Courts and science – talc and glyphosate probably do not cause cancer

I’ve written about this many times before – courts do not get to decide what is good or bad science. Although courts and science may not necessarily be incompatible, attorneys, juries, and judges are generally not trained in scientific research, scientific methods, scientific publications, and/or scientific reasoning.

Two relatively recent cases are strong evidence that courts and science can be quite incompatible. In the first case, a jury ordered pharmaceutical giant Johnson and Johnson (JNJ) to pay US$4.69 billion in damages to 22 women who claimed that the company’s talcum powder products caused ovarian cancer. In the second case, a jury ordered chemical manufacturer Monsanto to pay US$289 million to a janitor who claimed that Round-Up (glyphosate) caused his terminal cancer.

The problem with both of these cases is that there is, at best, some weak, unrepeated scientific evidence that supports their claims. However, if you refrain from cherry-picking articles on PubMed, you’ll find that the vast majority of research either doesn’t support their claims or even shows that there are no links between talc or glyphosate and cancer.

Let’s take a look at the science in both of these cases, and then, let’s find out why courts and science are not necessarily compatible. And remember, this isn’t a recent problem – an American court once rejected evolution during the infamous Scopes Monkey Trial. So science has been skeptical of the involvement of courts and science for a very long time.

Courts and science – talc

Let’s start right with the conclusions from two of the most premiere cancer research organizations in the USA – the American Cancer Society (ACS) and the National Cancer Institute (NCI), both filled with scientists who have more cancer science expertise in their pinky fingers than the judges, juries, and attorneys involved in these cases.

The ACS states that research on talc and ovarian cancer “have been mixed, with some studies reporting a slightly increased risk and some reporting no increase … For any individual woman, if there is an increased risk, the overall increase is likely to be very small.”

The NCI concludes that “the weight of evidence does not support an association between perineal talc exposure and an increased risk of ovarian cancer.”

So, how did these claims become so prevalent and become the basis of these lawsuits? The blame goes to a case-control epidemiological study from the 1980s published in the journal Cancer. These case-control studies, considered middle-level quality in the hierarchy of biomedical research, asked women, one group with ovarian cancer and another group without it, to recall their past diet and activities, including talcum power use.

Case-control studies have serious drawbacks – they rely too much on memory, which can, and often is, clouded by recall bias. Participants may forget what they did, how often they did it, or other key data points. Moreover, those who have cancer tend to overestimate their use of a suspected causal substance. On the other hand, individuals who don’t have cancer may be less motivated to remember details. Case-control studies are just incapable of determining causal links between talcum powder and cancer.

On the other hand, more powerful studies, called cohort studies, showed no link. Unlike the case-control studies, which rely on memory, these cohort studies followed a large number of women and monitored their health over time. The women recorded their activities in real time. These type of studies rank higher in the hierarchy of biomedical research because the data is stronger.

One of the most powerful of these studies, which included more than 61,000 women tracked over 12 years, found no correlation between talc and ovarian cancer. The authors concluded that “based on our results, perineal powder use does not appear to influence ovarian cancer risk.”

Another robust cohort study, published in Epidemiology in 2016, followed nearly 51,000 women over seven years, and once again, found no link. The scientists concluded that talc use was not “associated with increased risk of ovarian cancer.”

However, a recent systematic review (which are considered the pinnacle of biomedical research) seems to indicate that there might be a link between talc and ovarian cancer. As I keep writing, just because a systematic review has been published doesn’t mean it should be subject to analysis and criticism. And what I noticed in the paper is that the authors gave much more weight to case-control studies than to cohort studies. That shows an incredible amount of bias in the review.

But even if we think that there is some evidence of a correlation, more scientific work is necessary to show a causal link between a substance and cancer. And this is where many of the studies that claim a link fail.

Biomedical scientists use the Bradford Hill criteria to determine if there is a causal link between something and an effect. Here is that criteria.

  1. Strength (effect size)– this is one of the important parts of this criteria – the larger the effect from the cause, the higher the probability of a causal link. This doesn’t mean small effects aren’t important, it’s just that fields like science-based medicine favor larger effects. The link between talc and ovarian cancer is either nonexistent or very weak, with a tiny effect size.
  2. Consistency (reproducibility) – proposed causality needs to be observed in more than just one location. Consistent data published by different researchers in different locations with different population samples strengthen the possibility that there is a link between a cause and effect. If we look at the studies, they’re all over the place, and better studies show no effect.
  3. Specificity – causation requires a very specific population with a very specific disease with no other possible explanations of that causation. Again, the more specific an association is between cause and effect, the larger the possibility of a causal link. The research does seem to support this point.
  4. Temporality – the proposed effect must occur after the cause, and within a likely time period for which a link between cause and effect. Once again, studies just don’t support this.
  5. Biological gradient – there must be some sort of dose-response effect, that is, the higher the exposure to some cause should generally lead to a higher incidence of the effect. (There are cases where a lower exposure leads to a higher incidence, so we should observe the inverse effect.) None of the studies show a dose-response effect.
  6. Biological plausibility – as we will discuss next, there must be a biologically plausible mechanism between cause and effect. Of course, it is possible that we lack knowledge of all aspects of a biologically plausible mechanism between some cause and effect. Even then, the potential new mechanism must not violate basic principles of biology, chemistry, and physics. Although it is possible that talcum powder was contaminated with asbestos 50 years ago, that is not the case today. Talc is a form of magnesium silicate which has no known link to any cancer – the biological plausibility is simply not there.
  7. Coherence – does the proposed cause and effect fit with what we know about the disease.
  8. Experiment – does a group that lacks exposure to the effect exhibit a different outcome?

Now some may say that “well weak evidence means that there could be a link,” and that is why the jury is right. And that’s where courts and science differ – either there is evidence or not, there’s no “maybe.” The higher quality evidence actually indicates that there is no link, there really is no maybe it causes cancer, it actually says it doesn’t.

The only conclusive way to determine if there is a link would be a large, double-blind clinical trial that controls other factors that might increase or decrease risks of cancer. However, that kind of study suffers from two major issues – one, it’s probably unethical to recruit patients who might be in a group that has a higher risk, and two, even if we don’t think there is an increased risk, it might be hard to recruit patients.

In summary, there does not seem to be high-quality, robust evidence that supports a correlation, and less evidence to support causality. In fact, there is better evidence that shows no link between talc and ovarian cancer. And this is where courts and science are in opposition.

Courts and science – glyphosate

Glyphosate, also known as Monsanto’s Round-Up herbicide, is one of the most hated chemicals these days, which is probably the basis of the anti-Monsanto nonsense pushed by many people. ScienceBasedMedicine calls glyphosate the “new bogeyman.”

Ironically, glyphosate is one of the least toxic herbicides on the market today. It works by inhibiting a plant enzyme,  5-enolpyruvylshikimic acid-3-phosphate synthase, causing an accumulation of shikimic acid in plants leading to its death. The reason that glyphosate toxicity is so low is because that enzyme does not exist in animals. Although glyphosate may have another effect on some other biological process (and none have been found so far), the lack of effect on humans has always made me chuckle when pseudoscientists push a trope that it is dangerous.

But my believing that there is no biological reason to believe it is dangerous to humans does not make it so. Like I have said a million times, the only thing that matters to me (or any scientist) is evidence. So what is the evidence regarding glyphosate and cancer?

Well, let me start with Steven Novella at ScienceBasedMedicine, whose article reviewed several of the then current studies of glyphosate:

Meanwhile, numerous published systematic reviews show clear evidence that glyphosate has very low toxicity. More careful study when it comes to any agent being used as heavily as glyphosate is always welcome. Science is complicated, and it is always a good idea to consider factors that may have been previously missed. However, failure to show any adverse effect from glyphosate in epidemiological studies is very reassuring. Given its widespread use, any adverse effect must be tiny or non-existent to be missed by the evidence we have so far.

I also examined a large retrospective cohort study published in the Journal of the National Cancer Institute. The study included over 54,000 participants followed over 20 years. The researchers concluded that:

In this large, prospective cohort study, no association was apparent between glyphosate and any solid tumors or lymphoid malignancies overall, including NHL (non-Hodgkin lymphoma) and its subtypes.

In another systematic review, the authors concluded that:

Our review found no consistent pattern of positive associations indicating a causal relationship between total cancer (in adults or children) or any site-specific cancer and exposure to glyphosate.

In even another review of epidemiological studies examined the association between glyphosate and all non-cancer health outcomes. The review concluded:

Our review found no evidence of a consistent pattern of positive associations indicating a causal relationship between any disease and exposure to glyphosate. Most reported associations were weak and not significantly different from 1.0.

And finally, another systematic review, published in 2016, found that:

Overall, our review did not find support in the epidemiologic literature for a causal association between glyphosate and NHL or MM (multiple myeloma).

Those are a powerful group of high-quality studies that thoroughly reject any link between glyphosate and cancers.

Now, some of you might point to a 2015 International Agency for Research on Cancer (IARC) statement that was based on research data regarding Monsanto’s glyphosate weed killer – they concluded that glyphosate causes cancer.

The problem with IARC’s claims is that it was based on cherry-picked data that completely ignored many of the studies that I listed above. In fact, Robert Tarone published a paper in 2016 that criticized IARC’s decision regarding glyphosate. He concluded that:

It is shown that the classification of glyphosate as a probable human carcinogen was the result of a flawed and incomplete summary of the experimental evidence evaluated by the Working Group. Rational and effective cancer prevention activities depend on scientifically sound and unbiased assessments of the carcinogenic potential of suspected agents. Implications of the erroneous classification of glyphosate with respect to the IARC Monograph Working Group deliberative process are discussed.

Legitimate scientists, all across the world, have strongly disputed the IARC statement, not because they are Monsanto shills (or whatever other ridiculous conspiracy theory I’ve seen on the internet). It’s because the evidence strongly rejects a causal link between glyphosate and cancer. Well, unless you love cherry-picking bad research to support the belief.

Courts and science – why it doesn’t work

Courts don’t get to decide science, because they are not built to do so. I think there are some good reasons why they can’t, not just because I say so:

  1. Juries just aren’t competent in scientific evidence. As I’ve written before, science is damn hard. It takes thousands, if not tens of thousands, of hours of study and work to understand even a small sector of science. In addition, juries spend a few hours or days pouring over the evidence. The real scientific consensus is usually developed over years, if not decades, based on the whole body of evidence.
  2. Courts rely too much on false equivalence. It’s hard to describe the subtle and nuanced differences between a case-control and cohort study – from a non-expert viewpoint, all published studies are the same. But real science gives more weight to not only the quantity of research but the quality.
  3. Speaking of quality, because of cherry-picking, it’s difficult to show that the bulk of evidence is one side or another of a question. The anti-vaccine religion pretends that there is some mythical debate about the safety and effectiveness of vaccines, but if we really created a debate, there would be millions of physicians and scientists on one side and a handful of crackpots on the other.
  4. Court cases are adversarial. One side produces everything that supports their case without attempting to critically analyze it. And so does the other side. It feels like you could flip a coin to decide which side wins. This system is supposed to find “the truth,” but that’s not how science works. Science is based on the whole body of evidence, not what is presented by two interested and biased parties.
  5. Juries are swayed by emotion, whereas science is not. Science is dispassionate (except when defending it against pseudoscience and deniers). When a jury sees some men or women dying of cancer, there is a tendency to blame something, someone, anything for cancer.

Here’s a little secret – about 67% of cancers are not linked to anything but random chance. Dr. David Gorski, a surgical oncologist, wrote about this study back in 2015 in ScienceBasedMedicine. Although Dr. Gorski does criticize some parts of a paper by Tomasetti and Vogelstein, overall he does indicate that random mutations are responsible for a large majority of cancers:

Given the level of uncertainty inherent in such estimates, even if you interpret Vogelstein and Tomasetti’s conclusion that two thirds of cancers are due to “bad luck,” their estimate of the percentage of cancers that are probably not preventable is definitely in the ballpark of commonly-accepted estimates, albeit at the lower end. Does that mean they’re on to something in concluding that stem cell replication over one’s lifetime primarily determines the “stochastic” component of cancer risk for each organ? That remains to be seen, but their preliminary finding makes sense, both from the perspective of producing a result that’s in the ballpark of what we already know based on epidemiology and being biologically plausible based on basic cancer biology.

Does a court understand that the risk of any particular cancer may not be related to anything? That there is nothing to blame?

Summary

Unfortunately, courts and science are a necessary evil. There will always be cases brought before courts that require a decision be made about science.

But that does not mean those decisions are correct. And they certainly do not supersede high-quality scientific evidence.

Right now, there is little powerful evidence that establishes a causal link between talcum powder and cancer. And there is actually robust evidence that shows that there is no link between glyphosate and cancer.

Sadly, these arguments won’t matter, because those who have an agenda will push pseudoscience based on whatever cherry-picked evidence that supports their beliefs. And they will ignore the large body of evidence that does not.

Citations



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The Original Skeptical Raptor
Chief Executive Officer at SkepticalRaptor
Lifetime lover of science, especially biomedical research. Spent years in academics, business development, research, and traveling the world shilling for Big Pharma. I love sports, mostly college basketball and football, hockey, and baseball. I enjoy great food and intelligent conversation. And a delicious morning coffee!