to kill cancer cells and avoid healthy tissue. Perhaps most importantly, we will have ways to turn your immune system on so that it recognizes and destroys many forms of cancer. In short, a remarkably powerful array of weapons are coming online to contain and cure cancer.

How about cardiovascular disease, the other major killer in Western society, leading to heart attacks and strokes and accounting for nearly 50 percent of all deaths? Again, in the near future, we should see major advances to the point that most manifestations of heart disease will be treatable. Heart failure, the end-stage of heart disease, could be treatable, although that treatment will rely on advances in methods for rejuvenating aged hearts trending towards failure, such as ways to make heart stem cells “younger.” These advances might include the human analogue of the GDF11 protein. We should have much more sophisticated techniques to predict and prevent strokes: simple blood tests to give warning signals of such events so that appropriate action can be taken. However, treatment of brain damage after it has occurred as a result of a stroke may not be that much better unless we can develop new ways to remove dead brain tissue and stimulate new neuron growth to replace dead cells.

Focused attacks based on molecular-level understanding of genetic diseases such as cystic fibrosis, Huntington’s disease, or Alzheimer’s disease should soon result in improved treatments. As molecular-level understanding increases, rapid advances become possible; when you know what is causing the problem, the path to a solution is much clearer.

The rapid advances in accurate diagnostics that can be anticipated in the near future, and their availability to you, will challenge the medical establishment’s role as the gatekeeper of medical advances, because knowledge and power will be passed to you, the consumer. For example, the current fifteen-year wait time for a new medical advance to reach the doctor’s office — to reach you — will not be tenable when you know with certainty what disorder you have, and have done your research as to which therapy is most appropriate to you and where it is available.

Let’s look at a future scenario: You wake up one day feeling ill. You’re very tired and somewhat nauseous. On most days when you feel like this, you open up your smartphone and find a pop-up suggesting that you drink a bit less alcohol and get more sleep. But today your smartphone suggests you run a blood analysis, because the onboard sensors on your smartwatch or bracelet have detected that things aren’t right: perhaps your temperature has risen or your heart is beating a little faster. You pull out a disposable needle and prick your finger, just like diabetics do routinely, and daub a drop of blood on a disposable sensor that you plug into your smartphone. Instantly, a thousand proteins and metabolites in your blood are measured and compared against your normal levels. Meanwhile, your smartwatch and other onboard sensors are relaying your blood pressure, temperature, heart rate, body weight, respiration, and other data to be uploaded to the latest version of your digital data cloud — your digital you. Through your voice-activated personal data assistant (a.k.a. a super smartphone — Siri will work better by then), you ask your digital self, “What’s wrong with me, and what should I do?” Armed with the data, your digital self answers, “We are coming down with a type of flu that has a 98 percent probability of being the same as a local strain that has been recently detected in other people in our vicinity.” It works out the most appropriate individualized therapy for you, finding drugs that will work for you and that won’t induce some nasty side effect. It then notifies the nearest pharmacy to prepare your individualized therapy. You pick it up, and by the next day, you’re feeling your usual self again.

A second scenario: You are walking at what is usually a comfortable pace but suddenly become breathless. You sit down but can’t seem to catch your breath. In this case, your onboard monitoring systems are picking up warning signs — abnormal heart rhythm, low blood oxygen, and other signs pointing to heart failure. The information is relayed to emergency services, and your smartphone informs you that an ambulance is on its way, arriving soon enough so that emergency care, such as oxygen, can be given. On arrival at the emergency room, you find that the appropriate drugs for your condition have already been prepared for you, using input from your digital you to decide which drugs will work for you, which dosage to use, and which drugs to avoid. If conditions such as atrial fibrillation have set in, blood-clot–dissolving agents will be administered before more serious problems, such as stroke, can occur.

A third scenario: Perhaps you develop type 1 diabetes. Cells are taken from your skin or some other source, and the differentiation process that caused those cells to become skin cells is reversed, yielding stem cells capable of becoming any cell in your body. They are then induced to become beta cells capable of producing insulin in response to high blood-glucose levels. These beta cells are grown in tissue culture to the required amounts and then injected intravenously into your body, where they seed in your liver and other locations, sense the glucose levels in your circulation, release insulin as needed, and resolve your diabetes. Or you find that you’re trending to type 2 diabetes; you feel fine, but your onboard sensors have noted warning signs that your blood-sugar levels are rising. You receive increasingly insistent messages — a pop-up every time you open your computer or use your smartphone — that you must alter your lifestyle. You will be told to get off the subway one stop earlier or not to go back to the buffet table. You will eventually succumb to these intrusions as increasingly dire warnings flash up indicating the number of years of your life that are in jeopardy and the limbs you may lose as the diabetes progresses.

Personalized medicine heralds the start of an age of maintaining health, as opposed to treating sickness, and personalized medicine will become the major industry of the future, particularly as the health-maintenance industry increasingly engages in an anti-aging agenda. We see many signs of this now. Thirty years ago, fitness centers were almost unknown; today, if a hotel doesn’t have good workout facilities, guests are irate. The health and anti-aging centers of the near future will be something to behold. There will be detailed genomic, proteomic, metabolomic, microbiomic, and vital-sign analyses to begin with, followed by daily exercise routines and diets devised specifically for you. Motivation will be provided by very precise molecular measurements that will show definitively when you make even minor progress. From standing desks at work to regular visits to a health center, very few of us will spend less than an hour a day maintaining our health. Prehab instead of rehab will be normal rather than unusual. Who would look askance at somebody in rehab for two hours a day to recover from the effects of a stroke? Far better to spend an hour a day in prehab and avoid the stroke in the first place.

What else does the near future hold? Certainly, personalized medicine will be creating havoc within the medical profession. The role of doctors in making diagnoses will be increasingly supplanted by computer analyses of the digital you. Accurate diagnoses combined with advanced imaging techniques and analyses of genomic and other data in the digital you will mean that safe and effective treatments will be readily identified. Thus the role of doctors will be in transition, as it has been for some time. Fifty years ago, doctors cared for people who were really unwell: 80 percent of their job was looking after the dying or seriously ill. Today, the treatment of chronic disease has become the norm. Care of type-2 diabetes, high blood pressure, arthritis, and cancer survivors takes up the majority of time. As these chronic disorders become increasingly controlled through a molecularly based, personalized approach, and as diagnosis and treatment are largely decided by analysis of the digital you, only complex and severe problems will need the doctor. So what will doctors be doing?

Two scenarios are possible. Those who do not have access to a doctor — or advanced health care — will find the playing field dramatically leveled. Relatively inexpensive omic data — potentially in the range of $100 for a complete analysis — and free online analyses available through the Internet will enable patients around the world to access state-of-the-art diagnostic resources. This information, combined with Internet searches and social media such as PatientsLikeMe, CureTogether, and other disease-specific websites, will also make it possible for you to discover what the most appropriate treatment is and where it is available. You’ll be able to do some cost-comparison shopping as well as check references from satisfied (or unsatisfied) customers. Having decided on the best, most cost-effective therapy, you will then make an appointment and travel arrangements to get treated.

An alternative scenario — and one that people with adequate health plans and access to doctors will tend to move to: You will still have a doctor, but you will rely on him or her to prevent you getting ill, rather than to treat you after you become unwell. Your doctor will likely be associated with a health-maintenance center that you belong to, and it is likely you will pay your doctor according to his or her success in keeping you well. Your doctor will help keep you well by assisting you not only with the latest ways of gathering important personal data but also by helping you analyze and interpret your digital self and by advising you on the most appropriate course of action. You will probably fire your doctor if you get sick too often. This is a novel concept — paying doctors only for effective treatments and recommendations. Takes one back to the halcyon days of ancient Mesopotamia: according to Hammurabi’s code of laws, physicians who performed surgery were held responsible for errors or failures. If a freeman died as a result of surgery, the physician could have his fingers cut off. If a slave died as a result of surgery, the physician had to replace the slave with one of equal value. In any event, we may not need so many doctors with the training they presently have. The expert systems that interpret our personal data cloud will bear a lot of the load. But doctors who play the role of health coach will be very much in demand to manage and optimize our health in the same way that we now use financial professionals to manage and grow our investments or lawyers to manage and solve our legal problems.

But let’s move on to the really interesting bit: what’s in the cards for personalized medicine over the longer term — say, fifty years from now? Here we realize that the genie is certainly out of the bottle: a molecular-level understanding of ourselves has many consequences, and not all of them are unambiguously wonderful.

Right now, the efforts humankind has made to understand and cure our various ailments are starting to show signs of working. As Winston Churchill said after Britain won its first battle in the Second World War: “This is not the end, this is not even the beginning of the end, but it is, perhaps, the end of the beginning.”

So what is the end? This question is difficult to answer because the sky is the limit. We are only now coming to appreciate the incredible power that the focused application of science and technology can have on our individual selves. Only slightly more than 400 years after the initial attacks on magical thinking by Galileo and Newton, we are starting to come to grips with what we’re made of, how it’s put together, and how it can be fixed. Progress is accelerating wildly. Approximately 90 percent of scientists who ever lived are alive today. A large proportion of them are working to bring better health to all. Until 1900, human knowledge doubled approximately every century. By the end of the Second World War, knowledge was doubling every twenty-five years. Today, nanotechnology knowledge is doubling every two years, clinical knowledge every eighteen months, and total human knowledge every thirteen months. IBM is projecting the doubling of knowledge as the Internet is built out to be as short as every twelve hours. Knowledge drives technology drives change, and we are hurtling blindly into future change at an ever-increasing rate.

So if you think the rate of change now is way too fast, fasten your seatbelts. The rate of change is going to get a lot faster, particularly in medicine. The changes enabled by new knowledge will be aided and abetted by the fact that when it comes right down to it, we all want to escape from the natural order of things. The signs are all around us. If your hip or knee wears out, replace it. If your heart slows down, put in a pacemaker. If you can’t hear, get a hearing aid. If you can’t get an erection, use Viagra. Now it’s about to get much better — or worse, depending on your point of view. It is starting, obviously enough, with diagnosis and treatment of disease, and there is no way you can argue that this is anything other than good. Clearly, your cancer should be identified and treated in a way that actually affects the cancer and does not harm the rest of you. Clearly, it is ridiculous that after an operation to remove a cancer, you have to wait for three months or six months to see whether the disease is returning: you should have a simple blood test to map your progress on a weekly or daily basis. Clearly, you should not wait until a disease is advanced before you treat it; you should know well ahead that you are trending towards disease and take appropriate action. Clearly, you shouldn’t take a drug that doesn’t work to treat your disease; you should use only drugs that work on you and don’t harm you. It is all so clear, but there are many concerns.

Chief among these concerns is the probability that the rate of increase of knowledge and the associated rate of improvement in technology is a double-edged sword. On one hand, as applied to your health, the potential benefits are legion. On the other hand, as Donald Rumsfeld would put it, there are many unknown unknowns that could surprise us. Stanislaw Ulam, in a tribute to the great mathematician and physicist John von Neumann more than fifty years ago,1 recollected a conversation “centered on the ever accelerating progress of technology and changes in the mode of human life which gives the appearance of approaching some essential singularity in the history of the race beyond which human affairs, as we know them, could not continue.” Many serious thinkers today have similar concerns. Raymond Kurzweil, who is a director of engineering at Google, who received the National Medal of Technology and Innovation in 1999 (America’s highest honor in technology), and whom PBS named as one of the sixteen revolutionaries who made America,2 published a book in 2005 entitled The Singularity Is Near: When Humans Transcend Biology, predicting a “technological singularity” before 2050.3 This singularity is defined as a point where progress is so rapid it outstrips humans’ ability to comprehend it. Once that singularity has been reached, Kurzweil predicts machine intelligence that is much more powerful than human intelligence. What this would mean for the world, and our place in it, is not at all clear.

The global consequences of rapid technological change such as those suggested by Kurzweil are arguable, and some would dismiss them as science fiction. However, what is not arguable is that as a result of dramatically improving technologies, much more definitive information is becoming available about how we are made, what is wrong with each of us, and what will work for each of us, and that information in turn is opening the door to using new understanding of biology to cure our diseases, correct our defects, and extend our lives. It can be expected that these efforts will become increasingly intensive and that the rush towards personalized medicine in the near future will be an expression of this. There is an enormous demand for these services because we feel that we are captives of so many things we cannot fix or control. We are captives of disease, pain, and disability — particularly as we get older. We are captives of our bodies — robust or not, attractive or ugly. We are captives of life itself; as Jim Morrison, lead singer for the Doors, put it: “No one gets out of here alive.”

Thus the endgame of personalized medicine will be an ability to not only fix diseases we may have but also extend our lives and “improve” ourselves. The list of improvements we may want is endless: to make ourselves more intelligent, more attractive, more athletic, younger — the wish list can be pretty extensive. Whether this power will come in 50 years or 100 years can be debated, but what cannot be ignored is that in less than 500 years, a blink of an eye in evolutionary time, we have come to the rapidly expanding understanding of life that we have today. It would be delusionary to deny the potential for extending our life spans and fixing our imperfections. As our wishes come true, fundamental drivers in our civilization will be perturbed. The fact that we are going to die in the not too distant future drives a lot of our behavior; it drives a search to understand why we’re here, why we do what we do, and where we’re going, particularly after we die. This search has not been particularly fruitful, so we invent constructs such as nationality and culture and religion and invest these with a significance and importance that is not entirely rational yet makes sense of our lives and provides a set of rules to live by.

The probable reality is that we are exquisitely evolved survival machines, whose objective is survival of the species, and nothing more. Every attribute we have can be fitted into that framework. And in the Darwinian scheme of things, once we have procreated and raised our young, evolution has no further use for us, and that’s when we age and die. But our search for meaning in life will change significantly if we are able to eliminate pain and suffering and extend life indefinitely: we still won’t understand what the hell is going on, but it won’t be as pressing an issue if pain and death are not around the next corner. Eat, drink, and be merry, for tomorrow you may not die.

Personalized medicine that leads to dramatically extended life spans is an amazing, and sobering, prospect, and it is here that the darker side of the genie we have let out of the bottle begins to emerge. From the individual point of view, of course, this promise is wonderful. We may no longer be subject to the impersonal cruelty of Darwinian pressures, no longer have to die within some predetermined timeframe, and no longer have to endure the pain of terminal disease. The prospect of genetic surgery suggests the advent of designer bodies: If we are able to replace old stem cells with new ones that are younger, why not change the genetic code so that your eyes will gradually change to that piercing blue that you’ve always wanted? Why not code for that larger penis, or those longer legs, or neurons that work a little better? But we had better be careful, because we are changing the natural order of things and there will be repercussions.

From an environmental point of view, of course, the ability to extend life significantly, say to 150 years or more, would be an unmitigated disaster. Technology has already dramatically extended our life spans over the last 200 years, from 40 years in 1800 to 80 years in 2012. The fact that there are so many of us is at the heart of all environmental problems, and increased life spans certainly won’t help. Even more of a problem will be the lack of renewal and the frustration of younger generations when parents and grandparents don’t die off. And what of super-rich captains of industry or dictators who just won’t go away? Another 100 years of Donald Trump or Robert Mugabe? Or prolongation of ancient credos that keep women subjugated and old wounds festering, never healed by the renewal process inherent in death? There is little doubt that revolution will be in the air.

So the future will be interesting. For the readers of this book, if you want to enhance your health, the way is clear. First, exercise, eat healthful food, and don’t smoke. You should pay attention to this advice: it applies to all of us. Second, the molecular-level information you need to find out your own risks, diagnose your particular ailments, and discover the best treatments just for you is coming online. You should pay attention to this opportunity: it may save your life. Third, we are merrily changing the natural order of things to ensure survival of the individual as opposed to the species, with not a clue as to the consequences. You should pay attention to this phenomenon: it could lead to the end of the human race as we know it. You can’t stop our mad dash into the future, but you really do need to know what is happening. Personalized molecularly based medicine is driving the major revolution of your time.

We are all pioneers in a brave new world.