NATIONAL PROVISION FOR HEALTH REQUIRING MEDICAL RESEARCH WITH SEARCHING FOR RELEVANCE TO AND GOING BEYOND EXISTING PAGES NOT INSURANCE BUDGET, AND REMAINING GOOD PRACTITION PERFORMING UPDATE INFOS, AND AS THIS SITE SUPPOSEDLY, MUCH MORE THE BEING WELL LINKAGE TO EXISTING LEVEL THAN "IF NOT" BEING ORIGINAL AT THE PRESENT TIME

Mitosis and PCR

What is mitosis? Mitosis or cell division is an elegant process that enables organisms to grow and reproduce. Through a sequence of steps, the replicated genetic material in a parent cell is equally distributed to two daughter cells. While there are some subtle differences, mitosis is remarkably similar across organisms. There are several phases or steps in mitosis which include: interphase, prophase, metaphase, anaphase, telophase. Above is an animated GIF of the different phases of mitosis in a plant cell and followed by an animated illustration of how PCR (polymerase chain reaction) works. The longer orange and blue bars represent the two DNA strands, while the shorter bars represent the primers to each strand. When the temperature is high (see thermometer) DNA strands separate; at low temperature the primers anneal to the DNA strands (they compete very effectively with the companion strand, because the primers are in very large excess). After annealing, the reaction mixture is raised to an intermediate temperature. Now the polymerase extends the primers into new companion strands, using the dNTP's (not shown) in the reaction mix. Voila, DNA has been replicated. The cycle is repeated up to 30 times, doubling the concentration of the desired DNA with each cycle.

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Ann Carroll, PhD
 
New York State Task Force on Life and the Law

Dr. Ann Carroll is a policy analyst for health and science issues for the New York State Task Force on Life and the Law (Task Force) and an employee of Health Research, Inc. The Task Force is a bioethics commission of the New York State Department of Health that considers policy issues that result from medical advances. 
Dr. Carroll is a former biomedical research scientist and faculty member of the Department of Microbiology, Immunology, and Molecular Genetics at Albany Medical College, where she was a recipient of numerous research grants. She obtained her Ph.D. from Cornell University Graduate School of Medical Sciences. She studied policy and management at the New York University Wagner School of Public Service, from which she received a M. S. degree. She has authored numerous original research and review articles in biomedical and scientific journals.

Views expressed in articles or webcasts are the author’s. They do not reflect those of the New York State Task Force on Life and the Law, Health Research, Inc., or the New York State Department of Health.

The Human Genome Project and the New Genetic Tests

Introduction

Scientists recently announced a milestone achievement—they have deciphered the genetic blueprint of humans—the human genome. The international Human Genome Project has decoded a first draft of the genetic material, containing about 50,000 genes, that all of us inherit. Many experts agree that human genome research and new testing technologies will bring us into the age of “individualized medicine.” Within the next decade, doctors may routinely offer their patients a simple blood test or swab of a cheek to perform genetic tests to individualize medical care—to predict what diseases we may be most susceptible to, whether we are especially vulnerable to cigarette smoke carcinogens or workplace chemicals, and what drugs will work best for us with the least chance of harmful side effects.

What is the Human Genome?

The human body is made up of about ten trillion cells. Each cell contains a complete set of the human genome, in fact two complete sets, one inherited from the mother and one from the father. The chemical that makes up the genome is DNA. DNA is made up of a series of four chemical “letters” called A, C, G, and T. These four letters are the basis of the “alphabet” of the human genome, which contains three billion letters. A gene is a stretch of anywhere from one hundred to thousands of such DNA letters arranged to form “sentences” that direct production of human proteins—the tens of thousands of different proteins that make up our skin, hair, and organs and the enzymes that digest our food, clot our blood, and fire messages between nerve cells. Each gene accounts for one or more specific proteins.

From person to person, the spelling of our genes is remarkably similar—about 999 out of 1,000 DNA bases are identical, ensuring that all make the same essential proteins. But about one in 1,000 or so bases differ among the population, accounting for our unique traits—our height, eye color, and other inherited traits. These differences also account for the inherited component of susceptibility to diseases, including common diseases such as cancer, cardiovascular disease, and diabetes.

The “Old” Genetic Tests

The variations in our DNA base spellings, called mutations, may be harmful and contribute to disease. A clinical genetic test examines a particular gene, or the protein product of that gene, to detect specific variations of the gene that are associated with disease. Some genetic tests have been used for decades to detect DNA mutations associated with single-gene diseases—relatively rare diseases that result from inheritance of a single or double copy (one from the mother and one from the father) of a particular mutated gene. Examples include sickle cell disease, cystic fibrosis, and Huntington’s disease. Scientists have discovered the genes involved in many of these diseases and have developed DNA-based genetic tests to check the DNA base “spelling” of that particular gene—to look for harmful mutations. These tests are used to see whether healthy individuals in a family or a population group with a history of a particular disease are at risk for developing that disease in the future or of having a child with a disease.

The “New” Genetic Tests

Most of us do not inherit single-gene diseases. We all, however, inherit slightly different variants of each of our pairs of 50,000 genes, and these differences may affect whether we are more or less likely than other people to develop particular health problems or diseases. In fact, many cases of diseases, while not showing the clear inherited patterns of single-gene diseases, show family clustering patterns that are due, at least in part, to genetics. For example, some families show unusually high rates of breast cancer or colon cancer.

Researchers have begun to identify specific genes, and the harmful mutations within these genes, that account for some of these family histories. For some genes, the inheritance of harmful mutations, while not guaranteeing future disease, increases the chance that a person might develop a particular disease in his or her lifetime.

Genetic tests that detect inherited risks for future disease are sometimes called susceptibility tests. Examples of some of the new genetic tests are listed below:

Breast cancer susceptibility testing: This test looks for harmful mutations in two genes, BRCA1 and BRCA2. Inherited mutations in these genes contribute to between five and ten percent of all breast cancers. Inheritance of a harmful mutation in one of the BRCA genes increases a woman’s lifetime risk for breast cancer from about 12 percent (the average population risk) to as high as 85 percent. It also increases lifetime risk for ovarian cancer. The test is recommended only for women with a strong family history of breast and/or ovarian cancer. 
  
Colon cancer susceptibility testing: About three percent of colon cancers are associated with a familial form of cancer called HNPCC. HNPCC is suspected in some families that have multiple cases of colon cancer, often at an earlier than average age. Inheritance of a harmful mutation in one of five identified genes increases lifetime colon cancer risk from the average population risk of about five percent to about 80 percent. 
  
Susceptibility testing for iron overload disorder: About one in 300 adults of Northern European descent is at risk for developing hemochromatosis, a disorder caused by an abnormal buildup of iron in body tissues. The disorder is difficult to diagnose and can lead to liver cirrhosis, diabetes, heart disease, and arthritis. Researchers have discovered a gene, and harmful mutations within that gene, that may help predict who is at risk. 
  
Factor V susceptibility testing for blood clot risk: About five percent of the population inherit a particular mutation of a gene called factor V, which increases the risk of forming rare, but potentially lethal, blood clots. For women with this gene mutation, the use of birth control pills and other hormone supplements may further increase this risk, although formation of such clots still remains relatively uncommon.

What’s Different about the New Genetic Tests?

Powerful, Long-Range Prediction: Predictive DNA-based tests are very accurate, and they can provide disease risk information for a person decades before a disease occurs. A test performed on an infant can predict relative genetic risks for diseases that occur in adulthood.

Probabilities, not Certainty: Although predictive DNA-based tests are powerful, they generally provide information about a person’s relative risk of disease only. Most of these tests cannot predict with certainty that a person will get a disease. Whether or not a person who has inherited a particular gene mutation will actually develop a disease depends on many other factors, both genetic—other inherited gene variations we have inherited—as well as environmental factors. Environmental factors include our diets, behaviors, and exposures to hormones and other chemicals throughout our lives.

Implications for Family Members: Genes are shared within families. Because we inherit our genes from our parents, learning that a parent has inherited a particular gene mutation generally means that each child has a fifty-fifty chance of having the same mutation. (Each parent has two copies of the same gene and passes one copy on to each child). Siblings also share genetic risk. Testing decisions and results can raise psychological issues within families, especially when medical treatments for a predicted disease are lacking. Also, genetic tests may inadvertently reveal nonbiological relationships within families, such as mispaternity and adoption.

Considerations for Predictive Genetic Testing

To whom should testing be offered? Today, predictive genetic testing generally should be offered only to persons who have strong family histories that suggest a familial mutation. Tests offered to whole populations of people at apparently average disease risk are called screening tests. Before genetic tests are offered as screening tests, experts agree that the tests must be highly accurate and must offer a clear medical benefit. Some predict that experts will be ready to recommend screening tests for iron overload disorder in the next several years. 
  
What does it mean if the test finds a gene mutation? If a test detects a mutation that is known to be harmful, the result means an increased disease risk for that person relative to the general population. In most cases, it does not mean there is a 100 percent chance of disease. The degree of risk depends on the particular test, the mutation, the disease, and family history. For example, in some families, inheriting a BRCA gene mutation means an 85 percent lifetime breast cancer risk while for others it may be only 50 percent. 
  
What does it mean if the test does not find a gene mutation? DNA-based tests currently are not powerful enough to detect every possible mutation associated with disease risk. Therefore, failure of a test to find a mutation does not necessarily mean that one does not exist.

However, in cases of familial diseases, for example, familial breast cancer susceptibility, if previous testing of a family member has identified a familial mutation, a negative result (no familial mutation) in another family member means that that person has not inherited the high family risk. She still, however, faces the baseline 12 percent lifetime risk for breast cancer that all women face. This result, however, may reduce anxiety and allow a woman and her doctor to bypass heightened surveillance or treatments they might have chosen otherwise.

What are the medical options if you learn you have a harmful gene mutation? Medical benefits vary for different tests and diseases—there may be clear benefits for some and complicated choices for others. Also, there is some concern that laboratories may offer new predictive genetic tests before there are useful medical options for people who test positive for a harmful mutation. In this situation, learning that you have an increased risk for a future disease,  but knowing that there is little or nothing that you can do to prevent it, can cause anxiety.

Options for testing positive for some tests are:

For breast cancer susceptibility, there is an array of options—heightened surveillance, prophylactic surgery to remove breasts and/or ovaries, or chemoprevention—but no option has 100 percent effectiveness and some options may pose potential health or psychological risks.

For HNPCC, testing enables prevention or early detection of colon cancer by periodic colonoscopy exams.

For those who learn that they are at risk for hemochromatosis, there is a simple and effective treatment: periodic bloodletting to remove blood iron.

Factor V test results about relative risk for rare but serious blood clots might be useful to women and their doctors making decisions about birth control or other hormone supplements.

How should testing be offered? Because deciding who is at risk for carrying a particular gene mutation and what a positive or negative test result means for an individual is complicated, persons who are considering testing should get genetic counseling by a trained professional who can examine their family and personal medical history and discuss the potential benefits and risks of testing.

The Future of Predictive Genetic Testing

Dr. Francis Collins, Director of the National Human Genome Research Institute, predicts that most genes that undergo harmful mutations that increase susceptibility for common diseases of adulthood will be discovered in the next five to seven years and that new genetic tests will enter the clinic in the coming years. In addition to predicting future diseases, most experts agree that DNA-based genetic tests also will be used to guide individualized drug therapy.

These new tests offer great promise, but that promise requires responsible development and use of tests and understanding of both the benefits and risks of testing. Increased understanding about our genes and the part they play in our health and disease risks is an important first step toward realizing this promise.

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SUMMARY OF VIDEOS

VIDEO 1
 
Host: 
David R. Marks, MD , WVIT-TV, Connecticut (NBC) 
 
Participants: 
Marianne Legato, MD ; New York Presbyterian Hospital-Columbia University 
 
Benjamin H. Lewis, MD ; New York Presbyterian Hospital-Columbia University

Summary: 
That men and women have different bodies is news to no one. But with the advance of the medical sciences, more and more fascinating differences have been uncovered. Did you know, for example, that men and women often use different parts of their brain to accomplish the same task? Or that men produce more saliva than women? Join our panel of experts as they discuss some of these gender differences and address their implications for modern medicine.

Recorded Live: June 22, 2000

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VIDEO 2

Host: 
Meg Walsh , Oncology.com 
 
Participants: 
George Lundberg, MD ; Medscape 
 
Ed Fotsch, MD ; Medem

Summary: 
Some carry a traditional point of view about the delivery of healthcare; others are "guerillas" in the healthcare Internet Industry. Two of the industry's medical leaders will debate their tactics to reach physicians on the Internet. Hear their vies on when the Internet will become a key element in physicians' practices and what it will take to make this happen. How will it change their day-to-day patient interactions? How will the Internet change the scope and behavior of clinicians? Can traditional physician behavior be changed before medical schools actually change the scope and priority of education?

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VIDEO 3

Host: 
Bruce Fried , Shaw Pittman 
 
Participants: 
Molly Coye, MD, MPH ; Director, The Lewin Group 
 
Neal Patterson ; Cerner Corporation 
 
Hugh Greeley ; HCPro 
 
Gregg Meyer, MD, MSC ; Agency for Health Care Policy and Research

Summary: 
The Institute of Medicine Report has healthcare leaders focused on the need to reduce the high number of medical errors and has created a new sense of urgency on Capitol Hill related to healthcare quality, regulation and reform. This Super Panel will address how technology and the Internet can be used to create a safer healthcare system.

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VIDEO 4

Host: 
David R. Marks, MD , WVIT-TV, Connecticut (NBC) 
 
Participants: 
David Hoffman, JD ; Private Practice Healthcare Lawyer, NYC 
 
Aytan Y. Bellin, JD ; New York State Task Force

Summary: 
Few of us like to think about it, but it's possible that some day you'll be too ill to speak for yourself. Who will represent you and your medical preferences? To make sure it's the right person, it's important to choose a "healthcare proxy"--a friend or family member you can trust to make healthcare decisions for you. When and how should you do this? What rights does a proxy have? What factors should you consider when choosing your proxy? Our panel of experts will answer these questions and more as they discuss this important--but often neglected--medical issue. 
 
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VIDEO 5

Participants: 
Ted Marmor ; Yale University 
 
Eleanor Litwak ; New York State Council of Senior Citizens

Summary: 
Election Day is just a few days away, and everyone knows it's going to be a close one. 
One of the major concerns which may help decide this election is healthcare. Both candidates have spent a great deal of time promoting their own plans, but many people are still confused about the issues. What are the candidates proposing? How do their plans differ?

On our webcast we'll compare the advantages and disadvantages of each plan, focusing on the candidates' opinions on such issues as prescription drugs and universal healthcare. Joining us to clarify the issues are Yale University Professor Ted Marmor, and Eleanor Litwak, President of the New York State Council of Senior Citizens.

Recorded Live: October 30, 2000   
 
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VIDEO 6

Host: 
Mark Pochapin, MD , Weill Medical College of Cornell University, New York 
 
Participants: 
David Pearl ; Liver Transplant Recipient 
 
Julia Grivera ; New York Organ Donor Network

Summary: 
After years of suffering from a progressive gastrointestinal disease, David Pearl reached a point where his life depended on replacing his failing liver. He waited, and waited... and finally the call came. 
Join us as he shares his remarkable story of survival and renewal, and discusses the emotional challenge of receiving the gift of life from another person's tragedy.

For more more information on organ and tissue transplant, call 1 800 355 SHARE. 
 
 
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VIDEO TRANSCRIPTIONS: SELECT ALL TEXT IN ANY BOX AND COPY-PASTE TO NOTEPAD FOR READING WITH EASE.

VIDEO 1

DAVID R. MARKS, MD:  Welcome to our webcast.  I'm Dr. David Marks.  Men may be from Mars and women may be from Venus, but are they different medically?  It's the age-old question.  Joining me to help discuss this question are two guests.  First is Dr. Marianne Legato.  She is professor of clinical medicine and director of the Partnership for Women's Health at Columbia.  Welcome. 
MARIANNE LEGATO, MD:  Thank you.

DAVID R. MARKS, MD:  Next to her is Dr. Benjamin Lewis.  He is assistant professor of clinical medicine and a scholar at the Partnership for Women's Health, also at Columbia.  Welcome.

BENJAMIN LEWIS, MD:  Thank you.

DAVID R. MARKS, MD:  Why do we have this question to begin with after all of these years?

MARIANNE LEGATO, MD:  Ever since the 20th century began, we assumed that women were really small men and did research almost exclusively in men, partially as a desire to protect women from the consequences of clinical investigation, particularly women who were still in their reproductive years.  That all changed with the advent of feminism after World War II, and finally Congress listened to the wishes of women to have more attention to their health and legislated in the early 1990s that women were to be included in federally funded research grants.  To our amazement, we find that there are significant and important differences body-wide between men and women.

DAVID R. MARKS, MD:  But this is all just recent information.

MARIANNE LEGATO, MD:  Yes.

DAVID R. MARKS, MD:  So probably all of the results are not in, and we're going to find out even more down the road, I would think.

MARIANNE LEGATO, MD:  That's right.  But a significant number of interesting differences are already very much apparent.

DAVID R. MARKS, MD:  Why don't you tell us, Dr. Lewis, about some of the differences that we're finding?

BENJAMIN LEWIS, MD:  Some of the differences that are significant are, for example, how we test for coronary artery disease.  The testing where we do the conventional stress testing with an EKG has a fairly good track record for reliability in men, but when you apply those same criteria to women, there are a number of false positives.  That concept led to using nuclear scans for women that continue to have problems because of artifacts in the nuclear scan.  As a result there became a bias against the truth, which was that women do get heart disease, and women really had to present with heart attacks or manifest heart disease before it was taken more seriously.  I think now we understand that there are ways to look at the technology and find people earlier.  One of the key advantages has been in terms of using ultrasound, using exercise echo.

So I think we've learned that there are clear differences.  There are even differences, for example, in the normal heart size and heart mass per unit area between men and women.  So there are a number of fundamental differences.

DAVID R. MARKS, MD:  We hear about the fact that women and men think differently.  I know that that's true.  But is there a difference in the brain anatomically?

MARIANNE LEGATO, MD:  Yes, indeed.  There's a difference in every system, and the brain is probably one of the most interesting.  It's called sexual dimorphism, different shapes of the brain, different sizes of the parts of the brain, between men and women, and even a difference in the number and complexity of connections between brain cells between men and women.  The most interesting thing to illustrate how important it is is that if you and I had an identical task to perform, some problem to solve, different parts of your brain would light up with activity compared with mine.  We might both solve it, but use different parts of our brain to do that.

DAVID R. MARKS, MD:  Is this under hormonal control?

MARIANNE LEGATO, MD:  Not altogether.  Everyone thinks it's simply a question of hormones.  In the first place, both men and women have all three hormones: testosterone, estrogen, and progesterone.  It's just a question of concentration.  In fact, one of the most important determinants of how we are as male or female happens long before our hormones even begin to be produced in what's called gender imprinting, in which one of the parts of our chromosomes, the companion piece that we get -- we get one of each, as you know, from the mother and the father -- and some of the alleles, or parts of the chromosome, are silenced according to the sex of the --

DAVID R. MARKS, MD:  What's an allele?

MARIANNE LEGATO, MD:  An allele is a piece of a chromosome on which is contained a gene, and that may be silenced or made nonfunctional depending on the sex of the parent who contributes it to the finished product.  So imprinting is a very important determinant of how we are as a male or a female.

DAVID R. MARKS, MD:  What are some of the tasks that women may be better at than men?  Or men are better?

BENJAMIN LEWIS, MD:  Tasks as far as --

DAVID R. MARKS, MD:  Dr. Legato mentioned that some tasks are performed differently.  What are some of these?  Just examples.

BENJAMIN LEWIS, MD:  In terms of neurochemistry?

DAVID R. MARKS, MD:  Mm-hm.

BENJAMIN LEWIS, MD:  I'll let her speak to that, because that's actually fan area that she's more familiar with.

MARIANNE LEGATO, MD:  The question of whether women are more verbal and communicate more effectively and men are better at spatial tasks like negotiating through a three-dimensional space or rotating an object mentally in their minds through three dimensions is definitely different between men and women.  The difference is tiny but significant, and the overlap is great.  That doesn't mean women can't be physicists and men can't be poets, obviously, but there are real differences in basic expertise between men and women.

DAVID R. MARKS, MD:  There are some other things, other differences: saliva, metabolism.  What do those entail?

MARIANNE LEGATO, MD:  Saliva is quite interesting because the Procter & Gamble people with whom I spoke when we tried to found the Partnership for Women's Health were experts in dental care, and the R&D people there were unaware of the fact that salivary composition and flow rate was different in men and women, and one of the ways we got them interested in gender-specific biology as a way to making better products was to show them some of these differences.  Your flow rate is twice mine.  The ionic composition in the glucose content of our saliva is different, yours and mine, and women's salivary composition actually varies as a function of their menstrual cycle, which is kind of fascinating.  So maybe his and her toothpaste is a way to go.

DAVID R. MARKS, MD:  Dr. Lewis, is there any idea just from an evolutionary standpoint why we'd have these disparities?

BENJAMIN LEWIS, MD:  I don't know that there's any specific why there should be a distinct advantage evolutionarily.  I think that we could speculate that it's in part hormonal, but I'm not sure that I can think of an obvious reason it should be selectively advantageous.

DAVID R. MARKS, MD:  Just that's the way it is?

BENJAMIN LEWIS, MD:  I think someday I'm sure we'll know.  For now, we're almost in a period where so much is not known about women, again, because of the bias in studies not to be done on women, that a lot of this is observational, and I think from those observations will come mechanisms.  But I think we may have to work backwards a little bit.  Again, we can't assume that women are small men, and as a result I think a lot of this research really is going to go forward based on observations first.

MARIANNE LEGATO, MD:  A kind of interesting thing about the primitive parts of our brain is that at rest men's limbic system is most ready to achieve instant activity, a physical response in response to a stimulus.  The woman's base basal resting state is much more attuned to differences in expression and communication.  Evolutionarily speaking, that might help a man who is the stronger, larger part of the duet to respond to a physical threat, while the woman is much more attuned, say, a child or a member of the group's distress or pleasure, as she is the caretaker.  That's a very simplistic notion, but there might have been some selection of these differences over the millions of years of evolution.

DAVID R. MARKS, MD:  And then we are just finding out the results of these differences.

MARIANNE LEGATO, MD:  Yes, exactly.  As I said, they're very, very tiny, but they are significant and they're fascinating.

DAVID R. MARKS, MD:  And we'll be finding out more, I would assume, over the next few years as more study results come through?

MARIANNE LEGATO, MD:  Yes.  That's the name of the game.

DAVID R. MARKS, MD:  Thank you both for joining us.  Thank you for joining our webcast.  I'm Dr. David Marks.  Goodbye.

TRANSCRIPTION OF VIDEO 4+  DAVID MARKS, MD:  Hi, and welcome to our webcast.  I'm Dr. David Marks.  It's not fun to think about, but some day you might not be able to speak for yourself, and if you're sick and need medical care, you need somebody to stand up for you.  So the truth is now is the time to think about who that someone will be. 
To help us talk about this, we have two healthcare attorneys.  First is Aytan Bellin.  He's a healthcare attorney here in New York City.  Welcome.

AYTAN BELLIN, JD:  Glad to be here.

DAVID MARKS, MD:  With him is David Hoffman, another attorney in New York City who specializes in healthcare law.  Thank you.

DAVID HOFFMAN, JD:  Nice to be here, David.

DAVID MARKS, MD:  So, obviously, we need to have somebody stand up for us if we can't speak.  What are the vehicles to do this?

AYTAN BELLIN, JD:  All the states in the union, all the 50 states, have something called "healthcare proxy."  What a healthcare proxy is, it's a way of appointing someone to be your healthcare agent, to make healthcare decisions for you should you be incapacitated and unable to make them for yourself.  Basically, usually these healthcare proxies consist of a form that you fill out naming the people who you want to be your healthcare agents to make these decisions should you become incapacitated.

DAVID MARKS, MD:  More than one person?

AYTAN BELLIN, JD:  Usually the way the work is you appoint one person.  Some states allow you to appoint alternate agents in case the one person you've appointed is unable to serve as your healthcare agent.

DAVID HOFFMAN, JD:  This mechanism goes by different names.  In some states they're called "living wills."  In other states they're called "durable powers of attorney."  It can literally be any vehicle, varying from state to state, but any vehicle that enables you to both express your wishes -- what you want done in a particular circumstance -- and also to identify someone that your doctors and hospitals can turn to to get decisions about medical treatment in those situations where you haven't expressed any wishes.

DAVID MARKS, MD:  Is there a difference between healthcare proxies, livings wills, durable powers of attorney?

AYTAN BELLIN, JD:  Yes.  A healthcare proxy, as I said before, is usually when you appoint an agent to make healthcare decisions for you should you become incapacitated.  Living wills are documents in which you list your treatment preferences should you be on some sort of life support or need life-sustaining treatments, and there you, rather than a healthcare agent, make the decision.  You list in advance what sorts of treatments you want.  For example, someone could say, "If I become incapacitated, if I'm in a coma, I don't want to be put on a respirator.  I'd rather be taken off of the respirator."  And that's you making the decision rather than a healthcare agent.

DAVID HOFFMAN, JD:  But these documents need to be both specific and general at the same time, so you have to exercise some care in filling them out.

DAVID MARKS, MD:  What do you mean by that, "specific and general?"

DAVID HOFFMAN, JD:  For example, if you put in a healthcare proxy that "If I am ever terminally ill and there's no hope of a cure, I want all medical intervention to be terminated."  If you then find yourself, as a result of a head injury, in a coma, that's not a terminal illness.  Many states have interpreted advance directives, whether they're healthcare proxies, living wills, or durable powers of attorney, very specifically so that if the circumstance that you describe in your advance directive doesn't precisely fit with the circumstance you find yourself in, it will be considered inapplicable, putting you back in the same boat you'd be in if you didn't have an advanced directive at all.

AYTAN BELLIN, JD:  That's why some practitioners believe that healthcare proxies are probably the best advanced directive to use.  There are different circumstances that might call for something else, but with a healthcare proxy, the agent is appointed, and the agent is the one who can make the decision for you.

DAVID MARKS, MD:  The person.

AYTAN BELLIN, JD:  The person.

DAVID MARKS, MD:  The family member, loved one --

AYTAN BELLIN, JD:  A family member, a friend, a loved one.  Actually, that's a very important point.  When appointing who to appoint as an agent, you should really appoint someone whom you trust, who you've shared your values with and who you know will be able to make the decisions necessary to carry out your wishes?

DAVID MARKS, MD:  How do you go about finding a healthcare proxy or assigning one?

DAVID HOFFMAN, JD:  The actual form can be obtained from the state websites for most of the jurisdictions in the United States, and they include instructions on how to select an individual, who's the best person to have as your healthcare proxy.  Sometimes it's a spouse, sometimes you're better off having someone other than your spouse acting as your healthcare agent.  The healthcare agent also has to have some instructions about what your values are.  That can be in writing, but it can also be on the basis of conversations.  But what it is important for your healthcare agent to know is under what circumstances would you want all the heroic measures modern medicine has to offer, and under what circumstances you would want your healthcare agent to say, "Enough.  This is not the quality of life that my sister/wife/mother would have wanted.  It's time to stop."

DAVID MARKS, MD:  And obviously you have to tell the person that you want them to be your agent.  You can't just write down on a piece of paper, "My wife is going to be my agent," without her knowing about it, right?

DAVID HOFFMAN, JD:  It's critically important that you fill out the form, that you talk about these subjects with your entire family, not just the agent, and that there be copies of the form in as many places as possible, because one of the most difficult circumstances we run into in hospital settings is that a patient will arrive in the emergency department, certain emergency measures have to be instituted as soon as a patient arrives, and only afterwards does somebody show up with a copy of the healthcare proxy or a living will, and we find out the patient would not have wanted, for example, to be intubated or to be hooked up to an artificial feeding tube.  So it's important that that information be available.

It's also important to remember that it doesn't have to be on an official government form.  Any sort of representation of what your wishes are is valuable.

DAVID MARKS, MD:  Do you have to see a lawyer or see an attorney for this?

AYTAN BELLIN, JD:  Not necessarily.

DAVID MARKS, MD:  Now they have will maker software out there.  Can you do it just on your own, even writing on a piece of paper?

AYTAN BELLIN, JD:  For some healthcare proxies there are actual requirements, like having it witnessed by two witnesses.  I know that's the way it is in New York State and, I imagine, some other states have that as well.  Certainly, if you write out your wishes on a piece of paper, that's always important, but I think it is important to check, as David was saying, with the specific rules in your state.  Go on to the state website, or go on to the of Choice in Dying, Partnership for Caring, and they have instructions and the forms for every single state in the union.

DAVID MARKS, MD:  Talk about the importance, again, of filling something like this out.  I mean, a person could conceivably not want to be on life support, and if they never spoke to their family, they could end up on life support.

DAVID HOFFMAN, JD:  Absolutely.

DAVID MARKS, MD:  And I'm sure you're seen this before.

DAVID HOFFMAN, JD:  We've encountered lots of situations where family members will appear before a hospital ethics committee and explain what they know about their loved one's values and concerns about artificial nutrition and hydration, about artificial ventilation, and yet they don't have the specific information about what the patient would want in a given circumstance.

The opposite is also true.  Sometimes we find family members coming forward with the most unusual forms of advance directives.  One that sticks in my mind and I think about often, we had a family come to an ethics committee at a hospital that I represent with a copy of an Ann Landers column about termination of life support, and in the margin of the column, the patient wrote out years and years prior to the incident that arose, "Dear my son, my daughter, husband, sister, wife" -- long list of names -- "This is what I would want."  And from that we were able to discern that this patient, as a matter of personal conscience, would not want artificial nutrition and hydration if the condition were terminal such that there was no hope of returning to their prior quality of life.

AYTAN BELLIN, JD:  I think an important thing, also, to remember about healthcare proxies is that it's not only a document.  These documents are not only ways for indicate when you'd want certain treatments taken away from you.  They're also ways in which you can indicate what treatments you actually would want in certain circumstances.  Some people, because of personal beliefs or religious beliefs, might want to be kept on respirators and might want to get artificial nutrition or hydration even if they were in a coma.  So it's important to know that whatever your treatment wishes are, you can put them down in these documents.

DAVID MARKS, MD:  When should people start thinking about assigning a healthcare proxy or filling out a living will?

DAVID HOFFMAN, JD:  Today.

AYTAN BELLIN, JD:  You can't do it any earlier.  Today.

DAVID MARKS, MD:  The reason being?

AYTAN BELLIN, JD:  You just never know what circumstance you're going to find yourself in, and at whatever moment it becomes an issue in your life, that's the moment to take action, because most often, when we meet with families and discuss what the patient's wishes were, they'll tell us, "We talked about this, but we never put it down on paper, but when Uncle Sam was sick and he was in a coma for six months and he was having seizures, everyone said, 'I would never want to be like that.'"

DAVID MARKS, MD:  Okay.  Great.  Thank you very much for being here.  Don't leave it up to an Ann Landers column.  Think about it now, if you have to see an attorney, but do it as soon as possible.  I'm Dr. David Marks.  Goodbye.

TRANSCRIPTION OF VIDEO 6+  MARK POCHAPIN:  Welcome to our webcast.  We're going to talk about a topic that is becoming more commonplace with increasing and improved surgical and medical techniques.  That is transplantation.  Organ transplantation we often think is something that really belongs in science fiction.  But in fact, in 1998, there were 21,000 transplants performed, and over 64,000 patients were awaiting transplants.  With me today are two people who know quite a bit about transplantation.  A friend and colleague, David Pearl, who works with me, is a liver transplant recipient.  He is an ultrasound technologist at New York Presbyterian Hospital.  Welcome, David. 
DAVID PEARL:  Thank you.

MARK POCHAPIN:  Sitting next to David is Julia Grivera.  She is a professional educational specialist at the New York Organ Donor Network and is here to talk to us, as well.  It's nice having the two of you.

David, let's focus on your story for a little bit.  The reason I say "story" is because it really is quite a thing.  We've discussed this in the past -- we've presented it to some of the medical students -- but I think it's important for people to understand what you went through.  Currently you're an ultrasound specialist and you perform ultrasound on many people -- in fact liver ultrasounds, right?  But that wasn't always the case before you were quite ill.  I want to go back to the beginning of when you were diagnosed initially with not liver disease, but intestinal disease.  Tell us a little about that.

DAVID PEARL:  At the age of 18 I was diagnosed with colitis, which is basically an autoimmune disease where your body attacks your own intestines.  Initially, it was just the colitis, but they realized that some of the inflammatory process had worked its way into the liver and was attacking my liver.  I was diagnosed with an autoimmune disease called sclerosing cholangitis.

MARK POCHAPIN:  How old were you at that time?

DAVID PEARL:  I was 18 years old.

MARK POCHAPIN:  So you were 18 when you were diagnosed with the liver disease or with the colitis?

DAVID PEARL:  With the colitis and the liver disease at the same time.  Possibly the liver disease a few days later.  They had done a liver biopsy and they diagnosed me with the liver disease.

MARK POCHAPIN:  Now, the sclerosing cholangitis, as it's called, is a liver disorder.  What did they tell you when you had the diagnosis of this?

DAVID PEARL:  Actually, they really didn't handle it very well with an 18-year-old.  They had told me that they were doing a lot of research and that they didn't know what would happen down the road but that they had hoped that transplant would evolve to give me my life back.

MARK POCHAPIN:  So at this point, what year are we talking about, approximately?

DAVID PEARL:  This was, I think, in '75, '76.

MARK POCHAPIN:  So liver transplantation was really just something that people spoke about but wasn't, in fact, reality at that point.

DAVID PEARL:  Right, because they hadn't come up with the magic drugs to ward off the rejection.  They were just doing kidney transplants at the time.

MARK POCHAPIN:  So what happened to you clinically?  What type of symptoms did you develop?

DAVID PEARL:  With the combination of the colitis and the liver disease -- sclerosing cholangitis is a very slow-moving disease.  It's something that doesn't sneak up on you quickly.  It works very slowly.  So that wasn't so much of an issue.  Occasionally I would have bouts of jaundice, some fatigue and stuff like that.  But the colitis at that point, until they got that under control, was more of a difficulty -- frequent bowel movements, weight loss, trouble eating -- that was the issue at that point.

MARK POCHAPIN:  When did the liver issue become more of a problem, something that was not easily handled?

DAVID PEARL:  Actually, they were watching my enzymes as I saw a gastroenterologist through the years, and my liver enzymes were starting to bump up and get elevated.  I'd actually gone out to Minnesota, to the Mayo Clinic, to look at the transplant team out there.  I guess I was an educated consumer, but I was a little leery about being transplanted in New York.  Being a native New Yorker, maybe I thought if they couldn't fill the cracks in a street how could they give me a new liver?  So after I came back from Minnesota a few months later, I had gone up to Mount Sinai and I met the transplant team up there and I was very impressed with how well they had handled everything and spoken to me, and I was pretty comfortable with them.  Actually, the day after I saw the transplant team I had a bleed, an esophageal bleed.

MARK POCHAPIN:  What does that mean?  It means you were vomiting blood?

DAVID PEARL:  I was throwing up blood, projectile blood, which is very dangerous.  It's very easy for you to bleed to death at that point with a bad liver.

MARK POCHAPIN:  The medical term is called a variceal bleed, and the varices are due to the increased pressure in the liver trying to get the blood away from the liver, and the way we're wired up, it forms around the esophagus.  So you had a major life-threatening bleed the day after, in fact, you had seen this transplant service in New York.  Now, what year are we talking about?

DAVID PEARL:  This was December of '91.  It was the day after Christmas, December 26.  My wife was out -- she's a nurse -- she was out with a friend who is a doctor, actually -- and I just started throwing up blood and I had seen the transplant team the day before.  I called them up and they told me, "Get into the city right now."  Some of my friends drove me into Manhattan.  It was a gastroenterologist was trying to stabilize me at that point.  They were trying to tie off the varices in my throat and get me stabilized and assess the situation at that point.

MARK POCHAPIN:  Now, how long did you stay sick to the point where you finally did get a liver transplant?

DAVID PEARL:  I was sick, badly sick, from that day of the bleed until the transplant.

MARK POCHAPIN:  How did it come about that you found out you got a transplant?  Was it something that came about at a time when you were really critical, or could it have waited longer?

DAVID PEARL:  When I had the bleed, from what I understand, I don't think they would have wanted to transplant me.  They wanted to stabilize me.  I had blood clots in my lungs.  I was critical.  They had to get me a little bit more stable and put me on the list.

MARK POCHAPIN:  But you were in a life and death situation at this point?

DAVID PEARL:  Yes, yes.  What happens is, until you get the new liver, it's always life or death, because you could always have the next bleed, and the next bleed could be the one.

MARK POCHAPIN:  So did you think that you were going to die at that point?

DAVID PEARL:  I thought it was a good possibility.  I was pretty concerned.

MARK POCHAPIN:  So what happened?

DAVID PEARL:  What happened was, I went to the transplant clinic up at Sinai every six to eight weeks and watched my blood work, and I had to go back to work.  I had two kids, a wife, a house to support.  I couldn't stay home and wait for a liver.  I think it probably would have driven my crazy.  Probably my wife would have killed me, also.  But I had to go back to work.  I went back to work every day wondering if I was going to get a call.

MARK POCHAPIN:  So you were just waiting for a phone call.

DAVID PEARL:  Carrying a beeper and hoping that the phone would ring, yes.

MARK POCHAPIN:  What happened?

DAVID PEARL:  There is a picnic that they have every year or so up at Central Park for the Sinai transplant services.  I was on the list.  I was on for nine months at that point, and they knew that I was near the end.  I was going to meet somebody who worked for the New York donor network who is a heart recipient.  I was going to do a donor booth.  I wanted to try to raise awareness about the donor shortage.  They procured the liver that night.  I went home and got transplanted on my birthday.  Actually, the phone call occurred on my birthday, and they bring you in that night.  They brought my immune system down and started the pre-op stuff.  I got transplanted the day after my birthday.  I got the call on my birthday, and it was quite a nice birthday present.

MARK POCHAPIN:  What happened afterwards?

DAVID PEARL:  The road back was hard.  It's probably one of the biggest and hardest surgeries to undertake as a patient.  But I was back at work in four months at New York Presbyterian Hospital, and now I get to do the ultrasounds on the patients that are waiting, so it's quite ironic.

MARK POCHAPIN:  You got the transplant through someone else's misfortune.  We've talked about this before, but how does that make you feel?  What is that like?

DAVID PEARL:  It's actually hard to know that somebody died so that you could live, but you have to understand, there's always going to be people in car accidents and skiing accidents and pedestrian accidents and bicycle accidents.  At that point there's nothing that they can do for that person.  If that person is brain-dead, there is absolutely no chance of recovery.  It's not a coma.  They're on life support and there's nothing that's going to bring that person back.  Eventually all the organs will fail and the person will be buried with their organs that could have saved eight lives, 10 lives.  I feel awful for them, but I'm grateful for their decision.

MARK POCHAPIN:  What has happened to your life since then?  I know there was quite a blessing in life afterwards.

DAVID PEARL:  As I said, I went back to work after four months.  Eight months after my transplant I was backpacking in upstate New York, and three years later I had a daughter, Melanie.  She's unbelievable.  I had two sons before her, and they are just as cherishable.  They gave me my life and gave me my daughter and let me watch my children grow up.  It's fantastic.  You can never get a gift like that.

MARK POCHAPIN:  What would you say to the family that was involved in this donation, the donor family?

DAVID PEARL:  I've written them letters, and the reply was very favorable, and they knew that they had made the right decision.

MARK POCHAPIN:  Do you have a letter with you?

DAVID PEARL:  I have a letter, and they're very supportive of me, and they were very happy.  When I was transplanted in '92, there wasn't as much emphasis to try to make the circle complete.  But they've found now that a lot of the recipients and the donors want closure.  They want them to know that they had made the decision, that it was the good thing to do.  It was the right thing to do.  Out of all the heartache that they were going to face and the long road for their recovery, that somebody else was able to benefit from such a tragic thing.  That is, in essence, organ donation.  Somebody benefitting from a horrible incident where it's a lose-lose situation, maybe, for that family, and the other families that get transplanted, it's at least win for them.

MARK POCHAPIN:  It's life.

DAVID PEARL:  It's life.

MARK POCHAPIN:  David, do you want to share the letter that you wrote to the family?

DAVID PEARL:  Sure.  I have two letters that I wrote.  This is the letter that I wrote.  I unfortunately didn't bring the reply, but this was printed in a hospital activities thing that was sent out to all the people that work at New York Presbyterian.  It's called "The Recipient's Appeal."

"Dear Donor Family:

"It has been five years since our lives had crossed, and I must apologize for not writing sooner.  I am sorry for your loss.  Your family reached out from within at a time when most are not thinking of giving, when you had lost so much, and you gave.  You gave me life, and I will be forever grateful.  Thank you.  Please rest assured that I will safeguard and cherish this gift you have bestowed on me.  I hope you can be somewhat comforted by the fact that after I received my new liver on my birthday I returned to a completely normal life.  I continue to work and enjoy my family, but there is never a day that I fail to understand where I have gained so much, another has lost so much.  Life is precious.  Thank you for giving me back mine."

I got a beautiful reply from that, just very supportive.

MARK POCHAPIN:  It's an unbelievable letter.  So many of us take so much for granted every single day, and one thing I've learned from you, David, working with you is that every day is precious to you.  It's unfortunate that people have to go through these types of things to appreciate that component, but it is unbelievable that a family could offer you so much and, knowing you and being friends and working together, how much you give back.  I know patients who you do the ultrasound on, specifically for liver, are always amazed when they find out that you yourself are a liver recipient.

DAVID PEARL:  We've been doing a lot more liver transplants, and they've been coming for sonos.  They usually come and they say, "Give me the guy with the new liver."  It's nice.  They might be freshly transplanted and they might not have their strength and they might not be doing well at the time.  It's very nice for them. Kidney patients, too.  They come in... and they're not doing well, and I'm very supportive to them, and I visit patients occasionally.

MARK POCHAPIN:  Now, Julia, this is not an uncommon story.  You've heard this before.  I know you're involved with both a lot of donors and recipients and do a lot of education.  What is your impression on people who receive the organs?  Are they all as grateful as David?

JULIA GRIVERA:  Absolutely.  It is the greatest gift, and it's the miracle of life.  You see how our recipients take time.  First of all, there's an appreciation of life that is different from they way most of us handle life.  Second, there is an appreciation to share with others that very special story that upon death one can give life.  We come across that story all the time, and it becomes even more significant when we begin to bring families together, the recipients and the donor family members that made a very special decision.  As you were saying, it's the true Samaritan, the person that gives when they're in the middle of pain and sorrow, when they've crashed through the emergency room and all they're thinking is, "I want my loved to live."

MARK POCHAPIN:  It's hard to think about someone else at that time.

JULIA GRIVERA:  Absolutely.  And yet they do.

MARK POCHAPIN:  David, obviously, wants to reach out to the donor family.  Is this common, and how do they do it?

JULIA GRIVERA:  It starts with a letter.  David has received answers, right?

DAVID PEARL:  Yes.

JULIA GRIVERA:  It takes a while, once the family is comfortable.  Sometimes the family will tell the recipient in correspondence that they are ready to have that meeting.  Then the New York Donor Network works very closely with the transplant center and we're able to pull the families together.

MARK POCHAPIN:  Thank you both so much.  Thank you for sharing your story.

DAVID PEARL:  A pleasure.

MARK POCHAPIN:  We appreciate our audience joining us.  A very moving story.  It's hard to imagine that something so tragic can be converted to something that's so wonderful, that is, someone who donates an organ at a time when a family is in such grief can really give life, and something that we should all remember and keep in mind, and cherish our own lives every day.  I'm Dr. Mark Pochapin.  Thank you for joining us.

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Why Should Doctors Read Medical Books?
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Too often, it is the fashion of teaching at the bedside as well: "Name three other things that present like " or "List five etiologic factors in." One might object to calling this an approach to knowledge, saying that it does not produce literate, erudite, scholarly, intellectual, or polished physicians—words usually associated with the idea of knowledge. In fact, knowledge is not the word most often used to describe what is necessary to answer examinations, bedside quizzes, or even the questions of patients. What is wanted is information, and information is just what we get. Information is available everywhere you look or listen, it pours out at us from every crack and cranny. Make no mistake, I believe that this endless flow of information is marvelous, but there are problems.
Access to even the most technical information is inherently democratic; it is there for everyone. In fact, well-informed patients are no longer the exception. The effects of widespread dissemination of and easy access to information about medical science must give us pause. If the facts about medical science do the work in medicine, information about these facts should, like the Colt revolver of old, be the great equalizer, leveling distinctions between physicians and nurse practitioners, physician assistants, and even educated consumers. This implies that the physician is secondary in the care of patients: same science, different physician, same care. This ideological belief dies hard—witness the implications of the rise of practice guidelines and the call for evidence-based medicine.
The idea of an almost autonomous medical science is linked to the concept that physicians treat diseases, an understanding that held medicine in its thrall from the 19th century until it started to wane only a few decades ago. We know now—in fact, clinicians have always known—that physicians treat patients, some of whom have diseases and some of whom do not. In the past few decades, the patient has increasingly assumed center stage, and it can be said that this has been the century of both medical science and the centrality of the patient. The increasing importance of the patient is seen in the patient-centered care movement, contemporary consumerism, the rise of bioethics, debates about the right to refuse treatment, and the assisted suicide controversy. It is also known that the nature of the person in whom a pathophysiologic process is taking place modifies its onset, diagnosis, treatment, course, and outcome. This is true for acute diseases and is a central fact of the chronic illnesses with which physicians are increasingly concerned.
All of these developments mean that to treat patients most effectively, the physician must understand persons both sick and well, which requires much more than just information about medical science. It demands knowledge of illness, judgment, decision-making skills, and the ability to command technology and apply the advanced therapeutics of today's medicine. Many of these skills used to be called the art of medicine, but this romantic notion is no match for the environment of science and technology in which we practice. Many components of what might be called the clinical method—the skills and understanding that physicians need to best apply medical science to their patients—are just coming into their own, such as clinical epidemiology or communication. Others, such as the place of narrative in medicine, are only now being written about.
For clinicians, an adequate understanding of the psychology of illness and behavioral medicine remains barely visible. At the same time, aspects of molecular medicine new enough to be a mystery to many physicians are on the rise. The knowledge needed to apply modern therapeutics is well beyond that possessed by second-year pharmacology students, just as the understanding required to make the best use of diagnostic technology cannot be acquired by standing around a view box (important as this activity may be). To remain a good clinician, much new material must be learned.
With new kinds of knowledge making their debut in medicine, the problem is no longer merely absorbing an ocean of facts but rather figuring out how the new knowledge fits with the old. Real learning requires personal change. If that does not happen, the new knowledge has not become part of a person's basic understanding. A good example is the common experience that physicians do not pay attention to patients' desires not to be resuscitated. A recent study documented this fact, to the consternation of the public (1). Did this happen because these physicians do not care about the wishes of patients or because they do not know that patients have the right to refuse treatment? I think not. It reflects the fact that physicians do not know how, in terms of their medical actions, to make the patients' desires, needs, concerns, or wishes central. All of our long training has concentrated on the centrality of disease and medical science, learned decision making, automatic behaviors, rules of thumb, and algorithms. Too many of us have not yet incorporated the basic concepts of contemporary medicine into the matrix of ideas and actions that determine our treatment of patients rather than their pathophysiology.
How will physicians learn to change the focus of their actions and acquire the new knowledge and clinical skills needed to place the patient rather than the disease in the center of their thoughts? I do not believe that this will happen by scooping up information, even by the bucketful and from no matter what source. It is necessary to read books.
To prepare this essay, I went to the bookstore and looked at many textbooks of medicine. They reminded me of the Irish elk of evolutionary fame whose antlers, it is said, became ever larger in the course of its evolution until it could no longer get through the forests and perished from the earth. Aside from the immense size of medical textbooks (which requires that some of them have smaller books to tell you what is in the larger book), I believe that I can generally get what is in them from my computer at a similar speed. It is natural that they should have evolved in this fashion because their task has been to describe human disease in depth and give the associated details of pathophysiologic mechanism. These days, that takes up a lot of space. Clearly, these are not the books from which one can learn to reformulate one's actions.
The form and content of medical books, naturally enough, reflect the dominant theory of medicine of the era in which they are written. Typical of its era is Typhoid Fever and Typhus Fever (2) by H. Curschmann, translated from the German and edited by William Osler and published by Saunders and Company in 1901. This book contains precise, in-depth descriptions of typhoid fever and typhus fever and discusses their cause, pathology, diagnosis, prophylaxis, and treatment. Osler's textbook (3) was cast in the same mold. At that time, medical attention focused on diseases; the theory of medicine that arose early in the 19th century held that sick persons had a disease and that disease could be discovered by finding the structural (later, biochemical) abnormalities that characterized it. The idea of pathophysiology and the importance of mechanisms of disease began to take hold early in the 20th century and became entrenched by the 1950s. Books changed to reflect the new emphasis. When Homer Smith (4) wrote The Kidney in 1951, he did not merely describe various renal diseases. Instead, he illustrated the physiology of the kidney in mathematical terms, according to the growing ideal that biology should approximate physics. Physician-readers of such books struggled with the formulas (such as that for creatinine clearance) while they absorbed the new perspective on medicine. The same ideas ultimately became the basis for the current textbooks of medicine, and the streams of information that reinforce these same theories continue to dominate our thinking.
Now that knowledge is again changing, newer books focus increasingly on the centrality of the patient.The opening chapters of modern textbooks of medicine often offer excellent discussions about patients, medicine, and the experience of being a physician, subjects absent from Osler's textbook of medicine. (I am surprised that nobody has collected these often wonderful essays into the book of their own that they deserve.) More important, however, are the books about medicine that have appeared in the past decade or so that focus on the patient; these provide a perspective on and a way of understanding medicine found nowhere else. The Meaning of Illness (5), by S. Kay Toombs, is an excellent example. A philosopher with a highly readable writing style, Toombs has multiple sclerosis. Her book is an introduction to what illness means to the patient on many levels. Because of Toombs's training, keen intellect, and wit, the reader learns about the life world of the patient and how it contrasts with the technical world of physicians (toward whom she is sympathetic and about whom she is very knowledgeable). Just as the early pathologists taught clinicians how to look at diseases, books such as Toombs's teach us how to look at ill persons. Unlike the profusion of biographies of patients with illness, The Meaning of Illness is about illness and medicine, not its author. Although Toombs uses her experience with multiple sclerosis as the lens, she herself is barely visible. I cannot recommend this book too highly.
Much can also be learned from biographies of patients with illnesses, but there are so many that it is difficult to know where to start. Fortunately, Anne Hunsicker Hawkins (6), in Reconstructing Illness, provides an analysis of the genre that makes the task of deciding which books to read much easier. Howard Brody's Stories of Sickness (7) is a slim but substantive book that examines the meaning of illness from a philosophical and a medical perspective. Brody, a philosopher and a practicing family physician, shows how these disciplines enrich each other. In his book, one discovers many of the underpinnings of the current emphasis on narrative in medicine as he examines sickness from the point of view of the patient and of a person in a social world. Arthur Kleinman's The Illness Narratives (8) is another important work. Kleinman is a psychiatrist and an anthropologist; because of this dual background, he is keenly aware of the importance to patients of the meaning of their illness. Everyone, including physicians, reacts to objects, events, and relationships on the basis of what they mean personally, rather than on the basis of some objective standard for external reality. To act effectively for patients, clinicians must understand these meanings. One cannot finish Kleinman's readable book without comprehending what meaning-centered medicine is and the challenges it presents to our profession.
Physicians illustrate the meaning of events for each other by telling stories; in fact, medicine is awash with stories. We have heard of the dangers of anecdotal medicine, actions based on a series of one case, but I think an equivalent problem is that we do not know how to construct a good anecdote. Katherine Hunter's Doctor's Stories: The Narrative Structure of Medical Knowledge (9) confronts that problem head on. From a background in English literature, Hunter writes engagingly about what medical narratives are, their uses in day-to-day medicine, and their importance for understanding the work of physicians. She shows convincingly how much more could be done with narrative to understand patients, physicians, and the work of the medical profession.
All of the aforementioned books are well-written, highly readable accounts of a new trend in medicine. In this view, what happens to the patient in the course of the illness is an unfolding story into which physicians, medical science, and other caregivers enter and become participants. Successful outcomes are not cures, but a life of personal and social function continued to the degree permitted by the disease. The narrative of the illness after treatment should be free of suffering and unnecessary symptoms and coherent with the patient, even in terminal illness. Because of this trend, do not be surprised to see the narrative history and physical examination ultimately replace the current, disappointing problem-oriented record.
The centrality of the patient has become part of books devoted to technical medicine. For example, in Russell K. Portenoy and Ronald M. Kanner's Pain Management: Theory and Practice (10) and Alexander Waller and Nancy L. Caroline's Handbook of Palliative Care in Cancer (11), the underlying assumption is the central importance of the patient. In Ira Byock's Dying Well (12), the narrative and the technical aspects of medicine come together. Byock has written a series of engaging case reports about palliative medicine from which one can learn a great deal about caring for the dying in ways that enhance rather than diminish them.
Returning to the patient is also the compelling and unspoken theme of a unique book that demands special notice. Joseph D. Sapira's The Art and Science of Bedside Diagnosis (13) may be the most readable, aesthetically pleasing, and fact-filled physical diagnosis book ever written. By mentioning this book, I mean to make it clear that the centrality of the patient does not mean just the patient's narrative or the patient's psychology; it means all of the patient, body and soul, from the mitochondria to the community and every part in between.
One more thing: Evidence-based medicine, clinical guidelines, critical pathways, and the like are intended to ensure that physicians do the right (evidence-supported) thing for their patients. These systems for organizing modes of treatment, for all the good they may do, have a baleful effect. They are like computerized interpretations of electrocardiograms that ultimately reduce the ability of physicians to read them. They shrivel up the most important tool that physicians bring to patient care: the exercise of rational judgment. The silent theft of the ability to craft sound clinical judgments is best fought by reading medical books. A wonderful antidote to the diminishment of clinical judgment is Advanced Dermatologic Diagnosis by Walter B. Shelley and E. Dorinda Shelley (14). Reading the opening chapters on observation and diagnosis and seeing how the authors use the literature is a joy. The Shelleys open their acknowledgment section by stating that, "Thought doesn't grow on trees. It grows in the library."

Eric J. Cassell, MD

Cornell University Medical College 
New York, NY 10021
Current Author Address: Eric J. Cassell, MD, Cornell University Medical College, 1550 York Avenue, New York, NY 10021.
Ann Intern Med. 1997;127:576-578. Annals of Internal Medicine is published twice monthly and copyrighted © 1997 by the American College of Physicians.

References
1. A controlled trial to improve care for seriously ill hospitalized patients. The study to understand prognoses and preferences for outcomes and risks of treatments (SUPPORT). The SUPPORT Principal Investigators. JAMA. 1995;274:1591-8. 
2. Curschmann H. Typhoid Fever and Typhus Fever. Translated by W. Osler. Philadelphia: Saunders; 1901. 
3. Osler W. The Principles and Practice of Medicine. New York: D Appleton; 1892. 
4. Smith HW. The Kidney: Structure and Function in Health and Disease. New York: Oxford Univ Pr; 1951. 
5. Toombs SK. The Meaning of Illness: A Phenomenological Account of the Different Perspectives of Physician and Patient. Boston: Kluwer; 1992. 
6. Hawkins AH. Reconstructing Illness: Studies in Pathography. West Lafayette, IN: Purdue Univ Pr; 1993. 
7. Brody H. Stories of Sickness. New Haven, CT: Yale Univ Pr; 1987. 
8. Kleinman A. The Illness Narratives: Suffering, Healing, and the Human Condition. New York: Basic Books; 1988. 
9. Hunter K. Doctor's Stories: The Narrative Structure of Medical Knowledge. Princeton, NJ: Princeton Univ Pr; 1991. 
10. Portenoy RK, Kanner R. Pain Management: Theory and Practice. Philadelphia: FA Davis; 1996. 
11. Waller A, Caroline NL. Handbook of Palliative Care in Cancer. Boston: Butterworth-Heinemann; 1996. 
12. Byock I. Dying Well. New York: Riverhead Books; 1997. 
13. Sapira JD. The Art and Science of Bedside Diagnosis. Baltimore: Urban & Schwarzenberg; 1990. 
14. Shelley WB, Shelley ED. Advanced Dermatologic Diagnosis. Philadelphia: WB Saunders; 1992.

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