The second is the case of two missing computer hard drives containing classified information that went missing as a fire roared near the lab. Employees failed to alert officials that the disks were missing for three weeks. Fear abounded that the disks had been shared with foreign powers, but when they finally surfaced two weeks later (behind a copy machine in a secure area) an FBI investigation concluded that they had not been tampered with.

But that didn’t stop the alarm bells ringing in Congress. Hearings about the security lapses are ongoing, and the calls for greater vigilance at the nuclear weapons lab have come both from Republicans and from the Clinton administration, which has been attacked for years for alleged inappropriate ties to China. On Wednesday, University of California officials complained that budget cuts have made it impossible to maintain sufficiently tight security at the labs, which the university runs jointly with the U.S. Department of Energy.

Still, some scientists say the security problem is being exaggerated for political reasons. “What’s going on in Washington with all the hearings, it’s completely unrelated to any real problem at the labs,” asserts Hugh Gusterson, a professor of science and anthropology at MIT. “It’s all about party political advantage. If you look at the statistics this year, the security violations have been less in number than in previous years. I know the media has conspired to give this impression that security has gotten lax at the labs, but I don’t believe it’s true.”

Gusterson thinks politicians are shooting themselves in the foot. “The Republicans in Congress and the administration between them are pretty much wrecking the nuclear weapons program. If you’re against nuclear weapons I guess they’re doing the right thing,” Gusterson said. “But it is ironic to have disarmament by Republicans who are doing it in the name of increased national security.”

The pressure on the DOE is causing a backlash in the scientific community. An article in Sunday’s New York Times documented the dwindling number of Asian and Asia- American scientists applying for and accepting jobs at Los Alamos. Academic groups are calling for a boycott of the national weapons labs because they say a system of racial profiling is going on, with scientists of Asian descent systematically harassed and denied advancement. DOE officials have denied the allegations.

Asians and Asian-Americans make up more than a quarter of science and technology doctorates at the nation’s top universities. Without them, the talent pool of weapons designers would be drastically depleted.

“Disgracefully, there is evidence that the racial profiling issue is real,” says Steve Aftergood of the Federation of American Scientists. “This is not a concoction of hyper-sensitive activists. The larger issue is the vitality of the lab, and it’s just amazing to me that that is being missed by Congress.”

But it’s not just Asians and Asian-Americans who are feeling the scrutiny. Across the industry, talented scientists are looking at the government’s treatment of Wen Ho Lee, polygraph testing of lab employees and the security response as proof that working for the government carries too much risk and not enough reward.

“I’m told that a lot of the weapons designers are talking about looking for new jobs, especially the younger ones,” Gusterson says. “And the older ones are talking about early retirement.

What’s more alarming than the security breaches themselves is the level of paranoia about them, according to Jessica Stern, senior fellow at Harvard’s Belfer Center for Science and International Affairs. “There’s nothing more critical to U.S. national security than protecting legitimate secrets,” says Stern. But the current uproar over lapses at Los Alamos is only making matters worse.

“There does seem to be a kind of McCarthy-type atmosphere developing,” Stern says. “I think there is a fine line between prudence and paranoia. We may be slipping over the paranoid edge of that line.”

Stern now works on national security and terrorism issues. But from 1992-94, she worked at the Livermore National Laboratory in Livermore, Calif., one of three national labs that develop nuclear weapons technology — the others are Los Alamos and Sandia (which has sites in New Mexico, California, Nevada and Hawaii). She says she’s heard from colleagues that the Lee case has angered many scientists who believe, whether he is guilty or innocent, that the way he has been treated is grossly unfair.

Lee has been in jail since December on charges that he copied secrets “with the intent to injure the United States.” Only after the U.S. District Court judge in the case ordered prosecutors to be a little more specific were Lee and his lawyers told, on July 5, which countries he allegedly tried to give the information to back in 1993.

The prosecution’s theory has been that Lee was giving secrets to Chinese labs. But now, the list of countries prosecutors say Lee might have been spying for has grown amusingly broad — Taiwan, Australia, France, Germany, Hong Kong, Singapore and Switzerland — due to evidence that he sent tapes of his work to all those countries.

Lee’s defenders say he was concerned he might lose his job because of cutbacks at Los Alamos, and had been sending his résumé — including taped samples of projects he was working on — to labs in those countries at the time of his alleged breaches. Lee has not been charged with espionage, but he still faces the possibility of life in prison. The case is set to go to trial in November. Until then, he remains in solitary confinement. Officers put shackles on him during the one hour each week in which he visits his family.

His case has sent ripples of fear through the nuclear scientific community, according to Stern. “I think it is definitely creating an atmosphere that is not conducive to science and that it will stifle creative scientific research.”

Some scientists say Lee’s security breach is cause for concern. “The information he downloaded he shouldn’t have downloaded,” Gusterson says. “I don’t know anyone at the lab who thinks that it was OK for him to download it. I think every scientist at the lab cuts a corner every now and then on security rules. But what Wen Ho Lee did is really serious. If you say that some weapons scientists do the equivalent of going 65 miles an hour in a 55 mile a hour zone, what he did was like going 120 miles an hour in a 55 mile an hour zone.”

Still, Gusterson thinks the reaction to the Lee case has been unfair. Employees at Los Alamos are under strict orders not to talk to the press. But Gusterson says people he knows there are finding the increased security measures very difficult to work in. For example, he says, since the Lee scandal erupted, computers at Los Alamos no longer contain floppy disk drives, making it very difficult to work on a project on more than one computer. Employees are now required to turn off their computers and lock their safes every time they get up to go to the bathroom. “It makes it really hard to get your work done,” Gusterson says.

Besides that, Gusterson says, the Wen Ho Lee case has lowered morale. “That image of him shackled while he meets with his family haunts a lot of scientists at Los Alamos. They’re determined that they are not going to be the next person in that picture.”

And some observers say security lapses at Los Alamos have been a problem, but that the situation is not so dire as to endanger national security.

“People seem to have gotten a bit loose in the handling of secrets and classified information,” says Gideon Rose, deputy director of national security studies at the Council on Foreign Relations. “There’s no excuse for lax security. It’s not ideology — it’s just basic competence.

“This is something that’s always a bit of a problem,” but not cause to get paranoid, Rose says. “It’s bad practice and sloppy security practices rather than an imminent threat to the country.”

He sees the larger problem as part of a built-in tension between science and security. “The fact is, civilians and scientists do not take security as seriously as professional intelligence people,” he says. “They’re just not trained to think that way, and they’re lax. But that’s no excuse for not riding hard on them. It’s very difficult to keep up the kind of semi-paranoid attitude that makes you keep your secrets secure. Especially in a time of general peace and prosperity.”

“That’s definitely true,” Stern agrees. “There’s a natural, unavoidable tension between the desires and the needs of scientists and the legitimate concerns of security personnel.” Scientists essentially try to uncover secrets in a collaborative environment. “Without openness, it’s hard to push back the curtain of ignorance, which is what scientists aim to do. It’s hard to advance at the same time when scientists are working on matters related to national security, when secrecy is critical. So there is this tension that you can’t avoid.”

But Los Alamos spokesman Jim Danneskiold thinks that tension is overstated. “In some ways, saying there’s incompatibility between science and security at a place like Los Alamos is misleading,” Danneskiold said. “Security is part of everybody’s job here. The people who deal with classified information are trained and know how to handle it.”

He sees accountability as the key. “There is no security system that can prevent people from breaking the rules.”

In Stern’s opinion, one problem is confusion about what information truly needs to be classified. In the early 1990s, President Clinton announced a widespread declassification of scientific data that weren’t such big secrets anymore. Even so, “there’s much too much that’s called classified,” complains Stern. “The classification guidelines are not up to date — sometimes they’re too onerous and sometimes they’re not onerous enough.

“In the area of nuclear weapons,” Stern explains, “we have this whole history that anything related to nuclear weapons is classified. Sometimes it’s based on outdated concern. Whereas, in the area of biological weapons, I think more should be classified than is.”

Danneskiold says the issue there isn’t what’s classified, but as how such information is handled. At a Congressional hearing July 11, two senior officials from the DOE testified that part of the explanation for the lapses is the rollback of “strict formal accountability” procedures that occurred government-wide in the early 1990s. Those procedures ensured that every document was signed in and signed out, clearly marking the paper trail.

While such a system is harder to maintain in the digital age, Danneskiold believes it is desirable. “If you asked us even today, would the lab prefer strict accountability, I think we’d say yes,” Danneskiold said. “Clear rules are what people look for.”

But critics say the rules are strangling scientists.

“The rules now are stricter than they’ve ever been in living memory,” Gusterson says. “It’s not that they’re gong back to the situation in the early ’90s. They’re getting much stricter than that.”

With morale so low and fears running high, some of the most talented weapons designers might decide to bail out of government work.

Aftergood thinks the loss of such talent “is the most important issue which is in danger of being overlooked in the current security mania. I think many members of Congress and others are prone to forget that security is a means and not an end in itself. If security becomes an overriding concern, then the mission of the laboratories will suffer.”

Stern agrees. “We need to make sure that the laboratories are still an attractive place for America’s most promising scientists,” she says. “We want to make sure that they feel comfortable working there.”

She felt me watching, and after expertly projecting a quantity of blood-red spittle that shot six feet past the side of the boat, gestured that I ought to try some. I politely declined. I knew that betel nut chewing was a very respectable pastime among older Thai ladies, but I didn’t feel I had quite come of age.

I was 26, and had a good case of Thailand on the Brain. Upon my arrival, the smog and the clamor of Bangkok could not blot out the sparkly phenomenal world that crooked its finger, beckoning me irrevocably inward. The jeweled Buddhas in the temples slurped me up into their ears, where I swore I heard the quotidian chants of the monks in their faded robes. I bought fruit from street merchants who kept tables in the shadows of gargantuan billboards that pictured ice-cold Coca-Colas pouring into thirsty Thai mouths, Ouzi-laden movie scenes of people getting blown to oblivion or the Marlboro Man riding off into an American sunset.

The merchants arranged their wares into the divine shapes of stupas — dome-shaped Buddhist shrines — and I felt slightly profane trying to delicately dislodge a mangosteen without sending Nirvana rolling to the dirt. Children dodged cars, radios blared and people smiled so provocative I felt myself falling blissfully backward from the force of them. The Bangkok air was scented with the fragrance of diesel and flower-bedecked shrines, and I became convinced that invisible Buddhas and dragons dwelt there and I, like the adored betel nut, was alternately chewed, savored and spat out by each.

By the time I had reached that apex in my journey where my bladder and I had become one, I had burned my taste buds off with a plate of green curry. (The proprietor had inquired whether I wanted it “White-Boy hot” or “Thai-Boy hot.”) I had bought a lotus flower at the floating market and, as I bent to smell its fragrance, found it to be inhabited by a scorpion who menacingly brandished his stinger at me. When I almost blew my finger off with a firecracker I had bought at a street festival — where the various gunpowder-filled concoctions had names like “Hen-Laying-Eggs” and “Bright-Minded Balls” — I figured it was time to meander south.

The worst time to have to pee is when one is surrounded by water. The gentle lapping of waves against the side of a boat is like a radio ditty for a Palm Springs Resort: Relax! Enjoy life! Let go of your troubles, and anything else you are urgently holding on to! I did not relax. I double-crossed my legs, using about 12 different muscles in an effort to barricade my bladder. How I would later stand up and exit the boat was a bridge I would slosh across when the time came. I made a decision — that if I had to choose between having the sensation of needing to take a pee for the rest of my life, or being dead, I’d rather be dead.

We were nearing the Phranang shore. The Thai lady in the hat took a tea kettle out of a basket and poured some tea into a glass. She held it out to me. That does it, I thought, shaking my head, and I stood up, managing to hold it in for a few more seconds while I asked a woman who had a German flag sewn to her backpack if she would keep an eye on my stuff. I didn’t wait to hear her response before I dived into the sea, relief spreading through my body like a drug before I even hit the water.

When I surfaced, I had been born again under a lucky star. I swam, victorious, toward the fabled white sands of Phranang that shimmered in the setting sun, just another American fool, slogging out of the sea and over to where my German friend stood waiting, pissed off, with my pack. “Danka schvn,” I said, as she stomped away. I decided to sit on the beach and dry off a bit before looking for a guesthouse.

As I sat watching the stars sidle out, one by one, I felt as though I had untied a heavy anchor that had been weighing me down forever. The nerve endings on the surface of my skin seemed to spring to attention, and luscious pheromones exuded from every pore. Large populations of glittery creatures were fluttering in my bloodstream, silver dragonflies, pink butterflies and golden honeybees of love.

Alas! I had no fine sweetheart with whom to indulge in my randy persuasion. As I watched the waves, the sparkles I felt inside me seemed to be floating there as well, whole galaxies of twinkling heavenly bodies, and I wondered if perhaps back in Krabi, some up-country opium poppy seeds had been tossed in along with my tea. Dazed, I watched as a shimmering humanoid form rose up out of the water, glowing from head to toe.

It was one of those terrifying “Twilight Zone” moments. Yikes, I thought, and immediately flashed back to a high school-era peyote ritual gone awry that had manifested a 10,000-fold hallucination of my algebra teacher, Sister Ursula, with Hinduesque undulating arms, millions of chubby hands grasping chalk and a great omnipresent mouth that bespoke, “The sum of X is equal to the square root of Y.”

Realizing that the sparkle-clad figure was heading my way, I jumped to my feet and started running like the dickens, an instinct I am quite proud of. I ran along the beach, toward a rocky outcropping, and a glow that came from the rocks. As I got closer, I forgot about the strange figure, entranced by what I realized was a cave that was lit from within. An unfurling of incense and a flickering soft light beckoned me into its recesses, and dang! I bet you can’t guess what I saw!

Scores of wooden penises, painted a shiny red, were wedged, stacked, glued with melted wax to every spare inch of a candle-lit altar. They were penises, there was no mistaking them, they were the most alert-looking save-the-race representations I had ever seen. Something inside me churned. I watched as phallic shadows flickered on the walls of the cave, a contingent of jiggling johnsons. The whole spectacle was starting to give me the willies, when I heard a voice behind me.

“Have you come to ask a favor of the Sea Goddess?”

I jumped. There stood a man, a Brit, by the sound of him. He was dripping wet, must’ve just come from an evening swim. He wore the shortest, tightest cutoffs I’ve ever seen on a guy. Aside from this disconcerting stylistic detail, he was handsome — by my book, anyway — with fetching eyes and a dark, well-groomed beard. He smiled.

“I’m Walker. I saw you running, thought maybe something was wrong. Or have you come to place an offering on the altar?”

“Melinda” I gasped, catching my breath. “So …” I said, trying to act casual. “Penis Voodoo Cave, huh? … I’m afraid I didn’t bring an extra phallus with me today.”

He laughed.

“This is the Princess Cave,” he said. “The local fishermen place these wooden beauties in here to appease the Sea Goddess, hoping for luck and protection on the seas. Legend has it that she gave birth to an earthly man, whom she created to be her lover. He would come down to the water to meet her, and they would frolic in the waves.”

I shivered. “I saw,” I said, “I mean, I thought I saw a glow-in-the-dark person, I know it sounds weird …”

“It was I!” Walker said, a sparkle in his eye. “What you saw were phosphorescent plankton, microscopic algae that feed on diatoms. This particular type are dinoflagellates, with flagellating tails. You know, like sperm. They can stick to your skin. The dinoflagellates, I mean.”

Hmm.

We talked some more. Walker told me he was taking a break from anthropological fieldwork in Malaysia. Came to Phranang to do some writing.

“About life in the bush?” I asked.

“Not exactly. Poetry. Letting all the smells and tastes and everything I’ve absorbed for the last eight months float up to the surface, burst out of me and onto the paper.”

“I know what you mean,” I said. “I wonder if those dino-flago-thingies got into the drinking water. I’ve been sending cryptic postcards to my friends about being brainwashed by squids and Buddhas and Thai beach boys.”

“Lovely!” Walker exclaimed.

And he was. Lovely. Especially lit by candles and surrounded by penises, which I stared at to avoid flagellating into his hazel eyes. That little vial of rationale I kept for emergencies on a top shelf of my mind — the one that comes complete with a subliminal tape-loop of my mother’s voice, which to listen to is about the same as wearing a chastity belt — I could feel it shatter, exploding from the pressure of the high-voltage current coursing through me. As I felt the last few shreds of common sense take flight, I tried to recall all the variations I’d ever heard on the theme of male genitalia: Peter, Prick, Rod, Demon Stick, Dong, Manhood, Boner, Tumescence, Tool, Schlong, Old Betrayer …

“Would you like to go for a swim?” Walker said. It was a sportingly grand idea. I had to get out of there before I did something rash. I figured, in my state, water would be safer than the Princess’ Penis Palace.

“Ayo!” I said.

We walked down to the water. As it happened, I didn’t have my bathing suit on, but I was wearing underwear and a bra that were a reasonable representation of one. Although it was dark, I shyly slipped out of my clothes behind a palm tree. Unbuttoning my shirt and my fly in front of Walker seemed very provocative at the moment, even if only to dive into the sea. I didn’t need to whip myself into any more of a lather than I was already in.

The water was warm and calm, with glowing clouds of shimmering plankton creating a magical soup. We goofed around for a while in the water. Walker showed me how to play a “water drum,” making African-style water music while I attempted water ballet. I think we were talking about something, the mating dances of the Trobriand Islanders, maybe, when all of a sudden the sparkles on my skin and the sparkles on Walker’s skin had this overwhelming magnetic attraction to each other. It’s the only way I can explain it.

There is something about touching somebody while immersed in the sea that is pure molecular biology. Like reproductive cells that are composed entirely of single-minded purpose, the surfaces of two bodies, when united by water, unconsciously seek each other out. Then, a chemical reaction takes place, magically cleansing away one’s past, present and future sins. At least while in the water, anyway.

I won’t say that anything came between me and my Calvins that night, because it didn’t. But it just as well could have, for all the intoxication of that swim. During what liquidy conversation we did have, Walker mentioned that he was leaving on the late boat out of Phranang in a few hours, back to Krabi to catch an all-night bus to Singapore … and would I come along?

Sometimes in my life I feel as though I move through space as if propelled by a benevolent force. I dip into the shimmering poppy bowls of life, sucking nectar from each like a butterfly, seeing myself reflected in everything with wide-eyed familiarity. This, my mother says, is called narcissism. I fight against that idea. I am NOT a narcissist! the narcissist sobbed. Maybe I could explain what came after that evening swim by telling you how all that is good inside me became inspired to divide and multiply, a bizillion cells of beneficence splitting off into infinity. Maybe I could find a scientific explanation for why sometimes my feet don’t quite come in contact with the ground when I walk. Especially in places like Thailand.

Walker and I sat under a palm tree, dripping single-celled organisms, while I tried to figured out how to bail out on the beautiful inlet of Phranang, when I had hardly arrived. I told myself that the roaring tsunami wave of lust approaching from the horizons of my veins was not the reason I was catching an all-night bus to Singapore with a man I hardly knew. I convinced myself that it had to do with wanting the shimmery perfection of the moment to stay permanently fixed in my memory, without some bum moments busting in and taking over. Like getting eaten alive by bed bugs. Or getting the runs. Or running into those three Australian guys I met in Bangkok, whose vacation pastime was to go from village to village, sampling and comparing prostitutes. If I hung around that Penis Voodoo Cave much longer, I might unwittingly become an instrument of the Sea Goddess, my sole purpose being to beget more lovers for her enjoyment; or find myself addicted to the Love Sparkles in the water, forgetting who I was and where I came from, and never, ever be able to leave.

Armed with a dozen rational justifications, I left at 9 p.m. to catch the all-night bus to Singapore.

I could tell you about how Thais like to watch machine-gun videos at maximum volume at 2 in the morning while riding on buses that take mountainous turns at 45-degree angles, threatening to pitch themselves into the lush gorges below. I could tell you how two people can share a blanket and watch the glow of sparkles rising up and bursting through its surface. I could hypothesize how lust isn’t a nasty thing (or maybe it is). It’s about being a pilgrim of the flesh, making devotional offerings to the molecules of another, molecules that are, like Tuvan throat singers, chanting your name and the name of the universe multitonally, so they sound as one.

A scientific theory, anyway, that Walker and I thoroughly tested.

For all that modern medicine now knows, Nyland confesses that at least one anatomical mysery remains: Doctors are still puzzled by the spleen. Nuland also interlaces his historical anecdotes with operating room experiences to show how medicine has benefited from centuries of imaginative speculation about how the human body — especially the above-mentioned pieces — works.

When I phone Nuland at what I think is the hour of our appointed interview, it sounds as if he is in the middle of something. My call is a surprise.

“I’m sorry,” he explains. “It’s so strange. I’ve been reading my book and I’ve gotten so absorbed in it that I’m not even thinking about what I’m doing or where I am. This is the most peculiar egotistical thing.” As he speaks I realize I made a mistake and phoned 15 minutes sooner than I was supposed to.

“I read the reviews of my book,” he continues. “And one of the reviewers said ‘so and so and so and so.’ I said, ‘I’ve got to read that!’ So I read five or six pages. What I just started reading was the final chapter, as a matter of fact. The so-called epilogue. I read it about three times since the book came out. Once I start reading it, I become completely absorbed in it because even though I’ve gone over it so much, it always seems so …” Then he whispers, “I know it’s so strange.”

“Do you like your writing?” I ask.

“I love my writing!” he says enthusiastically. “You know why? Because I write out loud. I essentially talk my way through a book. And the kindest comments that I’ve ever had about my writing come from my friends, who say, ‘You know, we know you. This is the way you talk.’”

“You’re a very good writer,” I tell him.

“Thank you,” he answers. “You’re so kind.”

Now, would I want you to operate on me?

[Nuland is not amused.] Well. I didn’t get to be a professor at Yale without being a pretty good surgeon.

As a surgeon, do you have a favorite organ?

My favorite organs are the heart and the spleen. I go into ecstasies about the heart.

I’m not sure I understand what the spleen does.

Welcome to the group, my man. That’s why it’s called the organ of mystery. No one has ever been able to figure out why it is tucked up there under the diaphragm, why it’s that peculiar color [it's red when it's in your body but turns green when it's plucked out!] or what it does — although it has been increasingly discovered that it not only acts as a filter to get little particles out of the blood that don’t belong there, it destroys blood cells that are old and need to be destroyed so they can be re-created in the bone marrow. It’s very effective as part of the immune processes.

I have to make an intellectual confession. I refuse to believe that the four humors don’t exist. [In his book, Nuland writes, "The notion of the four humors is related to a doctrine developed in the 5th century by the Sicilian natural philosopher Empedocles. Empedocles taught that all matter is composed of one or more of four elements: fire, air, earth, and water." Nuland further explains that the four elements were represented in the human body by the four humors: fire = blood (heart), air = yellow bile (liver), earth = black bile (spleen, stomach) and water = phlegm (brain).] This is the most sensible thing I’ve read.

Why?

It means that I’m not one thing.

You have any proof that the humors exist?

A lot of time I believe I’m filled with black bile.

You have to admire something like this that flies in the face of proof to the contrary. I think it would be terrible if we lived in such a mechanistic universe that people weren’t free to believe in the four humors. I really feel that way. I hope something in this book liberates some of the readers to liberate themselves and think about the humors and believe in them. We wouldn’t have magic. We wouldn’t have poetry. We wouldn’t have romance if something in us couldn’t believe in the humors or some similar notion.

Is the human body perfect?

No. The human body is the result of evolution. If the human body were perfect, we wouldn’t have to wear clothes. We wouldn’t have to live in houses. The whole aim of evolution is to make the animal independent of the environment, if you can say evolution has an aim. We will never be perfect because what we’ve done with our culture has overcome our environment. We don’t have to be perfect. We’re not going to evolve anymore.

Could the human body be more efficient than it is?

Oh sure. We could digest far more efficiently. It could respond to certain dangers far more efficiently. It could control mutations in the cells more efficiently so we wouldn’t develop cancers. It could handle some of the food we eat in such a way that cholesterol wouldn’t get deposited in our blood vessels. It could have a brain of such nature that we could immediately recall every experience we’ve ever had. Those are plenty of ways in which it could be better.

You don’t talk about the brain in your book. I have these arguments with my wife about the brain. I believe that I am my brain. My wife believes the brain is just another organ.

I think you’re both right. It’s just another organ, but you’re in your brain. The brain, after all, is what the biologists would call the head ganglion. Everything proceeds from there; it’s the control center for everything we do. The mind couldn’t exist without the brain. The mind is a function of the brain.

Is Sherwin Nuland in his brain or his heart?

He’s in his brain. That’s one of the purposes of writing a book. He is thought to be in his heart in certain times. He is thought to be in his stomach. There are those who even thought he was in his diaphragm. Now we know conclusively that he is in his brain.

How do we know that?

Ha ha ha. Because we know that none of those other organs have any possibility of consciousness. We know based on CT scans, MRIs, that thoughts arise in the brain — that every stimulus that one responds consciously to is the result of activity on the brain. Parts of our brains are lighting up as you and I are talking.

You outline all the mythology surrounding the heart, but in the end the heart is just a muscle?

The heart is only a muscle with certain electric conduction systems in it that enable it to pump without needing to be stimulated with every beat. That’s all it is. But, of course, metaphorically the heart is the center of emotions. We’ve inherited it from several thousand years of civilization because they can feel the heart beating. They can feel the heart getting excited and beating harder. When we’re depressed we feel heavy weights on our heart.

You wrote that mysticism, superstition, philosophy, religion and deceit are in opposition to the science of medicine. What about faith? Is faith just faith, or can it become as concrete as science?

We wouldn’t call it faith if it were anything other than faith. We choose the word “faith” because we accept things on faith and don’t seek proof. Why do scientists reject those who have faith because there is no proof that anything they believe in is true? Those who have faith don’t want evidence. The great strength of their belief is faith. In fact, I have jokingly said if God were to appear on Earth, I wouldn’t be surprised if a lot of people stopped believing in him.

Here’s a real elementary question: I was interviewing a woman about the flu and realized no one can answer whether a virus is alive.

Oh, the question of the age. Oh, if I could prove that one way or the other, I could go off to Oslo and pick up my prize. A virus is alive in the sense that it can reproduce, but the criteria for life include things like spontaneous movement, digestion, respiration. A virus can’t do those things. So, strictly speaking, it does not fulfill all the criteria that a good biologist would expect of life. But the fact is, they can reproduce from each other because they have the DNA.

But what drives a virus to do what it does?

It is not driven to do what it does. It’s like any chemical; it’s a hunk of DNA. It’s a chemical compound, and when it gets near certain other kinds of chemical compounds it automatically, by the forces of physics and chemistry, functions a certain way.

Is there some different life impulse that transcends faith and virus? What did you call it in the book, vitalism?

Yes. The old belief that there’s a life impulse in there beyond the physics and chemistry. Vitalism has been dying a very slow death. In fact, it’s quite dead because everything that we ascribe to some special vital phenomenon can now be understood in terms of ordinary physics and chemistry.

So life is just chemistry and physics?

I wrote a whole book about this, “The Wisdom of the Body,” which is now called “How We Live” in paperback. We are creatures of physics and chemistry, but Bowman lives in your mind. We have created an entire culture of emotions and spirituality of poetry, music. And that’s what life really is. The mere fact that something is living by biological criteria doesn’t mean it contains life as most sentient, thinking human beings would define it. I write a column every three months for the American Scholar, and I talk about the fact that scientists during the next couple of decades will develop what is called the minimal genome, the number of genes to reproduce another living thing. You can call that life, but life is a philosophical concept. It’s a theological concept. It has all sorts of implications, so there’s no way to answer your question.

How do you repress being a philosopher when you cut someone open?

It’s necessary to get into a completely detached head space when you’re cutting someone open. If you attempt to think about that person’s life — whom they love and who loves them, who depends on them, what will happen to an entire life stream of people if things don’t go well — you’ll lose your objectivity. You’ll lose — how can I put this? — the coldbloodedness that is necessary to make decisions. It’s easier to raise a cup of tea to my lips if the person on the other side of the table is neutral in my life. If the person on the other side of the table is someone whom I’m falling in love with, my hands will shake.

There’s all kinds of symbolism in what we do in an operating room. We wash ourselves; we purge ourselves of any outside influences; we drape the patient so thoroughly so we don’t see this patient. The patient is asleep; he’s inarticulate; he’s unresponsive. He becomes a subject detached from his humanity. And all this comes out in the symbolism of the drapes and the gloves and the anesthesia. When we operate we’re a team. The patient is not one of us — he’s not part of that team. We work on him, we work for him, but we don’t work with him.

Do doctors ever question that procedure?

What procedure?

The one you just described. I can imagine a group of New Age doctors saying, “Let’s all put our foreheads on the patient’s body and heal her with our third eyes.”

There’s no such thing as a New Age surgeon. Surgery is an artistic kind of craft. It is real. Surgeons function essentially the way a craftsman functions: “I love the way this dissection is going. This feels so right to me. It’s beautiful to look at it. It feels just right. It’s coming together. Oh, I love this job.” Yet at the same time that surgery is the most direct thing you can do — because you’re holding it in your hand — it’s also the most abstract because you must abstract yourself from the reality of what the hell you’re doing here. You’ve got your hands inside a body of another human being.

Every once in a very, very great while, one gets into dreadful trouble operating. It might be once a year; it might be every couple years. One becomes panic-stricken at what one has done. I’m talking about the trouble you get into because you made a dumb move. What you’ve got to do is get out of your mind and remain absolutely ice cold.

This is a personal question: Are you an organ donor?

I’m 69 years old. The only organs of mine that are worth anything are the cornea and the skin.

Any thoughts about organ donation?

Different perspectives. A lot of people are dying because we don’t have enough organs. I’ve known several people dying waiting for hearts. One must encourage organ donations. There will come a time when we won’t need organ transplantation — in the meantime, one must do everything they can.

The reason I asked about organ donation is because of the cultural mysticism of the heart. Your heart really is you. Maybe it should be buried or burned with the rest of you. Maybe it screws up the transmutation of your soul if your heart is in another’s body.

[Laughs.] There’s a whole literature of interviews with people who have had others’ hearts transplanted into them and how it affected their psychological functioning. I once wrote a story in the New Yorker about a heart transplant. The patient is really obsessed with thoughts about “Who’s heart is this inside of me?” You don’t often hear people saying this about transplanted kidneys or livers, but the heart has a different symbolism.

Is it just symbolism? Couldn’t there be something really uniquely David Bowman about my heart?

You’re a good mystic — we need more like you. I’m scientifically trained. I refuse to believe in anything supernatural. I believe it’s straight symbolism.

I wouldn’t want to donate my brain to someone else. How do we know that there isn’t something individual that resonates in our hearts?

Let’s put it this way: The only neurological tissue in the heart is tissue that carries electrical impulse to make the heart beat. There is no tissue in the heart that is capable of thought or the transmission of information.

I hope I sound more like Dr. Frankenstein than some New Age guy.

No. You sound like the kind of guy who could write fiction and poetry and music, because the essence of the culture is this kind of metaphor. What I’m trying to get across in my book is that we’ve inherited this from thousands of years of mystical and magical thinking. What we have to do is accept this mystical and magical thinking for what it is and use it — use it to enrich our lives. [Pause.] But I wouldn’t rely on it to cure my pneumonia.

That’s because Mullis invented the polymerase chain reaction, or PCR, a technique that makes a billion copies of one tiny gene, thereby allowing scientists to study that gene in great depth. As the historic Human Genome Project pulls into its home stretch, physics passes on to biology the mantle of most revolutionary science. In the last century we conquered the atom; now we will conquer the gene. And we will do it with PCR.

So Mullis must be an august man, writing his memoirs at the National Academy of Sciences, receiving policy makers and reverent fellow scientists in his book-lined study the way Papa Einstein did, right?

No way, dude! Mullis is like hangin’ 10 in La Jolla, surfin’ every day, brewskies in the fridge, LSD whenever. (Hey, he knows how to make the stuff.) Aliens occasionally visiting. A sexy new wife (since all the women at scientific conferences finally got sick of his lechery). And he just had a book published with his naked bod on the cover. Far out!

Actually, neither of these descriptions is accurate.

But the second one, Mullis as the surfer loon, is the most pervasive. I first heard about it two years ago at a bar during a conference in Southern California. Two geneticists were joking about how they should go find Mullis, do some drugs and score some chicks.

“Isn’t he the guy who invented PCR?” I asked, surprised. Usually scientists are more respectful of their best and brightest. They said, yeah, Mullis may have invented PCR, but all those drugs, and all that womanizing, and all those crazy ideas about mind expansion had essentially placed his reputation in the alleyway trash bin, but he was fun to joke about.

When Mullis won the 1993 Nobel Prize in chemistry, journalists reinforced this stark morality tale: Boy genius invents a great thing but then behaves so irresponsibly that everyone laughs him out of science’s good graces.

With his own book, “Dancing Naked in the Mind Field,” published in 1998, Mullis fumbles the chance to show the world he isn’t a fool. His writing is not thoughtful enough to justify his eccentricities, and the book makes him seem the jester people say he is. He writes, among other things: O.J. Simpson was innocent and Marcia Clark’s a hottie, humans don’t contribute to global warming and HIV is not the cause of AIDS. He purports to have found astral planes by scientific method, he relishes old tales of seducing women and taking drugs and he pooh-poohs current science.

“I’d put 90 percent of our present expenditure for physics and space technology on [finding asteroids that might hit Earth],” he writes. “The other 10 percent should go to looking for aliens.” All of this is too challenging to simply glide over; and the lack of deeper explanations makes the man seem facile.

When I tracked down Mullis for an interview (his first for a major magazine in almost two years), I was primed to get some of those juicy “No way, dude; let’s do some LSD!” quotations to jazz up my profile. Of course, character being different from caricature, I didn’t get any.

During our hour-long phone conversation, Mullis spoke nothing like the bar-stool imitations of him I have heard scientists do. He has a soft voice that retains the diphthongal calm of his native South Carolina. It is indeed a good voice for a successful womanizer, but I was struck more by his consideration in answering my questions. His speech had none of the silly jumpiness of his book. I asked him why so many scientists dislike him.

“I’m not driven by being understood,” he told me without raising his voice. “I don’t try to be contrary, either. If I say, ‘Hey, there’s no reason to think that human beings have any long-term control over the weather,’ I am telling you what I know. No one contradicts me honestly; they just shout because they dislike what I say.”

He means what he says; it’s important to him. He has ideas that belong on astral planes. But there is also passion — the energy of a wide-ranging mind that disregards barriers of inquiry most of us heed. And there is hurt for being laughed at by the same scientists who have built their careers on PCR, the invention he gave them.

Mullis grew up in Columbia, S.C., in the late ’40s and ’50s. He showed a prodigal ability to blow things up: He gassed his grandmother (not lethally), and he torched some trees. At the time, he told me, he considered explosions part of a normal boyhood, and he laments the fact that today, “You can’t ask your pharmacist to stock larger quantities of potassium nitrate because you want to make a bigger rocket.”

Through Georgia Tech and graduate work at the University of California at Berkeley in the late ’60s, Mullis mixed things well. He was creative and exacting in his work because he loved chemicals and catalysts. He was creative and expansive in his personal life because he loved sex and substances.

One of his thesis advisors at the time, Henry Rapaport, remembers that he was in love with learning; he took so many classes, both in and out of science, that his advisors had to be taskmasters in getting him to finish. Rapaport, who wonders if he might otherwise have stayed forever, also notes that Mullis was “attracted to the obscure and unusual.”

It was at Berkeley that he learned to make LSD, and though he wouldn’t talk with me about it, a clear theme across the anecdotes in his book is that he likes it still. To him it is indeed a mind-expanding substance.

It doesn’t help his image that Mullis looks like a cross between David Letterman and Gene Wilder. His eyes smirk at the world. It’s not hard to imagine him smirking his way through his first marriage, through at-home experiments in which he tried to turn off lights by wiring himself into an electrical circuit and then “willing” the lights off, through the seduction of nurses from his wife’s medical school with this trick, through suggesting to the queen of Sweden at the Nobel ceremony that his son marry her daughter (she declined) and through the writing of his book, which begins — in a preemptive strike against those who will laugh at the rest of what he has to say — with the invention of PCR.

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He was smirking through the windshield of his Honda on a windy road in Northern California late on a Friday evening in May 1983. His girlfriend was in the seat next to him, and they were on their way to a romantic red-wine weekend for two. He held a job at the time in a small biotech company called Cetus, which had been founded by, among others, Carl Djerassi, the inventor of the birth control pill. As he drove, his mind was debriefing after a tough day in the lab. His work at Cetus involved DNA, and, like everyone who worked with DNA in the early ’80s, he wanted to be able to make more of it, to get it to copy itself in a lab so he could study and manipulate it. Watson and Crick had shown that DNA is the recipe for life; scientists were desperate for an easy way to read it.

Part of his work involved now archaic ways of getting genes to replicate — it took months and was heavily error prone. There must be a better way.

The muse descended, the idea came, Mullis pulled over. He searched the car for paper and pen and started writing, despite complaints from the girlfriend that they should go on to the house first. It was so easy, such an elegant idea, simple and effective. The polymerase chain reaction “was a chemical procedure,” Mullis later wrote, “that would make the structures of the molecules of our genes as easy to see as billboards in the desert and as easy to manipulate as Tinkertoys.”

Genes are double strands of chemicals, and the whole kit and caboodle of them, the entire recipe for life, is made of just four chemicals: adenine, thymine, cytosine and guanine. Think of each strand as a long string of these chemicals lined up in a row like beads. When two strands of DNA come together to make the familiar spiral-staircase helix (which graces the letterhead of so many biotech companies), these four chemicals get very picky: adenine (A for short) will only line up across from thymine (T) on the other strand. You never see two A’s or an A across from cytosine (C) or guanine (G). C and G likewise form an exclusive pair.

Here’s PCR in a nutshell: Put the gene you want to look at in a pipette with a little liquid. Heat it up and the double-stranded helix breaks apart. Each string of chemical beads drifts off by itself. Throw in a large and random assortment of loose A’s, T’s, C’s and G’s, and the individual chemical beads will seek out their pairs on the single strands. Once every chemical letter on each original strand has a new partner bead (the same-letter partner it always has because of chemical exclusivity), you cool down the mixture and the new rows of partner beads anneal into strands of their own, conveniently providing a new half to each original strand.

The helix reforms and — voil`! — you’ve made two exact copies of the one gene you started with. Heat these two up and you have four separate strands. Throw in more loose chemical letters, let them pair up and you have four identical genes. Repeat this process 30 times and you have more than a billion copies of that one piece of DNA you started with — cartloads of it in lab terms.

So begins the genetic revolution. Without PCR, genetics is like trying to do experiments on one droplet of milk sitting on a white plate. The milk is hard to find, and you only have enough of it to try one thing — such as add a droplet of orange juice and see what happens — and that’s it. You are limited in experimenting if you only have a tiny amount to play with. PCR makes genes by the milk pail, and scientists are thrilled.

Take Anne Blackwood, an oncologist at the University of Pennsylvania in Philadelphia who treats breast cancer patients and runs a lab looking for a cure. Cancer is caused by the slow accumulation of mutations in the genes of cells. To get any real sense of what’s going on in the earliest stages of cancer, when only a few cells are worth looking at, Blackwood needs PCR to multiply the mutated genes.

Blackwood is also developing a long-term database of breast cancer types. She has a library of microscope slides of tissue biopsies — tiny samples, some of them more than 10 years old. Using PCR, she can tease out the genetic profiles of each tissue sample and make a record of the mutations she sees. Such a large, statistical study of how cancer works is rapidly improving prognostic capabilities. It is also getting doctors much closer to a genetics-based cure.

Genetics-based cures are the Holy Grail of the Human Genome Project, the research that is mapping out all the genes in the human recipe book. Such mapping requires incredible amounts of gene replication; without PCR, it simply wouldn’t be feasible.

Since PCR is ubiquitous in all pursuits “genetic,” it is worth listing a few more: A hair left at a crime scene can find its owner through PCR. By the same token, DNA evidence, readable through PCR, has exonerated more than 60 innocent people on death row. (Mullis likes this one: “It always gives me a boost when some poor bastard that’s been in there for 10 years is set free.”)

President Clinton was discovered on a blue Gap dress, big boy writ large through PCR. Evolutionary biologists recently proved through genetics that hippos and dolphins are more closely related than hippos and pigs, despite fossil evidence to the contrary. Humans share just shy of 100 percent of our genes with chimpanzees — we are minimally different items. Lettuce and humans share 40 percent; lettuce and mushrooms share less.

Astrobiologists haven’t used PCR yet; but scientists at the National Aeronautics and Space Administration have launched a probe to bring dust from the tail of a comet back to Earth. If they find microbes in that stardust, they will run it through a PCR machine to see whether life on Earth was seeded by a comet.

Indeed, Ted Koppel and the rock stars cannot match PCR, and it is good of him to admit it. Neither can most living scientists, and yet they are not so generous. Why the sidelining, why the laughter? Why must Mullis wear the dunce cap? It depends, of course, on whom you ask.

Rapaport thinks it’s Mullis’ ego. Rapaport, who had close ties to Cetus, does not dispute that Mullis invented PCR on a roadside in Northern California — in a sense. But, he says, science hates the “Hollywood hero,” the notion that one person creates something complete at the moment of “Eureka!” What Mullis had, says Rapaport, was a theory, nothing more. From there, it took a handful of arguably equal intellects at Cetus months of hard work to take Mullis’ notion and create a real PCR, one workable enough for the Blackwoods of the world to do something with. “Reduction to practice distinguishes the brilliant idea from malarkey,” says Rapaport.

As for malarkey, says Dan Koshland, a famous Berkeley scientist who knew Mullis, look at everything else he’s done. It’s fine for a chemist to agitate about matters chemical, but when he sticks his nose into AIDS and global warming, he has crossed boundaries of professional knowledge that should be respected, Koshland says.

And the problem is his prize: He can’t be ignored. “He was a free spirit before he got the Nobel Prize,” Koshland says. “Now he’s a free spirit with a Nobel Prize.” And that’s just tiresome: “His views on social issues are irrelevant.”

“In the scientific community, there’s a great deal of mutual respect for everybody, the realization that every worthwhile invention is a series of small steps taken by many people,” says Rapaport.

Of course, the Nobel committee singles out scientists, and Mullis was very happy to be glorified all by himself, Rapaport says. Whereas most scientists do a less eloquent version of Isaac Newton’s “If I have seen further it is by standing on the shoulders of Giants,” Mullis’ book mentions only bitterness toward those at Cetus who tried to take some credit for PCR. Rapaport notes, “If he’d been on a desert island, he wouldn’t have come up with it.”

Rather than protect Mullis’ eccentricities, scientists mock them. But there is more to it than that: There are plenty of scientists, Nobel winners and others, who enjoy splendid suites on the top floor of the academy even though their kahuna-size egos prevent them from acknowledging that anyone might have helped them in that one great thing they invented once upon a time. So Mullis’ own explanation for his excommunication may have some merit.

To his mind, modern-day science is a sluggish beast that isn’t ready for the world-changing questions he’s asking about global warming and mind reading. “I am playing by what I consider to be the rules that have worked pretty well for science over the last four centuries,” Mullis says. “You make observations, write theories to fit them, try experiments to disprove the theories and, if you can’t, you’ve got something.”

When he applies these rules to certain topics he finds interesting, people don’t get it.

But come on, astral travel?

“Look at any notion that 19th century scientists held as unassailable truth about the universe,” Mullis retorts. “Anything: the nature of light, energy, matter, time, space. How silly those ideas, how wrong they are to us now.”

It is true: Einstein’s relativity shows that matter curves space and that time slows down when you speed up — concepts that Newton would have found more absurd than the existence of angels. One major reason we progressed past the absurdities to what we now call truth was the adherence to scientific equipoise — the concept that requires scientists, in the face of the unknown, to consider all possible explanations. So if astral planes and global warming are open questions (arguably they are), then the out-of-hand dismissal of Mullis demonstrates a lack of equipoise. Scientists therefore make a cultural decision, not a scientific one, when they marginalize Mullis as a fool.

Mullis identifies the cultural decision this way: “Science has not been successful by making up explanations of things that fit with the current social fabric.” But modern science, supported by taxpayer money and held accountable to a press and a public, is compelled to fit the social norm. It cannot afford to step out on limbs of revolutionary thought (though arguably it does — look at string theory). Mullis considers himself a revolutionary, laughed at by those who will only cling to the trunk of the tree.

No wonder they don’t like him, and they certainly won’t accept that reading of his ostracism. In part because of this ostracism, and in part because of his own love of other things — from surfing to LSD to writing to his new wife — Mullis has not done much new science since PCR.

But he told me he is involved in a new start-up that is using compact disc technology to read genes in blood. He could not tell me much about it for proprietary reasons, but the idea is that you could smear a little blood on a disc and read the genes there in a CD player. This technology will have to go head-to-head with the “gene chip” technologies already far into testing phases. The bedside genetic analysis of patients these technologies offer would bring about a revolution in medicine as large as PCR has already wrought.

Whether it will be Mullis who does it — a second time — remains to be seen.

I’ve done my reading and talked to the experts, yet remain confused and uncertain. My politically incorrect, shoot-from-the-hip conclusion is that more studies aren’t going to solve the problem. The controversy is here to stay because the problem is in the nature of medical studies in general. Questions for which there are few confounding factors and absolute, objective measures are relatively simple to answer. But once there are multiple interacting variables or the effects being measured are not entirely objective, all bets are off.

Let’s take a look at HRT and see what is and isn’t possible to understand. Estrogen helps prevent osteoporosis. We know this because we have a specific measure of bone density and can compare post-menopausal women who take and don’t take HRT. We can argue about measurements of bone density, but these are minor quibbles that can be resolved.

Similarly, we know that estrogen reduces the incidence of cardiovascular disease. Using objective tools such as EKGs, cardiac enzymes and MRI scans, we can objectively determine the incidence of heart attacks and strokes.

But what about HRT and breast cancer? Breast tissue contains estrogen receptors; estrogen stimulates cell growth. Most breast-cancer cells (perhaps two-thirds) are estrogen-receptor positive (respond to estrogen). There is a statistically increased incidence of breast cancer in patients on HRT. Tamoxifen, which blocks the effects of estrogen on breast tissue, is a major advance in chemoprevention of breast cancer, though not without significant side effects, including an increased incidence of endometrial cancer.

So isn’t estrogen bad for women at risk of, or who’ve had, breast cancer? It’s not that simple. High-dose estrogen (stilbestrol) was once a treatment for metastatic breast cancer, with large tumors undergoing dramatic, though temporary, reduction when exposed to estrogen. Several recent studies have shown that women taking HRT when their breast cancer was diagnosed had a better prognosis than those not on HRT. (Many doctors in the U.K. now feel that HRT is to be recommended for patients with a history of breast cancer.)

My first impulse is to wonder if some studies are better than others, or whether some overarching study might be able to answer the question. But I stop myself. The problem may lie elsewhere, in hidden possibilities and the unpredictability of interacting influences.

Though we are great at planning and calculating, we all recognize the profound role of random or inconsequential events — the missed planes, serendipitous meetings and odd mistakes — in shaping our lives. Such events, though we try to control them, also shape the outcome of medical studies.

A weather forecaster understands this dilemma, shrugging when we ask if it’s going to rain tomorrow. “Maybe. I’d say an 80 percent chance.” Because we can cover our bases by carrying an umbrella and a sun hat, we do not fret over the limitations of the weather report. Not so with medical studies. Too much is at stake and we need to feel in control of our health, so we act as though medical problems have more definite solutions than weather predictions.

(If you think that, with a proper design, all medical questions can be answered, consider the field of nutrition. Every week there’s a new study with different recommendations. I confess that it’s beyond me how to determine what is the optimal combination of vitamins, minerals, herbal supplements and fat and fiber content. It would be like predicting world weather for the next millennium.)

Which leaves women with this impossible question: If you are at risk for breast cancer, would you prefer to have a statistically greater chance of developing the disease or possibly a better prognosis if you already have it? Are the two statements in any way comparable or is this apples versus bananas? And how would we know?

Even more confusing is the relationship of estrogen to memory. At least with breast cancer, one can construct studies in which there are objective endpoints such as tumor recurrence or death. But what are we measuring when we study memory?

Neuropsychologists act as though memory is an entity that can be quantified via testing. Down deep we all know differently. Memory isn’t a white-blood-cell count or an X-ray. Anyone who has given any thought to the false memory/recovered memory controversy understands the slippery nature of the very process of remembering. Anyone who has taken speed or much caffeine or stayed up all night cramming for an exam or had major test anxiety understands how memory itself is affected by a wide variety of biological, psychological and environmental factors.

Compare the following: Psychologists at Montreal’s McGill University have recently concluded that estrogen maintains verbal memory in women, may prevent or forestall the deterioration in memory that occurs with normal aging and may decrease the incidence of Alzheimer’s disease and/or retard its onset.
Conversely, doctors from the Yale University department of internal medicine and a group of Finnish doctors feel that there is inadequate evidence to say that HRT improves cognitive function in post-menopausal women or women with Alzheimer’s disease.

Is one study is better than the other? What should we conclude? A study from Holland may shed some light on the problem. Sixty-two healthy post-menopausal women were given either HRT or a placebo and were told the purpose of the study. Those given HRT reported better sleep patterns as well as improved psychological and memory function than before taking the HRT, yet didn’t do better on memory testing than did the controls (the women who didn’t get the estrogen). Then the researchers repeated the study, but without telling the women the purpose of the experiment. This time no positive effects of HRT could be detected.

There are many possible interpretations, but one jumps out at me. Estrogen therapy can’t be given blindly — there are too many physiological changes that are easily detectable by the subjects, such as relief from hot flashes and/or vaginal dryness. So, in the first part of the study, the subjects knew what they were taking and what the researchers were looking for. They felt better (though not measurably better than the controls). When they knew what they were taking, but not what the researchers were looking for, however, they didn’t feel better.

Is the difference between the various studies I’ve cited due to a placebo effect, merely a reflection of how the researchers asked the questions, what kind of perfume the head nurse was wearing or whether free coffee and doughnuts were passed out along with the questionnaires? Were the subjects subliminally prodded toward the proper responses?

Besides the notoriously difficult-to-analyze placebo effect, I wonder how those in the control group felt about not getting estrogen, about having more hot flashes than those in the other group? Was the control group resentful, glad not to be taking estrogen, pleased to be part of a study, indifferent or a combination of the above?

What if one member of the control group read an Internet article about some new negative effects of estrogen and passed the word to the others in the group? If expectation influences results, what role does control-group psychology play? Is there such a thing as a control-group effect? And how would you know? Certainly not by comparing control groups — which would result in an infinite regression.

Surely there must be some shred of objectivity we can bring to the question.

A Yale pediatrician, Sally E. Shaywitz, has used functional magnetic resonance imaging to compare brain patterns of post-menopausal women taking estrogen supplements and those on a placebo. While on estrogen, the women showed brain patterns similar to those seen in functional MRI scans of young people. The areas of the brain that lighted up more extensively than predicted correspond to regions of the brain known to be rich in estrogen receptors.

Aha, you might think — at last a definitive objective measure of increased brain activity when administering estrogen. So far, so good. But Shaywitz made the mistake of testing the patients to see if they also performed better. Unfortunately, they didn’t. Objective evidence of brain activation wasn’t accompanied by any detectable change in memory function. Her conclusion: More subjects needed to be studied. Nevertheless, on April 7, 1999, the Associated Press headline about the study read: “Estrogen may improve memory in post-menopausal women” (a true but potentially misleading statement).

This problem of subjectivity extends to much of medicine, whether one is analyzing treatments for chronic pain, depression, social phobias, chronic fatigue or even the effects of zinc lozenges on the common cold. Symptom relief makes a lousy scientific endpoint.

We are stuck. We need a new way of asking medical questions and we need a new way of reporting results. For starters, I’d suggest that each medical article clarify whether the effects being studied were objectively measured (bone density) or were based upon a subjective endpoint (changes in memory, reduction in back pain, feelings of well-being). The article should address the very knotty problem of whether the question being asked can be answered. As consumers, we need to be comfortable with these distinctions, to know when an article represents a true scientific determination and when it simply represents subjective opinion. Only then can medical news avoid the horrible to-and-fro swings in opinion that do nothing but enhance our already considerable health anxieties.

I think of the judges at an Olympic diving competition. Each holds up two score cards — one for technical difficulty and one for artistic merit. Maybe each new medical study should be similarly judged. The connection between estrogen and bone density is a simple question. That between estrogen and memory is profoundly more difficult. We should have different expectations, depending upon what is possible.

And we should know what parameters scientists are using. An old story illustrates this: A scientist is seen crawling around under a streetlight. A bystander walks up to him and asks what he’s doing. The scientist says that he’s looking for his keys. The bystander asks him where he lost them, and the scientist points into the darkness beyond the pool of light from the street lamp. “So, why don’t you look out there?” the bystander asks. “Because I can see here,” the scientist says, continuing to search in the pool of light.

It is scientists’ obligation to tell us why they are looking where they are. It is up to us to know whether the keys can be found where the scientists are looking. Meanwhile, here is an interesting, well-balanced Web site dealing with HRT.