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A Coming Medical Revolution?

Scott Camazine/AndreaMosaic/Science Source
A digital mosaic of the brain, using images from X-rays, CT sans, and MRI scans

Spectacular advances in the scientific understanding of life processes since World War II have vastly increased the ability of physicians to diagnose, treat, and prevent disease. Nevertheless, even today there is much about the cause of most common diseases and their prevention or treatment that remains unknown. However, the huge and constantly expanding store of information in the medical literature is still mainly the province of physicians, who make most of the decisions about the use of health care resources. As always, patients depend largely on their physicians for counsel and treatment.

A new book by Dr. Eric Topol predicts that this is all about to change. He sees an exciting new era created by the increasing application of digital technology and computers to the study of human biology and health care, which he predicts will cause the “creative destruction” of medicine. Medical care will no longer be controlled by physicians. Neither will medical information be based on the results of studies of large populations, which Topol says give less precise information than do studies of individual patients. Instead, patients will largely manage their own care, based on their access to detailed and digitized information in the world’s medical literature and to information about their own bodily functions and individual genetic makeup.

Thus, Topol heralds the coming of “personalized” medicine, in which the convergence of digitized information from all these sources will enable patients to make most of the decisions now reserved to physicians. There will be a parity of knowledge between patient and doctor, which he calls the “democratization” of medical information.

According to Topol, patients will receive, in real time, continuous information about their own physiology, biochemistry, and general health generated by microchip wireless sensors embedded in, or attached to, their body. They will know about their genetically determined diseases, their risks of contracting diseases, and their probable response to therapeutic drugs, as determined by the variations in their fully sequenced genome. All of this vast store of information will be made instantly available and interpreted by their smart phone. Many health care decisions would be made or suggested by computers, some by patients themselves, and far fewer by physicians.

Physicians would continue to manage surgical procedures and the treatment of serious injuries. Even here, however, their direct hands-on activities would be limited to their control of robots, aided by electronic imaging. The result of all these changes, Topol says, will be better and probably less expensive clinical care. There will be much less use of hospitals and physicians’ offices, more rational, safe, and effective use of drugs and medical devices, and greater success in the prevention of disease and disability.

How much credence should be given to this description of a coming medical revolution? Although Topol’s account sounds like hyperbole, it cannot be easily dismissed, for he bears impressive credentials. He has had a distinguished academic career in cardiology, genetics, and medical education, and he currently is the director of the Scripps Translational Science Institute in La Jolla, California. So, when Topol tells us that patients’ biological information about themselves, monitored by digital wireless detectors, is going to produce a new kind of “personalized” medicine, his message deserves careful attention.

He has written his book for a wide public, so it is full of interesting information about new technologies. It describes many new types of micro-sensors and his experience with some of them. There is a helpful primer on genomics (“Genomics 101”), which alone makes his book worthwhile. His language is plain; nevertheless, some of his exposition will be tough going for scientifically uninformed lay readers. Topol and his contemporaries have lived with computers for their entire professional lives. I entered medicine a generation before him, and this may explain some of my skepticism about Topol’s prediction of a medical care future so dependent on, and regulated by, computers and digitized wireless devices. Still, I think he stretches current medical science too far. He is much too sanguine about the potential of new technology for providing clinical care and not sufficiently concerned about its limitations.

A particularly valuable section of the book describes recent advances in human genetics, including the sequencing of the total human genome. That sequencing is the process of determining the order of the four nucleic acids in a person’s DNA. Thanks to new technology, this stunning achievement is becoming faster and cheaper, and therefore more generally available. However, this instructive description is accompanied by predictions that invite disbelief. Topol envisions a time, not too distant, when every patient’s total genetic structure will be known and will be digitally accessible to him or her. He believes the unique variations and mutations in each genome will help to foretell susceptibility to diseases and will guide preventive and therapeutic interventions, including what drugs to use and at what dosage. As will be seen, I regard his predictions about genome sequencing skeptically.

Topol has an interesting chapter on the remarkable advances in digitized imaging of the internal structures of the body (e.g., pocket-sized echocardiographs, CT and PET scanning, and MRIs), which are replacing physical examination and old-fashioned X-rays. And finally, he discusses the application of electronic digital technology to medical records and doctor–patient communication, which is already beginning to replace handwritten records and personal encounters between doctor and patient. These technologies enable the creation of digitized records that at least in theory can be transferred between medical institutions and providers, and collected anonymously for analysis by public agencies, and would also be available to each patient on his or her smart phone.

Simply as descriptions of advances in medical technology, however glowing they may be, most of this material is not controversial. But Topol’s expectation that patients will want to attend constantly to the recordings of their bodily physiology and chemistry is, to say the least, questionable. And so is his belief that most people will pay close attention to the innumerable variations in their genetic code that might have a relatively weak statistical association with common diseases.

However, my major concerns are with Topol’s conclusions that digitized data recorded from each patient, together with information about his or her fully sequenced genome, will transform the practice of medicine, and will “reboot” the pharmaceutical industry. I also question Topol’s speculation about the rapidly approaching parity of knowledge between the public and the medical profession. He thinks that patients, aided by computerized access to the world’s medical literature and to computer-interpreted information about their own body and its unique genomal structure, will be almost as knowledgeable about their medical conditions as any physician, and therefore will be an equal participant with their physicians in the management of their medical care.

I doubt that most people will be able to analyze or fully comprehend the avalanche of information that would be available to them, even if recorded and interpreted by a computer. And this would be particularly true when the information is most important to them, i.e., when they are very sick, seriously injured, or simply terrified by the possibility that they might be dangerously ill. Not many people will be obsessive enough to keep up with all the available information about their own body, its vulnerability to disease and likely response to treatment. They will continue to rely on physicians for interpretation of the data and for objective, professional advice, as well as for help with any needed medical procedures. In modern society, with few exceptions, people turn to experts for help, and they probably always will—especially when threatened by a disease or injury they do not fully understand.

Topol also is more optimistic about the clinical benefits of genetic information than many experts would consider justified. It is true that advances in molecular biology have identified a few dozen relatively uncommon inherited diseases that are attributable to specific mutations in the structure of a single gene. Knowledge of the proteins encoded by those genes has helped to pinpoint and understand the molecular events causing the disease. Examples of such diseases include familial occurrence of very high blood cholesterol, cystic fibrosis, sickle-cell disease, Gaucher’s disease (fatty deposits in the liver, bone marrow, and other organs), Huntington’s disease, and a certain type of breast cancer. They usually follow Mendelian laws of inheritance. Knowledge of the genetic defect, the mode of inheritance, and the causative mechanisms of these diseases has often led to improved medical treatment.

But most diseases, including the most common ones, such as diabetes, asthma, hypertension, coronary artery disease, Parkinson’s disease, late-onset Alzheimer’s disease, and most cancers, are associated with many variations in the genome—not with just a single mutation. The identification of these multiple genetic variations has often established a statistical association with the disease—usually a relatively weak association—but not the cause.

Neither has genetic information about most of these common diseases led to specific and definitive treatment. This is not only because of the multiplicity of the genetic variations found in patients with these diseases, but also because most of the diseases have so-called “multifactorial” causes. That is, they are the net result not only of multiple inherited and acquired variations in the genome itself, but of many factors outside the genome, elsewhere in the body or in the environment.

These factors may affect the way the genome works, or may themselves be on the molecular pathway directly leading to the disease. As a result, although they may run in families, the development of one of these diseases in a particular individual cannot be reliably predicted by Mendelian laws. Their association with genetic variations is purely statistical and not causal. It will probably be a long time before genomal sequencing results in the conquest of one of the common diseases. Far more likely, and much sooner, we will make progress through increased understanding of the molecular events directly responsible for the disease rather than from the sequencing of everyone’s whole genome.1

Topol is an expert in medical genetics, and he must know the arguments against his optimistic predictions; in fact, occasional brief comments in his book suggest that he is aware of the limited use of genomic sequencing in most patients with common diseases. For example, after describing the initial excitement in the year 2000 over the first complete sequencing of the human genome, he acknowledges that “we have yet to gain real knowledge about what was discovered….” Later, when talking about the widespread application of genomic sequencing, he says: “It’s not immediately clear what the clinical importance of any of this information is.” But the burden and tone of most of his argument leave a different impression. He repeatedly implies that we are on the verge of a great revolution based on understanding how genes determine our health.

Recent studies of the genomic DNA that is not a part of any of the known 21,000 genes have confirmed what most geneticists have assumed: this so-called “dark” DNA controls the activity of the genes. The new work finds that many individual variations in the regulatory DNA have loose statistical associations with common diseases that cluster in families, but cannot be predicted from Mendelian laws of inheritance. Whether these associations will lead to advances in the prevention and treatment of disease remains to be seen.

  1. 1

    Much of the foregoing skepticism about the clinical applications of whole-genome sequencing is supported by a recent, concise, and authoritative review by Liam R. Brunham and Michael R. Hayden, two medical geneticists at the University of British Columbia, in Science (“Whole-Genome Sequencing: The New Standard of Care?,” June 1, 2012).They say at the start that “the vast majority of genomic data is, at this time, not medically actionable.” Later, they add: “With few exceptions, there is a lack of data to suggest that genetic testing actually leads to improved health outcomes.” 

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