分节阅读 Table of contents

• 1.INTRODUCTION

  • Dr. Mukherjee learns a hard truth about medicine.
    
    Many years ago when Dr.Siddhartha Mukherjee started his medical career in Boston, he was witness to a life-altering surgery. This is that story:
    
    Dr.Castle was the perfect senior surgeon. It was hard to work under him but, at the same time, it was an honor.
    
    One day, a woman was brought into surgery to have a tumor removed from her lower intestine. The resident assigned to the surgery called out sick, so a new resident was rushed in to replace him. Everything started off fine. The resident was talented and Dr.Castle watched over him like a hawk.
    
    Suddenly, the patient turned. The blood vessels around the tumor began to bleed. The resident struggled to stop the bleeding. A flood of blood blocked the tumor from being removed. The resident became flustered and shaken. He looked around helplessly, asking for information. He called out, "Does this patient have a known bleeding disorder? Was she on a blood thinner?" This not being his patient, he didn't have the answers himself.
    
    Dr.Castle turned to him and calmly asked, "What if you didn't know?  What if I told you I didn't know?"
    
    This time, the resident changed his approach and worked slowly around the blood vessels, treating each and every one delicately as if they might bleed any second. It took much longer to complete the surgery but, eventually, the resident was successful and removed the tumor without further incident.
    
    Dr.Castle turned to the resident and said, "It's easy to make perfect decisions with perfect information. Medicine asks you to make perfect decisions with imperfect information."
    
    This lesson Dr.Mukherjee carried with him to this day. Medical school offered Mukherjee plenty of information and fact. But it did not teach him anything about the spaces that live between the facts. He knows what drugs to prescribe and what the bones of the body are called. But school did not teach him how to deal with a specific leukemia case. How do you understand survival rates when every cancer case is different? How does a doctor wrap his brain around a patient who lies because he is ashamed about his poverty?
    
    The "laws of medicine" as Mukherjee describe them in his story, are really laws of uncertainty, imprecision, incompleteness and imperfection.

• 2.The 1930s and 1940s was the era of revolutionary modern medicine

  • Dr. Mukherjee spent the majority of his time as a medical student surviving his own fatigue and intellectual exhaustion.  He floated through the days, hours upon hours in surgery, barely getting any sleep in between. He didn’t have any personal life to speak of.  He only took enjoyment from two things – jogging and reading “The Youngest Science” by Lewis Thomas. 
    
    Thomas was also a doctor and the book is a tale about his own time as a medical student in the 1930s. He was entering the medical profession at a very exciting time. Before the 30s, medicine was reactionary and treatment was separated into three inadequate categories:  placebo, palliation and plumbing.
    
    Placebos were basically fake drugs that had no effect on patients beyond the psychological. Palliative drugs were real and very aggressive like morphine and opium. And plumbing, of which Dr. Mukherjee named himself, explains the treatments for ailing intestines and stomach. These treatments consisted of laxatives and enemas.
    
    Doctors before the 1930s would use one of these three treatments to tackle all their patients because basically it was all they had.  As Mukherjee puts it, "If you had a hammer, as the saying goes, than everything looks like a nail."
    
    Thomas noticed a shift in tactics during his tenure as a student. New doctors were now stepping back and studying their patients. They watched every movement, wrote down every cough, and made extensive notes. Medicine was changing from reactionary to observation.
    
    Because of this new approach to study, by the 1940s there was an enormous amount of collected information. We now knew why some people suffered heart failure and why some people fell victim to infection. And because we knew why, we could develop specific treatments to cure these ailments.
    
    Thomas wrote, "For an intern it was an opening of a new world. We had been raised to be ready for one kind of profession, and we sense that the profession itself had changed at the moment of our entry… We became convinced, overnight, that nothing lay beyond the reach of the future. Medicine was off and running.  It was the birth of the youngest science."

• 3.Dr.Mukherjee dreams to create laws for medicine

  • After reading "The Youngest Science" many times, Mukherjee was inspired.  He contemplated the science of medicine. Was it a science at all? Physics, mathematics and chemistry are sciences. They are based in crude facts that are unchanging and universal. Two plus Two is always four. And these sciences had their own set of laws like the law of gravity.
    
    But medicine did not have any laws. There weren't any absolutes. What happens with one patient may not happen for another. Mukherjee slowly became obsessed with the idea of discovering laws for medicine. He thought that these potential laws would help future students navigate an already tiring and hard subject. It started off as a small project but, over time, grew into his greatest passion.
    
    The following laws are the product of Mukherjee's research.

• 4.Law One: A strong intuition is much more powerful than a weak test

  • Mukherjee came upon this law by chance. In 2001, early in his career in Boston, a man was referred to him for diagnosis. This man, Mr.Carlton, was losing a tremendous amount of weight quickly and without any known cause.
    
    Mr.Carlton was middle-aged and lived in a good neighborhood in Boston. He seemed to live a normal, healthy lifestyle. He didn't smoke nor did he have a family history of cancer. Cancer was the obvious answer but test after test revealed only negative results. There was no cancer to be found!
    
    Every day Mr.Carlton grew weaker and weaker. His nurses complained that they couldn't draw blood from his shrunken veins. Mukherjee started to think that the answer would not appear before the man was dead.
    
    One day, he passed Mr.Carlton in the waiting room. Mr.Carlton was sitting beside a former patient of Mukherjee who was previously treated for an infection related to heroine use. There was something about the way Mr.Carlton and the man spoke that took Mukherjee's attention. He spent the day pondering his uneasy feelings. What was it that bothered Mukherjee when he witnessed this unusual conversation between a middle-class man and a downtrodden drug addict?
    
    And then it hit him. All the clues fell into place. The weakness, the weight loss and even the shrunken veins had meaning. Whether or not Mr.Carlton actually knew the man sitting next to him in the waiting room was not the point. The image of Mr.Carlton with this drug addict was enough to inspire a new path of inquiry. Mukherjee knew exactly what test to run and his speculation was proven correct. Mr.Carlton was a heroin addict. Mr.Carlton's test results came back positive for AIDS.
    
    "Every diagnostic challenge in medicine can be imagined as a probability game," says Mukherjee.
    
    Here are the steps to the game.
    
    First, you assign the patient a disease after making a good guess. Then, you gather evidence to prove or disprove your guess. This evidence is a mountain of information – a patient's medical history, a doctor's instincts, test results, rumors, hunches and even gossip.
    
    Mr.Carlton wasn't suspected of having AIDS because, at first, the likelihood was so low that it didn't occur to anyone to check. It wasn't until a new piece of evidence fell into Mukherjee's lap as he witnessed Mr.Carlton speaking to a drug addict and the idea came to him.
    
    Why can we not just test for everything, you might ask. A test can only be interpreted sanely in the context of prior probabilities.  It sounds complicated, like a puzzle but the reason for this is that in medicine there is always the risk of false-positive and false-negative results. That means the test gave the wrong answer. Impossible? Not at all! These poor test results happen all the time. Only after taking in the probability of the test result and studying the evidence can we start to believe the results. Perhaps one day we will have perfect tests that give perfect results but that day is not here.
    
    A doctor needs to weigh the evidence and make assumptions. A doctor plays with probability.
    
    This is true not only in medicine but many professional fields. Every banker, stock market trader and weatherman makes his diagnosis based on probability and collected evidence. It is a universal feature of all tests.

• 5.Law Two: "Normals" teach us rules, "outliers" teach us laws

  • Mukherjee starts with his inspiration for Law Two. Tycho Brahe was a famous astronomer in Denmark during the mid- 1500s. Brahe expanded on the work of Greek astronomer Ptolemy and the heretic astronomer Nicolaus Copernicus.
    
    Ptolemy's worked was based on the idea that the Earth sat in the center of the solar system and everything revolved around it. Of course, Ptolemy's theory was filled with holes and he had to explain it by creating ridiculous patterns where planets and suns went around the Earth and also around each other.
    
    Copernicus was much closer to the truth. His theory was that the sun was in the center and the planets revolved around it. But he also suffered from problems with calculations because he thought that the planets made perfect circles around the sun.
    
    Brahe joined both theories. He kept the Earth in the center. This time his theory stated that the sun revolved around the Earth but the other planets revolved around the sun!  His theory was amazing and explained all the movements of the planets – except one!
    
    Mars did not follow the pattern as all the other planets did. Brahe didn't know how to explain Mars so he asked his genius assistant, Johannes Kepler, to solve the problem for him. Kepler studied Mars and the planets for years, even after Brahe died. Then one day it hit him. All the planets revolved around the sun but they followed an elliptical pattern, not a circular pattern!
    
    In cancer pharmaceuticals, when a new drug comes out, 999 out of 1,000 people who take the test drug will still have cancer. Only one may find the drug beneficial. This is a waste to pharmaceutical companies and these trials are considered failures.
    
    In 2009, a young cancer scientist in New York named David Solit decided to run an unorthodox cancer research project. He sought out the sole survivor of a drug trial. After extensive gene research on the survivor he was able to identify two mutated genes, TC1 and NF2, that may have helped her combat the cancer with the aid of the drug.
    
    Solit then cross-referenced these two genes with other patients who had moderately good results with the drug. Some patients shared TC1 with the survivor. In the end, Solit was able to deduce that having TC1 was a good indicator that the drug would cure your cancer.  Imagine! Now you can screen patients to have this mutated gene BEFORE starting the clinical trial. The trial will be more efficient and more successful.
    
    Every theory carries an inherent possibility of proving it false. If medicine is to become a bona fide science, then we will have to take up every opportunity to falsify its models, so that they can be replaced by new and better ones.

• 6.Law Three: For every perfect medical experiment, there is a perfect human bias

  • Every science suffers from human biases. No matter how much data we accumulate, in the end, the results will be handled by a human heart. Doctors suffer from human bias all the time.  They WANT their treatments to work.
    
    In the early 1900s a famous American surgeon named William Halsted became obsessed with the idea that the reason for failed breast cancer treatment was that surgeons did not remove enough cancerous cells around the tumor. He called these "unclean operations".
    
    His response was what he named the "radical mastectomy." He would remove not only the tumor but also parts of the muscles that move the arm, the shoulders and parts of the chest.
    
    Yet his surgery did not always work. Women still relapsed back to cancer. What Halsted was not realizing was that cancer does not just sit in one place in the body but can float around an entire body. But because he believed his own theory so passionately, medical society was convinced around him that he was correct.
    
    Finally, in the 1980s, doctors challenged the painful and radical mastectomy and compared it to conservative surgery with localized radiation. Women recovered or relapsed at the same rates from either treatment. 100,000 to 500,000 women from 1900 to 1985 had radical mastectomies. The procedure is rarely performed today.
    
    To combat these biases in medicine, studies do everything they can to make sure tests are as unbiased as possible. Patients may not even know what study they are enrolled in so that they do not produce their own ideas, theories or feelings. But still, bias exists; someone has to choose the test subject, the test subject has their own set of bias as well. You think the study is random, but is it?
    
    And in the end, the results are still placed in the hands of a human doctor. That human doctor will then interpret the results and, therefore, add their own bias. It is inescapable.

• 7.The "youngest science" is also the most human science

  • History. Outliers. Biases.— These are the simple terms of The Laws of Medicine.
    
    In Philadelphia, a young six-year old girl suffered from leukemia. Doctors harvested her immune cells and created a virus to kill the cancer cells. They injected this virus back into her body.
    
    Hours after the virus was injected, the virus was working perfectly, destroying all cancer cells. But at the same time, the girl's body went into complete failure and she slipped into a coma.  Her body recognized her cells were at war and tried to shut down.
    
    Doctors panicked and sought out any hope. By pure chance, they decided to try a drug that treated arthritis because the anti-inflammatory components might help with her body's inflammatory response. The drug worked immediately and she woke from her coma. Her cancer also disappeared into remission.
    
    Will the cancer return? We don't know because she has no priors. Is her response normal or is she an outlier? We don't know because there is not enough data yet. How will we develop an unbiased study? Right now we can't.
    
    Mukherjee admit that these 3 Laws of Medicine are his own laws. They have helped him in his career and made him a better doctor. But that doesn't mean they are the only laws.
    
    Voltaire once said "Doctors are men who prescribe medicines of which they know little, to cure diseases of which they know less, in human beings of whom they know nothing."
    
    There will always be the unknown in medicine.
    
    The "youngest science" is also the most human science. It might well be the most beautiful and fragile thing that we do.

关于本书 About the book

Brimming with fascinating historical details and modern medical wonders, this important book is a fascinating glimpse into the struggles and Eureka! moments that people outside of the medical profession rarely see. Written with Dr. Mukherjee’s signature eloquence and passionate prose, The Laws of Medicine is a critical read, not just for those in the medical profession, but for everyone who is moved to better understand how their health and well-being is being treated. Ultimately, this book lays the groundwork for a new way of understanding medicine, now and into the future.

本书金句 Key insights

● It's easy to make perfect decisions with perfect information. Medicine asks you to make perfect decisions with imperfect information.

● The "youngest science" is also the most human science. It might well be the most beautiful and fragile thing that we do.

● Every theory carries an inherent possibility of proving it false. If medicine is to become a bona fide science, then we will have to take up every opportunity to falsify its models, so that they can be replaced by new and better ones.