It's all a plot

No, HIV was not developed in a secret U.S. government laboratory as a method of wiping out black people and other undesirables. However, the good Reverend is far from alone in thinking so. According to a survey done in 2002-2003 by Laura Bogart and Sheryl Thorburn, 30.5% of African American men and 24.5% of African American women agreed that HIV was produced in a government laboratory; and 21.3% of African American men agreed that it was specifically created to control the black population. This study is in the JAIDS behind the subscription wall, but you can read WaPo summary here. The response rate to this telephone survey was acceptable, but the substantial number of refusals suggests to me, anyway, that the results actually understate the prevalence of belief in these statements.

(These authors also considered it a "conspiracy theory" that "There is a cure for AIDS, but it being witheld from the poor," a proposition with which the majority of both men and women agreed. Although there is no cure, there are effective treatments, and it is absolutely true that poor people, particularly outside of the United States, do not have proportionate access to them, so I can see why many well-informed people might have agreed with that. Since this is the most widely endorsed "conspiracy theory" in their survey, it does tend to undermine their other conclusions. But I digress.)

Since this purports to be a science blog, I should mention that there has been extensive research into the origins of HIV, well summarized for lay readers here. It is pretty well established that the virus first developed in chimpanzees, who acquired two related viruses by eating monkeys. These viruses then swapped genetic material to create HIV. (The process of gene transfer among viruses that co-infect an animal is common. It's one way in which new strains of influenza emerge, for example.) People then acquired it from chimps, probably in the process of butchering them for food. This undoubtedly occurred multiple times, at least as early as the 1950s and likely considerably earlier, although HIV disease was not recognized until the early 1980s.

Barack Obama, obviously, is not responsible for Rev. Wright's beliefs. But it's important to recognize how prevalent they are among African Americans, and to try to understand why this is so. It reveals widespread distrust of government, and of other important institutions in society, notably in this case the medical institution. ("Institution" in this case is a social science term of art that does not refer to a single hospital but to a component of society.) That white people seem to have such a hard time understanding why this is so is just as big a problem. Note my parenthetical paragraph above, about the researchers' idea of what constitutes a "conspiracy theory." Maybe it's not so parenthetical after all.

Update: A few responses to comments.

Yes, there are other infectious diseases which are more prevalent among poor people, and among black people. The death rate from septicemia -- i.e., toxic shock, massive bloodstream infection -- is higher among black Americans, as are STD rates generally. While I suppose people will take the latter as proof that black people are all wildly promiscuous, the truth is that both facts are probably a consequence of lack of access to health care, and inferior care when people do get it. Your risk of STDs depends on their prevalence among the people you are likely to have sex with. Since the main STDs are curable with a shot, people who are part of communities where most people get good quality, regular health care are unlikely to be exposed.

There was indeed a great deal of denial in the early years of the HIV epidemic, particularly in minority communities -- notably African American, Latino and Haitian -- who felt themselves stigmatized by an alleged association with HIV, and which also are characterized by conservative social norms and strong stigmatization of homosexuality. Many preachers in these communities gave counterproductive sermons, and political leaders did not want to confront the reality of the epidemic either. I think the conspiracy theories were in part a response to the feeling that these communities were being blamed and stigmatized, so people reactively turned the blame back on the government scientists who they felt were doing it.

We've come a long way since those years. Nowadays support for nonjudgmental educational and behavioral interventions in African American communities is pretty strong. A lot of clergy have changed their judgments and their approaches. The same is true among Latinos and Haitian-Americans, although stigmatization of homosexuality continues to be a problem in all three communities.

Although HIV is a natural phenomenon, it has functioned as a particularly nasty kind of social experiment. It's revealed a lot about our culture and others, and brought out both the worst and the best in people. The social history of epidemics is usually pretty interesting, but this one is the ultimate. It's probably time for somebody to write the next book.

Blood and Treasure

The takeaway lesson from this meta-analysis published on-line by JAMA is a little bit complicated, and I don't think the general media have succeeded in explaining it very well. (Thanks to C. Corax for tipping me off to the NPR report; I've also read some of the newspaper and news network web site stories.) This isn't quite like those mass murder cases where drug companies knew their products were killing people and kept it a secret. It's more of a structural problem in the way the FDA and the drug companies do research, exacerbated by greed and ass-covering, to be sure, but not primarily about that. Those are a constant that must be allowed for in the way we design our policies for studying and approving drugs and other medical products.

The story begins with concerns about the availability and safety of blood for transfusions back in the '80s, stimulated in part by the HIV epidemic and other blood-borne infections, and the difficulty of making blood available in poor countries and remote places. Various companies developed and tested blood substitutes based on hemoglobin, which as you know if you remember your high school biology is the molecule in red blood cells which carry oxygen from the lungs to the rest of the body. What you might not have learned in school is that the gaseous compound nitric oxide NO is involved in regulating the constriction of blood vessels, specifically it causes them to relax and dilate. (This has to do with the mechanism of action of those erectile dysfunction drugs, BTW.) It also inhibits blood clotting.

Hemoglobin has a strong affinity for NO as well as for oxygen, but NO doesn't cross the membrane of red blood cells, so no problem. However, free hemoglobin in the blood stream soaks up the NO, causing blood vessels to constrict, and raising the risk of blood clots. You have already figured out that this is not good -- we're talking heart attacks.

This problem was understood before anybody even tried experimenting with a hemoglobin based blood substitute. The companies tried some tricks to reduce the risk, but in almost every trial, from the very beginning, whether in trauma or surgical patients, there was an increased risk of heart attacks, and usually of death. The problem is that in any one trial, the numbers were small enough that this risk did not rise to the conventional signicance level of p < .05, in other words there was at least a 5% chance that it was due to chance. This probably doesn't seem very reassuring, and I agree that this is already a problem, but that's how we're supposed to think. If it isn't "statistically significant," it doesn't exist, even though it probably does.

Anyway, the key issue here is that if you put together the results from two or more trials, you would see that the risk was indeed significant, and quite substantial, actually. The pooled results of all the trials the reviewers were able to use show the risk of MI to be 2.77 times as high in people who got the blood substitutes as in controls, who got usual treatment (blood, plasma or saline). The risk for death was 1.27 times as high.

However, and here's the kicker, most of these trials were never published. The FDA knew about most of them, but didn't consider the metanalysis in approving new trials. The information is considered to be a trade secret, so unless the companies chose to publish the data, nobody else could find out about it. (The reviewers who published the JAMA article still couldn't get access to much of the data, or they got it in compromised form. Chances are, the situation is even worse than what they found using the data they could obtain.) This meant that Institutional Review Boards didn't have access to the information. If they had, they never would have approved the studies. So, studies continued, and subjects continued to have heart attacks and to die. There are even studies going on now. Since there is not, in fact, a shortage of blood products, there isn't even a compelling need to be met by these products.

The conclusion is that clinical trials should never be secret. If a company is trying to get a drug or medical device approved, it needs to register all of its trials with the FDA, and the methods, results and raw data need to be publicly available. Congress must change the law in order for this to happen, regardless of the new president's bowling scores.

Catching up on my weekly reading

You probably haven't noticed, but Thursday is the day I normally read NEJM and JAMA and give you the straight dope on whatever is in there. Last week I was locked in a recording studio all day so I just got a round tuit.

Alastair Wood doesn't want us to blame the FDA for disasters like the contaminated Chinese heparin because a) the manufacturer has to be held responsible for insuring the quality of its products, they went to the Chinese suppliers purely because they were the cheapest, and why don't they do their own damn inspections? and b) Over the past 20 years Congress has piled more and more responsibility on the FDA without giving it enough funding. I'm not sure which of these he actually thinks is the problem -- the arguments contradict each other if you really think about it -- but he's half right anyway in both cases.

Here's what I think. First of all, you might want to know that nowadays, only 10% of active drug ingredients are made in the U.S. or Europe. I haven't been able to find quantitative info on where they are manufactured, but China and India are among the most important countries engaged in this business, along with other developing countries such as Mexico and Brazil. Given that we know so far of only a single example of a fake or contaminated ingredient making its way from a foreign supplier into a prescription drug sold in the U.S. (this is leaving aside the question of drug counterfeiting, which is a different matter altogether), the record actually doesn't seem that appalling.

However, I do agree that we can't just leave it to the manufacturer to assure the quality of purchased ingredients -- they're always going to be tempted by the lowest price. You could have a model similar to that in the airline industry, where they are required to conduct inspections according to federally mandated protocols and document those inspections, with spot checks by the FDA, as opposed to having the FDA do it directly, but that's really an administrative question. The government, one way or another, has to make sure that short-term commercial considerations don't trump safety.

On the other hand, why should the U.S. taxpayers and consumers pay to make sure that foreign suppliers are properly regulated? Shouldn't the Chinese be doing that themselves? Ultimately, it seems to me, this is a matter for trade policy. We should not buy Active Pharmaceutical Ingredients from countries that don't have their own, adequate regulatory regimes, along with labor and environmental standards that are acceptable to Americans. Put it in the trade treaty.

Where has I been?

Sorry for the absence, I spent the past two days working on the Spanish language voice over for a video teaching therapeutic massage to people who care for loved ones with cancer. This had me locked in a studio all day and driving back and forth from Boston to Portsmouth before and after. I swear I don't know how people keep this up every day when they have day jobs.

Anyhow, let me try to catch up a little bit. First of all, regarding the study on life expectancy, I pointed out, correctly, that of the old confederacy most of Virginia escaped the decline, but I should have noted that the southwest corner of the state -- the part that remains rural and Old South in character -- actually suffered the worst of it. While this certainly helps to prove the point, it also sharpens the question of why exactly this happened.

One can only speculate at this point but my hypothesis is that these areas have the worst of both worlds. In the old days, rural poverty wasn't so bad for you. People ate from their own gardens, did physical labor, walked a lot. Now they eat at McDonald's, work as retail clerks, in call centers or other sedentary but stressful jobs, and drive everywhere. I should note that while women suffered the largest declines in life expectancy, they still live longer than men. It's not that they're necessarily getting the worst of it, just that women in these places have lost much of their former advantage.

Our friend Ana points out some of the limitations of mortality statistics and I endorse her comments. Causes of death on death certificates are notoriously misleading. After all, everybody dies of cardiac arrest. When heart disease is coded as the principal cause of death, one might think of the real causes in a given case as diabetes, hypertension, hypercholesterolemia, any of which might be related in turn to diet, physical inactivity, obesity, tobacco addiction, all of which are potentially related to socioeconomic status but amenable to some extent to medical intervention. But the death certificate doesn't tell any of that story.

It's important for people to understand the artificiality of the life expectancy construct. It doesn't really predict the future, as it purports to do, but it is a useful way of summarizing the present. The decline in life expectancy does tell us that more people in these areas of the country are dying before they reach their seventies than has been the case recently.

But that does present a nice segue into the question of the future, which was the subject of my previous post. Like many people, I'm not necessarily optimistic that we can pull our chestnuts from the fire. I'm expecting hard times. I think Lester Brown is as well. However, you don't gain anything by undermining people's self-efficacy, individually or collectively. We need to do the best we can and we aren't going to do that if we despair. The more we can do, and the sooner, to make the necessary radical changes in our way of life, the less unwelcome change will be imposed on us.

My complaint is that politicians -- including, let's face it, Barack Obama and Hillary Clinton -- aren't telling the people the truth and aren't making serious proposals to address the crises facing humanity. I understand why -- they've seen what happens to politicians who try to intervene against the profound denial and narcissism of the American people -- but I desperately hope that once he's elected, President Obama will have the courage and wisdom to talk realistically about the terrible perils we confront. Meanwhile, whoever can do it has to yell and scream.

Hungry?

I'm not sure what the heck the Democratic nomination campaign is all about these days -- if anybody can clue me in I'd appreciate it -- but if either candidate is looking for a good issue they might consider this little problem of impending global famine. Not that it's up there with lapel pins or bowling, but it may demand the attention of the next president nonetheless.

Lester Brown, who has long been something of a gloomy Gus (and I know it's really Morning in America) offers a succinct analysis of the problem. This is not a temporary problem. It's a long-term, secular (as the economists say) trend. The planet is running out of stuff -- water, land, topsoil, petroleum, atmosphere. As Brown puts it:

Business-as-usual is no longer a viable option. Food security will deteriorate further unless leading countries can collectively mobilize to stabilize population, restrict the use of grain to produce automotive fuel, stabilize climate, stabilize water tables and aquifers, protect cropland, and conserve soils. Stabilizing population is not simply a matter of providing reproductive health care and family planning services. It requires a worldwide effort to eradicate poverty. Eliminating water shortages depends on a global attempt to raise water productivity similar to the effort launched a half-century ago to raise land productivity, an initiative that has nearly tripled the world grain yield per hectare. None of these goals can be achieved quickly, but progress toward all is essential to restoring a semblance of food security.

This troubling situation is unlike any the world has faced before. The challenge is not simply to deal with a temporary rise in grain prices, as in the past, but rather to quickly alter those trends whose cumulative effects collectively threaten the food security that is a hallmark of civilization. If food security cannot be restored quickly, social unrest and political instability will spread and the number of failing states will likely increase dramatically, threatening the very stability of civilization itself.

Y'know what? He's right. Maybe we ought to be talking about this, just a little bit. It might be important.

Stayin' Alive -- or not

I've been giving some props lately to JAMA and NEJM for making some of their articles of compelling public interest available to the selfsame interested public, but let's not forget that most of their material is still behind the prescription wall, while PLoS Medicine puts it all out there. This number crunching exercise by Ezzati et al has gotten some media coverage, but it does call for a brief comment by YT.

They used county-level data to do historic mapping of changes in life expectancy. There are various statistical acrobatics they used that I won't go into, but take it from me that this is basically legit. From 1961 to 1983, the disparities in life expectancy among U.S. counties broadly declined. Specifically, life expectancy* increased almost everywhere, but it tended to increase faster in those places where it had been lowest to begin with. From 1983 to 1999, however (well, not exactly 1999 -- sort of till the mushy end of the century. They used a three-year moving average to dampen noise in their data), the disparities started increasing. In fact, life expectancy for women actually declined in many counties, and for men in fewer but more than before. For both sexes, these were mostly the places where life expectancy was already on the low side, hence the growing inequality. Meanwhile, the places where longevity was highest saw continued increases.

I had already guessed the basic reasons before the authors got to the punch line. Cardiovascular disease, diabetes and lung cancer are the major contributors for women; homicide and HIV contribute more for men. We are seeing the delayed effects of the increase in smoking by women during the 1950s and 60s; the obesity epidemic; and HIV and violence. With the advent of antiretroviral therapy, the effect of HIV has largely attenuated since 2000, but we can't see that in this data. However, as people with HIV begin to die from the side effects of HIV medications -- yup, those are diabetes and vascular disease -- we may lose that benefit.

Now, here's the kicker: the declines in life expectancy are heavily concentrated in one region, the historic confederacy, from Texas to West Virginia. Virginia and the Florida penninsula, which are no longer so characteristically southern, are exempt. (For some reason Wyoming, which is very sparsely populated, was also a bad place for women, along with a spot here and there such a southern Oregon and Down East Maine.) This is also the region that is most politically conservative, most Republican, and also includes most of the poorest states.

We keep making similar findings -- that the Old South has the worst of everything, from health to education to income. You'd think they'd be the least conservative region, wouldn't you?

*"Life expectancy" is an artificial construct. Basically, you look at the current death rate within each age cohort, usually five year cohorts, then assume that the same death rates will be experienced by people born today as they pass through the life course, and compute the median age at which they would die in that hypothetical future. Of course the future won't be like that.

I am actually finding this hard to believe

Yesterday I noted the report in the new JAMA on Merck writing research reports about Vioxx and paying prominent academics to pretend to be the authors and investigators. That got a fair amount of coverage in the corporate media. Today I finally had a chance to read this piece by Bruce Psaty and Richard Kronmal, also free to the public. I thought I'd seen it all. I hadn't.

Maybe the reason this hasn't gotten a lot of coverage is because reporters find it slightly harder to understand; or maybe they're just too chickenshit to actually write down what this article says because they're afraid Merck will threaten to sue them or something. So sue me.

What this article says is that Merck murdered people. Here's the story in a nutshell. They wanted to prove that rofecoxib (Vioxx) could delay the onset of Alzheimer's disease or slow its progress. I don't know why they thought it might do that, but whatever, they tried it. So first they did a trial of almost 1,500 elderly people with mild cognitive impairment, half of whom got rofecoxib. It turned out that the people who got the drug had a significantly higher probability of developing Alzheimer's disease.

At about the same time they started a trial of 692 patients who actually had a diagnosis of Alzheimer's. Rofecoxib didn't work to delay progression. They started a third trial, but when it turned out the second one wasn't working, they stopped it. It isn't clear if they followed up with the patients.

Okay, too bad, it didn't work. But here's what it also did. It killed people. They're published report of the second trial said "there were no drug-related deaths during the study." For the first study, their report said "rofecoxib was generally well-tolerate. . . " But the truth is, according to internal company documents, they knew that the risk of death was more than 4 times as high for patients taking the drug in the second trial, and 2 1/2 times as high in the first trial, and combining all three, it was about 2 1/2 times as high -- including patients followed up after they stopped taking it. The main reason was heart disease, which is exactly the risk we now know to be associated with rofecoxib/Vioxx.

They knew this before the conclusion of the trials, yet they allowed the trials to continue, for two years. They even got new informed consent from people to allow the first trial to continue beyond its originally planned conclusion, during which time there were 8 exces deths among those receiving the drug. They did not inform the Instutional Review Boards overseeing the study of these events, and they did not even have a so-called Data Safety Monitoring Board, which is supposed to order trials terminated when such indications of risk emerge.

Psaty and Kronmal write, "Sponsors have a direct financial interest in their products and a fiduciary duty to shareholders to provide a return on investment. These interests disqualify sponsors from other important duties, including those normally accorded to DSMBs and IRBs." Gee, do you think so?

On the other hand, while they do have a duty to provide a return on investment, I had always thought there was also a duty not to commit homicide. But I guess that smacks of creeping socialism.

The Week in Review

I had to spend most of yesterday travelling around town to interviews, meetings, and finally a bar, so no post. Hey, I don't do this for a living, okay? So let me catch up on various matters.

So what else is new? You no doubt heard something about this piece by Joseph Ross and colleagues in the new JAMA. (JAMA, like NEJM, has felt the awesome power of Stayin' Alive and has started making material of broad public interest available to the public. They'd better not start backsliding or my wrath will know no bounds.) In a nutshell, they went through some internal Merck documents that became public through the Vioxx litigation and they found out that Merck had either written research reports itself, or had them written by consultants, and then paid prominent academic doctors to pretend to be the authors. That probably sounds to you like a major scandal but actually we've known for many years that this goes on all the time. In fact I'm pretty sure I've written about it here more than once but I'm too lazy to search down the previous posts.

So, the crime from the point of view of you, the potential consumer of pills, is that this practice gives a false impression that these supposedly august and supposedly independent researchers have designed, conducted and analyzed the studies that are reported in medical journals, whereas in fact the drug manufacturer conducted the study, analyzed the data, and wrote the report, and obviously the result might just happen to lean slightly in their favor. From my point of view as a struggling scientist, these guys are total scum, because the currency of an academic career is peer reviewed publications, and they're padding their resumes by lying and cheating whereas I have to scuffle for grants and then actually, you know, do the work. But what's really outrageous is that they pay no penalty. Their universities will not discipline, or even reprimand them. I guarantee it. They'll go on drawing their six figure salaries, and it won't even affect their ability to get published in the future. Just you watch.

Poison plastic? News this week that Canada is going to label a chemical called Bisphenol A as hazardous, which could lead to its being regulated or banned. This is a hydrocarbon which is polymerized to form certain plastics, and widely used in food packaging -- specifically as lining for steel cans -- and to make hard plastic bottles, including baby bottles. The problem with it is that it acts like a weak form of estrogen. In animal experiments it causes abnormal sexual development. I agree that it doesn't make a lot of sense to take chances with something like this, since there are readily available alternatives. There's no reason to think it will make you grow female breasts, if you aren't already so endowed, or otherwise cause any problems for adults, but I would certainly be inclined to keep it out of the diets of children.

However, it's curious that there is such a hue and cry over this particular chemical when we are constantly exposed to toxins which are known to be considerably more dangerous, such as the ultrafine hydrocarbon particles from automobile exhaust, organophosphate pesticides, and heavy metals.

What took them so long? department: The Robert Wood Johnson Foundation has decided to invest a fraction of the money it has put into trying to improve health care quality and access into finding strategies to keep us out of the clutches of doctors in the first place. Go for it.

Everybody's nuts: Here's a good, accessible interview with Charles Barber about how the drug industry has managed to turn the ordinary vicissitudes of existence into "diseases" for which we need to take pills. By the way, I'll have more to say about "happiness" shortly (see post before last), but Barber makes the important point that we've been conditioned to see it as an end in itself. If you're lucky enough to experience it, it's a byproduct. And I'll just add, it's not all it's cracked up to be.

"Debate": I didn't watch the waterboarding of the Democratic candidates last night because of my powers of precognition. I knew it would be unenlightening. Having read some of the reviews, I now thank the Cosmic Watchmaker that I was spared a serious danger of stroke. of course, most of the blame has to go to ABC and its lackeys Gibson and Stephanopolos who are pulling out all the stops to make the execrable John McCain president, presumably because of his position on capital gains taxes, but they couldn't have done this if Hillary wasn't staying in the race, and cooperating with the strategy. Please Senator Clinton, stop it.

Sports Section: You may have heard about the Boston Braves starting rotation of days of yore, "Spahn and Sain and pray for rain." I give you the Boston Red Sox bullpen of 2008, "Okie and Pap and a pile of crap." Theo's going to have to do something, pronto.

Multiple Linear Regression Analysis

Comments on the previous post remind me that I don't always explain stuff as well as I should. Most of them time, when you read about the latest amazing discovery in social science (left-handed lesbian steamfitters are more likely to live in neighborhoods with lots of one-way streets, or whatever), it's based on some form of multivariate analysis, and the most common method used is called multiple linear regression. That's the case with the prediction of happiness I talked about yesterday, and the source of the confusion I created. So here, to cut through the fog of math, is my latest attempt at statistics 101.

A linear regression equation is a way of explaining, or predicting, some fact as the sum of the contributions of a bunch of other facts -- in our example, how happy Americans say they are in response to a survey as a function of some of their other basic attributes. The equation looks like this:

Y = C + aX1 + bX2 + cX3 . . . + (whatever letter)Xn

"Y" is called the "dependent variable" (DV) -- in this case happiness, which we are trying to predict or explain.

"C" is called the constant -- think of it as though everybody starts out with some fundamental endowment of happiness, to which the other variables add, or from which they subtract.

X1, X2, X3 up to Xn are called the "independent variables" (IV) -- in our example, they include age, amount of education, income, sex, employment status, etc. (Wait -- how do you express "sex" as a number? Patience -- I'll explain.)

a, b, c etc. up to whatever letter are called "coefficients" -- the amount by which you multiply each variable to get the best possible prediction.

Now, the way you deal with so-called "nominal variables" -- variables which aren't numbers, but qualitative facts such as sex -- is that you make them what are called "dummy variables," coded as zero or one. For example, we might code men as 0 and women as 1. You could think of it as amount of femaleness, which is generally all or nothing, although I suppose in principle transgendered or androgynous people could be .5 or something. Anyway, if you're female you get 100% of the coefficient added to your score, if you're male you get nothing. (The coefficient could turn out to be negative, so it doesn't matter which category we initially choose to code as zero and which we choose to code as one.)

Where you have multiple mutually exclusive possibilities, such as employed, unemployed, student, homemaker, you have to code each of them separately, and you can get a "1" on only one of them. For mathematical reasons that you might be able to discern if you think about it hard enough but which are not worth trying to explain here, you have to leave one of the categories out entirely. That's called the "reference category." People who belong in that category get all zeroes.

That's easy to understand, but now we come to a couple of tricky things. The first is, how do you calculate the coefficients? Stop listening to your IPod for a minute and concentrate. The coefficients are chosen so as to minimize the average (or sum, same thing) of the squared distances of the data points from a line in an imaginary multidimensional space. If you think about a simple two variable regression this isn't hard to visualize. You have a Y axis representing the dependent variable, and the X axis representing the independent variable -- say, income and education. The points tend to fall along a line but they don't make anything like a perfect line. You pick the line that makes the average of the squared distances of the points as small as possible. The linear equation -- Y = C + aX -- specifies that line. In spaces of more than 3 dimensions, it's impossible to visualize, but the mathematics works just fine. The computation is easier than you might expect, but it involves something you didn't study in school, called matrix algebra, which is essentially a method for solving a whole bunch of simultaneous equations.

The second tricky part is that the coefficients are generally converted from their raw form into what are called Beta coefficients, which are the number of standard deviations of the variable (the "Z score") represented by the coefficient. (See my earlier post The significance of significance, for an explanation of these terms.) The reason for doing this is that the units of the different variables aren't necessarily comparable. Education ranges from 0 to maybe 16 years, age (since we're only surveying adults) from 18 to maybe somewhere in the 90s, income from the SSI minimum of a few thousand dollars a year to tens of millions. To properly understand the contribution of each variable to the DV, you need to express them in a way that the units don't matter, i.e. the proportion of the total variability, however it is measured. (To get a better fit, they converted the income variable into the log of income, as I mentioned yesterday. However, the resulting regression equation is still linear because the variable itself is still just a number, as is the coefficient.)

Okay, forget about all that if you want to, here's the stuff that matters. When you put a new variable into the equation, you are likely to change the coefficients on the other variables. Here's an example. I attended a conference once where an investigator presented her findings and made the claim that Latina women are just as likely to have abortions as other women. I knew that wasn't true and in fact, she hadn't found any such thing. Latina women in her sample were considerably less likely to have abortions than non-Latina women, but they were also much more likely to be Catholic. Once she put being Catholic into the equation, the coefficient on being Latina became non-significant. As a matter of fact, if I remember correctly, it turned slightly positive. Howsomever, that obviously does not mean that Latina women are more likely to have abortions than other women; they are still less likely to have abortions, but now we know that it's because they are more likely to be Catholic. Duhh. It follows that those Latina women who are not Catholic are not less likely to have abortions, but they are a comparatively small percentage of all Latina women.

So, now to what I was trying to say about the happiness of women in yesterday's post. It is possible to have a situation in which the average woman surveyed reports being less happy than the average man; but when you calculate your regression equation, the coefficient on being female turns positive. That would be the case if women were more likely than men to have other characterstics associated with being unhappy, such as unemployment, limited education, poor health, and low incomes. It would mean that in spite of these disadvantages, women are less unhappy than a man would be in the same situation.

The coefficient on being female is indeed positive, but it does not follow that the average woman is in fact happier than the average man. I was saying that just eyeballing the coefficients and flying by the seat of my pants, I'm guessing that the regression analysis is not deceptive in this way and that the average woman is in fact slightly happier than the average man. However, I could certainly be wrong about that.

Bitterness

Well no, we're going to look at the opposite frame, which is happiness, or sweetness if you like. Economists have long assumed that the desired end of all human activity is what they call economic growth, which means essentially humans converting more and more of whatever was here before we came into stuff that is more to our liking. One problem with this philosophy is that it doesn't pay attention to the destruction of the original resource that was converted. For example, as I have noted here several times, there is no such thing as oil "production," even though that's what economists call the process of extracting petroleum from the ground and, ultimately, destroying it.

Now that we might, just maybe, be running into a situation where "growth," as the religion called economics defines it, might have to stop, we need to think about what it will mean to live with that situation. If economic "growth" is not essential to human well being after all, maybe we can do it. So what does really matter?

I'll Carol Graham's article on Happiness and Health as a starting point. I hope it doesn't make you too unhappy, but you can only read the abstract. A couple of highlights are that, in the U.S., all other things being equal*:

1. Being male tends to make you somewhat less happy. Sexist we may be, but women are actually happier than men controlling for everything else -- which isn't necessarily fair since women could tend to have other problems that make them less happy because they are women, and we're controlling for those things which makes them seem to go away, but that's the trouble with multiple regression models. However, in this case I don't think it's correct.
   
2. Being married makes a big contribution to happiness. I'd better get going.
   
3. Having more education tends to make you slightly happier; income makes a big difference, but only toward the bottom of the income scale. Once you have a certain amount, getting more doesn't help much. (Technically, the regression model shows this by fitting the log of income, rather than the raw number. But Graham discusses this further and it is clear that as people get more, they just keep wanting more; there's never any such thing as enough and they aren't getting any happier.)
   
4. Being a student, or retired, or for that matter a homemaker (really) makes you happier than being in the labor force. However, if you are in the labor force, being unemployed really makes you unhappy. Being self employed, on the other hand, makes you a bit happier than being an employee.
   
5. Being healthier makes a big contribution to being happy. However, if you look at international comparisons, health and life expectancy increase as you go from the very poor to the slightly less poor countries, then they level off. The graph rises from Zambia to China, then it goes flat, all the way from Argentina to the United States.

It's a bit different in Latin America. Income seems even more important but that's presumably because a much higher proportion of people are down there where they really don't have enough. Being married is much less important, being retired makes you relatively unhappy instead of happy, but being a homemaker or self-employed are bad instead of good. But, being self-employed in El Salvador means something rather different than it does here. Being unemployed is still a drag, but being healthy is still a good thing.

So what does this tell me? We don't need more, we need more equality. There really is such a thing as enough income, and enough stuff, but there is also such a thing as not enough, and having some people with too much and some people with not enough is a problem. This article from the New York Times makes me barf.

Buyers this year have already closed on 71 Manhattan apartments that each cost more than $10 million, compared with 17 apartments in that price range during all of 2007. Last week, a New York art dealer paid a record $1.6 million for an Edward Weston photograph at Sotheby’s. And the GoldBar, a downtown lounge, reports that bankers continue to order $3,000 bottles of Rémy Martin Louis XIII Cognac.

“When times get tough, the smart spend money,” said David Monn, an event planner who is organizing a black-tie party on May 10 for dignitaries and recent purchasers of apartments at the Plaza Hotel; the average price there was $7 million. “Short of our country going on food stamps, I don’t think we’re doing anything differently.

And who are these folks dropping $3,000 on a bottle of booze? One example we're given is Lee Tachman, "a manager for a company that executes trades for hedge funds and the owner of “a handful” of buildings in New York." In other words, a useless parasite on society. Put him down for $60,000 a year, and the average level of human happiness rises. The economic gains of the past decade have gone entirely to people like him; if the pain of the next merely took it all away, there would be zero net loss to social welfare or human happiness.

Of course, it isn't going to happen that way.

Administrative update

I've added a slightly odd link to my blogroll, Miss Welby, who covers Italian politics (mostly in English). She wanted a link exchange because she's giving her readers a selection of American blogs, and I said, what the heck. Italian politics is wild and weird for sure -- and not in all the same ways ours is.

I haven't cleaned up dead or dormant links lately, they're staying mostly for historical/sentimental reasons. But if anyone wants to suggest new links to me, I'm receptive- exchange much preferred, of course.

Chimpy comes down on Nov. 20. Nominations for his successor will also be entertained.

Oh yeah: What Hunter says. Although I would say, it takes a certain bestial intelligence to be as stupid as Chris Matthews. I'm not entirely sure there is no design there.

Reading Around

I'm one of those old-fashioned types who subscribes to magazines -- you know, ink on cheap paper that they mail to your house every month. You have to read essays consisting of literally thousands of words, but with a little practice, you'll find it's possible. It can give you a whole different picture of the world than you get from TV, or even the newspaper. For example, the front page of the Boston Globe this morning had as its headline a story about Pope Benedict coming to the U.S. (which hasn't even happened yet). Other front pagers were bits about parents telling their kids to stop sending so many text messages, and falling housing prices making it possible for people of moderate means to once again move to the suburbs. Turning the page, we find that Barack Obama said people in the rust belt are bitter, which according to Hillary Clinton proves that he is an arrogant out of touch elitist who hates America. This is evidently the key issue confronting the voters.

The May 1 New York Review of Books contains some rather different concerns. For example, Tony Judt fears that we -- and by we he seems mostly to mean the Americans -- have failed to learn from the painful history of the 20th Century. "In the U.S., at least, we have forgotten the meaning of war." The great wars of the 20th century happened elsewhere, of course. Judt recounts the contrast between U.S. combat deaths in WWII of 420,000, compared with 2.1 million for Japan, 5.5 million for Germany, and 10.7 million for the Soviet Union. The U.S. suffered virtually no civilian casualties, whereas of course Europe lost tens of millions of civilian dead. And:

War was not just a catastrophe in its own right: it brought other horrors in its wake. World War I led to an unprecedented militarization of society, the worship of violence, and a cult of death that long outlasted the war itself and prepared the ground for the political disasters that followed. States and societies seized during and after World War II by Hitler or Stalin ... experienced not just occupation and exploitation but degradation and corrosion of the laws and norms of civil society. . . .War, in short, prompted behavior that would have been unthinkable as well as dysfunctional in peacetime. It is war, not racism or ethnic antagonism or religious fervor, that leads to atrocity.

Because the U.S. was insulated from the realities of war, writes Judt, "As a consequence, the United States today is the only advanced democracy where public figures glorify and exalt the military. . . . Politicians in the United States surround themselves with the symbols and trappings of armed prowess; even in 2008 American commentators excoriate allies that hesitate to engage in armed conflict."

Indeed, though Judt doesn't say so, it is considered offensive in the United States to criticize military leaders or to question their judgment. And Sen. Biden was forced to apologize for suggesting, in the case of John McCain, that dropping bombs out of airplanes did not constitute a qualification to be president.

Elsewhere in the same issue, Anthony Lewis discusses the official policy of the United States to torture prisoners. "I grew up believing that Americans did not torture prisoners, as Hitler's and Stalin's agents did," writes Lewis wistfully. "The corrupting effects of the adoption of torture as an American practice have been widespread. First of all, on the law. . . . The whole idea of secret official opinions defining the law should be anathema in a free republic. . . .Torture has had corrupting effects on our politics as well. Most Republicans in congress have defended President [sic] Bush's claim of the right to use such methods, apparently as a matter of political solidarity. . . . Language has been corrupted too."

Then I open up my March Harper's (just getting around to it) to read Scott Horton's piece on how the Justice Department maliciously prosecuted Democratic politicians, let corrupt Republicans slide, and converted the Office of Civil Rights into a project to disenfranchise black voters, all in an effort to create a one party state.

So Hillary, let me tell you something. I am bitter. I am particularly bitter that you and your fellow Senators have failed to stand up and defend the freedom of your fellow citizens, and the honor of the United States, against the criminal regime which you continue to enable and exonerate while you bicker inanely over trivia. I am bitter about the millionaire professional yammerers on television who provide an endless echo chamber for such idiocy. I am bitter because we have squandered the promise of our nation, and we have such cowardly leaders.

Exactly how screwed are we?

Back when I was in college -- not so long ago really -- the deep thinkers had us deep in the doo doo. Robert Heilbroner's Inquiry into the Human Prospect was required reading. Hint: He didn't think it was exactly fabulous. Some very convincing dismal futures were being painted by science fiction writers like John Brunner - The Sheep Look Up and Stand on Zanzibar made an impression on me, for sure. The Club of Rome, a group of high powered movers and shakers, foresaw catastrophic resource scarcities, the WorldWatch Institute was busy meticulously documenting the fall of civilization. There was Moment in the Sun and The Population Bomb and you name it.

The common theme was that the world was running out of resources to sustain its growing human population and the whole edifice of industrial civilization was heading for the crapper. Then two or three decades went by and the spring wasn't silent and the oceans weren't corrosive and whole nations didn't die of thirst. Our motor vehicles just got bigger and heavier and more and more of them and the so-called Green Revolution managed to feed a population that exceeded the maximum level of doom by a billion or more.

So was the whole thing a bunch of hooey, or were they just off by 30 years or so and now the hammer is coming down after all? This is a fair question. While we've been distracted by some important stuff, like Iraq, and some even more important stuff like bowling scores, there have been food riots in more than 30 countries. The UN has proclaimed that the era of cheap food is over and for people who spend 70% or more of their income on food already, that's very bad news.

Americans aren't going to starve, but they're definitely feeling it. The problem for us, assuming we think that massive famine from the Caribbean to Southeast Asia isn't our problem, is that people don't compare their situation to some abstract standard of need, or to people in distant lands. Americans' expectations have been for endlessly rising prosperity for about 60 years now and we're clearly headed into reverse. I'm not just talking about a typical 9 month recession, squeeze out the excess, have a little creative destruction and we're back on the highway to the Big Rock Candy Mountain, I'm talking a long period of declining living standards. Everybody who is willing to look at the situation honestly now sees this as likely.

Worldwide, we face absolute depletion of seafood, cropland, and water resources. While people disagree over whether worldwide petroleum extraction is headed for immediate decline (and those who don't think so are wrong, sez me), everybody agrees that it can't keep up with expanding demand right now, and only a few fringe characters think it won't go into absolute decline within a few years at the most. The problems associated with global climate change are already becoming evident in increasingly violent weather, and the really big problems -- elimination of water supplies from mountain glaciers, rising sea levels, and severe ecological stress -- are coming soon. The problems of an aging stock of fixed capital, short term financial disruptions, the bankruptcy of the United States, and looming recession are less fundamental, but they are going to expose these long-term structural problems and severely compromise our ability to address them in the coming years.

Then there's that little issue of war.

So how about it folks? How deep is the doo doo? Will we muddle through, or is the current presidential campaign an exercise in denial and avoidance?

(And for those of you who came here looking for public health, believe me, you're getting it.)

Inarticulate with rage

Apologies for not posting yesterday. I wasn't feeling well (which is permitted of bloggers, you know) but more than that, I was just so knocked out by the idiotic state of political discourse in this country that words seemed inadequate. They still do but I'm typing anyway.

The Emperor of Mespotamia is about to go on TV and tell us about his new, strong and resolute plan to win the long-promised Glorious Victory. While there has been concern among the courtiers in both the Pentagon and the corporate media over such problems as the state of military readiness and whether the current policy is Making Us Safer™, they are all pleased to note that the level of violence in Iraq has been dramatically reduced. It is fortunate that when American helicopters and fighter jets fire missiles into residential neighborhoods and kill dozens of people, it is not an example of violence, otherwise that statement might be untrue. Come to think of it, it isn't necessarily true anyway, but it is virtually true by virtue of incessant repetition.

While the question of whether "we" are safer preocuppies the Congress, Hani Mowafi and Paul Spiegel, in the new JAMA -- off limits to the public, of course, whose sensibilities are too tender to hear of such things -- discuss the Iraqi refugee crisis. According to the most authoritative estimate, by the UN High Commission on Refugees, 4.2 million Iraqis - that's 1 out of every 7, and a far higher proportion outside of Kurdistan and the homogeneously Shiite south -- have been driven from their homes. About half of them remain inside Iraq, in refugee camps, squatting in abandoned buildings, or if they are fortunate staying with relatives. But the 2 million expatriated Iraqi refugees now constitute, according to my calculations, more than 6% of the population of Syria, and more than 13% of the population of Jordan. That's the equivalent of 40 million refugees living in the United States, in case that helps you imagine the situation.

These people receive little or nothing in the way of services or succor. They are not in camps or organized communities, but dispersed in cities, where fewer than half of children attend school, 62% of heads of household are unemployed, and 80% depend on charity or are consuming their savings, according to sources cited by Mowafi and Siegel. Many women and children must resort to sex work in order to survive.

The responsibility for this catastrophe -- which is only going to get worse -- lies entirely with the government of the United States and its enablers and cheerleaders in the corporate media. The U.S. is in deep trouble in many respects -- in long-term and probably irreversible economic decline, with decaying physical infrastructure, a dysfunctional political culture and an increasingly ill-informed population retreating into irrational beliefs -- but this is nevertheless our obligation. We must pay the cost of the disaster we created. Nobody is talking about that.

Shrunken Heads

A week before Army Gen. David Petraeus updates Congress on the war in Iraq, two new studies have found that soldiers in Iraq and Afghanistan are suffering from especially high rates of post-combat psychological problems, exacerbated by an unusually high rate of repeat deployments.

Veterans for America’s (VFA) Wounded Warrior Outreach Program is concerned with the staggeringly high levels of mental health problems and neurological injuries experienced by today’s troops, and the lack of resources and rehabilitative programs available for our wounded.

Okay, let's imagine you're a U.S. Army psychiatrist.

Oh, so they attack your base with mortars every night? How does that make you feel?

Mmhmm, difficulty sleeping, I see.

Whenever you go out they what? Try to kill you with bombs, machine guns, and rocket propelled grenades? So do you think people are out to get you?

And how does that make you feel?

Anxious, afraid? Ah hah. Angry?

Well you know that's irrational, President Bush isn't shooting at you. And what else is bothering you?

You don't like shooting people. Well, we all have a job to do, it isn't always pleasant . . .

You're afraid of shooting the wrong people? What's that? Ten years old? Well now nobody's perfect, we all make mistakes. You musn't be too hard on yourself, I've made a few mistakes in my job now and again, but you just have to pick yourself up and keep on going.

Oh yes, well I'm sure I wouldn't like seeing my friends with their legs blown off or their brains spilling out either, it's only natural to be disturbed by those things.

Now, I know that people often don't like to hear themselves labeled with a psychiatric diagnosis, but it's very helpful in understanding and confronting the problem and giving us an idea of what to do about it. You appear to have a depressive disorder complicated by anxiety. I'm going to give you a prescription for Zoloft, which will make you feel less depressed, and Xanax, which will help with your anxiety. In a little while, I'm sure you'll get better.

Of course, I might have a different diagnosis of the problem, and a different prescription, but that wouldn't work very well in terms of the army mission.

It's nobody's fault

You've probably heard about the study that finds that over 7% of hospitalized children experience an adverse event from drugs, and given that some experience more than one, the total is 11 events per 100 hospitalizations.

That sounds appalling, but fortunately most of these events don't have any lasting consequences. Of course, they should never happen -- people are hospitalized to try to make them well, but hospitals are in fact dangerous places. It's not just the astonishingly high likelihood of being given the wrong medication, or too much of something. Hospitals are full of really nasty, antibiotic resistant germs, and the people in the hospital beds have extra holes in them with tubes going into the holes which help the bugs get in and out, among other unpleasant conditions. But we already know this.

What's new about this study is the rate of underreporting that it finds. Most of these errors were discovered only by critical analysis of the children's medical records -- noting that an antidote was given, or symptoms occurred which are probably medication side effects, etc. The responsible staff typically tried to sweep it under the rug. So, the new fashion is to try to modify hospital cultures and systems so that the incentives are to report errors, enable the administrators to make a full accounting of them, figure out why they are happening, and redesign procedures and the environment to make them less likely. That's how safety is handled in the airline industry, which does treat its customers like cattle in the chute at the slaughterhouse but, in the end, manages not to kill them very often. In fact flying is the ninth circle of hell, but it's quite safe. You might even be better off having your heart attack on an airplane than in the hospital, at least on a weekend evening. They have defibrillators and trained staff, and they'll get to you immediately. In the hospital, you might have to wait quite a long time.

Philosophy for Dummies

Let me put this as succinctly as I can. In the past 100 years or so, we have learned a great deal about the universe which has surprised us. We can now describe its age, history, extent and nature in ways that are utterly inconsistent with the ancient beliefs encoded in scripture. Far from being at the center of the universe, and a major preoccupation of the deity, the earth is utterly insignificant, in both space and time, lost in a universe so immense that our imaginations cannot encompass it.

In order to be convinced of this, you do not need to accept an arbitrary set of premises or rules of evidence. We have telescopes. We can see it. Mr. Berlinski, look through the telescope!

We do not know where this universe came from or why it is what it is -- if that is even a meaningful question. We are doing everything we can to explore further and at least draw closer to answering more questions. In the meantime, scientists and people who live by reason have learned to coexist with mystery. It isn't so hard, once you get used to it, really it isn't.

Making up arbitrary and ridiculous stories, and believing in them fervently, is not an appropriate or sensible response. And defending that practice does not make you a deep thinker. It makes you an idiot.

The latest fad in drivel

Lately we've seen a new kind of maneuver by the apologists for religion, exemplified by David Berlinski (The Devil's Delusion: Atheism and its Scientific Pretensions), which seems to have captured the fancy of the editors of Harper's Magazine, among numerous other people who ought to know better, who have published a couple of essays by Berlinski.

The argument always comes dressed up in a lot of poetically charming but vague rhetoric so it's a little hard to tease out. One may end up seduced, but with a bit of an effort one realizes that 95% of what one has just read is fluff, and the rest of it is wrong. The essence of the case is that scientists act like they know everything, but in fact "we do not know how the universe began. We do not know why it is here. . . We can say nothing of interest about the human soul. We do not know what impels us to right conduct or where the form of the good is found. [Scientific theories] do not treat of any faith beyond the one that they themselves demand." And so, we are told, science if just one more fundamentalist belief system, which is only convincing so long as we accept a set of arbitrary premises and choose to accept its rules of evidence, whereas we are perfectly free to accept others. Science is a faith no different from any other, and it cannot address the great mysteries. Hence science and religion simply rule different domains, have nothing to say to each other, and science is helpless to disprove the validity of faith.

For some reason, the name of Richard Dawkins generally gets mentioned in these sorts of reflections, so I will invoke it as well. I can assure Berlinski and everybody else that Richard Dawkins is as well aware as anybody that in spite of the scientific knowledge we have gained, immense mysteries remain, including how the universe originated and why it is the way it is. Berlinski fundamentally misunderstands science, and he is scientifically illiterate, as evidenced by the grotesque howlers he makes whenever he tries to discuss scientific disciplines and theories.

The first and most basic misunderstanding is that mystery and ignorance are in fact the only concern of science and the only realm in which it operates.

Berlinski also fundamentally misrepresents religion. Religion is not defined by awe in the face of deep mysteries or investigation into what compels us to right conduct, but precisely the opposite. Religious people don't ask these questions, they answer them, and they have very specific, very concrete answers. Generally, they take the following form.

The universe was created by an all-powerful, all-knowing, immortal sentient being. At one or more points in history, this being seized control of the minds of individual men (always men, the sexism is not mine) and caused them to produce texts, containing truths about cosmology and history; instructing us in how the deity requires us to behave, often including elaborate sets of very specific rules for conduct in the most minute affairs; how the deity demands to be addressed, and understood, and various rituals to be performed to demonstrate our obeisance; and what adventures we can expect to have after we are dead, in a realm which living people can never discover but which may be vaguely located somewhere in the sky. The history part includes numerous events which are ordinarily impossible.

Scientists spend their days investigating mysteries. They want nothing more than to be surprised, and can gain no greater prestige than to prove other scientists wrong. Priests, in contrast, spend their days telling people what to believe. New discoveries are by definition impossible for them, and, while they do indeed loudly proclaim that all the other priests who are not of their sect are not only wrong, but will be tortured for all eternity for their wrongness, they have no method of demonstrating it except to reiterate their own claims more loudly.

Science does have tools to prove religion wrong, and has done so on innumerable occasions. In order to rescue their God, priests must either continually reinvent him, and tuck him into smaller and smaller corners as the realm of the unknown retreats; or make utter fools of themselves by denying the incontrovertible truths that science has discovered.

Berlinski has it exactly upside down and inside out. As God is a human invention, so are the notions of The Good and the metaphysics which purport to come from God. Science has no problem at all explaining the sources of morality and meaning: they come from within us, they are products of our nature, as shaped by our evolution as social animals. That makes meaning no less meaningful and wonder no less wondrous than they seem when we imagine a deity. The deity is simply unnecessary.

Could some entity that is in some ways like what people have imagined God to be exist? Sure, its possible. But there is no particular reason to believe it. There might be giant intelligent photosynthesizing gas bags on a planet circling Tau Ceti, I certainly can't rule it out, but that's no reason to go around believing it. If we find them one day, then we will believe in them. In the meantime, it would be silly.

Rite and Wrong

So, now that we've cleared away the technical underbrush -- and I hope you'll forgive what may have been a self-indulgence, but I just love biology, for sheer wonder and amazement it beats the hell out of theology -- let's follow Prof. Korobkin as he parses the ethical issues, and add our own two cents -- or maybe two bucks.

The people who believe -- quite fervently in most cases -- that a single zygote, or a 16-cell blastocyst, is a "human life," and that destroying it is murder, obviously don't base that claim on any discernible resemblance between the object in question and what we normally think of as a human being. In fact, they don't generally try to justify it at all, they just proclaim it, but when forced to explain their reasoning, the usual response is that it represents the potential for human life, and that's close enough to being human life to deserve the same respect. (Note that they cannot base their claim on scripture, which makes no mention of abortion, nor for that matter can they blame it on Christian tradition as the Christian proscription of abortion is in fact a modern innovation.)

It is certainly easy enough to ridicule that claim. An acorn is not an oak, and raking up your backyard is not the same thing as destroying a forest. But even if potential human life is for some unspecified reason more like real human life than an acorn is like an oak, the claim's defenders have a big problem: the large majority of these precious human lives are destroyed already, by the most prolific mass murderer in all of history, the deity. Most naturally created zygotes fail to develop into babies. In fact, they fail to implant and are lost in what the woman probably thinks is just another ordinary menstrual cycle. If this is really the same thing as the death of a baby, then the Christian Coalition ought to be clamoring for the vast majority of medical research funds to be redirected toward preventing it, since it is the greatest public health catastrophe imaginable.

It gets even more ridiculous when you consider that the creation of the zygote is, after all, a purely arbitrary dividing line. The unfertilized ovum, and the spermatazoa, also represent potential human life. Every time a woman ovulates without getting pregnant, or a man ejaculates, potential human life is destroyed. Isn't it a sin, then, to fail to create a baby at every opportunity? You could argue that the uniqueness of the potential life is somehow established at the moment of conception, and that for some reason that's the key, but that's wrong too. Just because the genome is created does not mean we know what kind of person might result. Genes are not destiny; the phenotype -- the unique nature of the complete organism -- develops in a complex interplay between genes and environment. Your destiny was in no way sealed at the moment of conception, nor was your nature. You did not yet exist; there was only a cell, and then a ball of cells, after all.

Prof. Korobkin goes on to point out that if the Catholic Church and the protestant right truly believe that embryos are people and that killing them is immoral, their support for Mr. Bush's solution makes no sense. The law he proposed, and got through Congress, allows federal funding for research using certain HESC lines that already existed at the time, which had been derived from embryos left over from IVF. The rationale was that the sin had already happened, so we might as well use the cells; but no further embryos would be exploited in this way using federal funds.

But this makes no sense, because IVF continues to be legal, and it inevitably creates excess embryos, which inevitably are destroyed. If that's murder, it ought to be outlawed, but nobody is calling for that. Doesn't it make more sense, if the embryos are going to be destroyed anyway, to at least use the cells to potentially save lives in the future? The possibility of using new cell lines for HESC research does not in any way encourage the creation, or destruction, of more embryos than would have been created were that not possible.

And of course, it's still possible, just not with federal funding. If it's murder, it's still murder even if the federal government is not paying for it. The opponents of HESC research respond that since there is disagreement about the morality of the practice, at least people who disapprove should not be forced to pay for it with their tax dollars.

Uh oh. Just about everything the federal government does has destractors among the citizenry. Let's talk about, oh, I don't know, the occupation of Iraq, which costs a few thousand times as much as any plausible program of HESC research. I find it morally objectionable, yet I am required to pay for it with my tax dollars. And oh yeah, it destroys human lives -- not just potential ones.

So it's pretty clear that the Catholic Bishops and James Dobson are in a state of profound moral confusion. Their political position makes no sense at all. It's internally contradictory, and contrary to the most elementary common sense. But here's where Prof. Korobkin stops, and where I would like to go. How is that tens of millions of Americans have come to believe so fervently in such a transparent absurdity? What is really going on here? With real people suffering and dying all over the world, all too often with the assistance of the U.S. taxpayer; and the taxpayer doing so very little to save them, why on earth are these people yelling and screaming about microscopic balls of slime, under the bizarre delusion that they are human babies? And what could this possibly have to do with Christianity?

That is the really important question here. That's where the true moral atrocity is to be found. Perhaps a good Christian out there will care to respond.

Send in the Clones

It turns out that I'm going to do a bit more Bio 101 before getting deeper into the ethical issues surrounding HESCs and other cutting edge biotechnology. This is partly to address the issues around cloning which the commenters raise, partly because I think the ethical issues come into crisper focus when we have more detailed biological background, and partly just as a bit of self-indulgence.

It's hard to get used to thinking of ourselves as colonies of trillions of individual organisms, but in a sense we are. Actually if you want to adopt the most liberal view of matter, the number is in the quadrillions. We are examples of metazoans -- the multicellular animals. Metazoans are composed of eukaryotic cells, as are plants, which are in some ways even more fascinating, but I'll leave them aside for now.

Here's the Just So story, which is probably actually true. Sometime over a billion years ago, somewhere in the ocean, one particularly large cell swallowed a smaller cell of a type called archaea. Or maybe the archaea parasitized the larger cell, or just moved in. Anyway, the smaller cell was not digested and instead, it happily took up residence and started to replicate inside the larger cell. When the larger cell divided, each daughter cell took some of the intruders with it, and so it went. These cohabiting cells evolved together and, in the end, turned out to be more than the sum of their parts. The smaller cells were particularly good at an essential metabolic process which produces the cellular energy supply, a molecule called ATP, from breakdown products of sugar and fat. They came to specialize entirely in doing this, and gave up most of their DNA and the ability to live independently, but in exchange, they got fed and protected by the big cell in which they lived.

Something else happened, perhaps even more marvelous. The eukaryotic cells began to reproduce sexually. It's possible that another symbiosis is involved, and that the nucleus of the eukaryotic cell is, like the mitochondria, an endosymbiont which eventually captured most of the cell's DNA, except for that remaining in the mitochodnria, but that's fairly speculative. In any event, prokaryotes -- like the bacteria and archaea -- can exchange genetic material, but they don't do it in a systematic way and they routinely reproduce without bothering. Their DNA floats around aimlessly and is fairly simply organized. Eukaryotes, as I'm sure you know, have their DNA organized into packages called chromosomes, which come in pairs, one set donated by progenitor A and the other by progenitor B. Most of the details of which one we consider male or female can vary depending on the species but in my view, there is one determining factor: the female progenitor contributes all of the mitochondria, and the male contributes only nuclear DNA.

There would seem to be several disadvantages to this system, most notably, you can't reproduce unless you can find a partner. Actually, some metazoans, even among the highly complex tetrapods (i.e., certain lizards and fish), regularly reproduce asexually and they save sexual reproduction for special occasions, but still, why bother at all? And an organism with a terrific, kickass genome is going to find it's wonderfulness diluted in its offspring, by its inevitably inferior mate.

It turns out that the reason sexual reproduction is such an advantage that evolution has preserved it throughout the long history of the metazoans has to do with the dynamic nature of evolutionary fitness. Sexual reproduction remixes the genes with every generation, producing all sorts of variation on which natural selection can work. It also allows favorable mutations to spread systematically throughout a population. The two-chromosome system allows recessive genes, which may code for characteristics that are not favorable this year, to continue to lurk within a population so they are available when times change. Sexually reproducing species are better at evolving, and in the long run, that's even more important than being better at living in the here and now. Hence it is the eukaryotes, with their fabulous gift of sex, who developed the complex colonies of cells we call animals, whereas the prokaryotes never got past elaborate forms of slime.

There are trillions of cells in your body, of more than 200 different kinds. Together they maintain an internal ecosystem, which also happens to be inhabited by something like 100 trillion bacteria. On a good day, 100% of those bacteria are harmless, if not beneficial. They are an essential part of the ecosystem which is you. If you want to count your cellular endosymbionts, the mitochondria, that's where we get into the quadrillions.

I know, I know, you already knew all of this. But it's good to review it and get it all straight once in a while. Now, what is a clone?

A clone, most broadly, is simply a line of cells derived from a single cell and therefore all having the same DNA. In that sense, your whole body is a clone, specifically it is a clone of the zygote, the fertilized ovum, from which you arose. But, if you took a cell out of your cheek and managed to culture it in a petri dish, the resulting mass of skin cells would be a clone as well. So when biologists speak of "cloning," they don't necessarily, in fact they don't normally, refer to creating whole metazoans.

But they could. One result of cloning could be a second (or third or fourth) complete organism with the same DNA as an original organism. In order to get that to happen, however, you would have to get the clone not only to continue to reproduce asexually to produce larger numbers of cells, you'd have to get the cells to follow the developmental program that produces the whole animal. All of those 200+ cell types in your body are ultimately descended from the zygote, so they must have gone through various changes to get to their present state. They all have the same DNA. They way they become specialized is to have particular stretches of DNA turned on or off. Cells that still have the potential to become any kind of specialized ("somatic") cell are HESCs. There are other stages of stem cells that can become various subcategories of cell types, but not any cell type.

So, although that mass of skin cells in a dish is indeed a clone of your cells, it's not much use, because those cells cannot give rise to anything but skin cells, which you probably don't need because your body can heal skin wounds naturally. But suppose you need neurons -- nerve cells -- which don't normally replicate in the adult? You would need a supply of stem cells which can give rise to neurons. Or suppose you wanted to grow a whole organ, consisting of various cell types, organized into a complex structure? Ditto, you'd need stem cells that could begin to follow the developmental program for your kidney or heart.

So here's where so-called therapeutic cloning comes in. Although you can clone many kinds of somatic cells, you need stem cells. What do you do? Get a zygote that has exactly your own DNA. And that's where Somatic Cell Nuclear Transfer comes in, a special kind of cloning intended to create HESCs. Just because the result is called a clone does not mean that anybody has either the intention, or for that matter the ability, to grow a person from it.

In fact, regardless of what people may think are the ethics of it on other grounds, there is no ethical way to attempt it because there is no guarantee that the resulting person would be healthy. Right now, if we could make a person the same way Ian Wilmut made Dolly the sheep, we would expect that person to be unhealthy, specifically, to age prematurely. This is because, if you take the nucleus from a somatic cell, that cell is the product of many cellular divisions since the zygote first formed. In natural conception, the zygote gains a new genetic endowment provided by specialized cells in the body called germ cells, in the testes or ovaries. These DNA molecules are fresh, as it were, destined to replicate many times. But each time they do, terminal structures on the ends of the DNA molecules called telomeres shorten. Eventually, the DNA can replicate no more, and the cell line is extinguished. This is why death is inevitable.

The zygote produced by SCNT has old DNA. It is abnormal. Can that ever be fixed? Maybe, but meanwhile, when we talk about cloning people to produce HESCs, we are not, repeat not, talking about making genetically identical copies of existing people. Well, almost identical - remember that the mitochondria have their own DNA, which comes from the donor of the ovum, and unless that happens to be your mother, they won't be identical.

So we aren't talking about anything that will ever become a human being, although we are talking about something which is otherwise just like a human embryo, at a very early stage, except that it's sitting in a petri dish rather than a woman's fallopian tube.

So, with all that out of the way, what's wrong with that? Even if the mitochondria is bovine?

Some technical background

Returning now to Stem Cell Century, Prof. Korobkin argues along very much the same lines we have argued here about the moral status of the zygote and the embryo. It seems apparent that the qualities that give a creature moral status have to do, first of all, with sentience. We respect the rights of others because they can perceive, and feel, they are self-aware. Hence we generally agree, for example, that someone who is brain dead but whose body continues to live thanks to a respirator and a pacemaker is not really a living human being and that it's morally permissible to harvest the person's organs and turn off the machines.

Now, let us consider the process for obtaining human embryonic stem cells (HESCs). At the time Stem Cell Century went to the printer, there was one way it was already being done, and another way that seemed just over the horizon which offered potential advantages for medical applications. Since the book was published, there are indications that a third method may be possible, one that Prof. Korobkin did not consider at length because it did not yet seem plausible.

Both the methods he did consider require the creation of human embryos. They do not actually necessarily require the destruction of human embryos in principle, but the embryos in question are likely to be destroyed because nobody has any other use for them.

The first method is to use embryos created by in vitro fertilization. There are tens of thousands such embryos available that were created for infertile couples. Fertility clinics always create lots of extras because they want to select the best looking specimens, and because implantation can fail and they may need to try again. The surplus embryos are generally destroyed eventually, when the couple no longer has any potential use for them. So, just take one out of the freezer, thaw it out, remove one or more cells, and culture them.

This works fine for research purposes up to a point, but it will not be ideal should we come to actual therapeutic applications. The promise of HESCs is that they are "pluripotent" -- they can potentially yield every kind of human cell, and hence be coaxed to grow into replacement organs or tissues of any kind, thereby repairing the damage from a wide range of injuries or diseases. The problem with cells harvested from fertility clinic leftovers is that they will not be a genetic match to the recipient, and hence you have the same problems you do with organ transplants -- rejection by the host's immune system and the need to take immunosuppresive drugs.

The solution is a procedure called Somatic Cell Nuclear Transplant, or therapeutic cloning. This means taking the nucleus out of one of your cells -- a so-called somatic cell, any of the specialized cells of the adult body, probably a skin cell -- and inserting it into an ovum from which the nucleus has been removed. This is how Dolly the sheep was created. A full complement of paired chromosomes inside the cellular environment of an ovum equals a zygote, in other words you now have the equivalent of a fertilized egg, and with luck, it will begin to develop into an embryo, an embryo whose nuclear DNA is identical to that of the person who donated the nucleus.

The downside to this is that you need a supply of ova, and harvesting them from humans is painful and not 100% risk free. Some ethicists -- among them notably the feminists at Our Bodies, Ourselves, but others as well -- aren't comfortable with creating an extensive market in human ova. I won't get into that, but to answer Roger's question, that's why the researchers in the UK did SCNT with a human nucleus and bovine ovum -- to eliminate the need for human ova in doing this procedure.

So, now you end up with HESCs which it is hoped can be grown into organs or tissues that can be implanted in the person who donated the nucleus, which the person's immune system will perceive as self, eliminating the rejection problem. Yup, a brand new liver or new dopamine producing cells in the brain or whatever you might need, and it's really yours. Not quite -- the mitochondria, specialized organelles in the cells which are the engines of cellular metabolism, have their own DNA, which comes from the egg donor, human or, just maybe, cow. No matter, the immune system doesn't know the difference.

Okay now. Embryos are not sentient, they can't perceive, think or feel, they have no self-awareness. In fact, we are talking about balls of just sixteen cells that are nearly invisible to the eye. The people who did the trick with the cow ovum have no intention of allowing the embryo to develop beyond that stage, and even if they did, you would have a human embryo, that assuming it was otherwise normal would grow into a normal human being in every respect, except that a genetic test of its mitochondria would reveal something strange. (Conceivably bovine mitochondria are more or less efficient than human mitochondria and you would have some difference in metabolic rate or athletic ability as a result, but as far as I know that is not the case.)

So, two questions:

What, if anything, is morally wrong with harvesting HESCs from fertility clinic leftovers?

Is there something morally different about the SCNT embryos?

And finally (one which Korobkin did not consider), what about the SCNT embryos using non-human ova? Any ethical difference, for better or for worse?

These are matters of intense public controversy, which we will take up tomorrow.

Manimal!

I'm not sure why this hasn't gotten any attention in the U.S. - perhaps it will hit the fan shortly - but researchers in the UK have created what the BBC is calling a "part human, part animal hybrid embryo. Actually it isn't really. What they did, as far as I can tell from this scientifically illiterate story, was to use somatic cell nuclear transfer to place a human nucleus (the story just says "human DNA" but that doesn't make sense) into a cow ovum. They allowed the embryo to develop into an early stage blastocyst. I'm a bit surprised it did actually, but there you are. Previous attempts at somatic cell nuclear transfer with human material have resulted in embryos that would not grow past the 8 cell stage, so if this is correct, it's much more of a breakthrough than the BBC reporter seems to realize -- it really is the first human clone that appears to be viable.

Anyway, if I'm interpreting what happened correctly, the embryo is not really a human/animal hybrid. It's human except for having bovine mitochondria -- the endosymbiotic descendants of ancient archea that do the essential work of cellular metabolism. Were such an embryo to be allowed to grow into a human, I would expect it to appear entirely human and show no more abnormalities than a clone made with a human gamete.

Naturally, the Catholic Church is crying "abomination." Rather than talk about this further here, I'll finally get around to discussing Rusell Korobkin's stem cell century, specifically his chapter on the ethics of somatic cell nuclear transfer. The cow ovum is a bit of a wrinkle, but it really doesn't add much to the basic ethical problem, in my view -- although it may seem like a major issue at first glance.

Bomb, bomb, bomb . . .

John McCain started to launch into song on one memorable occasion, but he never gave us the complete lyrics. Here is my humble offering to fill the need I'm sure everyone is feeling.

I was down by the White House the other night,
Heard them all a singin' nearly died of fright.

Bomb Ira-a-an,
Yeah that's the pla-a-an
Cheney's pushing it on Chimpy
He says Chimpy don't be whimpy
Bomb Iran

(bomb bomb, bomb bomb Iran
bomb bomb bomb, bomb bomb Iran)

Bomb Iran,
Yeah that's the plan
Hillary voted to allow it,
She still won't disavow it
Bomb Iran

(bomb bomb, bomb bomb Iran
bomb bomb bomb, bomb bomb Iran)

Bomb Iran,
McCain's the man
People say that he is senile,
But bombing is so penile
Bomb Iran

(bomb bomb, bomb bomb Iran
bomb bomb bomb, bomb bomb Iran)

Bomb Iran,
Bill Fallon's canned.
He was the voice of reason
But to Chimpy that is treason
Bomb Iran

(bomb bomb, bomb bomb Iran
bomb bomb bomb, bomb bomb Iran)

Bomb Iran,
Peace is so bland.
Wolf Blitzer's salivating,
Cause war is good for ratings
Bomb Iran

(bomb bomb, bomb bomb Iran
bomb bomb bomb, bomb bomb Iran)

Sorry about that, it's what happens when I have trouble falling asleep. Feel free to contribute your own verses.