The consequences of casual concepts of causation

Exposure to X-rays can cause cancer, so their use as a routine and repetitive screen for tuberculosis (and, for readers old enough to remember, to look for the fit of shoes at a shoe-store), or for routine CT scans, and so on, is questionable.  Dental x-rays seem to be so safe that their risk, which is probably not zero, is nearly unmeasurable and presumably worth the dental problems they can find (hopefully, though not certainly, they are not taken too often as a source of profit).

Developing breast tissue in young girls is vulnerable, so they were not routinely given chest x-rays.  But breast cancer is common and serious, so mammography was seen for a long time as clearly a valuable life-saver, if used on peri- or post-menopausal women.  But recent studies have raised questions.  Interestingly, this is not because of new cancers that may be caused by the screening (though the number may not be zero).  It was because they could detect small anomalies that were then followed up.   Some would turn out to be cancer, even if in an early stage.  But the follow-up is psychologically traumatic and has its own unexpected consequences.  And even more, studies have shown that some of these cancers would regress on their own.  So mammography, despite so many being convinced of its value, is now under scrutiny:  when and how often and on who is this false positive risk too great to justify routine mammographic screening?

PSA testing has become routine for finding prostate cancer in older men, because prostate cells that are too active churn out PSA (prostate specific antigen), so high PSA levels, just as with suggestive mammograms, have been considered indicative of the need for follow-up.  Again, that has its own morbidity--including, gulp, impotence!--so it, too has come under scrutiny.  Indeed, as with mammography, studies have shown that the intervention's risk and the fact that many of the tumors would regress, or would stay silent until some other cause took the poor guy away, suggests that routine PSA testing be stopped.

Now, a new report suggests the same thing for ovarian cancer screening.  The reasons are the same, and surely there will be as much controversy.   What is this all about, and what is one to do, and why do we see this?  Surely and hopefully, it cannot be all, or even primarily, due to the profitability of screening services and follow-up.

More likely this reflects the belief in technology, fed by and into the hunger for early diagnosis and treatment of very nasty diseases that threaten the quality of life or even life itself.  Is it that early ideas about what might be early risk factors, based on some first rounds of studies, lead researchers anxious for important findings, and clinicians anxious for effective detection, to believe what are not very sound results?  This must be the case, unless the early studies were seriously flawed in their methodology.

Probably more importantly, this reflects a profound modern-day problem in science: the way that complex, multi-factor causation is studied by statistical studies, and the difficulty of getting good enough samples, well-enough understood, to generate reliable results.  Plus, many factors are lifestyle-related, and they change over time.

But could these findings be a reflection of a point we often wonder about, and that applies to evolutionary reconstructions as well--namely, that the assumptions underlying statistical studies of these types make and test assumptions?  Is it that the methods assume a type or level of regularity that simply does not reflect how things really are?

If that is the case then we have to await the next brilliant insight that will transform  how we think.  Meanwhile, we are apparently stuck not knowing why results and opinion change so often, or whether we can trust the latest study more than the previous studies it overturns.....or whether we have to believe that the latest study, too, will shortly be overturned.

Either the situation is straightforward but we just haven't done the right studies, or we're in a deeper epistemological hole than most people would like to think, calling for the kinds of creative thinking that no grant or research 'system' can order up, but simply depend on the lucky arrival of the required genius.

Loving hands, or 'go finger!'

Remember the Fickle
Finger of Fate?

WARNING:  This message contains adult content (along with something that purports to be 'science').  Digital discretion advised.

Well, we often hear that someone with loving hands is a good lover.  This can be taken both literally and as a figure (or finger) of speech.  The structure of hands isn't often thought of as a sexual attribute.  But maybe that has to change.

Not long ago Holly posted about the finding that Neanderthals were sex-obsessed thugs, based on the length of their finger bones, which indicates apparently how much exposure they had to testosterone in utero.

Now, to add to the complexity of the sexual finger is a story in the British Journal of Cancer about male finger configurations and the risk of prostate cancer. 

The ratio of 2nd and 4th digit length is fixed in utero (2D : 4D ratio), and is sexually dimorphic, lower in men than in women. To date, only one longitudinal study has investigated digit ratio and prostate volume, PSA level and the prostate cancer risk. The ratio (2D : 4D) is negatively related to testosterone and related phenotypes, such as sperm counts, and positively related to oestrogen concentrations. Accordingly, digit length pattern may act as a proxy indicator for the underlying prenatal testosterone levels. We therefore investigated this in a large case–control study of prostate cancer to explore whether there is any association between hand pattern and prostate cancer risk. 

That is, men whose index finger (2D) is longer than their ring finger (4D) were a third less likely to develop prostate cancer than men whose ring finger was longer.  But on the right hand only, not the left.  (Handedness even in sex!)  And, the previous study mentioned is the "Korean Cohort study" of 366 men, which found a negative association between digit ration and PSA, a measure of prostate cancer that is notoriously not terribly sensitive. 

As the BBC sums it up,

Being exposed to less testosterone before birth results in a longer index finger and may protect against prostate cancer later in life, say researchers at the University of Warwick and the Institute of Cancer Research.

Does this mean that if you are at high risk of prostate cancer, you're also a sex-obsessed rapine thug?  Or, does this mean that Neanderthal men all had prostate cancer? Have our noble investigators thought (yet) about getting a grant to give DREs (digital research exams, that is) to prisoners convicted of sexual crimes?  When will DRE results be admissible evidence in sexual abuse trials or preventive surveillance?

So this study is based on two assumptions -- one, relative finger length is indeed a reflection of testosterone levels during the development of the hand, and two, embryonic testosterone levels in fact influence risk of prostate cancer sixty or seventy years later. 

However, neither of these assumptions is tested by this study.  The study itself even says, cautiously enough, that digit length ratio "may [our italics] be a proxy indicator for prenatal testosterone levels." And the authors write that other adult diseases have been associated with uterine hormone levels.  The implication being: Thus, why not prostate cancer? 

This is on the nearly silly side, another use of research funds that probably shouldn't.  In addition to the issues we mention above, more than half of men have the Fickle Finger trait (wait, does this mean that the other 1/2 of men are not sex-obsessed? Impossible!  Who ever heard of a man who was not sex-obsessed?), yet the risk of clinical prostate cancer even by old age is only about 150 per 100,000 men.  Indeed, just as with PSA testing, the Finger Test could lead to a lot of screening in the Long Fingered, that could, like PSA testing, cause more morbidity and problems due to intervention than it solves. That's because most males of elder years have some prostate cancer, and most of those lesions never progress to a clinical stage before something more serious (and fatal) intervenes.

Of course, on the positive side, a glance at the hand is less embarrassing than a real DRE (digital rectal exam), or a PSA test to look for prostate cancer.   It may be as useful, at least in terms of risk.  It's a lot cheaper.  Of course the PSA testing companies are likely to resist this current interpretation. And with similar disinterest, what do the investigators say?  "We need a lot more research" (of course).

It all goes to show that even since our ancient fossil ancestors, women should be doing a size test on the guys they date, rather than just casually holding hands--and be prepared for what he might be want to do!  He may want his hands all over you....but it may be in his genes, so to speak, and how could he be blamed??

Give them the finger, but not the needle!

The pressure to abandon costly but clearly ineffective biomedical testing is always a battle with vested interests, and shows why science is by no means just a matter adjudicated by the 'facts'. A recent example, that we've remarked on briefly before, is PSA testing to detect prostate cancer in men.

The test itself is mostly painless (a needle-prick for a small blood sample, and a budget-prick to pay the Pharma that makes the test). But it is too non-specific and greatly over-diagnoses prostate cancer. First, because it is not specific to cancer, it gives alarm where there's no need. Second, many if not by far most prostate cancers go away on their own or grow so slowly that something gets the guy before the cancer does. Third, a positive PSA reading leads to invasive and reportedly painful tests that thus have their own costs and risk, including psychological ones as well as risks of impotence or incontinence, and so on.

The alternative test is euphemistically known as the DRE ('digital rectal exam'....or finger up the rear). This can directly detect enlarged prostates (almost universal in aging men) and suggest when some other follow-up test might be called for--often the PSA.

But the most prestigious medical journals are now calling for a stop to routine testing in men over age 50, and even the guy who discovered PSA as a molecule specifically produced by the prostate gland and that circulates in the blood, is calling this a human health disaster, in a NYTimes op-ed piece. But, just as vested interests slammed last fall's recommendation by the US Preventive Services Task Force that mammography be done less frequently than current practice, those who profit from PSA testing, and follow-up tests and treatment, are standing firm in supporting its continued use.

It's always a battle when evidence-based recommendations disagree with vested interests. Health care is big business, so that the bottom-line is always on top, and always must be, as a duty to shareholders, the primary consideration when decisions about practice are made. This is as true when withholding treatment is best for the bottom-line, as for insurance companies (which, of course, is why they cherry pick their customers, refusing to cover people with 'pre-existing conditions' because they might cost money), as when testing enriches those who do the testing, such as doctors with stakes in the testing lab. And, when testing is state-of-the-art, a physician has to be pretty confident when he or she chooses not to order it, as that may risk a law suit.

Pity the poor physicians! Even those trying to be up to date and do their best, without any conflicts of interest with labs or drug companies. Which pain in the butt should get priority--the finger up the back of their patients or the patient's lawyer on their back? For a client--er, we mean a patient--over 50, they have to ask themselves whether or not to order a PSA test. It's very hard and takes the doctors' rather than the patients' guts to say no, and make the gamble that nothing will turn up later. Or to have a positive test and tell the patient just to let things ride. And what medical literature should they take seriously, when they are too busy to read much of it carefully, much less being reasonably expected to be able to actually judge the quality of the research? Should they pay any attention to the drug detail-men, or what they hear at the Pharma's expense at their 'education' conferences in the Caribbean?

This will all get more problematic when their HMO is run by a wonk with an MBA in cost-effective procedure management, and the MD is in the office trying to care for an actual human being (the patient, seen by the boss as a customer number). Who's 'evidence' will be used? Who will decide? Some are actually trying to do this right, but clearly not everyone is.

So when you get told to have your test.....what will you do: refuse to bend to the system, or just bend-over?

If genetic causation is complex, why should risk factors be any less so?

Every day, it seems, the forces of biological simplism -- the hunger for, and vested interest in simple answers to complex questions -- suffer a setback. Today, it's large-study results that show that screening for a simple marker for early prostate cancer detection seems to be ineffective ( New York Times prostate cancer article ). It may be harmful in the sense of leading to the detection of benign cases, and then some intervention with its associated risk of morbidity. Earlier this year somewhat similar results appeared for mammographic screening for breast cancer. The point is not to coldly denigrate attempts at early detection, but to show the importance of recognizing nature's complexity. Those who suffer from cancer--and we all know such people, and many of us will be such people--deserve all the care and concern that can be mustered. But can we think of better ways to approach this genetically complex problem? Is standard reductionism, trying to identify individual risk factors, or even single risk factors, the way to go? Or will some smart young researcher give us the benefit of conceptually innovative ideas?

For most risk factors, genetic or otherwise, the situation is similar: cholesterol, blood pressure, even obesity have complex and poorly understood associations with subsequent disease outcomes, and with prior genetic risk factors. It is already known, however, that the most effective way to head off chronic diseases is not to smoke, get exercise, and eat a moderate, balanced diet (including even to have a drink now and then!).

But, that conceptually innovative idea is not going to come anytime in the next month or so -- biology is on holiday. This is not like France, where everyone goes to the seaside in August. No, it's because of our 'stimulus' package's ad hoc grants program. Like lemmings to the sea, or hogs to the trough, every scientist and his relatives (living or deceased) is charging headlong for the new money. Whether this is a moral way to spend these funds is an open question. But everyone's now too busy putting together their hoped-for bonanza grants to do any actual scientific work. Ironically, the stimulus package's 'challenge grants' may turn out to be a NON-work initiative for science!

Presumably, the crush will end and we'll all get back to work. One can predict that, due to the gold rush the funding percentages won't be any better, and they may be worse for this 'easy money'. Time will tell.