The eve of Thanksgiving brought a truce to the stem cell wars. When two scientists, Shinya Yamanaka of Kyoto University and James A. Thomson of the University of Wisconsin, announced in separate papers that they had succeeded in creating embryonic stem cells from ordinary human cells, they laid claim to the holy grail of stem cell research -- a limitless supply of embryonic stem cells generated without destroying human embryos. This surprising success has set off a worldwide scramble among scientists to duplicate their results.  If the results are successfully verified, scientific progress stands a chance of moving into the 21st century without the opposition of that nutty minority that thinks destroying a tiny clump of cells is too high a price to pay to save the human race. 

Personally, I am encouraged, not in the least part because I have always been one of those nuts who opposed embryonic stem-cell research. But before we pop the corks and reserve Thomson and Yamanka tickets to Stockholm, let's take a breath. There are yet a few problems to overcome. Most importantly, the new technique uses a retrovirus to infect normal cells with four genes that convert them to stem cells. This technique could be dangerous, because these four genes sometimes insert themselves into regions of the host DNA that, when activated, trigger the infected cells to spontaneously convert to cancer cells. The good news is that most researchers are optimistic that this problem can be worked out. The bad: It may take a few years to do so. In the mean time, we are stuck like parents of a child who won't move out after graduation -- eventually we know the problem will end, but we can't say exactly when.

 

In my medical practice, I take care of many patients afflicted with illnesses that stem cell research may eventually help cure. Unfortunately, while all of them want a cure now, I have to tell them that they need to be patient. This is difficult advice to give because the proponents of stem cell research are proclaiming the opposite. Listening to them, one would conclude that the cure for every known disease is weeks away if only the power of the stem cell is unleashed. Not only is this untrue, but it tempts people to blur ethical issues that need not be blurred, and may encourage short-term moral compromises that we may not be happy with in the end.

But first a few facts. Embryonic stem cells are primitive cells that emerge very early after an egg is fertilized. An embryonic stem cell is completely undifferentiated, meaning that it has the ability to develop into any cell type found in the adult, be it brain, bone, or bowel. As biologists put it, an embryonic stem cell is a totipotential cell. (To keep our terminology clear, there is another common class of stem cell, the adult stem cell, which can differentiate into a few related tissue types but not every tissue type. Adult humans have adult stem cells throughout their bodies, but only embryos have the embryonic type.)

Embryonic stem cells have been the subject of intense interest since scientists successfully cloned a sheep in 1996. That event prompted speculation that scientists could use similar technology to manufacture large numbers of embryonic stem cells for medical purposes. These stem cells, the thinking went, could then be induced to differentiate into a cell type of interest, which then would be infused into a patient to replace cells damaged in a disease process. For example, in type 1 diabetes, when the beta islet cells of the pancreas fail, causing a drop in insulin and resultant high blood sugar levels, stem cells could replace the lost cells and hopefully cure the disease.

In a turn of events rather rare in public life, this arcane line of biological thinking has become a hot political topic. If stem cells can cure diseases, laypersons wondered, what are we waiting for? Let's spend all available scientific resources in this field! This vigorous response short-circuited the customary forums for medical discussion, and quotidian public events like elections, charity fund raisers, and even movie award shows have been expropriated by celebrities and politicians urging unabated stem cell research. And, as often happens when public figures try to summarize and espouse scientific theory, misconceptions abounded.

Is this a semantic argument? Are we simply applying words to an insignificant cell, and worrying ourselves unnecessarily? I think not. Labels may be a human convention, but they also allow us to think with greater clarity and precision. When we blur what we mean by life and human, we begin to siphon away any ability we have to place limits on what researchers do in the lab of the future.

Does this sound a little like the abortion debate? Yes, but with a major difference. While an abortion has a direct impact on the life of the mother and the fetus, stem cell research has no direct impact on an adult human life. Remember, the benefits of stem cell research are wholly theoretical, and could be decades away. The remoteness of the benefit only strengthens the argument that we should minimize the harm now.

Many of the people who take the full-speed-ahead approach argue that religious beliefs should be taken out of the discussion. If we are to do this, we still have to have ethical ground rules. I propose "Killing is wrong" as a reasonable starting point. I concede that this starting point does not solve the problem of embryonic research, but at least it allows us to escape the groundless "you're imposing your religion" complaint. Though religions do regard an embryo as human, science also recognizes the embryo as alive in a biological sense and human in the sense that it is not chicken or mouse. If we can agree to this much, the issue becomes how do we apply this knowledge -- a much more useful proposition than asking why we should even bother.

Proponents of stem cell research argue that their adversaries are nothing more than fundamentalist zealots who would rather see children die than give an inch in a debate. They often go on to roll up the stem cell nuts with those who believe evolution is an error and that criminal cases should be decided in deference to the Ten Commandments.

Yet this need not be the case. I believe fully in the validity of evolutionary theory, and support the separation of church and state. But embryonic stem cell research blithely glosses the reality that we are coming closer and closer to creating human life in the laboratory. Few seem to be concerned about that, as long as we benefit from the progress. This is tantamount to saying there should be no limit to how we tamper with human life as long as there is a payoff.

I frequently tell my patients that there are cures for many diseases, but there is no cure for mortality. Cure a person of diabetes and they will die of something else eventually. We cannot even be sure that the extra years gained will be happy ones. Of course we should try to relieve suffering (I would not be a doctor if I thought otherwise), but if there is any chance that scientific advances could cheapen our appreciation for life by ingraining the idea that it is acceptable to create life and destroy it for our own benefit, we need to approach the issue with much more seriousness than we have done so far.

Nor is this concern for the sanctity of life unique to conservatives. Strict vegans often believe that we should not eat animal flesh because we humans do not have the right to kill other animals for food. Though I am not personally a vegan, I can understand and respect the desire not to kill, even if such a change, carried out to its limit, would cause significant social upheaval (think of the many people, from cattle farmers to sausage makers to waiters at Outback Steakhouse, who would be out of work if no one ate meat). I find it difficult to understand how someone could admire the morality of a vegan, and then sneer at someone else who opposes stem cell research.

At the very least, I hope for a faith in scientific progress. A realization that there are ways around problems if we try hard enough, and that there may be technological solutions for at least some of the moral dilemmas we will face in medicine over the coming decades. At the most, I dream that those not sensitive to moral issues in science will come to understand that very soon we may be capable of doing astonishing, even shocking, things in medicine, and that we might serve ourselves better if we started asking more serious questions about the meaning of human life.

This week we find that Zetia, a commonly prescribed anti-cholesterol medication, does not work as advertised. According to the ENHANCE study, a clinical trial involving 720 patients, patients who took Zetia plus the common anticholesterol medication Zocor had the same number of heart attacks as patients who took Zocor alone. In other words, Zetia did nothing to lower heart disease risk. There was even some evidence that Zetia increased the rate of plaque accumulation in coronary arteries.

Zetia-plus-Zocor is commonly known as Vytorin. Perhaps you have seen the Vytorin ads on television, the spots with a split screen that has a food dish on one side, and a person who resembles the food on the other.

The Vytorin reps have been knocking on my door for over two years. Every month of my life I listen to one rep or another as she waves a bar chart in my face purportedly showing that Vytorin has a greater cholesterol drop than any of its competitors. Vytorin is the best, they crow. You should put all your patients on Vytorin! What will they say this coming week? My guess is they won't be coming at all.

This week, doctors all around the country are being bombarded with phone calls from nervous patients wanting to be taken off Vytorin and Zetia. But not at my office. I haven't started a patient on Vytorin in my life. One, that I can recall, on Zetia, but none on Vytorin. Not to say that I have never written a prescription for Vytorin -- I have written a few, mostly refills for patients started on it by other doctors. However, I have never started anyone on it myself.

Why not? Step into my office. Chez Hébert, you will get state-of-the-art medical care -- for the year 2003. I prescribe medication the way I buy electronics. I wait until the product has been out for a while and proven its value before I consider adding it to my personal palette. An iPhone? Maybe next year. A Blu-Ray DVD player? Next spring, thanks. I am just starting to add medications to my regular practice that came out in 2004.

This isn't simply a game, or a matter of inattentiveness. My patients are not guinea pigs, and I do not believe as a rule that they should take medications that are not thoroughly proven. All drugs that make it onto the U.S. market have proven safety in clinical trials. But these trials usually only involve a few hundred to a few thousand individuals -- not nearly enough to prove safety and efficacy for the millions more who may use them.

I prefer reading textbooks to reading medical journals. Most of the papers published in medical journals are not even applicable to my practice, but those that are usually involve small trials of a few hundred subjects. Most of these studies lack the statistical power, in my opinion, to justify changing my standard clinical practices. But over the years, as these drugs are used more and more, more physicians become familiar with them and their true value comes out. Eventually this accumulated wisdom makes its way to the major textbooks, and at that point I know I am dealing with real knowledge, not hype.

There are two criticisms people may lay against my conservative approach. First, a new drug could be a major step forward, and in my slowness to adopt it, my patients suffer. Basic blood pressure medications, like metoprolol and lisinopril, were brand new once, and by my rules I would not have used them initially. To that I would point out that for every metoprolol there is a Vioxx, for every simvastatin there is a Zetia. Since there is no way to tell which new treatment is the superdrug and which is the superdud, I would have to try them all to get any real benefit. I find a good number of the latest and greatest turn out to be nothing of the sort, and while hitting .500 might be wonderful in baseball, it is a poor record in medicine. Do you want to spend thousands of dollars a year for a medication, as Zetia users have, that may not do you any good?

The critic's rebuttal: Isn't it your job, as a doctor, to review the literature and separate out the good from the bad, and improve your average? Well, yes, but how do I do that if the data are insufficient? For example, a new class of blood pressure medications, the angiotensin receptor blockers, seems to lower pressure very well. However, so far I have seen no evidence that this very expensive (and for the drug companies, very profitable) class of drugs works any better than its dirt-cheap cousin, the ACE inhibitors. So why write for a $120 drug when a $4 drug does the same job? I don't. I will only add a medication to my routine practice if it adds something to the capabilities I already have.

The second criticism is that if we don't use the new stuff, how will we find out if it works? This is a more substantial point, but also erroneous. Medicine shouldn't be guesswork, unless guessing is all we are left with. Sometimes guessing is all we have -- all the usual treatments don't work, and so, in desperation, we have to try things. This approach is acceptable if all proven treatments are exhausted and the condition being treated is serious enough to warrant taking risks. High cholesterol is a serious condition, and even now I might use Zetia if I had a patient with dangerously high numbers and everything else failed. On the other hand, if the condition is not serious, I would be very reluctant to experiment with a brand-new drug.

A few years ago Novartis launched an irresponsible public campaign to promote a very expensive ointment called Elidel. I watched sadly as many of my peers yielded to the hype and wrote for truckloads of the stuff. Elidel is a treatment for allergic skin rashes. In the vast majority of patients, skin rashes are not serious enough to merit a medication that costs nearly $100 an ounce. And it was a new medication -- the long term risks were unknown. Sure, the reps said it was safe, but they always say that. I rarely used it. In recent years there have been some concerns that Elidel may cause skin cancers, although this has not yet been proven. At any rate, it has never been shown to work better than a $5 tube of hydrocortisone.

The Vytorin/Zetia news was a heavy blow to Merck & Co. and Schering-Plough, its manufacturers. Merck is also the maker of the ill-fated Vioxx; it is fair to say that Merck has really taken some shots in the last few years. I wish I could say I feel an ounce of pathos for them, but I can't. The ENHANCE study was completed in April 2006, and Merck and Schering-Plough have been sitting on the results for more than a year and a half. Their excuse was that the data generated by the study were complex and required careful analysis. As the study release date was pushed back again and again, medical professionals, the FDA, and finally the U.S. Congress started pressuring the companies to release the data. You know things are bad when Congress has to step in to force a drug company to release medical data that ethics would dictate should have been released immediately.

Merck and Schering-Plough are mounting two defenses against the study. First, they point out that the study is small. It looked at only 720 patients, and this small number may mean the results do not apply to the general population. Secondly, the patients studied suffered from a severe, genetic form of hypercholesterolemia that is uncommon and therefore, that the results once again do not generalize.

Cry me a river. Zetia has been out for years, and if Merck and Schering-Plough had wanted to run a large study in the general population, they could have done so. They didn't because they were afraid that if the results were not favorable, they would have killed a very profitable drug.

That is how it works in the drug business. Most drugs are not tested as throughly as they could be because drug makers know they stand to lose billions if the study results are not favorable. The only solution to this problem is for the government to start funding large-scale clinical trials for FDA-approved drugs to see if they are living up to their promises. It would be expensive, but so is spending $120 a month on a drug that doesn't work. Take your pick.

To read this serial novel from the beginning, go here.

A Night In Damascus 

 
Cardinal picked up the pen. "Mr. and Mrs. Fertus E. Patriot, Ypsilanti, Michigan." The hotel clerk collected the paperwork, then went into the back to retrieve the electronic key.

Marsha shifted from one foot to another, obviously annoyed. "Well, I'm proud of you," she said in a low voice. "You spelled Ypsilanti correctly, and on the first try."

"Now settle down," Cardinal said softly. "We're in love, remember, dearest?"

"Oh, of course," she said. "You have been the love of my life since I met you. I was a high school freshman and you were thirty-two."

"That's the spirit. Remember, we're Americans in Damascus. We will attract attention. You have to sell this all the way. That means keeping your loving husband happy, if you know what I mean."

Marsha looked the other way. "You know, I never would have thought Damascus would have a Super 8 motel. No better than the ones stateside, though I guess the housekeepers aren't Hispanic."

"Honey, you know how I feel about illegal immigrants. You wouldn't want to spoil the mood of your adoring husband."

"Any adoring husband of mine would do better than the Damascus Super 8."

They went up to the second floor to their room before she spoke again. "I'm not all that comfortable with this husband and wife thing."

"That's your doing, not mine," Cardinal said. "We are traveling in the Middle East. You wanted to come along, and you know a woman traveling alone would attract attention. This works better."

They sat in the room, arguing like that for fifteen minutes. The phone rang. It was Ali, a CIA operative and their contact in Damascus. "I don't suppose you speak Arabic, do you?" he asked.

"Arabic? Nah, can't help you with that. My specialty is mayhem. I'm a liability until the bullets fly, and then I'm in my game."

"The people we are dealing with have no problem killing either," Ali said. "I wouldn't assume courage is your clear advantage."

"Courage, no, that's not what it's all about. Amorality, that's the thing. I have no inhibitions. I operate solely through a system of pain and pleasure. Like a Pavlov dog."

"Yes, I've been briefed about you. We will see if this amorality is the advantage you think it is. I have my doubts. I warn you, Mr. Cardinal, that I will set up this deal with you, but I have no intention of risking my life on your prowess. Don't look for me to have your back."

"Gotcha," Cardinal said. "I know you CIA people work. You gather the information, then leave it to us paramilitary types to get the job done. Just get the hell over here so we can get started. And bring a half dozen grenades and a flamethrower with you. I'm feeling kinda naked."

Monday was a TV night. The LSU Tigers were playing for the national championship, and so I budgeted my evening for nothing else. In the dead hours running up to the kickoff, I cruised the cable news channels to see what the pundits were saying about the upcoming New Hampshire primary.

I was aghast at what I saw, and considering how much shoddy journalism is on cable these days, this was saying a lot. All of the political experts were going over the latest polling data, which showed Hillary Clinton trailing Barack Obama by an average of eight points. Some polls, they were saying, suggested a double-digit victory for Obama. If the pundits simply stopped with reporting the facts, this would be acceptable, but this was not the case. Everyone agreed that since Clinton was going to lose New Hampshire, she would lose the next state, South Carolina, as well, and then get wiped out in the massive 20-plus state primary on February 5. Hillary Clinton's political career was over. She'd be lucky if she won her home state of New York.

I watched with continued amazement as these so-called professionals viciously competed to write Clinton's political obituary. Certainly reporters have a right and even a duty to call it as they see it, but this crossed a line. It crossed way, way, way over the line. Hillary Clinton was still the favorite in many national polls to win the Democratic nomination. She had millions of dollars in campaign money in the bank. She is arguably one of the most famous women in the entire world. And this clan of idiots was calling her career over when less than one fifth of one percent of Americans had even had a chance to vote, on the eve of an election, before a single voter in New Hampshire had even cast a ballot.

There has to be a rule of journalistic ethics that says reporters cannot attempt to influence elections. Yet clearly, this is what they tried to do. Over and over they played a video of Clinton tearing up as she answered a question on Monday morning. They speculated that Clinton was falling apart, that she was too weak to win an election, that she was not tough enough to be president. A few stray comments about this video might have been appropriate. To prattle on about it for hours was cruel, and in my opinion, an intentional effort to make Clinton look weak.

Ordinarily I am not the type to accuse the media of conspiracy. And it is not my intention now to argue that all the pundits got together on Monday afternoon and decided to torpedo Hillary Clinton. But in a national primary season in which 50 states are supposed to be heard from, it is outrageous for a bunch of bloodthirsty semiliterate punks to spend hours trying to explain why the Clinton campaign had already failed when over a hundred million people had yet to be heard from. I don't get to vote in a primary until March. By then the nominee may already be decided, but in the interest of democracy I would hope the election stays competitive as long as possible. Democracy is about choice. It is not about declaring a major candidate dead after a single primary. The pundits were trying to kill off Hillary Clinton and hand the crown to Obama. In short, they fancied themselves kingmakers, and Monday night they collectively tried to exercise their power.

The ugliness of this competition to embarrass Clinton is truly offensive. Some of the media outlets offered a half-apology today, admitting that the polls were wrong and perhaps they had overplayed their importance. On the other hand, they also defended themselves by arguing that all the polls were in agreement -- Clinton was going to lose -- and they were simply stating facts.

Except that they weren't. Saying that Clinton would likely lose in New Hampshire is stating facts. Saying the Clinton's campaign was dead was an extrapolation of facts that was truly irresponsible. Even if Clinton had lost New Hampshire, what right did they have to say that it was impossible for her to come back?

What kind of journalistic neutrality is this? Mike Huckabee was running at 11% in all the polls, far below the 30% or so Clinton was expected to get, and no one was saying Huckabee's candidacy was over. No one shoveled dirt on Bill Richardson, who ran a distant fourth, or even Rudi Giuliani, who barely got 2%. But Clinton, at 30%, was finished forever.

There is no other way to interpret this than as blatant character assassination masquerading as journalism. I can't remember seeing a worse night of political reporting. Ever.

Hillary Clinton deserves an apology. More that that, we the voters deserve an apology. I am not saying I will definitely vote for Clinton if I get the chance; I am only saying I want the chance to cast a vote for her if I want to. This can't happen if the national press keeps trying to brand her as a failure before the polls even open. Think about it. How many candidates could endure that kind of pressure and come back to win? That kind of pressure would have knocked a weaker candidate, an Edwards or a Richardson or a Ron Paul, out of the race entirely. If the media can pull that garbage once, they can do it again -- and probably will.

If you want to see how unapologetic and cruel the media remain even after Clinton showed them up by winning in New Hampshire, check out the awful, irresponsible editorial Maureen Dowd wrote for the New York Times today. Entitled "Can Hillary Cry Her Way Back to the White House?" this pathetic piece of trash argues that Clinton won New Hampshire because the voters felt sorry for her. Aside from the fact that this article sneers at the idea Clinton could have won because she was a good candidate, it insults voters by implying that they are stupid enough to be manipulated by a woman's tears.

But that is exactly the point isn't it? The media think we the voters are stupid, and that it is up to them to choose our president for us.

Yes, we deserve an apology. Right now.

. . . comes courtesy of the McComb Enterprise-Journal.

 Happy New Year.