Hunt was right to resign – Nobel laureates must set an example to their field, not bring shame

It's been a rough two days for Hunt. Paloma Baytelman/Flickr, CC BY-SA

Should I should be pleased that Sir Tim Hunt has resigned from his post as honorary professor at University College London after his unbelievable sexist remarks about women in science? He certainly has whipped up a tornado of emotions and outrage, which has spread like wildfire through the media.

Well, I am delighted that he has fallen on his now-tarnished sword but a part of me is saddened that this may mean that his views and opinions creep back into the undergrowth. And it would be a shame if he no longer had to publicly address his Victorian beliefs. He should also address whether he is well placed to continue working in academia at all. Let’s not forget that he’s still an emeritus scientist at the forthcoming Francis Crick Institute. This is a post way more significant than being an honorary professor, which is a title of recognition rather than an actual job.

So the debate must continue. It is important, because Nobel laureates have a privileged place in society that marks them out as individuals to be held in high regard, a role model for the next generation and, above all, people with the intellect to ensure that their actions are commensurate with the greatest award bestowed upon them. Hunt has said himself that he does think Nobel laureates should act as ambassadors for science.

How sad for Hunt that he has lost the credibility of the scientific community in just one day. It may have taken only a few minutes to comment “that the trouble with girls” in labs is that “you fall in love with them, they fall in love with you and when you criticise them, they cry”. But the implications of this statement are much further reaching than his attempt “to inject humour into his lecture” – humour that shocked his audience and shattered his reputation. Humour that no one found funny.

Nobel bigotry

However Hunt is not the only Nobel laureate to have caused offence. The great scientist James Watson who worked with Francis Crick to unravel DNA was also ostracised for his public comments stating that people may like to think that all races are of equal intelligence but that those “who have to deal with black employees find this is not true”. As a result, he was suspended from the Cold Spring Harbor Laboratory outside New York, USA.

James Watson, fellow disgraced Nobel Laureate. EPA

Like Hunt the media outrage at Watson’s statement knew no bounds. Watson was subsequently shunned from the scientific community, losing his place on prestigious committees and opportunities to give public lectures. In his own words he became an “unperson”. In 2014, seven years after his remarks Watson put his Nobel Prize medal up for auction in his attempt to re-enter public life. Is this the same fate that awaits Hunt?

Back to the stone age?

What is particularly sad about Hunt’s comments is that they undermine a genuine appetite to address gender imbalance, particularly in the science subjects where there is a dearth of female senior academics in higher education.

The Equality Challenge Unit with its Athena Swan Charter, which gives awards to departments that are making progress on gender equality, has been a key catalyst for changing this. In the ten years since it was first launched we are at last beginning to see the sorrowful statistics gradually change. This has happened by addressing conscious and unconscious bias in attitudes and actions and addressing cultural barriers.

This agenda somehow seems to have bypassed Hunt. Has he lost the ability to keep up with the times, stagnated or simply stopped using his enquiring mind that had previously taken him to a level that many could only aspire to?

Hunt ultimately did the right thing by resigning, sending a message that he takes public concern seriously. Whether this is enough to restore some of his reputation remains to be seen.

Retraction of scientific papers for fraud or bias is just the tip of the iceberg

Taking a closer look at the details. Small print by Shutterstock

Publishing clinical trials in medical journals can help doctors and scientists rise through the ranks of the research hierarchy. While most play the publication game fairly, some cheat. Whereas all misconduct undermines the public’s trust in science – such as the recent retracted paper about gay canvassers – health research scandals put the health of millions of patients around the world in jeopardy.

Professionals and patients depend on results from systematic reviews of clinical trials, which evaluate all the evidence on a particular issue, to know whether or not treatments are safe and effective. However, those of us who coordinate the preparation of Cochrane systematic reviews of treatments for seriously injured patients believe that these types of reviews can no longer be entirely trusted because of research misconduct and publication bias. An argument we recently made in the BMJ.

Falsified reports

Most medical journal editors and systematic reviewers take clinical trial reports at face value with little or no effort to confirm whether a particular trial even took place. A Cochrane systematic review showing that the infusion of high-dose sugar solution prevents death after head injury, for example, was later retracted after our review editors were unable to confirm that any of the included trials took place.

As part of the investigation, the London School of Hygiene & Tropical Medicine editors contacted the editor of the journal that published one of the doubtful trials. His response? That there had been doubts about the data but that doubts were difference from concluding that it was fabricated.

Similarly, the conclusions of a review of starch infusions in critically ill patients changed substantially after excluding seven entirely fabricated trials by Joachim Boldt.

Investigating fraud is hard work, and it is easier for journal editors to ignore the problem and perpetuate the myth that peer review of trial reports ensures their scientific quality. But how can systematic reviews claim to provide “trusted evidence” when all evidence is taken on trust?

Bias in reviews

The second major problem is that the medical literature contains a biased sample of clinical trials. Clinical trials showing that a particular treatment is effective are much more likely to be published than those showing no benefit or harm.

As a result, systematic reviews based on published research are biased – they emphasise the positive and eliminate the negative. Despite decades of exhortation about trial publication, around half of all clinical trials remain unpublished – and so even the most diligent efforts to synthesise the results from all relevant clinical trials are in vain.

Cherry picking the data. Cherries by Shutterstock

Even when trials are published – information on side effects is often neglected from published reports. Clinical trial information is too important to depend on the publication game – after all, patients’ lives depend on it. Reviews of research evidence should be based on the actual trial data obtained from compulsory clinical trial registers. These registers would specify in advance the information that is to be collected in the trial – and when the trial was completed they would provide the actual raw data. Providing all the information collected would avoid the bias associated with publishing only some of the findings.

The public need to know what the trial found rather than a given doctor’s spin on the results – usually designed to make results look more interesting or newsworthy.

However, medical journals and publishers of systematic reviews have no incentive to change. They make good money putting a sophisticated gloss on whatever research manuscripts are available to them. When fraud scandals break they throw up their arms in horror but there is no structural change.

Although clinical trial research is heavily regulated, fabricated research is completely immune to this regulation since all it requires is a doctor who has lost the plot and has access to a computer. There is no shortage of medical journals who will publish – and with no questions asked. Progress will only be made when the general public becomes involved.

Accurate health research information is a public good that is as important as safe clean drinking water. We need a health research information system that delivers pure research information that is untainted by the career interests of scientists or the commercial interests of publishers.

Every citizen scientist will soon have the tools of a specialist

Spring watchers Shutterstock

Ordinary citizens have become increasingly important to scientific research over the past decade. Today, mobile phone technologies, relatively cheap cameras and almost ubiquitous internet connectivity have opened up new opportunities for conservation organisations to engage with ordinary citizens and encourage citizen science.

A citizen scientist is a volunteer who collects and/or processes data as part of a scientific enquiry. This could mean noting the plants found on a day trip or more systematically recording wildlife in a special area. While citizen science projects can be in any branch of science, my focus is on wildlife research.

The list of citizen science projects is long. This year’s BBC Springwatch, which concludes this week, has highlighted a number of mass participation projects in which people can become involved, such as recording the first signs of spring. All such schemes are predicated on the idea that people will go out and report what they see.

But technological advances are also changing the way that professional scientists collect and record data on animals. These changes often require specialised equipment and resources beyond the scope of most amateurs. Now that new technologies are changing the working practices of professional ecologists, what does this mean for citizen science?

DNA testing

Until recently, the way to ascertain the presence of great crested newts in a pond was to go and look. Because the newt is a protected species, disturbing it is illegal. But just looking for the adults or their eggs is not. Today, however, finding great crested newts and other aquatic animals can be done using environmental DNA (eDNA).

DNA is released into the water by plants and animals in a host of ways: from their skin, faeces, mucous, hair, eggs and sperm, or when they die. By simply collecting and analysing a water sample from the pond or stream, we can find traces of eDNA and identify the animals living there, even if they are hard to recognise.

DNA barcoding allows species to be identified using short genetic markers in an organism’s DNA. And actually, these barcodes can be obtained from tiny amounts of tissue even by non-specialists. All that is required is the correct DNA processing and sequencing technology.

New tools of the trade. Shutterstock

Genetic identification is not the only way in which technological advancement is changing the way that we record the species around us. Noting the birds in a woodland is more often than not a case of listening and identifying the songs rather than seeing the birds themselves.

Eco-acoustics or soundscape ecology studies the relationships between animals and their environment based on sound. There are now technologies available that allow birds and amphibian communities to be identified from sound recordings.

This means that it will soon be possible to place an audio recorder in the field and walk away while it records birdsong and other sounds over an extended period of time. The aim is that the recordings can be analysed automatically using software to draw up a species list for that area.

Raising standards

But if the collection of wildlife data is to reveal useful information, it needs to be done systematically. Recording the presence of a wildlife species only tells you that it was there at the time that it was recorded. To spot trends, the recording needs to be repeated in the same way over a number of years.

This can be difficult when relying on volunteers, but it is not impossible and there are many good examples of systematic surveys, but these are mainly carried out by people with a little more than basic knowledge.

In fact, technology is now progressing to the point that it can do the work of a specialist on behalf of any citizen, helping to standardise measurements and carry out complex analysis instead of just simple observations. For example, a new app enables visitors to the New Forest to search for cicadas - last sighted in the forest in 2000 - by analysing sound recordings of background noise captured with a mobile phone. It’s not hard to imagine similar projects asking people to collect and study samples of eDNA or make regular recordings of the dawn chorus using easily available tools.

Mass recording of wildlife sightings such as those requested by the BBC and the Mammal Society are not simply about recording wildlife for scientific enquiry. They are about individuals, couples and families going outside, exploring and connecting with their environment. Discovering what is there and being part of a larger group of people. It is about making new discoveries together.

But with new technologies, the details of citizen science will change. Future technological advances will present new ways to continue our long established heritage of amateur natural history.

Ancient DNA reveals how Europeans developed light skin and lactose tolerance

Slurp and thank the Yamnaya. Samantha Jade Royds/Flickr, CC BY-SA

Food intolerance is often dismissed as a modern invention and a “first-world problem”. However, a study analysing the genomes of 101 Bronze-Age Eurasians reveals that around 90% were lactose intolerant.

The research also sheds light on how modern Europeans came to look the way they do – and that these various traits may originate in different ancient populations. Blue eyes, it suggests, could come from hunter gatherers in Mesolithic Europe (10,000 to 5,000 BC), while other characteristics arrived later with newcomers from the East.

About 40,000 years ago, after modern humans spread from Africa, one group moved north and came to populate Europe as well as north, west and central Asia. Today their descendants are still there and are recognisable by some very distinctive characteristics. They have light skin, a range of eye and hair colours and nearly all can happily drink milk.

However, exactly when and where these characteristics came together has been anyone’s guess. Until now.

Clash of cultures

Throughout history, there has been a pattern of cultures rising, evolving and being superseded. Greek, Roman and Byzantine cultures each famously had their 15 minutes as top dog. And archaeologists have defined a succession of less familiar cultures that rose and fell before that, during the Bronze Age. So far it has been difficult to work out which of these cultures gave rise to which – and eventually to today’s populations.

The Bronze Age (around 3,000–1,000 BC) was a time of major advances, and whenever one culture developed a particularly advantageous set of technologies, they become able to support a larger population and to dominate their neighbours. The study found that the geographical distributions of genetic variations at the beginning of the Bronze Age looked very different to today’s, but by the end it looked pretty similar, suggesting a level of migration and replacement of peoples not seen in western Eurasia since.

One people that was particularly important in the spread of both early Bronze-Age technologies and genetics were the Yamnaya. With a package of technologies including the horse and the wheel, they exploded out of the Russian and Ukrainian Steppe into Europe, where they met the local Neolithic farmers.

Yamnaya skull Natalia Shishlina.

By comparing DNA from various Bronze-Age European cultures to that of both Yamnaya and the Neolithic farmers, researchers found that most had a mixture of the two backgrounds. However the proportions varied, with the Corded Ware people of northern Europe having the highest proportion of Yamnaya ancestry.

And it appears that the Yamnaya also moved east. The Afanasievo culture of the Altai-Sayan region in central Asia seemed to be genetically indistinguishable from the Yamnaya, suggesting a colonisation with little or no interbreeding with pre-existing populations.

Mutations traced

So how have traits that were rare or non-existent in our African ancestors come to be so common in western Eurasia?

The DNA of several hunter gatherers living in Europe long before the Bronze Age was also tested. It showed that they probably had a combination of features quite striking to the modern eye: dark skin with blue eyes.

The blue eyes of these people – and of the many modern Europeans who have them – are thanks to a specific mutation near a gene called OCA2. As none of the Yamnaya samples have this mutation, it seems likely that modern Europeans owe this trait to their ancestry from these European hunter gatherers of the Mesolithic (10,000-5,000 BC).

Reconstruction of a Yamnaya person from the Caspian steppe in Russia about 5,000-4,800 BC. Alexey Nechvaloda

Two mutations responsible for light skin, however, tell quite a different story. Both seem to have been rare in the Mesolithic, but present in a large majority by the Bronze Age (3,000 years later), both in Europe and the steppe. As both areas received a significant influx of Middle Eastern farmers during this time, one might speculate that the mutations arose in the Middle East. They were probably then driven to high levels by natural selection, as they allowed the production of sufficient vitamin D further north despite relatively little sunlight, and/or better suited people to the new diet associated with farming.

Another trait that is nearly universal in modern Europeans (but not around the world) is the ability to digest the lactose in milk into adulthood. As cattle and other livestock have been farmed in western Eurasia since long before, one might expect such a mutation to already be widespread by the Bronze Age. However the study revealed that the mutation was found in around 10% of their Bronze Age samples.

Interestingly, the cultures with the most individuals with this mutation were the Yamnaya and their descendents. These results suggest that the mutation may have originated on the steppe and entered Europe with the Yamnaya. A combination of natural selection working on this advantageous trait and the advantageous Yamnaya culture passed down alongside it could then have helped it spread, although this process still had far to go during the bronze age.

This significant study has left us with a much more detailed picture of Bronze Age Europeans: they had the light skin and range of eye colours we know today. And although most would have got terrible belly ache from drinking milk, the seeds for future lactose tolerance were sown and growing.

It’s a crying shame when Nobel laureates are exposed as sexist

There were no women around to distract Hunt when he received his Nobel. EPA

I’m not sure whether I’m weeping tears of laughter or sorrow at the comments made by Nobel Laureate and English biochemist Tim Hunt. Poor man – he certainly has stirred up a storm of debate following his inadvised remarks about single-sex laboratories and women crying when criticised.

I say poor man, but I don’t really feel sorry for him. He should have known better. OK, it is important to have a sense of humour, and most people are able to laugh when someone makes a light-hearted joke at their expense. But there are limits, especially when addressing a group of people that you don’t know very well, who might have different social or cultural reference points. Someone as senior as Hunt should have realised that his remarks were going down like a lead balloon, and been able to change the tenor of his comments.

There are (at least) two aspects of Hunt’s remarks to take issue with. The first is about workplace relationships: “Let me tell you about my trouble with girls … in the lab … You fall in love with them, they fall in love with you". In saying this, he seems to be marking laboratories out as seething dens of sexual iniquity. [Humorous aside: chance would be a fine thing …].

OK, perhaps I’m exaggerating a bit – though I did meet my husband when we sharing a laboratory as fellow PhD students. We celebrate our 29th wedding anniversary this year. Because of university administration cycles, for several years he was my boss, then I was his boss. We still work together, publish together and collaborate on a variety of projects. Sometimes, workplace romances can even serve as a source of inspiration rather than distraction.

Thank god she’s covered up at least. wavebreakmedia/Shutterstock

But laboratories are certainly not the only workplaces in which colleagues form relationships. Indeed, workplace relationships are so commonplace that reports have been written about their effect (positive and negative) on the work environment. There is even a Wikipedia entry about the subject, which cites a number of references to academic papers.

Before the spread of online dating sites, the workplace was one of the main locations where partnerships formed. If we take Hunt’s comments to its logical conclusion, then all workplaces should be segregated on the basis of sex. Gosh, where does that leave consideration of our LGBT friends and colleagues?

Workplace bullying

The second comment which deserves debate is the assertion that “women start crying when you criticise them”. As far as outrageous and outdated sexist comments go, this must be fairly close to the top. This to me is more serious.

I was reduced to tears following a reprimand – once. The person who criticised me was several years older, and several grades more senior. He was notorious for his bullying tactics. I was furious – with him, and also with myself for caring about what he had said. There is no excuse for being so destructive that a woman, or man, is reduced to tears.

If you know you have to deal with someone who doesn’t take criticism easily, then temper how you speak to them. That isn’t having to hold back, but is showing a sensitivity that will get much better results than boosting your own ego by causing someone to cry.

As far as I am aware, I have never reduced any of my colleagues to tears following a reprimand. And if I have, it was inadvertent and I apologise. There are much better and more effective managerial tools: praise, discussion, suggestion of alternative approaches to problem solving.

As others have pointed out, Hunt may be of a previous generation, where there were fewer women in senior positions. But that is not an excuse for his comments. I see from his biography that he is married to a fellow scientist. The biography does not say whether they were laboratory colleagues … I wonder what they’ll be discussing over the dinner table tonight.

Disclosure

Monica Grady receives funding from the STFC and is a Trustee of Lunar Mission One.

In sport's drug-testing arms race, the cheats are usually a step ahead

Ouch. Shutterstock

Yet another big name in sport has been caught up in allegations surrounding a doping scandal. Alberto Salazar, coach to several star athletes including double Olympic gold medallist Mo Farah, denies allegations by the BBC he broke anti-doping rules one of his trainees, Galen Rupp. Farah is not accused of any wrongdoing but UK Athletics has confirmed it will be scrutinising his previous tests.

Salazar once said an athlete might “not even consider it cheating if they believe all their top competitors are doing it”. Does this mean many elite athletes are doping? If so what are they using and how do they evade the tests?

Testing has improved over the past 20 years. Equipment is more sensitive and specific to particular substances. This means testers can find smaller amounts of a substance in each sample and so any drug used will be detectable for longer.

If these new and improved tests worked more efficiently you would expect the percentage of athletes caught to increase. However, this number remains fairly static at around 2% of all athletes tested. This is very low compared to the estimated 14-to-39% who are thought to dope, based on questionnaires and some lab testing. This gap tells us many athletes are doping in a way to avoid testing positive for a banned substance.

Cat and mouse

Most new drugs are detectable in urine samples once testers have worked up a method. Pharmaceutical companies and WADA are now sharing information on new drugs in development, meaning labs start to develop tests before the drug is released. But these tests still require considerable time and resource to develop, years in some cases. Validation is not simple, complicated by the body breaking down the drug before it reaches the urine.

As such, a game of cat and mouse can ensue between dopers and testers. CERA, a synthetic form of the hormone known as EPO used to increase red blood cell production, was approved for use in kidney disease patients in early 2008. A test was developed by the middle of the year but it was presumed athletes were using the drug before testing caught up. This was later confirmed when the test was used without warning in the Tour de France and on samples frozen from earlier in the year.

As well as equipment changes, there have been step changes in the thinking behind tests over the past decade, most recently with the creation of the “athlete biological passport”. This looks for evidence of doping but not necessarily the substances used themselves. For example, it detects increased ability to carry oxygen in the blood that is likely caused by use of EPO or similar drugs. Results are then stored on a database and compared to an individual’s profile.

Alberto Salazar: under suspicion Steve Dykes/EPA

The athlete biological passport has had successes and some cyclists and athletes have been suspended through its use. But it has struggled to catch those using microdosing - taking small regular doses of drugs like EPO rather than single large doses.

The knowledge required to avoid testing positive is certainly not beyond medics working with athletes. If they know the time the drug remains in the body they can calculate how long before a competition use must be stopped. They also know the “at risk” period following use when an athlete may get caught.

The best way of not testing positive in this period is not to be tested. Athletes give their whereabouts for one hour of each day in advance. Athletes have been known to give incorrect addresses to avoid testers or to simply hide if they know they are at risk. There is a rule that three missed tests over 18 months constitutes a doping offence. That gives you one or two chances to avoid testing and blame logistics or disorganisation, a risk some athletes are willing to take.

Playing the system

Athletes will also seek to exploit loopholes in the regulation. The increased sensitivity of testing has created a greater likelihood of positive results from contaminated supplements or food. A drug detected in urine from contamination is impossible to differentiate from deliberate use just through testing, creating more scope for athletes to contest the results.

Exactly what drugs should be off-limits to athletes is itself a major topic of debate. The substances in the Salazar allegations are testosterone, which is banned at all times in sport, and prednisone (used to treat asthma) and the thyroid medication thyroxine, which are just controversial.

The question is whether substances such as these are required to treat pre-existing medical conditions or are just being used to help athletes recover from intense training sessions, gain energy or lose weight.

There are two types of medicines that fall into the grey area of medical treatments that may not strictly be required. One set are on the World Anti Doping (WADA) banned list and require medical assessment before they can be used. The second set, which includes prednisone and thyroxine, are neither monitored nor recorded.

There have also been examples of drugs not available to the public being detected in sports samples. And there are even some drugs being used such as GW1516 which was considered unfit for human use.

Who is winning the race? In general the athletes are one step ahead most of the time, but occasionally testers get on top. One thing is for sure: as long as people have incentives to win, it is very unlikely doping will be eradicated.

Caffeine may reduce stress – but it won't solve your problems

That menu suddenly looks very affordable! David Hodgson/Flickr, CC BY-SA

Coffee addicts have been saying it for years – now an experiment on mice has found that caffeine does indeed help one stay cool in stressful situations – and has pinpointed the neurochemical pathways involved in the process. The researchers even suggest that the study may one day lead to medical therapies for stress-related illnesses in humans.

But while the research itself is important, we must not forget that stress is a normal human reaction to events rather than brain chemistry. The last thing we need is another psychiatric drug that ignores the root of the problem.

Previous research has shown a number of positive effects of caffeine, for instance on preventing depression. This study is the first to uncover the neurochemical pathways that enable caffeine to prevent some of the negative effects of stress on the brain.

Caffeine is known to inhibit receptors in the brain for the chemical adenosine. The researchers found that these receptors also control the negative effects of chronic stress and that stress-induced behaviour can be reversed by blocking the receptors.

The results are important, as we do indeed know that chronic stress affects people very badly. In mice, the (rather unpleasant) stressful situations in this experiment included as damp bedding, sharing living space with others, food and water deprivation, cold baths and cages tilted at 45°. And these poor mice unsurprisingly showed the behavioural and neurological consequences of this stress.

In humans, chronic stress can also have disastrous consequences. For example, my colleagues have shown that the economic crisis in the years between 2008 and 2010 can be blamed for as many as 1,000 people in the UK taking their own lives. We do, absolutely, need to understand how stress affects us. And we definitely need to find ways to help people (and mice) affected by stress.

Handle with care

But I do have a nagging concern. The paper suggests that a drug blocking this particular receptor could be used to treat illnesses stemming from chronic stress such as depression or anxiety.

Yummy molecule Greg Rodgers/Flickr, CC BY-SA

It’s this that I question. While I don’t doubt that the study has revealed something fascinating about how the brain responds to chronic stress, it’s a little less certain that the research tells us anything about “disorders”. The mice seemed to respond normally to an abnormal – stressful – situation. It would be unfortunate to extrapolate that understanding to infer that such a response is a sign of abnormality, especially in humans.

Stressful events make us stressed, emotionally and physically; they have negative cognitive, emotional, physical and behavioural consequences. Given that we process information in the brain using neurotransmitters, it’s obvious that there will be a neurological route or pathway behind stress-induced behaviour. It’s great to know more about that pathway – and maybe that will even help us become more resilient or recover faster from stressful life events.

Swerves and steering wheels

An analogy might help. If a driver swerves and crashes a car, we don’t usually regard the steering wheel as the “cause” of the crash. The steering wheel was absolutely necessary (almost certainly the steering wheel was a necessary part of the causal chain), but it didn’t “cause” the crash. OK, we can imagine a weird scenario where a fault in the steering wheel (grease on the grip, perhaps) might be to blame. But such scenarios are vanishingly rare. Essentially, the wheel is a part of a mechanism whereby the cause (the driver’s swerve) translates into the crash.

It’s fantastic that this research has been conducted. It’s genuinely important – and potentially useful. As a scientist and I believe passionately that knowledge (and depth of knowledge) can help us understand the full implications of the embodied human experience. That includes understanding how the brain works and the neurochemical pathways of our response to stress. But it doesn’t necessarily mean that these molecular pathways are the “cause” of psychological distress. It’s probably better to think of them as enabling our normal human responses, not causing them.

This is important. The unfortunate tendency to label undesirable emotions as “symptoms” of “illness” may well cause us to treat people with less empathy than we should, to ignore the root causes of distress and to turn to inappropriate medical treatments. I’m all in favour of understanding how our brains work. I’m slightly less keen on mistaking mechanisms for causes.