Have you noticed the word “Classic” beside the Coca Cola logo in some of its products? What is so classical about a can of coke?
In 1980s, Pepsi launched an aggressive advertising campaign to boost sales. People at my age would probably remember television advertisements featuring a boy or girl trying two cups of unlabelled coke and being asked to choose the better one. After he/she had made the decision, the better coke always turned out to be Pepsi. You may think this is rubbish. We can always hire an actor to do this, right?
The Coca Cola Company certainly did not trust it either. However, being a big company, it decided to be cautious and secretly performed similar tests on volunteers. Much to their distress, Pepsi really seemed to be winning. Over 60% of testers thought Pepsi tasted better. The company saw this as a potential disaster, and quickly changed the formula of the drink with “New Coke” on 23 April 1985.
The result? The company converted a potential disaster to a real one. Customers just hated the new products and protested. Sales dropped. The company quickly returned back to the original formula in less than 3 months. To be absolutely sure that the customers were pleased, it added the word “Classic” next to the logo.
What went wrong? In a sip test, a tester only takes a mouthful of soft drink. The sweeter product is more likely to win. In real life, people drink the whole can of coke, not a sip. In such settings, it may taste too sweet.
Therefore, you must understand what an investigation is measuring before you can use it. Misusing an investigation is not useless. It is worse than useless. It is misleading.
Some weeks ago, I noticed a young doctor checking blood for carcinoembryonic antigen in a patient with anemia. “This is not supposed to be a screening or diagnostic test,” I said.
“A positive test increases our suspicion of colorectal cancer,” the doctor protested. “Taking some blood causes no harm anyway.”
“No,” I disagreed, “you can still harm the patient. Imagine what would happen if you decide not to perform endoscopy to rule out cancer if the blood test is negative.”
19 Mar 2009
12 Mar 2009
Air Pollution Index
Last month, a group of medical students from our sister university took to the streets in protest and urged the government to update the Air Pollution Index (API). Do I support the act? Of course. Do I support the proposition? I am afraid not.
The protest was an excellent piece of civil education. I hope our students would join some of these activities, too. The real question is – does updating the API do any good?
Currently, the Environmental Protection Department provides the API based on the level of 6 atmospheric pollutants, including sulfur dioxide, nitrogen dioxide, suspended particulates, carbon monoxide, ozone and lead. The index and air quality objectives were set in 1987. Actually, the medical students were not the first to criticize that the index was not update. In October 2005, Task Force on Air Pollution has already stated that the current API is ‘meaningless’. First, some harmful components are not measured. Second, our cutoffs fall short of the World Health Organization Air Quality Guidelines.
I do not doubt that the experts know a lot more about the relationship between air pollution and disease. But what if we update the API? Can we shut down a few factories in Guangdong on bad days? Can we ask our drivers not to drive? Don’t be silly. You may argue – at least we can warn patients with lung diseases not to go outdoors, right?
People working in hospitals in Hong Kong may recall that we have an alert system for avian influenza. It is funny to use the word ‘recall’ for something in the present. The trouble is we are always on yellow alert. When you are always on alert, you have no choice but to ignore it. According to Prof Anthony Hedley of the Task Force, the air pollution of Hong Kong should be stated as ‘absolutely sky high’ most of the year. Can we ask the poor men to stay at home most of the year?
At the end of my hematology rotation as a medical student, I gathered my guts and asked. “Professor GC, our patients come in every few weeks for blood transfusion, but most of them do not have a diagnosis. Wouldn’t it be nice if we perform bone marrow exam and know what we are dealing with?”
“Investigations should only be done when they change the management,” the hematologist answered. “If these people suffer from myelodysplastic syndrome, I will provide supportive transfusion. If they turn out to have leukemia, I will still provide supportive transfusion.”
So forget about more investigations. The government certainly knows that the air pollution is bad. What we should push for is the means to combat pollution, not how to measure it.
The protest was an excellent piece of civil education. I hope our students would join some of these activities, too. The real question is – does updating the API do any good?
Currently, the Environmental Protection Department provides the API based on the level of 6 atmospheric pollutants, including sulfur dioxide, nitrogen dioxide, suspended particulates, carbon monoxide, ozone and lead. The index and air quality objectives were set in 1987. Actually, the medical students were not the first to criticize that the index was not update. In October 2005, Task Force on Air Pollution has already stated that the current API is ‘meaningless’. First, some harmful components are not measured. Second, our cutoffs fall short of the World Health Organization Air Quality Guidelines.
I do not doubt that the experts know a lot more about the relationship between air pollution and disease. But what if we update the API? Can we shut down a few factories in Guangdong on bad days? Can we ask our drivers not to drive? Don’t be silly. You may argue – at least we can warn patients with lung diseases not to go outdoors, right?
People working in hospitals in Hong Kong may recall that we have an alert system for avian influenza. It is funny to use the word ‘recall’ for something in the present. The trouble is we are always on yellow alert. When you are always on alert, you have no choice but to ignore it. According to Prof Anthony Hedley of the Task Force, the air pollution of Hong Kong should be stated as ‘absolutely sky high’ most of the year. Can we ask the poor men to stay at home most of the year?
At the end of my hematology rotation as a medical student, I gathered my guts and asked. “Professor GC, our patients come in every few weeks for blood transfusion, but most of them do not have a diagnosis. Wouldn’t it be nice if we perform bone marrow exam and know what we are dealing with?”
“Investigations should only be done when they change the management,” the hematologist answered. “If these people suffer from myelodysplastic syndrome, I will provide supportive transfusion. If they turn out to have leukemia, I will still provide supportive transfusion.”
So forget about more investigations. The government certainly knows that the air pollution is bad. What we should push for is the means to combat pollution, not how to measure it.
5 Mar 2009
Sixteen
(The original version of ‘Sixteen Things About Vincent’ appeared in Facebook on 31 January 2009. Thanks to my friends’ feedback, the arrogant phrases were modified.)
My mentor tagged me. I guess I just have to follow suit.
1. I studied in three primary schools. My mother thought that was like Mengzi’s mother, who moved house three times to pave the way for the great scholar. Through the process, I did learn how to adjust to new environment. In essence, you have to make friends quickly, and respect that others may do things differently in different places.
2. I entered primary school at the age of 5 and have been the youngest in class ever since. While I was OK with language and mathematics, I could never manage craftworks.
3. Contrary to what child educationists may suggest, my mother constantly emphasized that I was not smart at all when I was in primary school. She believed this would make me more hard-working. Some of my friends would probably agree with her – that I am hard-working and not smart.
4. I am a Wah Yan boy. Although the Wah Yan spirit has never been formally defined, most Wah Yan boys think they get it. It is very much like the Dragon Scroll in Kungfu Panda.
5. I thought I was good at physics. I am humbler now. I am glad that Stephen Hawking deleted most mathematical formulas in A Brief History of Time.
6. I was made the producer of a joint-school musical play when I was in Form 6. While all my classmates were busy dating girls, I was worried sick about how to settle the budget everyday. This was meant to be a fund-raising project for the Hong Kong Cancer Fund, but the stage staff and actors spent almost every penny in the end. During the last rehearsal, the stage curtain was torn in half by a handrail at the edge of the set, costing another $5000 (I know. Similar things happened when Jesus died on the cross.). This was the only time when an opera moved me to tears. After the event, I was rather depressed and ashamed for letting the Cancer Fund down. In retrospect, this was no big deal, and we learned a lot through the project. But it took me years to forgive myself.
7. I can play piano, violin and pipa. If you only want ‘Twinkle, Twinkle, Little Star’, I can almost play any instruments.
8. I learned handball in the university. Two other medical students attended handball class with me, but I was the only one who had scored at all (only 3 goals in 10 games).
9. Prof Jean Woo was my Physician on my first day as a resident. I later learned that she did not want a first-year trainee, but Dr Michael Fu convinced her that I would be good enough. Of course I can never be good enough. I only strived to become better everyday.
10. After my MRCP exam, Prof Sung told me that I failed. I was glad he got it wrong this time.
11. I presented an abstract in a European meeting right after the MRCP exam. After I stepped down from the stage, Prof Anna Lok praised me. This was very important for my development. Before that, I had quite severe stage flight. Now I try to praise young doctors and students whenever I could. If you have read Henry’s notes, you will know that Prof Sung and Prof Lok are the grandparents of my career.
12. I wrote my first paper with Dr Nancy Leung and Henry. I could not find ‘chi-square test’ in the pull-down menu of SPSS, and Prof CC Szeto taught me right away. I did not mention his help in the acknowledgement section because it was quite embarrassing to thank people for teaching me chi-square test in a scientific paper. I would like to thank him now.
13. My wife and I prepared a presentation on osteoporosis in my final year. The presentation went badly, but I got my wife.
14. My favorite movie is The Pianist by Roman Polanski. My wife thought I was crazy when I repeatedly played Chopin’s Ballade No. 1 in the movie. Now that my daughter is 3 years old, we can only watch Strawberry Shortcake at home.
15. I tell my daughter bedtime stories every night. Since I am bored with her story books, I have started making up stories. The latest hits included Strawberry Shortcake meets Spiderman and Strawberry Shortcake meets Mr Incredible.
16. I know I seldom attend social gatherings now. But on the first day I went to work after the New Year holidays, my daughter complained to my wife. “My Daddy doesn’t miss me.” What else can I do?
Want to read the arrogant version in Facebook? Don’t be silly. I have already modified it.
My mentor tagged me. I guess I just have to follow suit.
1. I studied in three primary schools. My mother thought that was like Mengzi’s mother, who moved house three times to pave the way for the great scholar. Through the process, I did learn how to adjust to new environment. In essence, you have to make friends quickly, and respect that others may do things differently in different places.
2. I entered primary school at the age of 5 and have been the youngest in class ever since. While I was OK with language and mathematics, I could never manage craftworks.
3. Contrary to what child educationists may suggest, my mother constantly emphasized that I was not smart at all when I was in primary school. She believed this would make me more hard-working. Some of my friends would probably agree with her – that I am hard-working and not smart.
4. I am a Wah Yan boy. Although the Wah Yan spirit has never been formally defined, most Wah Yan boys think they get it. It is very much like the Dragon Scroll in Kungfu Panda.
5. I thought I was good at physics. I am humbler now. I am glad that Stephen Hawking deleted most mathematical formulas in A Brief History of Time.
6. I was made the producer of a joint-school musical play when I was in Form 6. While all my classmates were busy dating girls, I was worried sick about how to settle the budget everyday. This was meant to be a fund-raising project for the Hong Kong Cancer Fund, but the stage staff and actors spent almost every penny in the end. During the last rehearsal, the stage curtain was torn in half by a handrail at the edge of the set, costing another $5000 (I know. Similar things happened when Jesus died on the cross.). This was the only time when an opera moved me to tears. After the event, I was rather depressed and ashamed for letting the Cancer Fund down. In retrospect, this was no big deal, and we learned a lot through the project. But it took me years to forgive myself.
7. I can play piano, violin and pipa. If you only want ‘Twinkle, Twinkle, Little Star’, I can almost play any instruments.
8. I learned handball in the university. Two other medical students attended handball class with me, but I was the only one who had scored at all (only 3 goals in 10 games).
9. Prof Jean Woo was my Physician on my first day as a resident. I later learned that she did not want a first-year trainee, but Dr Michael Fu convinced her that I would be good enough. Of course I can never be good enough. I only strived to become better everyday.
10. After my MRCP exam, Prof Sung told me that I failed. I was glad he got it wrong this time.
11. I presented an abstract in a European meeting right after the MRCP exam. After I stepped down from the stage, Prof Anna Lok praised me. This was very important for my development. Before that, I had quite severe stage flight. Now I try to praise young doctors and students whenever I could. If you have read Henry’s notes, you will know that Prof Sung and Prof Lok are the grandparents of my career.
12. I wrote my first paper with Dr Nancy Leung and Henry. I could not find ‘chi-square test’ in the pull-down menu of SPSS, and Prof CC Szeto taught me right away. I did not mention his help in the acknowledgement section because it was quite embarrassing to thank people for teaching me chi-square test in a scientific paper. I would like to thank him now.
13. My wife and I prepared a presentation on osteoporosis in my final year. The presentation went badly, but I got my wife.
14. My favorite movie is The Pianist by Roman Polanski. My wife thought I was crazy when I repeatedly played Chopin’s Ballade No. 1 in the movie. Now that my daughter is 3 years old, we can only watch Strawberry Shortcake at home.
15. I tell my daughter bedtime stories every night. Since I am bored with her story books, I have started making up stories. The latest hits included Strawberry Shortcake meets Spiderman and Strawberry Shortcake meets Mr Incredible.
16. I know I seldom attend social gatherings now. But on the first day I went to work after the New Year holidays, my daughter complained to my wife. “My Daddy doesn’t miss me.” What else can I do?
Want to read the arrogant version in Facebook? Don’t be silly. I have already modified it.
26 Feb 2009
Unnatural Selection
Learning from Mother Nature, a creature or institution will thrive and survive environmental changes if it can do the followings:
1. Allow mutations or new ideas to occur.
2. Let mutants compete with wild types.
3. Accept the result of natural selection.
Unfortunately, most institutions overlook the latter two points. When a new policy comes up, it replaces the old one totally although there is no evidence that it is superior. Many people hate conservatives who reject all new policies – ward arrangement, teaching timetable, office renovation, you name it. Nevertheless, conservatives are very important. They preserve the good old days as far as possible and put the burden of proof on those who propose changes. Since bad ideas outnumber good ones in general, brutal replacement of old policies with new ones tends to result in disaster in the long run.
In the January issue of Proceedings of the National Academy of Sciences, Chris Darimont and colleagues described vividly the result of unnatural selection. Under normal selection pressure, the mortality rate of a species is usually limited, and immature and younger organisms die first. In contrast, in ecosystems affected by human predators such as hunters and fishermen, the mortality rate is higher, and the largest and mature organisms are the main targets. As a result, evolution under this unnatural selection is much faster. Interestingly, the size of organisms decreases by an average of 20%, and the life cycle shortens by nearly 25%. The poor preys just have to reproduce earlier to avoid extinction.
Sadly, the result of this report reminds us of ourselves. Good clinical research takes years or even decades of careful observation. Under the current method of research assessment, academics who only do big and long-term projects will die first because of insufficient research output. Next time when you read a me-too study or non-definitive study reporting dubious surrogate end points, don’t laugh. Those people are just shortening their reproductive cycle because of unnatural selection!
1. Allow mutations or new ideas to occur.
2. Let mutants compete with wild types.
3. Accept the result of natural selection.
Unfortunately, most institutions overlook the latter two points. When a new policy comes up, it replaces the old one totally although there is no evidence that it is superior. Many people hate conservatives who reject all new policies – ward arrangement, teaching timetable, office renovation, you name it. Nevertheless, conservatives are very important. They preserve the good old days as far as possible and put the burden of proof on those who propose changes. Since bad ideas outnumber good ones in general, brutal replacement of old policies with new ones tends to result in disaster in the long run.
In the January issue of Proceedings of the National Academy of Sciences, Chris Darimont and colleagues described vividly the result of unnatural selection. Under normal selection pressure, the mortality rate of a species is usually limited, and immature and younger organisms die first. In contrast, in ecosystems affected by human predators such as hunters and fishermen, the mortality rate is higher, and the largest and mature organisms are the main targets. As a result, evolution under this unnatural selection is much faster. Interestingly, the size of organisms decreases by an average of 20%, and the life cycle shortens by nearly 25%. The poor preys just have to reproduce earlier to avoid extinction.
Sadly, the result of this report reminds us of ourselves. Good clinical research takes years or even decades of careful observation. Under the current method of research assessment, academics who only do big and long-term projects will die first because of insufficient research output. Next time when you read a me-too study or non-definitive study reporting dubious surrogate end points, don’t laugh. Those people are just shortening their reproductive cycle because of unnatural selection!
19 Feb 2009
Competition
Between 1405 and 1433, Zheng He of the Ming Dynasty led a fleet of more than 20,000 men to explore the ocean west to China. The countries he visited included Indonesia, Yemen, Iran and Somalia in East Africa. The largest ship could carry 200 sailors and 1000 passengers. This took place before Christopher Columbus was born (1451-1506). The fleet was also much larger than the one led by Columbus. Although Zheng He’s mission was never meant to be colonization, we can still expect that the international influence of China would grow with time if similar voyages continued.
However, the policy of the Ming Dynasty changed suddenly afterwards. The country not only abandoned further sea adventures, but also cut off most international interactions. A number of hypotheses explained the change. Some said that the emperor used up all the finest lumber to build the Forbidden City. Others said that the main reason was the political rivalry between eunuchs and the royal family (Zheng He was a eunuch).
While we consider the abandonment as one of the foolish decisions in Chinese history, one may wonder why the same thing did not happen in Europe. New ideas are like mutations. If the idea of going out to search for unknown land (Columbus’ calculations and predictions before his voyage were almost completely incorrect) is a mutant, the wild-type would be minding your own business. In fact, when Columbus approached John II, King of Portugal, for funding, he hesitated. That is why Columbus had to turn to the Spanish Queen. The interests in sea adventures also fluctuated among different European countries.
What set Europe apart from China was the keen competition among countries. The great success of the Spanish campaign brought in gold and resources, building Spain into an empire in the 16th century. Other countries sensed the selection pressure and had to follow suit. This resulted in a long history of colonization. In contrast, China did not experience major economic and political competition from neighboring countries, and could live contently on her own until the European navies knocked her door.
However, the policy of the Ming Dynasty changed suddenly afterwards. The country not only abandoned further sea adventures, but also cut off most international interactions. A number of hypotheses explained the change. Some said that the emperor used up all the finest lumber to build the Forbidden City. Others said that the main reason was the political rivalry between eunuchs and the royal family (Zheng He was a eunuch).
While we consider the abandonment as one of the foolish decisions in Chinese history, one may wonder why the same thing did not happen in Europe. New ideas are like mutations. If the idea of going out to search for unknown land (Columbus’ calculations and predictions before his voyage were almost completely incorrect) is a mutant, the wild-type would be minding your own business. In fact, when Columbus approached John II, King of Portugal, for funding, he hesitated. That is why Columbus had to turn to the Spanish Queen. The interests in sea adventures also fluctuated among different European countries.
What set Europe apart from China was the keen competition among countries. The great success of the Spanish campaign brought in gold and resources, building Spain into an empire in the 16th century. Other countries sensed the selection pressure and had to follow suit. This resulted in a long history of colonization. In contrast, China did not experience major economic and political competition from neighboring countries, and could live contently on her own until the European navies knocked her door.
12 Feb 2009
Mutation
New ideas are like mutations. In Built to Last, James Collins and Jerry Porras illustrated how companies that encouraged new ideas outperformed those that explicitly avoided changes. The mutations allow the companies to change over time and face up new challenges. In Chinese history, many dynasties upheld the belief that ancestral decrees should never be disobeyed, and headed towards ruin when the environment changed.
Therefore, I cannot fully support those who reject all new policies such as the education reform and ward admission system. Of course, this is not to say that the results of these new policies are gratifying. In fact they aren’t. Supporters of conservative approach may point out that though the dynasties collapsed, they had each lasted for several centuries. In contrast, Wang Mang (王莽) established the Xin Dynasty (新朝) and was well known as a creative politician and scholar. He was described as a ruler who announced a decree in the morning and changed it in the evening (朝令夕改). The empire only lasted from 9 to 23 AD. In Fooled by Randomness, Nassim Nicholas Taleb explained the cost of progress (or change):
‘People tend to infer that because some inventions have revolutionized our lives that inventions are good to endorse and we should favour the new over the old. I take the opposite view. The opportunity cost of missing a “new new thing” like the airplane and the automobile is minuscule compared to the toxicity of all the garbage one has to go through to get to these jewels (assuming these have brought some improvement to our lives, which I frequently doubt).’
This leads us to fundamental questions – Does the outcome depend on the quality of the mutations? Is there an optimal mutation rate?
If we turn to Nature for an answer, the first question is obsolete. Mutations are random processes. History tells us that bad ideas outnumber good ones. Great minds do not guarantee better ideas. We only know that bad ideas by great people usually result in worse disasters (think about Karl Marx). So we have to accept the co-existence of good and bad ideas.
Similarly, microorganisms with the highest mutation rate are the most robust. HIV, hepatitis B and hepatitis C viruses can all produce mutations at any point in the genome within one day. They are also very successful in developing drug resistant mutants.
Then what went wrong? Why do the government and some institutions do badly even though the officials bombard us with innovative ideas all the time?
Therefore, I cannot fully support those who reject all new policies such as the education reform and ward admission system. Of course, this is not to say that the results of these new policies are gratifying. In fact they aren’t. Supporters of conservative approach may point out that though the dynasties collapsed, they had each lasted for several centuries. In contrast, Wang Mang (王莽) established the Xin Dynasty (新朝) and was well known as a creative politician and scholar. He was described as a ruler who announced a decree in the morning and changed it in the evening (朝令夕改). The empire only lasted from 9 to 23 AD. In Fooled by Randomness, Nassim Nicholas Taleb explained the cost of progress (or change):
‘People tend to infer that because some inventions have revolutionized our lives that inventions are good to endorse and we should favour the new over the old. I take the opposite view. The opportunity cost of missing a “new new thing” like the airplane and the automobile is minuscule compared to the toxicity of all the garbage one has to go through to get to these jewels (assuming these have brought some improvement to our lives, which I frequently doubt).’
This leads us to fundamental questions – Does the outcome depend on the quality of the mutations? Is there an optimal mutation rate?
If we turn to Nature for an answer, the first question is obsolete. Mutations are random processes. History tells us that bad ideas outnumber good ones. Great minds do not guarantee better ideas. We only know that bad ideas by great people usually result in worse disasters (think about Karl Marx). So we have to accept the co-existence of good and bad ideas.
Similarly, microorganisms with the highest mutation rate are the most robust. HIV, hepatitis B and hepatitis C viruses can all produce mutations at any point in the genome within one day. They are also very successful in developing drug resistant mutants.
Then what went wrong? Why do the government and some institutions do badly even though the officials bombard us with innovative ideas all the time?
5 Feb 2009
Darwin
My colleagues were surprised when I celebrated the 200th anniversary of the birth of Charles Darwin in a public talk on hepatitis B recently.
Explaining the evolutionary theory to non-specialists is a bit tricky, but people working on antiviral therapy use the theory all the time. The essence of the evolutionary theory is ‘survival of the fittest’. During reproduction, gene mutations sometimes result in phenotypic changes in an organism. Most of the mutations are hazardous, but a minority confers competitiveness. Organisms bearing more competitive mutations have a better chance of giving birth to offsprings, and eventually the new gene will dominate the population. People working with viruses are seeing a fast-forward version of evolution. Viruses replicate quickly and produce a lot of mutations because of their lack of proof-reading during gene transcription. When an antiviral drug is given to a patient, viral mutants that do not fear the drug will replicate more effectively and soon become the dominant strain.
Actually, before Darwin published his book On the Origin of Species, a few other scientists had already noticed the gradual phenotypic changes of animals and plants. However, most considered the changes a well-planned evolution by God. It was Darwin who spotted that the changes were random, and the evolution was driven by natural selection – ‘survival of the fittest’. For those with basic knowledge on genetics, the theory may seem pretty easy to understand. However, one must remember that genetics did not exist at Darwin’s time (although Gregor Mendel was actually humbly doing his cross-breeding experiments at roughly the same time). Imagine how difficult it would be for me to explain the last paragraph again without describing anything about genes and mutations.
Like all great theories, the implications extend well beyond the original territories. I will elaborate this further next week.
Explaining the evolutionary theory to non-specialists is a bit tricky, but people working on antiviral therapy use the theory all the time. The essence of the evolutionary theory is ‘survival of the fittest’. During reproduction, gene mutations sometimes result in phenotypic changes in an organism. Most of the mutations are hazardous, but a minority confers competitiveness. Organisms bearing more competitive mutations have a better chance of giving birth to offsprings, and eventually the new gene will dominate the population. People working with viruses are seeing a fast-forward version of evolution. Viruses replicate quickly and produce a lot of mutations because of their lack of proof-reading during gene transcription. When an antiviral drug is given to a patient, viral mutants that do not fear the drug will replicate more effectively and soon become the dominant strain.
Actually, before Darwin published his book On the Origin of Species, a few other scientists had already noticed the gradual phenotypic changes of animals and plants. However, most considered the changes a well-planned evolution by God. It was Darwin who spotted that the changes were random, and the evolution was driven by natural selection – ‘survival of the fittest’. For those with basic knowledge on genetics, the theory may seem pretty easy to understand. However, one must remember that genetics did not exist at Darwin’s time (although Gregor Mendel was actually humbly doing his cross-breeding experiments at roughly the same time). Imagine how difficult it would be for me to explain the last paragraph again without describing anything about genes and mutations.
Like all great theories, the implications extend well beyond the original territories. I will elaborate this further next week.
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