Saturday, March 19, 2005

Lessons from the Acquired Immunity

Evolution has no foresight. Neither do we.

This is an age of insecurity. Hijacked planes, suicide bombs, weapons of mass destruction, phishing emails, computer viruses. We are under attack everywhere and everyday.

But this is also an age of protection. National security advisory code, airport shoe check, National Missile Defense system, liberation of Iraq, sophisticated message encryption, antivirus software, firewalls, deadbolts on the doors. We live behind the shields of better and better defense.

But are we protected? A recent commentary published in the journal Immunity should make us thinking again.

In his article, Stephen Hedrick re-exams the usefulness of the acquired immune system. The acquired immune system is vertebrates' second line of defense against pathogens, and it is activated when the first barrier against infection, the innate immune system, is breached. The acquired immunity employs a sophisticated mechanism -- somatic hypermutations combined with thymus or germinal center selections -- to generate pathogen-specific T-cells and B-cells to search and destroy the invaders. These T-cells and B-cells then remember their specific targets, and become a fast response force against any recurring infection. Thanks to the acquired immunity, we do not get many diseases twice, and we can be vaccinated against these diseases before they strike. In contrast, the innate immunity, which is universal to vertebrates and invertebrates alike, uses seemingly mundane mechanisms: cell membranes and coagulation to deny pathogen's access into host, defensins and lysozymes to destroy the parasites before their entry, and other brute force measures.

Until now, the majority of immunologists view the acquired immunity as an optimal defense system, a superior weapon that confers great health advantage onto vertebrates over invertebrates. Hedrick's commentary overturns this conventional view. He argues that the acquired immunity overall does not benefit vertebrates as a kind. Comparisons between insects and vertebrates have yielded several surprises. For example, the morbidity and mortality of insects due to infection are not higher than that of vertebrates. Compared to the pathogens for invertebrates, the pathogens that infect vertebrates have developed more adaptive strategies to evade the acquired immune system. Influenza is one best known example of this adaptability. Not only the acquired immunity can be easily rendered useless by the evasive pathogens, it can also be exploited by the viruses for their replication, as in the case of AIDS, or backfire on the host and cause autoimmune diseases such as arthritis and lupus.

Instead, the acquired immunity appeared to be an evolutionary misstep. The strain that first developed the acquired immunity had a temporary advantage over the rest of the animal kingdom, so it multiplied, eventually developing into the vertebrate subphylum. Unfortunately, it underestimated the infinite resourcefulness of the pathogens. The fateful genetic mutation that gave rise to the acquired immunity inadvertently escalated the war between the pathogens and the vertebrate hosts, one that had inflicted heavy costs and casualties on both sides for the past four hundred million years. Meanwhile, the acquired immunity becomes an absolute necessity for vertebrates, because any deficiency in it will make the individual defenseless against the highly evolved pathogens.

Hedrick’s insight should reach beyond immunologists.

So much as our sophisticated acquired immunity cannot make us impermeable to germs, any defense that we can mount against foreign or domestic attacks can be defeated by a clever enemy. It is an arms race that no one wins in the end. The National Missile Defense system will not protect us, because it will be easily overwhelmed by inexhaustible possibilities of countermeasures. Hundreds of billions of dollars will only buy the Americans a false sense of protection, and will prompt the Russians and the Chinese into a race to develop missile technologies capable of circumventing NMD.

Neither will the antivirus software make our PCs virus-free. After all, it can only recognize a known virus and is useless against any new strain. It seems that the real defense against computer viruses is plain caution: do not visit suspicious websites, do not download programs without a proper certificate, do not open emails from unknown senders. It is just like the innate immunity, mundane but effective.

Yet all is too late. The acquired immunity is here to stay. So is the National Missile Defense, so is the antivirus software, so is the spam email filter. They have all become the cause of their own necessity. We pay for their existence because they protect us from all known forms of attack. But by the force of the unknown future, we remain in the shadow of menace.

Monday, March 14, 2005

Gender Equality with Wheelchair Access

To promote women, we must demote men.

When I first went to Columbia University, the Department of Chemistry had one female professor. A year later, the department hired a young woman as an assistant professor, doubling the size of its female faculty. The department had a total of twenty faculty members at that time.

In University of California, San Francisco, on the floor that I currently work, there are twenty one faculty members. Three are women.

When I interviewed in the Department of Chemistry in University of Washington, Seattle, I met 16 professors, out of whom only one was a woman. She was newly tenured in the department, along with four male junior professors.

Why are there so few female professors?

According to some people, including Lawrence Summers, the president of Harvard University, women lag in science partially because they are biologically different from men. Perhaps testosterone stimulates mathematical genius; estrogen suppresses it. Perhaps women are innately more susceptible to beauty in a flower bouquet than beauty in a mathematical formula, more adept at counting inventories than counting neutrons, more disposed to mixing cooking recipes than doing chemical synthesis.

Wait a minute. As I remember, from primary school all the way to college, the top-scoring student in my class had always been a girl. In the College Entrance Exam administered by the Chinese Bureau of Education, girls do just as well as boys.

Anticipating such retorts, Dr. Summers contends that although average math aptitude may be analogous between the sexes, more men tend to occupy the tails of the distribution. In other words, the dumbest and the most ingenious are male. Women can surely do calculus, but only men can prove Fermat’s Last Theorem.

But that argument does not hold water either. Once appointed, female professors are as successful in contending for research grants and career fellowships as male professors. The McArthur fellowship, widely dubbed as the genius award, has been awarded to many outstanding women in the past decade. I have personally met many women who are absolutely the top-tier scientists in their field.

Well, if estrogen does not poison the brain, what hinders women’s advance in science?

In a different way, women are shackled professionally by their own biology. The optimal child bearing age of a woman coincides with that of the critical stage of her career. A twenty-two year old woman, just out of college, faces the tough choice between rearing children and pursuing a career. If she wants to go into academia, she will have to postpone having children indefinitely. Five years of graduate school, three years of postdoctoral study, six years of untenured junior professorship, that is fourteen intense years almost impossible for her to have a baby. Even fourteen is the most conservative estimate. Finally, at thirty-six, way past the optimal child bearing age, she is ready to have a baby, if she is fortunate to have a man who is willing to be patient for so long.

In a recent op-ed in New York Times, David Brooks advocated a rounded alternative: the sequential life style. In a nutshell, the sequential life style suggests that a woman out of college spend five years at home, rearing a child. She will then reenter the work force and pursue her career uninterruptedly like her male colleagues.

Superficially, Mr. Brooks laid out a perfect plan. But at closer scrutiny, this sequential life style does not hold up. Not only does it outright bereave women five years of their professional lives, it takes away five of their best career years, the years when they are mint with skills, knowledge and connections acquired in college, the years when a person’s drive to succeed is the strongest. Not to mention that these women will be competing at a disadvantage with men five years younger.

Some women chose to sacrifice their procreative rights for a fair game in their careers. But a great sacrifice it is. In science, quite a few successful female professors over forty are single and childless. Sadly, the highly successful but childless professional women will be out of the gene pool in just one generation.

Up to this day, the effort to promote gender equality is focused on creating more opportunities for women in the professional world. This emphasis is epitomized by the affirmative action – should a woman and a man equally qualify for a professional opportunity, be it a job or a promotion, the opportunity will be preferentially awarded to the woman.

Unfortunately, affirmative action, or many other similar measures, does not address a more fundamental problem rising out of the inherent biological difference between women and men. Only women can carry children, and breast-feed them. Most women still view maternity a responsibility and a joy. Yet it conflicts with their careers.

Therefore it is not enough to give women jobs. It is equally important to create an environment where women can excel professionally without sacrificing their personal, especially maternal, needs.

When I first came to the United States, I was surprised by the number of handicapped people I saw on the street and at work. In China, I rarely met a handicapped person. Was it because there were more handicapped people in the States than in China? Not likely. The true reason is that more convenience is extended to the handicapped population in the States than in China. From designated parking to the wheelchair accessible bathrooms, the American society has created an environment where the handicapped enjoy as much mobility as the otherwise privileged population. In contrast, China, until recently, has not provided the same facilities for its handicapped population, who are consequently confined in a narrower living space.

Similarly, if we want to foster women’s professional success, we must not only give them the initial access to an opportunity, but more importantly, we must create an environment where they can excel with as much ease and freedom from biological burdens as men. This is especially important for women with babies. A firm that provides wheelchair access to its handicapped employees should similarly allow new mothers to bring their babies to work and provide the necessary breast-feeding stations. It should provide daycare centers so that young mothers can go to business meetings without worrying about their children.

Significant changes must also be wrought upon social conventions. Feminists have long been arguing that men should share the burden of rearing children. Yet this is difficult to practice as long as the society exercise the conventional pressure on a man’s professional success. Just like women, men cannot simultaneously shoulder the responsibility of rearing children and pursuing their careers. Something has to give. The society must relent on its obsessive value set on men’s professional success. Women should cease to select mates based on their career success. Only when men can proudly declare themselves house-makers, can true professional gender equality be achieved. A single, childless woman should arouse no more pity than a single, childless man. Neither should a jobless househusband receive more frown than a housewife. Only then is gender equality a reality.

In Sex and the City, Miranda marries Steve. Samantha falls in love with Jared Smith. That should be a heartening ending for the professional women.

Life on the Crutches

Seeing the bus leaving the stop, I ran after it. My life changed for the next three weeks.

Exhibit 1. The swelling was still visible a week after I sprained my left ankle.

The accident

When I was thirty years old, I went on crutches for the first time. The accident happened on a Thursday night, when I severely sprained my left ankle as I ran to catch a departing bus. That night, Bosco and I were heading to Chinatown to get some authentic Cantonese noodles with beef tripes. Bosco, a chronic procrastinator, took his time in the men’s room. By the time we came to the bus stop, the bus was already leaving. I ran toward it, waving my hand. As the bus was stopping for us, the accident happened. My left foot twisted, the ankle bent sharply inward, and I started to fall. Yet my obstinate body resisted it, exerting a strong torque on my ill-positioned left ankle. The pain shot up my left leg and tore my brain. I wanted to lie down and wait for help. But I knew that the passengers on the bus must have seen my amusing accident, and I fear of being laughed at. Driven by that fear, I limped forward onto the waiting bus.

“Are you okay?” Bosco followed behind me, taking a seat.

In the next hour, we had our authentic Cantonese food. I ate the entire meal with my left hand pressing a bag of ice against my left ankle. Yet the ice was not enough to suppress the swelling. By the end of the meal, my left ankle doubled in size and looked like an orange wrapped in a sock. Clearly I needed to go to an emergency room.

“You want to come with me?” I asked Bosco as I stepped into a taxicab.

“No, I think I will just take the Muni home.” Bosco thought it inappropriate to share a cab with someone needing emergency care.

Emergency room

I had seen quite a few advertising posters for some hospital’s ER service. The posters generally showed some hapless yet jolly souls getting into an accident, such as falling over a banana skin, and a big “Whoops”. The text at the right corner said emergency care under 30 minutes in Blah-Blah hospital.

After a full hour of waiting in the corridor of the emergency room of UCSF Medical Center, I tried to remember the name of the hospital advertised in those posters. With an ice pack wrapped around my left ankle, I waited patiently for a nurse’s attendance. There was only one more waiting patient, a man sitting in a wheelchair next to me. “I have been here since six o’clock”, he said, “and I am still waiting.” I was dismayed. It was past ten.

Finally a nurse took me into a room, measured my blood pressure, put me onto a wheeled bed, and pushed me into a ward. Ward 20, as marked on the ceiling. The wards were separated by plastic curtains. There was a small bedside table, and a phone.

I called two friends. I hoped to have someone drive me home after treatment; if I could not have that, I wanted to have someone at least carry my laptop home for me. I called Wendy first. Not only because she had a car, but also because the companionship of a woman is preferable.

I got Wendy’s voicemail. “Hello, Wendy. This is Huafeng. I sprained my ankle and I am in ER. I wonder if you can drive me home tonight.”

Next I called Yu Chen. He did not have a car; but he lived nearby and he could at least take my laptop home for me.

Again, I got the voicemail. “Hello, Yu Chen. This is Huafeng. I sprained my ankle and I am in ER of UCSF Medical Center. If you can stop by on your way home and take my laptop home, it will be great. I am in Ward 20.”

For the next twenty minutes I stared at the ceiling. The ward was surrounded by curtains on three sides and a wall in the back, so I could not see anything outside. Everything in my view was white, including the phone. I imagined myself to be in a modern art exhibition, where the pieces had been variations of the white color on canvases. I imagined myself to be a wounded soldier in a World War, surrounded by dying fellowmen, neglected by the nurses and my government. I let my thoughts drift through the whiteness.

The curtain was pulled open, and a nurse came in. I thought my wait was over. She handed me a walkie-talkie-phone. “You have a phone call from your friend.” Surprised, I took the phone. It was Wendy. She just received my message and wanted to know my condition.

“Since the doctor has not attended to my case, I guess I am not dying.” I attempted humor.

Wendy wanted to know when I would get out of ER, so that she could pick me up and drive me home. I had no idea, and told her that I would call her again if I got out before some reasonable hour. I narrated my embarrassing accident. We chatted for some time. It was wonderful not to be alone in the ward.

After some time, Yu Chen called. He came in after another ten minutes. As usual, Yu Chen spoke of his trouble in finding the ER, and in finding my ward. Then we talked about this and that. Yu Chen stayed until a nurse came to take X-ray of my ankle. He left his Time magazine to me. “Just remember to return it to me when you are done. I want to keep this issue.” He carried my laptop away.

The nurse who X-rayed me was a chubby young Asian girl by the name Jacquelyn. She was either easily amused or professionally polite, laughing at every one of my jokes. As a result, I have forgotten all the jokes that I made to her. Having a nurse who laughed at my jokes at least made me temporarily forget my physical pain. The white, gigantic X-ray machine sat in a spacious room. Jacquelyn pulled the X-ray barrel over my left ankle, put a heavy apron over my chest, and walked into the adjacent operator’s room to push the button. She shuffled between my bed and the operator’s room several times, twisting my left ankle into different positions for panoramic effects. All the time, I tried to keep the jokes flowing.

A few X-ray bombardments later, I was wheeled back into my ward, and was greeted by an unexpected visitor, Wendy. Sitting in a chair, she smiled with genuine amusement when she saw me pushed in lying in the bed. I was very pleased when I saw her: female companionship, the best medicine for a man in pain.

With Wendy’s company, waiting for doctor was far more endurable. The meetings between Wendy and me were always far between, so we had a lot to update each other. I told her about my upcoming marriage proposal. She laughed at the formality of “popping the question”.

Soon came the doctor, a slim, kind-looking lady appearing to be in her late thirties. She introduced herself as Doctor Her-last-name, and informed me that my bones were fine, and the ligaments were badly stretched but not torn off, so I would be fine after sometime on crutches.

Somehow I mentioned I had a Ph.D. in chemistry.

“You should have let us known that earlier. I would have come to you much sooner had I known you were a chemist.” Doctor Her-last-name said.

I gathered that chemists had more vulnerable ankles.

After Doctor Her-last-name, a young, strapping ER technician brought me a pair of brand-new aluminum crutches. He smiled broadly, his dental braces flashing with a metallic sheen above his thick goatee. He sympathized with my sprained ankle. “But at least you have your wife here with you.” He tried to comfort me.

“Wendy is a friend of mine.” I corrected him.

“So you are dating this guy?” The technician said to Wendy. Apparently he did not believe in pure friendship between sexes.

Ten minutes later, I moved out of ER on the new crutches. Wendy drove me home.


Wendy was one of my fiancé’s best friends. I met Wendy in Columbia University a few months after I came to the United States, even before I met my fiancé. Later, through my fiancé, Wendy and I became better acquainted, although we rarely met. She moved to San Francisco after college. Two years later, I came to San Francisco for postdoctoral study in the University of California. We had met a few times since then.

Wendy was a rarity among my friends. She had more academic concerns for the world than pragmatic concerns for her own life. Three years after Columbia, two years after Berkeley, Wendy was still only half way descending the Ivory Tower. She worked as an engineer in P.G. & E., but aspired to a career in writing and journalism. Not completely a wild dream, since she had already published a few political essays in newspapers.

Like all Columbia graduates, Wendy was an ardent feminist. Although in heart I am a women’s rights activist, I sometimes speak to the contrary with Wendy just to instigate a more interesting debate.

But the ride to my home was too short for any debate of the political sort. Wendy helped me upstairs to my room, left Shere Hite’s book on female sexuality and a movie set in the Chinese Civil War, and drove back home.

Life on the crutches

The next morning I woke up with my left leg raised by four pillow cushions. The pain was still on my ankle. I clasped my crutches, sat up slowly, stood up on my right leg, and balanced myself on the crutches. I needed to go to the bathroom. Going to the bathroom, so easy before, now seemed a tremendous undertaking. Opening and closing each door, lifting up and setting down the toilet seat, getting down and getting up, between each action, I had to pause and rebalance. As I moved back step by step to my bedroom, I had an inkling of the difficult days ahead.

Going to work was out of the question. I lay in bed and read Shere Hite’s book. But the pulsating pain in my ankle made sexuality uninteresting. I flipped through the pages, nonchalantly reading women describing their sexual fantasies and orgasms. Later in the morning, Yu Chen stopped by and dropped off my laptop and two more movies. I ended up watching three movies on that day.

At noon I tried to fix myself some lunch. It was Mission Almost Impossible. I carried a pitcher of water while walking on my crutches, and I spilled water all over my pants and the floor. I managed to boil some dumplings in my rice cooker. But as I stood on one leg and scooped the dumplings into a bowl, I knew that was the last meal I would cook for myself for days to come. I left the rice cooker open and unwashed. In ten days, when I finally had the strength to clean it, I found a dead black spider in it.

In the evening, Yu Chen brought me dinner, a juicy cheeseburger from Sliders. He continued to bring me food for the next two days. He was a true friend.

For two days, I remained in my little room, venturing out no further than the bathroom. Immobilized, I began to realize how much of our lives depended on mobility. With a sprained ankle, my life was reduced to no more than a hundred square feet. I had no internet access. I had no desire to read. I was bored. On Saturday morning, I stared out of the window and looked at a beautiful Californian day. I normally would run six miles on such mornings, but not on that morning, not on the Saturday mornings of many ensuing months. I felt like an impotent man lying in bed with a beautiful woman, tormented by lust and shame. I was shrinking, body and mind.

On Sunday, the confinement became unbearable. With Yu Chen’s help, I walked outside on my crutches. Getting down the stairs was a challenge, but by the last few steps I had mastered a technique for descent. We went to the closest restaurant. I rested a couple of times along the way. When we finally reached the restaurant, my back was damp with sweat, my armpits sore. But I was as happy as a drowning man who surfaces above the water and takes a breath.

I stayed on the crutches for the next three weeks. When I crossed the streets, cars waited patiently. When I hopped on a bus, other passengers yielded the front seats to me. When I flew to New York, I enjoyed priority boarding. I was granted the convenience given to the handicapped, but I was not an object of pity. Because struggling as I was, I would soon rid of the crutches, and walk again.

Saturday, March 12, 2005

Letter Writing in the Digital Age

Don't write beyond the subject line.

In the information age, brevity comes first. I sent the following message to invite my friends to a popular Peruvian restaurant:

Near the intersection of Valencia and the 17'th Street sits the legendary Limon restaurant, whose succulent ribeye steaks and tender grilled scallops have earned its reputation far and wide in the Bay Area. To this restaurant I invite you to join me, on the wondrous Thursday of March the Tenth, at the felicitous hour of 7:00pm.


Soon, I received a reply asking why I sent an email talking about a restaurant. It dawned on me that the person did not read beyond the first sentence.

Email was just getting popular when I entered graduate school. My very first emails were sent to American schools inquiring about their application procedures. Internet was still a rarity in China at that time, and I paid 20 cents per minute to type my letters in the terminal room of the chemistry department of my college. I wrote short messages to save money.

Then I went to Columbia University. Immediately I had a free email account with unlimited letter writing privileges. I could write for free to all my friends who were similarly blessed with an email account. The internet revolution had started in earnest. Two and a half years after its launch on the Independence Day of 1996, Hotmail had more than 30 million active users. It seemed that suddenly everyone in the States was sending emails, and our inboxes exploded. Our workdays were transformed: the morning would begin with composing, reading, replying to and deleting emails; frequent visits to the inbox would punctuate the day; one last peek of the inbox would invariably precede our departure from work.

With the advent of every new technology, an old way of life must die. The victim of email is the post; email is killing letter-writing. Before email, I corresponded by hand-written letters with my friends and family. The letters were infrequent but thoughtfully composed. In them, I not only narrated the most significant events happening in my life, but also told of my ideas and opinions. Every letter was an intimate conversation, and the delay in the reply provided anticipation and suspense.

To send a postal mail, one has to seal the letter in an envelope, write down the send and the return address, put on a stamp, and drop it in a mailbox. Emails, in contrast, are different. Push one button and the message is on its way. This ease exercises a subconcious pressure on one's mind: the letter can, and therefore should, be sent as soon as possible. As a result, one rushes to complete the letter, pushes the send button, and moves on to the next message. Convenience is the enemy of depth.

I am probably one of the few surviving dinosaurs from the postal age who still read my friends' emails from the beginning to the end. But I have an advantage: my friends' emails tend to be short. They average two paragraphs, consisting of no more than three sentences each. They fall into the following general format:

I did some cool stuff. The stuff I did was really cool. I wish you did the same cool stuff too.

Want to do some cool stuff together sometime?

After proposing to my fiancee, I sent an email to my friends, telling my engagement story with details and great excitement. I fell cold on seeing the following reply:

Congratulations! So how did you do it?

The subject of my email was: "I am engaged!" The narrative of the full experience began in the first paragraph of the text.

Friday, March 11, 2005

Harvard Exchange

Harvard University did not offer me a job, for one good reason.

This year I looked for faculty positions. I sent my application to Harvard University. It lead to the following exchange of letters.


Department of Chemistry and Chemical Biology
Harvard University

Dear Members of the Search Committee:

Please consider my application for the junior faculty position in Physical Chemistry advertised by your department in C&E News. I have enclosed with this letter my curriculum vitae, a list of my publications and patents, and a statement of my research interests.

I look forward to hearing from you.


Huafeng Xu


Department of Chemistry and Chemical Biology
Harvard University

Dear Dr. Huafeng Xu,

Thank you for your application for our assistant professorship in Organic Chemistry. We have received a very large number of excellent applications this year and can only interview a few candidates.

Unfortunately, the Department is not in a position to offer you an assistant professorship at this time.

Our best wishes for your future plans.


Akira R. Shave


Dear Dr. Shave,

I recently received a letter from you which stated to the effect that your department was not in a position to offer me an assistant professorship in organic chemistry. I am writing to assure you that the regret in your letter is completely unjustified and unnecessary.

Harvard is not the only school that is not in a position to offer me a job in organic chemistry. No institution on this planet is: I am not even an organic chemist! Sure, I took organic chemistry in college, and spent some time making pheromones in an organic lab. But that's it. I have not been near any toxic chemicals since graduate school. Consequently, I have decided to accept an offer in computational chemistry from another institution, and continue my chemical-free career.

I wish you success in identifying the best organic chemist in the world.

Sincerely Yours,