Saturday, June 1, 2019

Screening for Prostate Cancer and Breast Cancer: It's More Complex Than You May Think


Published in Skeptical Inquirer Volume 43, No.1 (Jan/Feb 2019)

Translated to Portuguese here.

“Pink October” and “Blue November” are campaigns to promote awareness for breast and prostate cancer respectively. In Brazil, as well in other countries, the population is encouraged to do tests such as the PSA for prostate cancer and mammography for breast cancer.

  The main idea is called screening: to perform tests in healthy persons to detect and to treat diseases before their symptoms appear – to increase the cure chances and even to offer a less aggressive treatment. A good example of cancer screening is for cervical cancer, where incidence of the advanced cases decreased after Papanicolaou test was introduced (Adegoke et al. 2012). However, studies that assessed the efficacy of screening for prostate or breast cancer show that in reality things are more complicated than usually advertised by those campaigns.

On May 2018, the US Preventive Services Task Force (USPSTF) reviewed studies of PSA screening for prostate cancer (Fenton et al. 2018). Only two randomized controlled trials were of sufficient quality to assess impact on mortality. The PLCO1 did not show differences in mortality. The ERSPC2 trial showed that screening reduced prostate cancer mortality in men aged 55-69. Even in that case, it’s far from simple. In order to avoid 1 prostate cancer death and 3 cases of metastatic prostate cancer, 1000 men aged 55-69 have to be screened every 4 years during 13 years. Of those, 27 men received treatment—prostate surgery and/or radiation therapy. More important, the majority of those who were treated, 24 patients, received aggressive treatment with no benefits, only the harms caused by the treatment itself. Regardless of screening, 5 men died from prostate cancer. See Table 1 for complete estimates.

So a careful analysis of cancer screening must consider harms of treatment. The USPSTF review found that, of those who undergo complete prostate surgery, 1 in 5 men develop urinary incontinence and 2 in 3 experience impotence. More than half of who receive radiation therapy develop impotence and 1 in 6 men develop bowel symptoms, including bowel urgency and fecal incontinence (Fenton et al. 2018).


The overall picture that prostate cancer screening might cause more harm than good it’s far from new. A 2013 Cochrane meta-analysis (Ilic et al. 2013) of five studies showed no reduction in mortality and in 2012 USPSTF recommended against screening regardless of age. Now, the USPSTF concluded the benefits and harms of screening for men aged 55-69 are balanced, recommending an individualized decision after a careful consideration of potential benefits and harms. For men aged 70 and older, the USPSTF recommended against screening. See link for USPSTF decision aid. 

Regarding breast cancer, the evidence might look more favorable to screening with mammography, but again not crystal clear as the campaign messages suggest. A 2018 JAMA article (Keating and Pace 2018) estimated that 10 of 10 000 women in their 50s screened annually with mammography during 10 years would avoid breast cancer death. But 940 women would have unnecessary biopsy and 44 would be treated needlessly with surgery, radiation, chemotherapy, or hormonal therapy. Despite screening, 62 women would still die from breast cancer. Since breast cancer treatment improved dramatically as trials were conducted, screening benefits might be even smaller today than those reported in trials (Keating and Pace 2018). To offer benefits while reducing the possible harms, the USPSTF recommends mammography every 2 years for women aged 50-74 and recommends against teaching breast self-examination.
               
This situation is not restricted to breast and prostate cancer. Between 1975 and 2009, the incidence of thyroid cancer in United Stated tripled – from 4.9 to 14.4 in 100 000. But the mortality rate remained constant: 0.56 in 100 000 (Esserman et al. 2014). A study in Finland detected thyroid cancers in autopsy of 36% of patients that had died for other causes (Esserman et al. 2014).

Autopsy studies in prostate in patients that died for other causes also show a great disease reservoir (Sandhu and Adriole 2012). In autopsied men aged 60-79, the incidence of prostate cancer varied between 14 and 77%. Astonishingly, prostate cancer was found even in autopsied men in their twenties, with an incidence of 8-11% (Sandhu and Adriole 2012).

What these data are describing is called overdiagnosis (Welch and Black 2010; Carter and Barrat 2017). Screening detects mainly non-lethal or harmless cases of cancers – if it weren’t for screening we would die from other causes not even realizing that we also had cancer. Overdiagnosis is not a false-positive result, which is a positive test that subsequent evaluation shows no signs of cancer. In overdiagnosis, the lesion detected actually meets the diagnostic criteria for cancer, but would not have been diagnosed in the absence of screening (Welch and Black 2010; Carter and Barrat 2017).
Overdiagnosis and its consequences are the main harm of screening. Since at the time of diagnosis, it is impossible differentiate harmless lesions from lethal ones, almost all cases are treated (Welch and Black 2010). Estimates suggest that between 20% and 60% (Fenton et al. 2018; Carter et al. 2015) of screen-detected prostate cancers were overdiagnosed. Of screen-detected breast cancers, overdiagnosis estimate from trials is 19% (Keating and Pace 2018), while an analysis of screening programs reported 52% (Jørgensen and Gøtzsche 2009). Then, a few might benefit from prostate and breast cancer screening, but more patients face harms of aggressive treatment they didn’t even need it in the first place.

One of the premises of screening is that cancer has a linear progression, which would always allow detection before it’s lethal. But this premise is outdated. Cancers are heterogeneous, with different progression rates (Figure 1) (Carter and Barrat 2017). Screening is more likely to detect cancers that grow slowly or would have regressed. Critically, most lethal cancers, those that grow fast, are less likely to be detected by screening because they tend to cause symptoms between screening rounds (Carter and Barrat 2017).

Figure 1. Heterogenity of cancer. Not all cancers have the same progression rate (Carter and Barrat 2017; adpated from Welch and Black 2010).
While the messages encouraging screening tests rarely mention overdiagnosis, they often come with claims like: “If it is early diagnosed, the chances of cure are 95%, but it’s 20% if detected in advanced stage”. However, when overdiagnosis exists, the rate of cured patients is biased – the number of patients that survived cancer increases “automatically” because those patients with new harmless cases are now classified as “cured”, even when screening offers no benefits. Ironically, the rise in cancer incidence and inflated rates of cure due to overdiagnosis might reinforce the efforts to screening leading to even more overdiagnosis3 (Brodersen et al. 2018).

Another way the survival metric is biased relates to how many years the patient has lived after the diagnosis. Screening is only effective if it can detect diseases earlier. Consider for instance that without screening patients are diagnosed due to symptoms at 70 years of age and die at 75. Consider also that these patients would be diagnosed by screening at 65 years and die due to cancer at 75. With these descriptions screening looks beneficial since whoever does screening has a survival of 10 years and who doesn’t only survives 5 years after the diagnosis. In both cases, the patient died at the same time; screening only made the diagnosis to occur earlier, without actually increasing the life expectancy. This is called the lead time bias (Raffle and Grey 2007).

Due to biases, survival statistics do not show the efficacy of screening. If screening works, incidence of advanced cases must reduce. After the introduction of breast and prostate cancer screening, it was expected an increase in the incidence of early cancers. That should be followed by, as the population ages, a compensatory decrease in advanced cancers, while overall incidence remains unchanged (Esserman et al. 2009). Note in Figure 2 that the incidence of early breast cancers increased significantly, while the incidence of regional cancers decreased very little and rate of distant metastases remained stable. Interestingly, although breast cancer mortality is falling, the fall was larger in young women that were not invited to screening (Narod et al. 2015). In addition, breast cancer mortality decreased in a similar way over the world, but the start of screening differs between countries (Gøtzsche 2015a). Similar observations could be for prostate cancer. After screening, there was not a significant decrease in invasive cases as expected and different rates of screening and treatment in different regions were unrelated to prostate cancer mortality (Esserman et al. 2009). These trend analyses, while does not show causality, indicate that screening leads to considerable overdiagnosis of early disease and its impact on breast and prostate cancer mortality is small at best.   
Figure 2. Incidence of different stages of breast cancer standardized by age in the United States White. SEER 9, 1975–2011 (Narod et al. 2015)
The best approach to measure screening efficacy is using randomized controlled trials, like PLCO and ERSPC. Trials compare screened group with control group, looking for a reduction in deaths caused by the cancer being screened forwhat it’s called cancer specific mortality. It is the reduction in cancer specific mortality that prompts the claim that screening “save lives.” But as women overdiagnosed with breast cancer might receive radiotherapy, which increases mortality due to lung cancer (Gøtzsche 2015b), screening could cause more deaths than breast cancer deaths averted. Since deaths by treatment are usually classified as other causes, cancer specific mortality is biased in favor of screening. This bias is avoided by using overall mortality. What might be shocking is that cancer screening trials do not show overall mortality reduction. As Vinay Prasad and colleagues wrote in the BMJ (Prasad et al. 2016), “cancer screening has never been shown to save lives.4” Does screening increase deaths from other causes? We don’t knowmaybe it’s just chance, since millions of people are required in a trial to look for a difference in overall mortality. Prasad and colleagues argued those large trials are needed to know screening effects. In contrast, researcher Peter Gøtzsche think such trials are not an ethical thing to do, since a large number of people would have to be screened without knowing whether this will increase their lives, while it will make them less happy due to psychological distress caused by false-positives results and overdiagnosis (Gøtzsche 2015a). Due to small, if any, benefit in mortality but documented harms, Gøtzsche has stated that mammography screening would have been withdrawal from the market, had it been a drug (Gøtzsche 2015b).

Other scientists, like Laura Esserman, think that we should focus on ways to make screening better. For example, she and colleagues suggested not to call cancer those indolent cases, which are usually detected by screening (Esserman et al. 2009). Since a cancer diagnosis is associated with a lethal disease that causes suffering in the mind of patients and physicians, renaming those indolent lesions might reduce needlessly treatment. This was firstly proposed almost ten years ago, but as late as August 2018 other scientists are still asking for those changes (Nickel et al. 2018). Esserman has also proposed to move to a risk-based screening, which targets people at high risk of cancer. Testing whether risk-based screening can reduce mammography use without increasing advanced cancers is the objective of the Wisdom study (Esserman et al. 2017).         
                    
Meanwhile, the public needs to be properly informed. The prostate and breast cancer awareness campaigns must be used to clearly tell the population the complexities regarding screening. This is very important; according to surveys women overestimate the benefits of mammography screening by a factor of 10-200 (Wegwarth and Gigerenzer 2018). Also, as screening is often promoted as prevention, 68% of women in a survey wrongly believed that mammography reduces their chance of developing breast cancer (Domenighetti et al. 2003). As a perspective article in New England Journal of Medicine (Biller-Andorno 2014) pointed out, “How can women make an informed decision if they overestimate the benefit of mammography so grossly?” This might be explained by doctor’s failure to communicate screening risk: in a survey of 300 US screening patients, 90% of them had not received information about possible harms of screening by their doctors (Wegwarth and Gigerenzer 2018).

That’s not the whole story. A 2017 systematic-review showed that doctors usually overestimate screening and treatment benefits while they underestimate its harms (Hoffman and Del Mar 2017).  A survey with primary care physicians in the United States suggests that doctors misunderstand screening statistics: 76% of doctors participants were misguided by the survival metric discussed earlier (Wegwarth et al. 2012). They wrongly thought patients diagnosed by screening with better 5-year survival rates than patients diagnosed by symptoms means screening test saved lives. As asked in an article (Wegwarth and Gigerenzer 2018), "Why is risk literacy so scarce in health care?" The authors discussed that the difficulties to access risks and benefits in health likely lies with how statistical information is presented, from biased reports in medical journals to the use of relative risk and misleading statistics by the media. And research shows that decision aids help patients to be more informed regarding screening decisions (Stacey et al. 2014). The researchers beautifully concluded: “A critical mass of informed citizens will not resolve all healthcare problems, but it can constitute a major triggering factor for better care (Wegwarth and Gigerenzer 2018).”

Notes

1.    PLCO: Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial
2.    ERSPC: European Randomized Study of Screening for Prostate Cancer.
3.    This has been called the popularity paradox: “The greater the harm through overdiagnosis and overtreatment from screening, the more people there are who believe they owe their health, or even their life, to the programme.” (Raffle and Grey 2007, 68).
4.    Lung cancer screening with CT in heavy smokers in a 2011 trial reduced lung cancer and overall mortality. Even though this is case of screening in a high-risk group, Prasad and colleagues considered the best evidence for overall mortality reduction in a cancer screening trial. However, as discussed by the authors, a 2013 meta-analysis for the USPSTF have not shown overall mortality reduction (Prasad et al. 2016).     

Interesting popular readings

· Overdiagnosed: Making People Sick in the Pursuit of Health by H. Gilbert Welch, Lisa Schwartz and‎ Steve Woloshin (2012);

· Mammography Screening: Truth, Lies and Controversy by Peter C. Gøtzsche (2012)


References

Adegoke, O., S. Kulasingam, and B. Virnig. 2012. Cervical cancer trends in the United States: a 35-year population-based analysis. Journal of Womens Health (Larchmt) 21(10):1031-7. doi: 10.1089/jwh.2011.3385

Biller-Andorno, N. 2014. Abolishing Mammography Screening Programs?  A View from the Swiss Medical Board. New England Journal of Medicine 370(21): 1965-1967

Brodersen, J., B.S. Kramer, H. Macdonald, et al. 2018. Focusing on overdiagnosis as a driver of too much medicine. BMJ 362:k3494. doi: 10.1136/bmj.k3494

Carter, J.L., R.J. Colett, and R.P. Harri. 2015. Quantifying and monitoring overdiagnosis in cancer screening: a systematic review of methods. BMJ 350:g7773. doi: 10.1136/bmj.g7773

Carter, S.M., and A. Barratt. 2017. What is overdiagnosis and why should we take it seriously in cancer screening? Public Health Research and Practice 27(3):e2731722. doi: https://doi.org/1017061/phrp2731722

Domenighetti, G., B. D’Avanzo, M. Egger, et al. 2003. Women’s perception of the benefits of mammography screening: population-based survey in four countries. International Journal of Epidemiology 32:816-21

Esserman, L.J., H. Anton-Culver, A. Borowsky, et al. 2017. The WISDOM Study: breaking the deadlock in the breast cancer screening debate. npj Breast Cancer 3:34. doi:10.1038/s41523-017-0035-5

Esserman, L.J., I.M. Thompson, B. Reid, et al. 2014. Addressing overdiagnosis and overtreatment in cancer: a prescription for change. The Lancet Oncology 15: e234-e242. doi: 10.1016/S1470-2045(13)70598-9

Esserman, L, Y. Shieh, and I. Thompsom. 2009. Rethinking screening for breast cancer and prostate cancer. JAMA 302(15):1685-92. doi: 10.1001/jama.2009.1498.

Fenton, J.J., M.S. Weyrich, S. Durbin, et al. 2018. Prostate-specific antigen–based screening for prostate cancer: A systematic evidence review for the U.S. Preventive Services Task Force. Agency for Healthcare Research and Quality, Evidence Synthesis No. 154. AHRQ Publication No. 17-05229-EF-1.

Gøtzsche, P.C. 2015a. Commentary: Screening: a seductive paradigm that has generally failed us. International Journal of Epidemiology 244(1): 278-80. doi: 10.1093/ije/dyu267.
———. 2015b. Mammography screening is harmful and should be abandoned. Journal of the Royal Society of Medicine 108(9): 341–345. doi:10.1177/0141076815602452

Hoffman, T.C., and C. Del Mar. 2017. Clinicians’ expectations of the benefits and harms of Treatments, Screening, and Tests: A Systematic Review. JAMA Internal Medicine 177(3):407-419. doi: 10.1001/jamainternmed.2016.8254.

Ilic, D., M.M. Neuberger, M. Djulbegovic, and P. Dahm. 2013. Screening for prostate cancer. 
Cochrane Database of Systematic Reviews, Issue 1. Art. No.: CD004720. doi: 10.1002/14651858.CD004720.pub3  

Jørgensen, K.J., and P.C. Gøtzsche. 2009. Overdiagnosis in publicly organised mammography screening programmes: systematic review of incidence trends. BMJ 339:b2587. doi: 10.1136/bmj.b2587

Keating, N.L., and L.E. Pace. 2018. Breast cancer screening in 2018: time for shared decision making. JAMA. doi:10.1001/jama.2018.3388

Narod, S.A., J. Iqbal, and A.B. Miller. 2015. Why have breast cancer mortality rates declined? Journal of Cancer Policy 5: 8-17 https://doi.org/10.1016/j.jcpo.2015.03.002

Nickel, B., R. Moynihan, A. Barratt, et al. 2018. Renaming low risk conditions labelled as cancer. BMJ 362:k3322 doi: 10.1136/bmj.k3322

Prasad, V., J. Lenzer, and D.H. Newman. 2016. Why cancer screening has never been shown to “save lives”—and what we can do about it. BMJ 352:h6080 doi: 10.1136/bmj.h6080

Raffle, A.E., and J.A.M. Gray. 2007. Screening: evidence and practice. Oxford University Press. ISBN  978-0-19-921449-5

Sandhu, G.S., and G.L Adriole. 2012. Overdiagnosis of prostate cancer. Journal of the National Cancer Institute Monographs (45):146–151

Stacey, D., F. Légaré, K. Lewis, et al. 2014. Decision aids for people facing health treatment or screening decisions. Cochrane Database of Systematic Reviews CD001431.doi: 10.1002/14651858.CD001431.pub5

Wegwarth, O., and G. Gigerenzer. 2018. The barrier to informed choice in cancer screening: Statistical Illiteracy in Physicians and Patients. Recent Results in Cancer Research 210: 207-221. doi: 10.1007/978-3-319-64310-6_13.

Wegwarth, O., L.M. Schwartz, S. Woloshin, et al. 2012. Do physicians understand cancer screening statistics? A national survey of primary care physicians in the United States. Annals of Internal Medicine 156:340-9. doi: 10.7326/0003-4819-156-5-201203060-00005.

Welch, H.G., and W.C. Black. 2010. Overdiagnosis in cancer. Journal of the National Cancer Institute 102:605–613

Wednesday, March 7, 2018

Did Dogs Become Smarter Through Domestication? An Interview with Dr. Brian Hare













by Felipe Nogueira

Dr. Brian Hare is an associate professor in the Department of Evolutionary Anthropology at Duke University and in the Center for Cognitive Neuroscience. Hare is a pioneer and a key expert in the field of dog psychology. Together with Vanessa Woods, Brian Hare has written about the revolution in the study of dog cognition in the fascinating book The Genius of Dogs: How Dogs Are Smarter Than You Think. The book, in their own words, is “about how cognitive science has come to understand the genius of dogs through experimental games using nothing much more high-tech than toys, cups, balls, and anything else lying around the garage.”
Hare and other researchers showed many times that dogs are good at understanding humans’ communicative intentions. With the help of a brilliant experiment with foxes begun by Dmitri Belyaev in the 1950s and continuing to the present day, Hare’s research uncovered what allowed dogs to develop this remarkable skill: domestication After 45 generations, Belyaev’s foxes in the experimental group had floppy ears, curled tails, and were much better reading human gestures than the foxes in the control group. The key point is that Belyaev didn’t select for foxes better at reading human gestures; instead he selected for foxes less afraid and friendlier towards humans. As Hare and Woods note in their book: “Domestication, selecting the friendliest foxes for breeding, had caused cognitive evolution.”
In order to understand even more the limitations and flexibility of canine cognition, researchers have created dedicated laboratories, such the Duke Canine Cognition Center, created by Hare. 

Dr. Brian Hare
Nogueira: In your book, you talked about the genius of dogs. But what do you mean by being a genius?
Hare: If you’re talking about high IQ, or who is going to be recruited to work for NASA, that would make a very short book. In my opinion, the big discovery in the cognition revolution is that cognition it’s not a unique dimensional trait. Actually, it’s a whole set of skills that can vary independently and we don’t know how many there are. For instance, one can be great at math, but a terrible communicator. Regarding species, each one evolved to solve a set of problems that helped them survive and reproduce in their particular environment; dogs are no different. My book The Genius of Dogs is all about trying to understand how a species that seems utterly unremarkable can can be so successful. Dogs are successful from an evolutionary perspective because, everywhere there are people, there are dogs. It’s the most successful mammal—aside from humans and maybe cows. That’s what the book explores: do dogs have some type of genius psychologically or cognitively? Yes, they show unusual degree of sophistication and flexibility for solving problems.

Nogueira: Tell us how you started researching dog cognition.
Hare: Michael Tomasello, a developmental psychologist and my research supervisor at the time, was explaining to me how important gesture communication is in human development. He thought it was not only crucial to human evolution but something unique to humans. His theory was that kids developed the ability to use human gestures and to understand communicative intention. Then I told him that my dog could do the same thing. That’s when I learned what science is, because even though it was an important idea for how humans evolved, Tomasello became curious. He said to me: “I will help you to come up with a way to prove me wrong.” That’s incredible! When he discovered that he was wrong about dogs, he was excited, telling us to keep doing more experiments. People think science is about people in lab coats coming up with genius ideas, but in reality it’s a way to falsify ideas.

Nogueira: How was the first experiment with dogs?
Hare: We use a powerful, but very simple technique: we hide food in one of two containers. Then we pointed to where we hide it, trying to help the dog search for it. Great-apes are terrible at this task. They don’t show much cognitive flexibility, since they have to learn the gesture. And every time you use a new gesture, they have to learn again. In contrast, in kids around age 12 months, you can use gestures they’ve never seen before, showing a degree of flexibility that it’s not seen in great apes. With dogs we performed the same series of experiments that had been done with apes and human children. The big surprise was that dogs are more like children.

            This was a controlled experiment: dogs were not using their noses nor reacting to motion. In science, there are two steps. First, you have to demonstrate a phenomenon. If it’s gravitational waves or dogs following gesture, you have to demonstrate the phenomenon. Then, you try to explain it. Often, people are so busy trying to explain something before they even demonstrate it exists. Once we demonstrated that dogs were following a pointing gesture, we wanted to know if they, for example, just smelled the hidden food. We found that wolves, dogs and foxes all preferred to use their eyes. When they can’t get the information they need from their eyes, then they use their nose. In these experiments, we found that dogs prioritize information from their eyes and memory over their nose.

Nogueira: One of the fascinating experiments with dogs you mentioned in the book uses an opaque barrier. Could you elaborate on it?
Hare: This is the work of Juliane Kaminsky, Michael Tomasello, and Josep Call. They have placed a ball behind two barriers, one opaque and one transparent. The dog can see both balls. In the experimental condition, a human, on the opposite side of the barriers, asks the dog to fetch the ball. The amazing thing is that dogs didn’t take the ball from the opaque barrier, which the human can’t see through; they favored the ball from the transparent barrier. In the control condition, where the human and the dog are on the same side, seeing the same thing, the dog choose the balls randomly. This experiment suggests that dogs know what humans can or cannot see.
Experiment conducted by Kaminski et al [2].
Nogueira: What are the possible explanations for why dogs are so good at reading human gestures?
Hare: One level of explanation is that, since dogs have seen these gestures several times, they slowly learned them. You can test this idea by using a gesture they’ve never seen before, for instance, point with your foot. You can also use a crazy gesture, like putting an object on top of the container where the food is located. Human children and dogs follow those gestures, but chimpanzees don’t. So, this hypothesis of slow learning was ruled out. But the hard part is this: how do you know if dogs really have a sophisticated flexible strategy, a theory of mind, which would mean that they’re thinking about the thought of others individuals?. The best evidence about other animals that have a theory of mind comes from great apes and maybe corvids. Regarding dogs, in fact, we don’t have the smoking-gun experiment to rule out alternative explanations. Then, we don’t have overwhelming evidence that dogs really have a theory of mind. For instance, the experiment with the opaque barrier, when the dog knows what people can or cannot see, hasn’t been replicated. Moreover, when you are studying something like a theory of mind, you want multiple experiments where an animal shows the same set of skills. We have that with great apes, but we don’t have with dogs yet.

Nogueira: From where do these remarkable skills of dogs come?
Hare: We tested several hypotheses. The first was that they were related to wolves, which are clever and maybe are also good at reading human gestures. The other was experience: they interacted with us and have slowly learned it. Finally, we considered if it’s something that happened during domestication. The evidence is mostly in favor of domestication: selection for friendliness is what allowed dogs to become more skilled at reading and using humans to solve problems. That was a surprise: why would being selected to be friendly make you smarter?

Nogueira: How has the Belyaev’ fox research helped to answer that question?
Hare: This brilliant experiment was conducted by a group of scientists in Siberia headed by Dmitri Belyaev. They have a control and experimental line of foxes, separated from each other. The control line was bred randomly. In the experimental line, Belyaev selected foxes that were attracted to or enjoyed interacting with people and weren’t fearful. In other words, Belyaev selected friendly foxes and let them breed together. Over many generations, the experimental foxes show a high frequency of traits that Belyaev didn’t select for, such as floppy ears, curly tails, and multi-color coats. The foxes also had physiological changes related to reduction in aggression and increased friendliness. This experiment was important to our research because they have a population that was experimentally domesticated. This was a great opportunity to test the idea that if domestication really is selection against aggression and for friendliness for people. It makes sense: how can you have a domesticated animal if it just wants to attack you or is too scared to come near you? The foxes also led us to questions about psychology: Is this remarkable ability of reading human gestures and to use humans as social tools also a product of selection for friendliness? The answer is yes: the domesticated foxes acted like dogs regarding their ability to read human gestures while the control line did not; they behaved like wolves.

Nogueira: You mention in your book that, “without an experiment, we were slipping from science into the realm of storytelling.” Could you elaborate why we need experiments? 
Hare: We published a paper in Science ruling out the first two hypotheses.1 The first is that dogs’ remarkable skills of reading human gestures evolved in wolves and were inherited. Second: lots of experience gives dogs these skills. We didn’t find any evidence for these hypotheses, so by default we favored the domestication hypothesis. We didn’t have evidence for it; we only had evidence against the other two hypotheses. If Belyaev had not done his domestication experiment, we would have been stuck at that point. Belyaev’s work established the possibility of testing if domestication made dogs able to read human gestures. We did an experiment with the foxes and we were surprised: even though they were not selected to be smarter or to be better at using human gestures, they were as a result of being selected for friendliness. We had direct evidence that it was domestication that did it.2 People might think that we domesticated dogs and made them smarter, but it does not mean it’s true.

Nogueira: If it’s not true, what probably have happened?
 Hare: People tend to think we created dogs as our own image. The best evidence suggests that animals had an advantage if they were friendly to people; they will reproduce more. I was in a restaurant eating outside and there were sparrows stealing food in a few inches of my feet. Those sparrows are eating tons of food, they are fat and healthy. That’s because they’re not afraid of people. I think something like that happened with dogs. In some point of human evolution, humans created a new food resource that if you could be friendly enough and not fearful of human population you were a big-time evolutionary winner. So, a population of wolves chose us; we didn’t choose them. Since hunter-gathers competed with wolves, it does not make sense to bring animal like wolves close to your children. The wolves realized, just like the birds under my table realized, the wonderful resource is scraps around human camps. After a few generations, they would show morphological changes, like those we’ve seen in the foxes, so people could tell the difference between those and the other wolves we competed with. That would be a major selection advantage.

Nogueira: How evolution is related to those changes?
Hare: Selection against aggression and for friendliness toward people creates several changes beyond that in morphology and psychology. Once these new differences are there, selection can act on that too. The point is that these new changes were not created; humans did not think to create dogs with floppy ears, for example. Some individuals had floppy ears because selection against aggression. Then people could breed these individuals to make more floppy ears. In other words, we took the advantage of the variance created by the selection against aggression. Evolution is not any different to gravity. If I drop a ball, I can’t stop it from dropping; it’s unstoppable force. Evolution is also unstoppable. Just because you can’t see, it does not mean it’s not acting all the time. Another example is that there is a white deer that comes to eat in my front yard. Normally, deer coming near humans is a bad idea. If you live in hundred yards from my house, a deer in your front yard would soon be dinner. But where I live in the suburbs everybody think deer are cute and adorable. Where I live, there is higher proportion of deer with different color coats; there are more white and albino deer. Research already shows that deer that are invading urban areas are larger, more social and have more offspring than deer living far away from humans.*

Nogueira: This process of domestication that happened with dogs probably have happened with other animals well, which we called convergence of evolution. What do we find, for example, when we compare chimpanzees and bonobos behavior regarding aggression, attitudes towards strangers and so on?
Hare: Bonobos served as a test-case for the hypothesis that natural selection, and not artificial selection, caused domestication. We called it self-domestication: species, through natural selection interfacing with its environment, end up like a domesticated animal. When we compare chimpanzees and bonobos to wolves and dogs, many changes between wolves and dogs were found between chimpanzees and bonobos. Chimpanzees are like the wolf of the ape family. Weather we’re talking about morphological or behavior characteristics, bonobos are really the dog of the Ape family.



Nogueira: At Skeptic, we advocate for evidence-base thinking. Since you had communicated with the public, what do you think is the best approach to shift people from faith-based thinking to evidence-based thinking, increasing, for example, the acceptance of evolution?
Hare: In US, people think that Christians have a problem with evolution, but the Catholic Church says evolution is consistent with Catholic doctrine. People love to play the “in and out” group card: science is something that other people do. If one is religious and faithful, one can’t believe in science, since science is anti-religion. That’s the typical in-out group response. People use strategies to target science, or evolutionary thinking, as the out group. As someone who studies evolution, the first thing is to notice that humans evolved to see in-out group everywhere. If you say something like “you’re religious and you’re not like me”, it’s over. As a science communicator, I’m going to say that Catholic Church has no problem with my research in order to turn-off the in-group out-group response. The entire intent of my book The Genius of Dogs is to get people who had never read about evolution and cognitive science excited to read about it, because they care about dogs. Darwin intentionally started The Origins of Species with a chapter about domestication, because he knew people were familiar with and were not threaten by it. I think we have to do the same thing.

Nogueira: Thank you for this amazing interview and keep up the fascinating research!



References
1.    Hare B, Tomasello M. 2005. Human-like social skills in dogs? Trends in Cognitive Sciences 9: 439–444. https://www.ncbi.nlm.nih.gov/pubmed/16061417.  
2.    Kaminski J, Bräuer J, Call J, Tomasello M. 2009. Domestic dogs are sensitive to a human’s perspective. Behaviour 146: 979-998 https://doglab.shh.mpg.de/ pdf/Kaminski_et_al_2009a_dogs_sensitive_humans _perspective.pdf.
3.    Hare, B Hare, B., Homo sapiens Evolved via Selection for Prosociality. Annu Rev Psychol. 68:155-186: https://www.ncbi.nlm.nih.gov/pubmed/27732802
4.    Hare B., M. Brown, C. Williamson, and M. Tomasello. 2002. “The domestication of social cognition in dogs.” Science. 298: 1634-6.
5.    Hare B., et al. 2005. “Social cognitive evolution in captive foxes is a correlated by-product of experimental domestication.” Current Biology. 15: 226-30.

Notes
* Here I corrected a minor mistake that was published in the original version at the magazine. I also corrected Figure 2's subtitle: the correct reference number is 2 (Kaminski et al, 2009).