Bioblog: Biology in the News

As discussed by Professor Chambers in the clip below, there’s no doubt that schools have become largely segregated again. Most efforts at integration ended years ago, during a post-1960’s conservative backlash, and now although it is rarely discussed, we’re pretty much back where we were - the only difference is that segregation has happened on its own, without government enforcement as was the case pre-Brown v. Board of Education.

It seems that the mainstream conservative position on this can be adequately summarized as, “So what? As long as there is freedom in where people are allowed to live, there is school choice (and hey while we’re on the topic, aren’t vouchers a great way to increase school choice?).” It is an argument crafted from the point of view of individual rights, which many people have trouble disagreeing with in principle.

But liberals, on the other hand, tend to see segregation as more evidence of institutionalized racism. They might respond, “How can you say that minorities have choice? A higher proportion of minorities live in poverty, and the associated lack of opportunity means that they have to go to schools that are populated mainly by other people just like them (ever heard of white flight?). Plus, they have the double whammy that keeping property-tax spending on schools local means that the poor kids who need a leg-up in education the most are stuck in the worst schools.”

The key problem we need to recognize is that while there are some political reasons for the re-segregation of schools, on a simpler level there always is a natural human tendency to gravitate toward groups of people more “like us,” whether that similarity lies in wealth, race, religion, etc. It goes both ways - it’s not just whites and rich people who gravitate toward each other, but blacks and poor people as well. A white man I know who was involved in a voluntary busing program in Denver in the 1960s told me that the bus driver had to take a different route each day because if he went the same way, people of both races would throw rocks at the bus.

So if this tendency is natural, what’s wrong with it? Identifying the difference between “in-group” and “out-group” members is a clear byproduct of humans’ evolutionary history as social animals. The rules we make about distinguishing these probably worked fairly well for us in pre-technological times. But as horses, ships, trains, planes, telephones, and now the internet brought more and more disparate groups of humans into casual contact with each other, the problems associated with our love of in-group increased exponentially. The high-level of internet vitriol aimed from one group to another is a direct result of the lack of social cost to negative interactions, which are almost inevitable when interactions are anonymous.

In our now small yet heterogeneous world, we interact continually with people on a much larger scale than did the original social groups which shaped our evolution, and it turns out that our natural circle-the-wagons tendencies are damaging on that larger social and political scale, because the larger scale affects us all a lot through state and federal policy.

And this brings us to why integration is so important. School integration has been known to have positive academic effects on children (that is, actual integration, not the political violence that has often accompanied it) for a long time (Maynor and Katzenmeyer, 1974). Although some argue that racial tensions can be raised by forced integration, this is likely an artifact of time and scale. There is no doubt that a lot of bigotry comes from the ease in which the out-group can be placed in the category of “other”; if people actually interact face-to-face with the “other” on a daily (and equal) basis, much of the knee jerk conflict disappears. As an obvious example of this, just notice what is currently happening with acceptance of gays in this country. When gays were largely closeted, very few heterosexuals believed that they knew any, so it was easy to demonize them. The reason that younger people are clearly so much more accepting of homosexuals is they have grown up among open gays. These days, almost every heterosexual has a known gay acquaintance, if not friend, and with that knowledge comes the realization that gays are actually human beings pretty much the same as the rest of us. This realization takes time for some people, but although there are of course violently anti-gay holdouts, the great majority of people come around eventually to a more sympathetic point of view. The same holds with people of a different race.

Race relations are far from ideal, but no one can deny that they progressed mightily in the 60s and 70s. Integration must have been part of the reason. But backsliding is a real danger with the current generation if people go back to their segregated lives, whether or not it is due to active ideology, or just complacency. Our innate social tendencies make this the path of least resistance, so for us to stay on the alternate path toward racial equality, we have to work at it continually. Even if this is ultimately a sisyphean task, and we can never reach a stable end point, the very act of trying will make us a better country in the long run. When we give up the ideal of racial integration and equality because of the notion that the only way to achieve it violates individual rights which are sacrosanct, society becomes more fractured and the isolationism feeds back on increased resistance to coming back together.

A fundamental difference between conservatives and liberals seems to be that conservatives believe that individual rights should always trump all else, while liberals see societal cohesiveness as at least equally important (whether or not a given liberal’s proposed methods to get there are valid or not is a separate issue). Sociobiology tells us that the needs of the social group support the needs of the individual - we know that individual humans cannot survive without society. Societies, though, have to have lots of rules for them to function properly (meaning, for individuals to be successful within that society). Whether or not individualists like it, the security and stability of our planet depends on us overcoming our innate small-group tendencies to recognize that our default social group is now largely defined on a much, much larger scale than our brains want it to be. The issues in figuring out how to get along better may be complex and difficult, but this does not change the imperative. We can start to retrain our brains though, by spending less time in the echo chamber of the internet, and more time making an effort to interact face-to-face, and with an open mind, with people who are not like us.

Reference

Maynor, W., and Katzenmeyer, W.G., 1974. Academic performance and school integration: a multi-ethnic analysis. The Journal of Negro Education 43(1):30-38

The comments on my last essay about science denialism suggest that in public discourse there continues to be a pervasive and unhelpful conflation of science and politics, which should always be kept separate. Unfortunately, this conflation is not restricted to the vocal lay public and politicians (from whom it might always be expected) but is also commonly perpetrated by well-meaning scientists who are passionate in their reasonable belief that science should inform policy.

Many commenters seemed to believe that I lament the fact that discourse about developing scientific theories is no longer (if it ever was) confined to the scientific community, but in fact I simply provided my interpretation of how the internet has affected the recent history of scientific consensus. My argument is that scientists need to recognize the reality of the eavesdropping of laypeople (and the subsequent manipulation of what they believe they heard), and realize that they must hold themselves to a high standard in what sort of public face they put on science, because vocal nonscientists are affecting policy apparently more successfully than science is.

We can no longer wave off science denialism as a quirk of uneducated publicity hounds and ignore its importance, because this common response to denialism is somewhat justifiably viewed as arrogant; in truth the burden is squarely on the shoulders of scientists to address this growing problem. More than two years ago I argued here that the scientific community itself is largely responsible for poor scientific understanding by the public, because of the tendency of scientists to try and make their work sound more important by the common use of jargon and self-important language that by objective standards demonstrate extremely poor communication skills.

The lack of interest that most of us seem to have in properly communicating what we do to nonscientists has disastrously combined with the thoughtless conflation by scientists of science with policy. Scientists as a community continue to struggle with the idea of whether or not they should be advocates of particular policy positions related to their scientific fields, as evidenced by a recent editorial [Lymn, N and S. Silver (2010) A fine dividing line. Frontiers in Ecology and the Environment 8(1):3] in the journal of the Ecological Society of America (ESA), Frontiers in Ecology and the Environment (excerpted here):

One of the thorniest debates among ecologists is whether they should become involved in policy making and politics…there has always been some tension between ESA members who believe ecologists should focus solely on their research and those who assert that they and their colleagues should engage in policy outreach, making ecological knowledge relevant to decision makers.

The reason this debate occurs is because scientists so often make a botch of their advocacy. There are two main problems. The first is that many scientists do not make clear to their audiences, both intended and inadvertant, that the process of science is free from ideological advocacy, and that their own advocacy is completely separate from their work as scientists. This is hard to do, of course, which is why some scientists feel strongly that advocacy should be left to nonscientists (e.g., Al Gore), so as not to give the mistaken impression that advocates are representing science itself, which properly has no ideology.

This is the key to a lot of the anti-science vitriol: scientists are becoming increasingly viewed by many as some sort of political interest group equal to all the ideologically based lobbyists, and thus science itself is questioned and assumed to be opinion-based, because scientists are not properly separating their advocacy from their work. It should be noted that ESA as an organization takes great pains to show that their only function in policy is as a resource to which policy makers can turn when they want to know what the science objectively states:

ESA is one of hundreds of organizations with a presence in Washington, DC. As a scientific society, what distinguishes it from advocacy organizations is that the Society works to inform decision makers, based on the ecological expertise of its 10 000 members. In contrast to advocacy organizations, ESA doesn’t make the policy decisions in advance and then lobby policy makers to act accordingly. Instead, through congressional briefings, position statements, and one-on-one meetings, the Society lays out a menu of options - based on the best available science - for decision makers to consider.

Part of the reason that people view the concept of “scientific consensus” suspiciously (if not downright hostilely on these and other pages) is that scientists are lousy at explaining how scientific consensus is reached. Here is one scientist’s attempt to do do:

While anyone can see that throughout history ideology has certainly affected what sort of studies certain scientists have done and how they have interpreted the results of those studies, the key here is that because real science is not ideological, ideologcially based “scientific” ideas will be fairly quickly weeded out from mainstream scientific consensus, because they will be shown to be unsupported when rigorous scientific methods are applied. Scientific consensus is not necessarily the truth (e.g. the best understanding people had of geological processes before plate tectonics), but as evidence accumulates, it will be altered if necessary. This is the important difference between ideology and science. A person’s ideology rarely changes in the face of facts that contradict that person’s world view. Scientific consensus absolutely does change all the time, as can be seen repeatedly over history, because it is based on data accumulated under very particular standards.

Yes, there is a lot of bad peer-reviewed science out there. Identifying bad science with the intention of steering it in a more rigorous direction is one of the primary functions of Bioblog. This type of recognition of bad methodology followed by research with better methodology is actually how scientists move any field along to better understanding.

So, my various commenters, you can’t pick and choose which science you “agree” with and which you don’t, as if the science itself were a policy position. The scientific consensus in any field is the best we can say about that field at this time, and it is always evolving, but when 98% percent of scientists in a field agree on the general conclusions, you can bet that the data are pretty solid. Yes, conclusions can change when valid new data are introduced into the mix. That’s what’s good about science, not what’s bad. Applying some sort of ideological test to scientific consensus simply makes no sense.

Scientists who decide to become policy advocates have been guilty of muddying the waters so that people equate science with ideology, because they have not made clear that their opinions regarding policy have nothing to do with the scientific consensus. There is another problem too: many advocates of what they might consider science-based policy do not at all understand the science that they use to support it, so they say stupid things that makes them sound like idiots, which the public interprets as weakness in the science, rather than foolishness of the messenger.

Although I am an ecologist, I am not comfortable explaining the science of climate change (rule of thumb: if you can’t teach an upper-level undergraduate course on the subject, you definitely don’t know enough to spout off to the public). Climate change is an incredibly complex field involving ecology, meteorology, chemistry, physics, oceanography, and probably other specialties. Thus it takes decades of work in the field for someone to be a true scientific authority on climate change. Even though the accumulated decades of data and conclusions supporting anthropogenic climate change satisfies my standards as a scientist, if I were out there trying to explain the science of climate change to laypeople in order to convince them to support a particular policy, I would not be at all effective, because my superficial understanding of the science would undermine it and make the evidence seem flimsy and unconvincing to nonscientists. (This is another reason that the mindless ideological rejection of a fact so clearly established as evolution has been elevated to a “debate” - unfortunately there are many well-meaning scientists who are not evolutionary biologists, but think wrongly that they understand and can explain the intricacies of a subject that people get doctorates in. You do not see this phenomenon with other scientific fields such as, say, particle physics.)

In the end, scientists will always have a difficult battle with ideology, because the playing field is not level. Denialists have a much easier time than scientists do in promoting their ideas, because by definition their pronouncements do not have to meet any minimum standard of rigorous evaluation (although they like to pretend that they do). But scientists need to start separating their political beliefs from their position as scientists, because when they try to exploit that position to add authority to their statements, they are more likely to undermine that authority - and science itself - because they just end up sounding like ideologues in their arguments. Civic-minded scientists who just can’t help themselves have an added and crucial responsibility to separate their advocacy from their work, even if they know the field backwards and forwards. Because science never advocates; it simply explicates. It is unfortunate that this is not more widely understood.

An article at the New York Times’ Well blog on the retraction of the 1998 Lancet paper that was instrumental in sprouting the anti-vaccine movement is a prime example of a new, internet-enhanced relationship among scientists, media, and the public.

As alluded to in the blog, it used to be that internal scientific squabbles and tossing-around-of-wacky-ideas were never in the public eye. Scientific papers were discussed within the scientific community, and only after consensus emerged about a new idea did that idea enter the public realm; this process generally took years.

But the internet coming into popular use changed all that, in several stages. First, years before the internet was widely used by average citizens, scientists were already online in the 1980s, collaborating and having discussions via email and news groups (now known as chat groups). This allowed ideas to flow more freely and widely to a larger scientific audience, generally to the benefit of science.

Then, beginning in the late 1990’s, journals finally began producing online editions instead of being in print only. At the same time, use of the internet skyrocketed among the public. So suddenly, anyone could do a search and look at paper abstracts online (full articles still require expensive subscriptions) whereas before this, a person had to make the effort to go to a scientific library to locate a specific journal article in the stacks, which had to first be identified through obscure search engines generally only available to academics.

Naturally journals and institutions producing research have always tried to garner publicity, so they have always produced press releases that got some science in the news. But only recently has it become much easier for interested non-scientists such as journalists or bloggers to regularly follow discussions that used to stay in the scientific community.

Unfortunately, many scientists still believe they are living in a world in which science is controlled by the scientists until they make it available for public consumption, even while numerous recent “controversies” have belied that belief. While there have always been wacky scientists who promote ideas that are unsupported by the overwhelming scientific evidence, they used to be collectively relegated to the scientific fringe and generally ignored, their occasionally published rants unknown to the general public.

Now, the availability of the internet has caused the problem that these fringe scientists collect a devoted following among the scientifically illiterate, and their discredited ideas go viral on the internet, sucking in people who want easy answers that science cannot always provide. Why does a particular anti-science idea gain traction? In the case of climate-change denialism, there are obvious short-term economic motivations by powerful interests. In the case of vaccines, there seems to be an intersection of many regular people wanting answers for a condition that does not yet have any clear answers, and an anti-medical establishment/corporate anger and paranoia that is easy to fuel given the grain or two of truth in the idea that pharmaceutical companies do not always have the general public’s best interest as their number one priority.

(Ironically, the anti-vaccine furor has also been so easy to stoke because vaccines have all but eliminated many deadly and debilitating diseases from our society, and thus people do not truly grasp anymore the magnitude of the benefits they provide; they simply take those benefits for granted, believing that the vaccines must not be necessary (see many “homeopathic” web sites for examples). Simply reminding someone of the lives that used to be destroyed by infectious diseases is not enough for denialists, because they have no personal connection to that particular tragedy; their personal connection is to a condition for which they would probably gladly embrace a vaccine, if we had one.)

One more example of a large denialist community is among the HIV/AIDS connection deniers. They have been in the scientific news as well because of an unfortunate sequence of events in which anti-HIV papers were published in the journal Medical Hypotheses, and then retracted. This has sparked a heated discussion (see comment thread in the above article) about the role of peer review and scientific consensus in the application of scientific ideas. What is only being touched on in these discussions is how interactions among scientists are now, for better or for worse, in the public view, and what the consequences should or should not be for the scientific progress.

It is good that the Well blog has begun a discussion on the implications of fringe (non)scientific ideas going viral in the public, but that still leaves the question of whether or how scientists should address these in how they conduct themselves. It is this scientist’s opinion that scientific business-as-usual must change if we want to keep control of a narrative that we are actually the ones trained to deliver. It is simply not working in the world of the internet to tell the public, “The scientific mainstream knows best, so listen to us,” because in the growing trend of anti-elitist populism, this will not be accepted; in any case the statement is undermined by the growing awareness that a scientist is a human being just like everyone else, with his own ambition and agenda that can color scientific conclusions. Science simply must change to accommodate this new reality, and this will be the subject of a future essay.

Estrogen is a hormone that in females has many functions. We still do not have a complete understanding of the relationship between estrogen, estrogen-like compounds (which can bind to an estrogen receptor), and cancer.

Several factors complicate these relationships. First, there are estrogen receptors all over the body, and there are at least two types of estrogen receptors, alpha and beta. These different receptor types are distributed differently in the body, and activate different genes, sometimes in opposition to each other (Palmieri et al., 2002).

When a compound binds with an estrogen receptor, it has different effects depending on the part of the body that the receptor is in. Non-estrogen compounds such as tamoxifen may mimic estrogen in their actions in some body parts, while acting as an estrogen blocker in others. In fact, when tamoxifen was first introduced, it was believed it would be an estrogen blocker across all receptors, when in fact it blocked estrogenic effects in cancer cells, and mimicked them in bone cells (thus helping to prevent bone loss in women taking the drug for its anti-cancer properties).

The association of estrogen with breast and endometrial cancer (McGuire, 1973) makes sense because the action of estrogen in several contexts is to cause the proliferation of cells, in the breast or uterus. Every menstrual cycle, cells in the breasts and uterus proliferate, and then die off if a pregnancy does not occur, because estrogen levels drop. Over time, our cells acquire mutations, for many reasons. The problem for women is that the more menstrual cycles there are, the more chances that a cancer-causing mutation exists in a few of the cells, and that estrogen will stimulate them to proliferate out of control (Henderson et al, 1988).

One of the reasons that using birth control pills increases cancer risk is that the pills were designed to mimic “natural” cycles in women, even though there is no known physiological requirement for women to bleed as often as every month. This causes a high cumulative number of cycles for women who take the pill for years (plus they have more cycles because they have not had any pregnancies). Having a late first pregnancy (over age 30) is also a slight risk factor for breast cancer even above having no children at all, because not only has there been a lot of time and menstrual cycles for mutations to accumulate, but following mutation with long term exposure to estrogen during pregnancy can then cause those mutated cells to proliferate. (All breast lumps should be investigated, but if a lump appears in the breast of an older mother soon after giving birth, it should be considered doubly suspicious.)

But, as it turns out, estrogen mediates lung cancer in too: lung cancer is twice as prevalent in female smokers as it is in male smokers (Dougherty et al., 2006), twice as prevalent in female nonsmokers as in male nonsmokers (Wakelee et al., 2007) and estrogen stimulates tumor progression in females with lung cancer (Hammoud et al., 2008).

Because as yet not enough is understood about how the different types of estrogen receptors mediate gene activation both normally and in cancer cells, we also know little about the mechanisms of phytoestrogens, despite ubiquitous claims of both benefit and harm (Rice and Whitehead, 2006).

Phytoestrogens are compounds in plants that can bind with estrogen receptors. They occur throughout the plant kingdom, but are especially highly concentrated in flax and soy. There have been debates for years about whether phytoestrogens are protective against breast cancer or promote it, or whether they could spark a breast cancer recurrence through estrogenic activity. Because non-estrogen compounds that bind with estrogen receptors may have either estrogenic or estrogen-blocking activity, and the mechanisms of phytoestrogen effects are still not well understood, these questions have not been answered definitively.

Coming soon: a discussion of recent research on phytoestrogens and soy diets which provides another piece to the puzzle of the role of estrogen-like compounds in cancer risk and prognosis.

More information about cancer and estrogen receptors is available from the National Cancer Institute.

References

Dougherty SM, Mazhawidza W, Bohn AR, Robinson KA, Mattingly KA, Blankenship KA, Huff MO, McGregor WG, Klinge CM. Gender difference in the activity but not expression of estrogen receptors alpha and beta in human lung adenocarcinoma cells. Endocr Relat Cancer. 2006 Mar;13(1):113-34.

Hammoud Z, Tan B, Badve S, Bigsby RM. Estrogen promotes tumor progression in a genetically defined mouse model of lung adenocarcinoma. Endocr Relat Cancer. 2008 Jun;15(2):475-83.

Henderson BE, Ross R, Bernstein L. Estrogens as a cause of human cancer: the Richard and Hinda Rosenthal Foundation award lecture. Cancer Res. 1988 Jan 15;48(2):246-53.

McGuire WL.Estrogen receptors in human breast cancer. J Clin Invest. 1973 Jan;52(1):73-7.

Palmieri C, Cheng GJ, Saji S, Zelada-Hedman M, Wärri A, Weihua Z, Van Noorden S, Wahlstrom T, Coombes RC, Warner M, Gustafsson JA. Estrogen receptor beta in breast cancer. Endocr Relat Cancer. 2002 Mar;9(1):1-13.

Rice S, Whitehead SA. Phytoestrogens and breast cancer–promoters or protectors?Endocr Relat Cancer. 2006 Dec;13(4):995-1015.

Wakelee HA, Chang ET, Gomez SL, Keegan TH, Feskanich D, Clarke CA, Holmberg L, Yong LC, Kolonel LN, Gould MK, West DW. Lung cancer incidence in never smokers. J Clin Oncol. 2007 Feb 10;25(5):472-8.

The recent medical opinion that anthracyclines (such as Adriamycin) are not effective in breast cancer patients that are HER2 negative is now joined by a potential test to further refine who will benefit from these chemotherapy drugs, which generally make patients very sick and are dangerous enough to cause permanent heart damage in some people.

Two genes were studied, and the mechanism of the action of one of the genes is fascinating: cancer cells with this gene sequester the toxin outside the nucleus, where it needs to be to kill the cell. The result is high resistance to Adriamycin (doxorubicin), which up to this point has been offered commonly and indiscriminately to many women with stage II cancer and above. So women with the gene who suffer through a common chemotherapy such as TAC (Taxol-Adriamycin-Cytoxan) are much more likely to have a recurrence than women without the gene.

About 20% of sampled patients in the study had the gene, and they had worse outcomes than the majority of women. The good news is that the authors find that cancer cells resistant to this class of chemo drugs are still susceptible to others. And, genetic tests these days are pretty simple and cheap to conduct (despite what companies like Myriad Genetics might tell you).

Big Pharma shouldn’t be too worried. Surely they will fight tooth and nail to patent as many genetic tests related to cancer as possible. But they’d better get cracking, because they missed this one. And it’s easy to imagine that perhaps an executive or two at a few companies would secretly rather this information weren’t available at all, because that will cut in on their profits. But perhaps this is overly cynical - surely it’s just those who don’t know someone with breast cancer who would have a tendency to feel that way. Of course, at the rate things are going, eventually most of them will.

The ecological conditions that cause a given introduced species to become invasive are complex and rarely well understood. One of the problems in attempting to promote legislative barriers to the introduction of alien species, which continues at a high rate in the U.S., is that invasions seem to follow roughly what is known as the “Ten Percent Rule.” That is, about ten percent of introduced species become naturalized, and about ten percent of naturalized species become expensive and destructive pests.

When only one in a hundred species will be an economic problem, it is not easy to take political steps to prevent the importation of aliens in general, which most ecologists would prefer. If we knew which species were most likely to cause damage, we might have better success with a regulatory pathway, but unfortunately the problem remains that ecologists are not yet capable of predicting which particular species will get out of control (with a few exceptions - Burmese python in Florida was pretty much a no-brainer).

Our current policies are clearly not working to prevent new invasives, because the species importers (pet stores, commercial nurseries) currently get all the financial benefit of importing new species, without any of the societal cost for those that become invasive. Some argue sometimes that even if a species becomes a pest, the local ecosystem will just eventually adapt to its presence. It’s not really a great argument given that multiple native species affected by the invasive could go extinct over a much shorter time scale than evolution would normally act to curb it, but a recent paper could (unfortunately) give this idea some legs.

Some species become invasive because they have been released from their natural predators, making them much more prolific in the new habitat. Nils et al. (2009) found that cropping up are a few cases of native predators adapting to invasives, so there will be potential for control. There are several reasons why this might happen, but in most cases it is because predators are forced to use a less-preferred prey because the preferred one is decreasing in abundance (often due to negative interactions with the invasive).

Of course there is likely to be a lag in this process, but the authors find several hopeful examples, including turtles and Great Lakes whitefish eating zebra mussels; native snakes eating cane toads in Australia; and red rock crabs eating European green crab in North America.

The authors avoid the issue of “evolution taking care of aliens,” but instead comment on the intriguing notion that because some of the adaptive predators are harvested by humans, we have a new factor that we need to consider when defining a sustainable catch of those species. In fact, populations of alien species that have so far been kept in check by natives, without us even realizing it, could start to spread out of control if catch limits are set too high for that ecosystem function to be preserved. Up to this point, such food web considerations have not been made in setting harvest limits.

The trouble is, harvest limits usually have little basis in any ecological information. From the perspective of a resource economist that I know, this is probably partly because ecologists have not done a great job historically of quantifying ecological impacts (although partly due to invasive species impacts, economic measures of ecological issues have more commonly entered into ecological discussions). But when I asked if it would ever be realistic to take information on novel ecological interactions - such as presented in this paper - into account, he didn’t see any reason why not, if ecologists obtain reasonably quantified data that they could deliver to resource economists for use in their model.

It seems at this point (when it is almost too late anyway) that it will be a stretch for such a politicized issue as harvest limits to take into account the more subtle effects of food-web interactions, but community ecologists should certainly take note of Carlsson et al.’s findings, and start to attempt to quantify the ecosystem value of key predators (and the resulting economic value, when costs of damage and control of invasives are quantified) , starting with those that are preyed upon by humans. If they don’t, not only might native communities continue to collapse, but a slew of invasive species may become a whole lot more damaging than they already are. We shouldn’t be spending $10 on a crab that truly costs us thousands of dollars in the end.

Reference

Nils OL Carlsson, Orlando Sarnelle, David L Strayer, 2009. Native predators and exotic prey - an acquired taste? Frontiers in Ecology and the Environment 7(10):525-532

Apparently the “several top cancer doctors” interviewed by the New York Times (about a couple of recently presented studies suggesting that oral bisphosphonate drugs, such as Fosamax, prevent breast cancer in some women) haven’t been keeping up with the literature in their field.

To be sure, in a scientific vacuum, their skepticism would be warranted. They rightly point out that one should be cautious interpreting data associations in the absence of randomized studies, which these are not. Women choosing to take bisphosphonates are those with weaker bones, which may have been caused by lower estrogen in the first place. Lower estrogen also reduces risk for hormone-positive breast cancer, so lower breast cancer and use of oral bisphosphonates may simply have low estrogen in common; thus there could be no direct causal effect of taking oral bisphosphonates.

But the data did not emerge in a vacuum. For example, it has been known for some time now from randomized trial data (Gnant et al, 2008) that breast cancer patients taking the closely related drug zoledronic acid (Zometa) (which is taken intravenously rather than orally) have somewhat fewer cancer recurrences than comparable patients who do not. In fact, zoledronic acid was originally used to treat cancer patients with bone metastases, and has only secondarily been prescribed for osteoporosis.

So, it is quite possible that there is indeed a preventative effect being seen in the observational studies with oral bisphosphonates, despite the problems of interpretation associated with non-randomization.

But even if it can be shown that bisphosphonates help prevent cancer, that doesn’t necessarily mean everyone should take them. As with all drugs, there are risks that anyone considering medication should discuss with her doctor. Unfortunately our cultural yearning for cure-all drugs, stoked to a high-stakes quest by pharmaceutical companies trying to make a profit, will likely lead to a distorted interpretation of the data that results in these drugs being pushed hard on all older women. Already, far more women take bisphosphonates than really need them for bone health, partly due to clever manipulation of the definition of “disease” by drug companies. No doubt because of this announcement we will see shortly another big push to get as many more women as possible on these drugs.

I have already heard at least one doctor assert that every single American should be on statins, because they prevent heart disease in a subset of adults.  But if there were a pill to prevent each disease you could possibly get in your lifetime, would you take them all? A hundred pills would certainly not be practical, but would you draw the line? Where should doctors and insurance companies draw the line?  People who claim loudly to believe in unlimited health “care” (i.e., are anti-”rationing”), would perhaps believe there should be no line.  Just remember, though, that drug companies absolutely support that view, but not so much for philosophical reasons. Drugs such as bisphosphonates and statins may or may not benefit a particular individual, but every individual taking them absolutely benefits the drug company. It’s a fine, blurry line between health and profit.

Reference:

Gnant M, Mlineritsch B, Schippinger W, Luschin-Ebengreuth G, Poestlberger S, Menzel C, Jakesz R, Kubista E, Marth C, and Greil R. 2008. Adjuvant ovarian suppression combined with tamoxifen or anastrozole, alone or in combination with zoledronic acid, in premenopausal women with hormone-responsive, stage I and II breast cancer: First efficacy results from ABCSG-12.  Journal of Clinical Oncology 26 (May 20 suppl; abstr LBA4)

A new paper enters the cancer screening fray: Shappley, W.V. III, Kenfield, S.A.,Kasperzyk, J.L., Qiu, W., Stampfer, M.J., Sanda, M.G., and Chan, J.M. 2009. Prospective study of determinants and outcomes of deferred treatment or watchful waiting among men with prostate cancer in a nationwide cohort. Journal of Clinical Oncology 27:4980-4985.

The study, which showed no statistical difference in outcome between cancer patients who deferred treatment and those that did not, was weak in many ways. The most obvious problem was that it was not controlled, but instead compared men who made their own decisions either to monitor their cancer for awhile, or to treat immediately. This led to not only a skew in sample size (the waiting group was 10% of the total) but in significantly different initial pathologies in the groups.

But, in a way, the unequal comparisons show why this study is important. The patients who chose to wait had were unsurprisingly older, and had cancers at an earlier stage, with lower Gleason scores. So from one perspective, it is easy to say that the waiters did as well as the treated because their cancers were less likely to progress anyway. If the treatment group had more aggressive cancers, those men were still likely to die, despite treatment.

From another perspective, though, this study demonstrates exactly the pathologies for which deferred treatment, or “watchful waiting,” makes sense. As an accompanying editorial (Zietman, A., 2009. Evidence-based medicine, conscience-based medicine, and the management of low-risk prostate cancer. J Clin Oncol 27:4935) points out:

Contemporary data do show that local failure is now infrequent after radical treatment but it is also true that symptomatic local progression is unlikely even without treatment and thus little, in reality, is gained.

It is easy to fall into the trap that if I was treated, and I got better, it must have been because of the treatment. This study is important because it clearly demonstrates the fallacy of that reasoning.

Another important point of perspective is that the percentages of both death or metastasis after an 8-year follow-up were comfortingly low: death rates ranged from 0.72% to 4.5%, and metastasis rates ranged from 2.6%-10.5%. Thus, even with sample sizes of 2989 in the treated group and 342 in the waiting group, there were too few events to show any statistical difference in outcomes:

We found the relative risk to be similar between the patient groups, but the numbers of metastases and deaths as a result of PCa were low, potentially underpowering this analysis.

But what does “underpowering” mean in this context? It means you have to collect a whole lot of data to find any significance in the effect you are looking for. Some people think this means that researchers have a responsibility to collect enough data to find a statistical effect. But someone actually trying to place what is being studied in a biological context might notice that if an event you are trying to measure (in this case metastasis or death from prostate cancer) is so rare that you need a giant sample to detect a difference in the event between groups (in this case treated or untreated men), then how important is that event really, in the large scheme of things?

Very important, would say many people injecting themselves in the current health care debate. If one life can be saved by treating dozens more men, we shouldn’t even question it. We all have a bias if ours is the life being saved, and so at an individual level, some consider any amount of time and expenditure to save it is worth it - even necessary. This, precisely, is what the outraged charges of “rationing” are all about. The logic goes: if even one life is lost because a bureaucrat says that a group of people with a particular diagnosis cannot have a particular treatment, it is a moral travesty.

But of course this argument can be shown to be fallacious at its logical conclustion. Putting aside the curious lack of outrage by the “anti-rationers” at the fact that nearly 50,000,000 people in this country are rationed completely out of any but emergency care (and many of them die due to this current rationing), anyone with any intellectual honesty at all understands that unless you want to give everyone a complete body scan every week, an absurd proposition for many obvious reasons, a lot of people are going to continue to unfortunately die from cancers that weren’t “caught early” - because many cancers grow too fast to catch them early, under current yearly screening guidelines. Limiting screening to yearly visits for just a few cancers is rationing. We have rationing now, and under any possible system, we always will. The only rational point of contention is where to draw the line. Anyone who claims that line is obvious and absolute, for any type of screening, is disingenuous and talking through his hat, because anyone’s location of the line is based on their own preferred cost/benefit ratio, a matter purely of opinion.

Except, there really is only so much money out there. So even the most vocal of the “anti-rationers” will recognize that a barrier to constantly increasing care, based on cost, is eventually reached.

The accompanying editorial contained some surprisingly forthright statements that need to be discussed in the mainstream health media. For example:

The training of resident doctors has to date been so focused on cure, and the culture of early detection/early treatment so deeply ingrained, that it is little wonder that this shift in thinking is yet to reflect itself in everyday practice. What is respectfully acknowledged at major meetings and in editorials is not, in the daily reality of the clinic, being applied to patients…

The PCPT (Prostate Cancer Prevention Trial) trial reported in 2004 demonstrated that systematic needle biopsy could find prostate cancer in 27% of all men with a normal prostate-specific antigen (PSA).

It may sound surprising, given the shrillness of the current debate, but the idea that cancer exists at at least a low and nondangerous level in many of us is not a new one. A 1985 autopsy study in Finland (Harach, H.R. Franssila, K.O., and Wasenius, V.-M., 1985. Occult papillary carcinoma of the thyroid. A normal finding in Finland. A systematic autopsy study. Cancer, 56(3):531-538) found carcinomas in the thyroids of 36 out of 101 people who died of other causes. The prevalence of tumors, or their size, was not correlated with age, suggesting that thyroid cancers arise at a young age, and most do not progress:

To conclude, the smallest forms of OPC [occult papillary carcinoma] of the thyroid are, according to our series, so common in Finland, possibly also in other countries, that they can be regarded as a normal finding.

The authors conclude by suggesting that doctors avoid using the word “cancer” in regard to any small tumors found in the thyroid, because it is so loaded down with baggage that results in overtreatment. So none of this is new. It is just becoming highly relevant as we discuss what to do about medical costs that are spiraling out of control, and leaving more and more ruined lives in their wake.

Bottom line: if you look for potential problems through scans of perfectly healthy people, you are going to find a lot of them. The logical extension for those who are demanding more and more screenings (to be paid for by somebody else) is constant full body scans. And setting aside the impossibility of this, imagine the disaster of overtreatment that would ensue as we treat more and more asymptomatic conditions.

And as a final note, putting more and more money into screening does nothing to solve the problem that we are focusing too much on looking for and treating disease, rather than health itself. The same amount of money spent on prevention rather than treatment can help a whole lot more people. But, as another commentary (Esserman, L., Shieh, Y. and Thompson, I. 2009, Rethinking screening for breast cancer and prostate cancer, Journal of the American Medical Association 302(15):1685-1692) points out, the entire medical culture of the U.S. causes this:

Three barriers hinder the acceptance of prevention: failure of physicians to make clear to patients (and patients to understand) their individual risk of cancer, the belief that early detection and “cure” are ensured with screening, and organized medicine’s focus on treatment rather than prevention.

If Tea-Partiers really want to have control over their own health care, demanding more screening is not the way to do it. Instead, they should educate themselves about what the actual value of screening is, and know before they screen how they would approach treatment. They just might find themselves rationing their own care.

The U.S. Preventative Services Task Force agrees with Bioblog that it is finally time to admit that there are risks to cancer screening, in addition to benefits. It turns out that the benefits are marginal at best for women under 50 being screened for breast cancer.

Not too surprisingly (in fact, rather laughably, given their blatant conflict of interest), the American College of Radiology has gone, shall we say, hysterical on the issue, declaring that if the USPSTF’s recommendations are followed, “countless American women may die needlessly from breast cancer each year.” This hyperbolic statement is completely belied by the data that show clearly that screening affects mortality minimally at best.

In fact, the “classic” breast cancer screening study, known as the “HIP” (Shapiro, 1997) found a modest drop in mortality associated with mammography; in absolute terms, the difference in death rate was 5 deaths over 10 years over 1000 people, versus 7 deaths - hardly an example of “countless” women dying needlessly.

In addition, this and several other studies were reviewed (Olsen and Gøtzsche, 2001) with the conclusion that it had major methodological flaws (explained in more detail in Welch, 2004). The first was that deaths whose cause was unclear were more likely to be called breast cancer deaths in the non-screening group than in the screened group. This effect could account for half the observed difference in death rate.

Second, more women were excluded from the mammography group for prior history of breast cancer (once the trial started) than from the non-screened group, because women in the screened group were examined more closely than those in the control group, who did not actively participate in the trial, but rather went about their business. Because women in the screening group were far more likely to be identified as previous breast cancer patients, there were probably hundreds more previous cancer patients in the control group.

Both of these methodological problems clearly skew the results towards a conclusion that screening prevents deaths.

And here’s another serious problem with screening resulting in overtreatment that you have not read about in any of the articles describing this controversy - surgery itself can cause the spread of cancer (Retsky et al., 2003):

As a result of screening, cancers are found at an earlier stage than would be found without screening, which is favorable, but then surgical intervention to remove the primary tumor accelerates metastatic growth, offsetting the early detection advantage.

The fact remains that the panel changed its recommendations with regard to screening (since recommending it much more favorably in 2002) because the data simply aren’t there to show an obviously positive effect, and more and more negative effects of overtreatment are coming to light. It would be most beneficial to be able to separate screening from treatment in our minds; but the fact is that our lawsuit-happy society combined with the “cancer=death” attitude promoted by the very people who push screening on us in the first place makes it nearly impossible for any doctor/patient combination to adopt a “watchful waiting” approach when cancer is found.

Another fact is that radiologists rake in a pile of money for cancer screening. Obviously they are scared to death that their cash cow might be slaughtered, so they are resorting to extremely un-Hippocratic scare tactics to make sure it is not. The USPSTF’s report lists the breast-cancer screening recommendations of various national and international groups, and their new suggestion is far from radical; it fits right in a large range. The assertion that “countless” cancer deaths will be caused by their analysis is outrageous and irresponsible and ignores reams of data that say otherwise.

All the health advice given by all kinds of official-sounding groups can be dizzying. But a good rule of thumb is to ignore recommendations from groups that have a financial stake in what they are recommending. That’s pretty obvious when it comes to pharmaceutical companies, but organizations representing doctors are influenced by money too. It’s another example of the irrational distortions created by the “fee for service” system, which needs to be eliminated in favor of salaries for doctors, in order for health care reform to succeed.

References

Olsen, O., and Gøtzsche, P.C. 2001. Cochrane review on screening for breast cancer with mammography. The Lancet 358(9290):1340-1342.

Retsky M, Demicheli, R., and Hrushesky, W. 2003. Breast cancer screening: controversies and future directions. Current Opinion in Obstetrics and Gynecology 15(1):1-8.

Shapiro S., 1997. Periodic screening for breast cancer: the HIP Randomized Controlled Trial Health Insurance Plan. J Natl Cancer Inst Monogr 22:27-30.

Welch, H.G., 2004. Should I Be Tested for Cancer?: Maybe Not and Here’s Why
University of California Press, Berkeley, CA.

A federal judge has recently denied the defense’s motion to dismiss the the class action suit against biotech company Myriad Genetics and the University of Utah. Thus, one small hurdle on the hopeful road to repealing disastrous patent rules, allowing gene sequences to be locked away from scientific research for decades, has been overcome.

Others have pointed out that you are not allowed to study 20 percent of your own genome (even if you have the skills to do so). At this rate, eventually no one will even be able to do a cheek swab on themselves without having to pay royalties to a corporation.

Is this really what patent law was supposed to achieve?

The case most often cited as the landmark in biological patent law is Diamond v. Chakrabarty (1980). While it might be a reasonable argument that a human-designed organism was created, and thus constitutes a patentable invention, it is unclear why this precedent led to patents for genes, which are existing natural products. The isolation and sequencing of a gene is a completely different act from the creation of a new biological organism, and these should never have been lumped simply because they are both biological.

Most people do not realize that there are hundreds of mutations to the BRCA genes patented by Myriad that make people more susceptible not only to breast cancer, but any cancer involving hormone targets, including ovarian and prostate cancer. But no one is allowed to study any of these sequences without paying Myriad Genetics royalties or getting their express permission (which comes with a lot of restrictions about reporting research results). Thus, most of the data languishes in a cybervault, unstudied by Myriad Genetics or anyone else, even though these mutations could potentially tell us a lot about the genetics of cancer susceptibility.

Most of the outrage against Myriad is because their patent allows them to charge thousands of dollars and take a week or more to do an analysis that could be done in any molecular lab in the country (including the one at my small regional liberal arts campus) in less than a day for around a hundred dollars, if the genetic code were freely available to work with. Myriad’s argument that no one would do this test if they could not charge thousands of dollars to do it is absurd. This is just the sort of thing that public health labs do all the time.

Or think of it this way: in the normal world of patents, people use their knowledge of nature to build a machine. Someone else has access to the same knowledge, to build a better machine, if possible. If genetic data were freely available, anyone could develop a patentable test for it. In fact, different people or companies could compete to produce the best test possible. This is the kind of world that all the Rand disciples, so common in the business world, should be supporting. When the natural phenomenon itself has been patented, we are left with one company doing a test, and we have to just take their word for it that it is the best test to do. Any competition to produce a better product has been eliminated. Not very free-market.

From an academic perspective, the most important issue is of patents that tie up genes so that research cannot be done by other scientists, and thus scientific progress is retarded. Genetic data from most organisms goes into GenBank, a public sequence database that is invaluable to researchers who want to build on the work of others.

Building slightly on previous work is all that Myriad did. Their discovery of the exact sequence of nucleotides making up the BRCA gene was made possible by taxpayer-funded groundwork laid by other scientists, particularly Mary-Claire King, who identified the region on chromosome 17 where BRCA turned out to be located. One of the founders of Myriad himself, Mark Skolnick, was the recipient of more than $5,000,000 in National Institutes of Health grants given specifically to look for BRCA1 (one of two genes he later patented through his company) (Williams-Jones, 2002). Myriad simply won a race to sequence the genes, because they spent more money to run more sequencing machines than anyone else.

Of course it is not necessarily wrong for taxpayer money be spent in a way that will create jobs and growth in certain sectors of business. This is the point of many government programs, not least the current stimulus package. And certainly anyone who creates something of value, even when the work that led to the creation was publicly funded, should be able to profit from it. Many patents developed in this way benefit society and the economy.

But patents are supposed to be there to protect people who actually did the work to create something. Leaving aside the argument that Myriad (and for that matter, any scientist who worked on any step of the process) created nothing in the first place, all the dozens of other people who worked hard to lay the scientific foundation for Myriad’s patent claim had no say in the decision to allow Myraid to have complete rights over that genetic data that they had a significant role in revealing. Most biological researchers and scientific organziations (including the American College of Medical Geneticists) believe that genetic data should be open source, because they themselves never would have been able to do their own research without “standing on the shoulders of giants.”

Imagine if each small step of the long process that has now led to the fairly trivial final step of gene sequencing and patenting was itself patented along the way. The result would be a completely prohibitive cost and complication of doing basic research, because of the royalties needed to pay out along the way. It is this belief of thousands of government and academic scientists, that the pursuit of knowledge for the benefit of society is more important than profit, that has led to companies like Myraid even having the opportunity in the first place to make their big bucks.

For a University to be one of the codefendents in the lawsuit is a sad state of affairs indeed for the pursuit of scientific progress. The argument that without the patenting of genes all scientific progress will grind to a halt is mythological. If scientists cared only about making a lot of money for what they do, why would any of them work for a university? In acutality, as put by Williams-Jones (2002):

If the BRCA patents stand, hundreds of other gene patents are likely to follow, exacerbating the current rush to patent genes – what former [Canadian] Premier Harris described as the ‘Wild West’ situation. This will have a direct impact on the manner in which scientific knowledge and discoveries are commercialized and transformed into clinical practice. Unrestrained DNA patenting could lead to a situation where all genes are patented and new research becomes prohibitively expensive, what Heller and Eisenberg have described as a ‘tragedy of the anticommons.’ Unrestrained gene patenting would also have a significant impact on the provision of genetic services through the public health care system, potentially making genetic tests and therapeutics unaffordable, and thereby raising serious issues of justice in access to medical services.

Of course, we don’t have a public health care system, at least not yet. But really, what difference does it make? Most of us pay large health premiums, so we are indeed paying these outrageous royalties to companies who performed the now-trivial act of running a sequencer - or a whole bunch of them. (If companies chose not to pay for the tests, it just would not do, because that would be rationing!) So, if you could benefit from a genetic test, you will be happy to realize now that you have paid for the test twice - first as a taxpayer, for the research that led to the test, and now as an insurance holder.

Isn’t capitalism great?

Reference

B. Williams-Jones, 2002. History of a gene patent: Tracing the development and application of commercial BRCA testing. Health Law Journal 10: 124-146.