The Future of Medicine: Megatrends in Health Care That Will Improve Your Quality of Life

Read an Excerpt

THE FUTURE OF MEDICINE

Thomas Nelson

Chapter One

We have entered into a new era in medical care, the era of genomic medicine. In coming years, we will see an improved ability to diagnose a disease and even to predict diseases to come later in life. A much more accurate prognostication of what will happen as the disease progresses and how it responds to medications will be offered, and treatment will improve. Drug therapy will change so that new drugs will be more effective and much safer. Physicians will be able to select a drug based upon an individual patient's personal way of responding to that drug, both in terms of greater effectiveness and in terms of reduced side effects.

Even the foods we eat will be understood in terms of how they affect a specific individual. Vaccines will be "designed" for an individual patient who has, for example, a particular type of cancer that has been reduced but not totally eliminated. Finally, actual gene therapy-the introduction of a new gene to correct one that is diseased or will cause disease-will become commonplace, such as a true cure for sickle cell anemia or perhaps cysticfibrosis. Genomics will permeate all branches of medicine.

Medical practice changed dramatically in the middle of the last century. Earlier, a physician attempted to understand what disease was present so that he could tell the patient and family its likely outcome. Specific therapies were few and far between. Then medicine became a true science with an increasing understanding of the cellular and molecular mechanisms that underlie each illness. With that developing knowledge, doctors could begin to treat disease with greatly improved medicines, such as penicillin for infections, tPA for breaking up blood clots in a stroke or heart attack, and drugs like phenothiazides for serious mental illnesses like schizophrenia.

Doctors and patients both saw penicillin as a miracle drug when it first was used to treat serious pneumonias. I am still in wondrous amazement when I see a person with a stroke come to the emergency room unable to move his left side, only to watch him stand up and walk an hour later after receiving tPA. And the state mental hospitals-long used to "warehouse" individuals with chronic mental illnesses-have been eclipsed by the use of potent drug therapies that get people back home and enjoying life again.

But now we are entering a whole new era. The genomic era will allow for a change in your physician's basic approach, from one focused on detecting a disease and treating it, to one where she is focused on predicting a disease later in life and prescribing a preventive approach. (I use the pronoun she here to emphasize another major trend in medicine-today over 50 percent of medical school students are women.)

Consider Anna Blumenthal, a thirty-four-year-old single woman employed as a financial consultant with a major accounting firm in the mid-Atlantic area. She began to have intermittent episodes of breathing difficulty and her doctor diagnosed asthma, a condition in which the smooth muscles around the airways deep inside the lungs begin to constrict, making it difficult to move air in and out and creating the characteristic wheeze during exhalation. Her doctor reviewed a variety of things she could do at home to reduce her chance of developing asthma attacks and gave her some preventive medications as well. He also gave her a prescription for an albuterol inhaler and told her to keep it handy for use in case of an asthma attack.

She followed her doctor's instructions, making some changes in her environment and taking the preventive medications regularly. However, at about two o'clock one morning, she woke up, struggling to breathe. Alone at night, it was scary. But she remembered the albuterol that was in her medicine closet. She had read the instructions before but now read them again.

Albuterol comes in a spray canister; you put your lips around a mouthpiece, press down on the canister, and out comes a measured amount of very fine spray. The idea is to press the canister while taking a deep breath in, so that the medicine will get deep into the lungs. Albuterol works because it interacts with a receptor on the lining of the airways of the lung, a receptor that can relax the smooth muscles that are causing the constriction. When albuterol finds that receptor, it breaks the action of the smooth muscle constriction. It doesn't cure the underlying cause that created the constriction in the first place, but it can turn the attack around in the short term. This receptor is the product of a specific gene that is part of our DNA. So we can say that our DNA directs the production of this receptor along our airways that will respond to albuterol.

Anna knew that after breathing in the albuterol she should begin to feel relief within a few minutes. She put the mouthpiece in, depressed the canister, breathed in the spray, and repeated it about a minute later, as directed. Then she waited, but nothing happened. Indeed, it was getting more difficult to breathe not less difficult. Now she really was scared because the promised relief had not arrived. Why? Because Anna is one of those rare people who are born with a gene that directs the production of a slightly different receptor on the lining of her airways, and this slightly different receptor does not respond to albuterol.

The middle of the night during an acute asthma attack is hardly the time to discover that you are among the unfortunate few. But for years physicians have been unable to predict which patients would not respond to albuterol. As a result of genomics, soon it will be possible to know who will not respond, so that an alternative medication can be prescribed and a long night of distress-and fright-can be avoided.

DNA and the Creation of Proteins

The genomics era began at the start of this century with the preliminary sequencing of the entire human genome, a task that was completed in 2003. What does this mean? How does it affect your medical care? A brief review of the structure and activity of DNA will be helpful before I attempt to answer these questions.

Deoxyribonucleic acid (DNA) is made up of molecules of four substances (nucleotides) that are named adenine (A), thymine (T), cytosine (C), and guanine (G). For our purposes let's just use the letters A, T, C, and G. They are attached to a "backbone" of sugars and phosphate. DNA has two main jobs. One is to replicate itself and the other is to direct the production of proteins.

Replicating itself allows a copy of DNA to be created whenever a new cell is created. Proteins are critical cellular compounds that control a cell's basic functions and structure. DNA ultimately establishes what a cell is and what it does. Proteins, in turn, are made up of molecules called amino acids of which there are twenty types, all arranged in a specific sequence that is different for each protein. DNA directs the sequential arrangement of amino acids, a task accomplished by the arrangement of the A, T, C, and Gs of DNA.

Each and every cell has our entire DNA. Half of it comes from Mom and half comes from Dad. It's arranged in units (chromosomes), twenty-three from each side of our family for a total of forty-six. DNA is basically a long chain of those four letters A, T, C, and G. These four letters make up the genomic alphabet. They can be put together in groups of three that code for a specific amino acid.

For example, ACA is the code for the amino acid histidine, which is one of the twenty that make up proteins in the body. CAC is the code for threonine, another amino acid that makes up protein. These three-letter codes are called codons, and we can think of each of them as a "word" in our genetic dictionary. Consider a long chain of ACACACACACACAC, and so forth. This would be a code for alternating the amino acids histidine and threonine.

A set of codons, which we can call the gene, is the blueprint for the structure of a protein. In my example of ACACACACAC, we are not making a true protein but an alternating chain of these two amino acids. The process goes like this: Our gene, which would be part of the entire strand of DNA, directs the creation of a related compound called mRNA (messenger RNA). The mRNA, which holds the same code,2 travels to a part of the cell called the ribosome; a ribosome is basically a protein manufacturing factory. The ribosome takes the mRNA and follows the code, in this case alternating ACA, CAC, ACA, etc., and puts together the alternating amino acids histidine and threonine.

A real protein, such as insulin or hemoglobin, is made up of many different amino acids and usually is many hundreds of amino acids long. After it's manufactured by the ribosome, it "folds" into a complicated shape that might look like a ribbon sort of wiggled together on the floor after coming off a Christmas package. In fact, that shape is very specific and allows for the creation of an active site on the protein, which is the part of the protein that causes something to happen, such as relaxing the smooth muscles around the airways.

How much DNA do we have in each of our cells? If we were to "read" one letter each second it would take about one hundred years to read all the DNA in those forty-six chromosomes. We have about thirty thousand genes and more than 99 percent of these are exactly the same in each and every human being. It's the few that are different that create the differences among us and explain why one person will respond to a drug and another will not. Or why one person will have no side effects while the same drug in another person will cause major toxicity. But more about this later. What I hope you have gathered so far is that DNA is indeed the "code of life" and that our new understanding of the genome will open many previously closed doors.

IMPLICATIONS OF GENOMICS ON MEDICAL CARE

Still to come is to understand the exact sequence (those coded four letters A, T, C, and G) in each of the thirty thousand genes and to determine the function of each gene.

As this is done during the coming years, it will become possible to predict who might be more susceptible to a disease, such as atherosclerosis (clogging of the heart's blood vessels), diabetes, or perhaps colon cancer. Knowing that a person is at higher risk will allow the physician to recommend a preventive approach, such as diet and lifestyle changes, for each of these diseases-attention to cholesterol levels for the person at risk for atherosclerosis, weight control for the person predisposed to diabetes, and to an early start with screening colonoscopies for the person at risk of colon cancer. It will allow drug companies to create specific drugs to counter a disease while avoiding unwanted side effects and will allow the physician to choose the drug that will be known to work in a given patient and known not to cause any unwanted toxicities.

As we'll see as we move forward, genomics also is allowing scientists to better understand bacteria and viruses. For example, remember when the serious infection SARS started in Southeast Asia a few years ago and quickly spread to a number of distant cities such as Toronto, Canada? Microbiologists were able to quite quickly figure out the entire genome of that virus. That helped them understand how it would spread and infect-and possibly how it could be treated. Luckily, the SARS epidemic died out, but not before scientists discovered the nature of this particular "bug" faster than had ever been done before.

Genomics also has led to gene expression profiling, a new technique that we'll discuss later. But in a nutshell, gene expression profiling creates an opportunity to understand a tumor in much more detail. Scientists can determine if it is likely to spread or not (which aids in determining the long-term prognosis) and as a result recommend proper therapy. Profiling will also allow us to determine the risk of a disease, such as a heart attack (acute myocardial infarction), and genomic analysis will let us look at how a person is likely to respond to a drug, such as those used for seizures.

I suspect it will be some time before there will be much true gene therapy, that is, the insertion of a new gene to counteract for a deficit or abnormal gene. So in the meantime, medicine will focus on changing the environment rather than the genetics. If we know that a person won't respond to albuterol, then we can simply prescribe a different drug.

If we can identify a gene, then we can move on to identify what proteins or enzymes the gene produces and what that protein or enzyme actually does inside the cell. With that information we can then create a diagnostic test and from that either develop a preventive approach or we could modify the treatment. So in Anna's case it will one day be possible with a simple finger stick in the doctor's office to know that she will not respond to albuterol. In her case the doctor would prescribe a different drug.

Another result of identifying a gene and then its protein product is that we can now understand the basic defect in a disease and as a result create a specific drug. We can call this approach to medicine "targeted therapy." Chronic myelocytic leukemia (CML) is a good example. Two pieces from two chromosomes that have broken off rearrange themselves so that the piece from the first chromosome-containing part of a normal gene called BCR-attaches to the other chromosome next to a normal gene called ABL, creating a new gene and hence a new protein, each called BCR-ABL. The problem is that this is not a normal protein, and this new protein is what causes the disease we call chronic myelocytic leukemia.

The abnormal BCR-ABL protein allows this one cell to divide and divide and then divide again until eventually there are millions and then billions of these abnormal cells in the person's body. Until now, the approach to treating this disease has been to use fairly aggressive forms of cancer chemotherapy to kill off the dividing cells. But these drugs all have their own side effects, and they kill off other dividing cells as well. Knowing the underlying gene (BCRABL) and its protein product (BCR-ABL protein) and using some sophisticated techniques, such as nuclear magnetic resonance imaging and X-ray crystallography, researchers determined the site of the active protein-the part that causes something to happen, such as cell division. With this information in hand, scientists found a compound that would neatly insert itself into this active site, blocking the action of the protein. This compound, Gleevec, has had a major impact on those who suffer with chronic myelocytic leukemia.

Taking the drug blocks this active site and hence the disease seems to "disappear." Of course, because the underlying abnormal gene is still there, it will continue to produce the abnormal protein. But as long as the patient takes Gleevec, the abnormal protein's action is suppressed. This is one of the first examples of what is known as "targeted therapy," meaning that the drug is selected specifically because it blocks the action of this very specific abnormal protein.

In the past, if drugs were found to be effective and free of major side effects, then they could be used for whatever conditions seemed to respond. The difference here is in precisely knowing the activity of the BCR-ABL protein and what it does that is abnormal in the cell-and then learning what the active site is and how to specifically block it. (The Novartis Corporation actually had the drug Gleevec on its shelves. Developed for a different purpose years ago, it didn't work. But when scientists discovered the active site of the BCR-ABL protein, they were able to review a large drug database and determine that Gleevec might well be what was needed. And indeed it was.)

PHARMACOGENOMICS

All this is leading to pharmacogenomics, a new field that will create these targeted therapies. Watch the newspapers and magazines, and during the coming years you'll see quite a few drugs that have been created to respond to an understanding of how the protein actually works within the cell. The new science of genomics will also give us some other opportunities to advance medicine.

We will be able to determine in advance whether a drug will work and whether it will work in a specific person. Likewise we'll be able to determine in advance whether a drug will cause side effects or toxicities in an individual person. This is the beginning of what some are terming "personalized medicine." Will a drug work? Let's return to Anna Blumenthal, her asthma, and albuterol.

(Continues...)

---

Excerpted from THE FUTURE OF MEDICINE by STEPHEN C. SCHIMPFF Copyright © 2007 by STEPHEN C. SCHIMPFF . Excerpted by permission.
All rights reserved. No part of this excerpt may be reproduced or reprinted without permission in writing from the publisher.
Excerpts are provided by Dial-A-Book Inc. solely for the personal use of visitors to this web site.

---