Studying uterine cancer in man

For centuries, experts have studied groups of men and applied the results to all of us. The problem is that not all of us are men - more than half of us are women. One of the most egregious examples took place at Rockefeller University in New York in 1986. Scientists were studying the effects of obesity on the activity of oestrogen and the tendency to develop breast and uterine cancer. All the volunteers were male. Surprisingly, the researchers missed the crucial link between hormones, calcium, and osteoporosis in women. Really surprising is that, according to one of the researchers, this was done deliberately because men are cheaper to study because their hormone systems are simpler. There are countless other studies where the male body is the standard and women are not included (e.g. in the 10-year study on cholesterol and heart disease). Even though this number one killer of humans doesn't exclude women.

At the cellular level, men and women are unique

Historically, women have been incredibly underrepresented in clinical trials. Part of this gender disparity in clinical research stems from the early misconception that men and women are biologically the same. We now know that men and women are unique at the cellular level. As a result, they respond differently to drugs and medical therapies. In the last century, researchers preferred to work with male subjects for two main reasons.

• Male volunteers experience fewer hormonal fluctuations than the average menstruating woman. The researchers were concerned that the frequent changes in hormone levels could affect the final results of the clinical trial. 
• It was taboo to test on a pregnant woman because of the safety risks to both mother and baby. Therefore, women who were pregnant or who might become pregnant during the course of the trial were often excluded.

The male body is still the norm and the sex bias in drug dose trials leads to overmedicated women

You don't have to be a scientist to question the fact that designing your clinical trial to get the best possible result is more than a little sub-optimal. More importantly, this gender bias goes beyond the diversity or woke debate.

Women are more likely than men to experience adverse effects from medicines because the dosages of medicines have historically been based on clinical trials conducted in men. New research from UC Berkeley and University of Chicago supports this finding. Scientists analysed data from several thousand medical journal articles and found clear evidence of a gender gap in drug dosing studies for 86 different FDA-approved drugs on the market, including antidepressants, cardiovascular drugs, anti-seizure drugs, and painkillers. This suggests that as many as half of all these patients are being given too much medication.

The second point regarding the exclusion of women of childbearing age from drug trials until the early 1990s was based on medical and liability concerns. Exposing pregnant women to drugs and the risk of harm to their unborn babies is a no-go. This was the case with thalidomide in the 1950s and 60s, which caused limb birth defects in thousands of children worldwide.

If the dose is based on male-dominated studies, a one-size-fits-all pill will not work.

There are fundamental biological differences between the male and female body. In the trials analysed by UC Berkeley and the University of Chicago, women received the same dose of the drug as men. They had higher levels of the drug in their blood. It also took longer for the drug to be cleared from their bodies. In more than 90% of cases, women experienced worse side effects, such as nausea, headache, depression, cognitive deficits, seizures, hallucinations, agitation, and heart abnormalities. Overall, they experienced almost twice as many adverse reactions as men. Although the inclusion of women in drug trials has increased in recent years, many of these newer trials still do not analyse the data for sex differences. It is important that medical research, the medical professionals and the pharmaceutical industry become more aware of the biological sex and gender differences that put women at a disadvantage when taking prescription medicines.

Close to your heart - Gender differences in heart failure biomarkers and diagnostics

Cardiovascular disease (CVD) is a leading cause of death in both men and women worldwide. However, recent studies have shown that there is a gender bias in the diagnosis of CVD, with women less likely to receive timely and accurate diagnosis and treatment than men. Women with CVD are more likely to be misdiagnosed and/or undertreated and are more likely to die from CVD compared to men. One of the major CVDs is heart failure (HF).

The term HF can be frightening. It sounds as if the heart is not working at all. In fact, HF doesn't mean that your heart will stop working. This means that the heart muscle isn't pumping blood around your body as well as it should, or that it is not relaxing as well as it should. Your body relies on the pumping action of your heart to deliver oxygen- and nutrient-rich blood to your cells. If you have HF, your weakened heart won't be able to pump enough blood to the cells. This leads to tiredness, shortness of breath and some people experience excessive coughing. Everyday activities such as walking, climbing stairs or carrying shopping can become very difficult.

The same but different

There's no cure for HF. But there's a lot you can do to manage it. By taking your medication, following a HF action plan and making lifestyle changes, you can feel better, stay out of hospital and continue to lead an active and fulfilling life. Circulating HF biomarkers are often used to determine the right dose of medication, the action plan, and the lifestyle changes. The biomarkers are in use every day by clinicians without regard to gender. However, there are significant gender differences in the levels of several HF biomarkers in blood plasma.

Among healthy people, women tend to have higher levels of natriuretic peptides (ANP and BNP) and galectin-3 (Gal-3) and lower levels of cardiac troponin (cTn) and soluble suppression of tumourigenicity 2 (sST2) levels than men. These proteins are used as diagnostic biomarkers for myocardial injury (e.g. heart attack) and as prognostic markers for HF. Plausible biological explanations for these sex differences have been postulated, such as differences in body composition, fat distribution or sex hormones. However, several clinical studies have shown that these differences are attenuated in patients with HF, and they do not reflect different pathobiological mechanisms in HF between women and men. However, it does not necessarily mean that different diagnostic cut-offs need to be used for each gender in clinical practice. It implies that it can be crucial to be aware of reference values.

To date, the sex-specific prognostic value of HF biomarkers for risk stratification is an unresolved issue that needs to be addressed by future research. It should be on the agenda of diagnostic companies to explore the clinical value of considering possible sex differences in specific HF biomarkers with the aim of improving HF management and patient care.

The immortal life of Henrietta Lacks and how one woman revolutionized biomedical research

Have you ever wondered how scientists study human tissue in the lab? They use real human cells for the body. Normal cells in the body have a limited number of replications, which limits their lifespan. Cancer cells escape this limit and replicate indefinitely, making them ideal for research that requires a constant supply of fast-growing cells. In other words, these cells do not stop dividing or die, they are immortal. Today, thousands of different proliferative human cell cultures are used as biospecimens in biomedical research. They are called “cell line”. HeLa cells were the first human cell line to survive and thrive outside the body in a test tube. Since then, the HeLa cell line have been used in more than 100’000 scientific PubMed publications on a range of topics including cancer, cell biology, genetics and infectious diseases.

The HeLa cell line is still alive today, and the excitement about HeLa cells has crossed industrial and geographical boundaries. In 1964, some of the first spacecraft to travel into space carried HeLa cells. They have been used to study the effects of radiation after atomic bomb explosions. They have been used by the beauty industry to test potential side effects of new cosmetic products and played a crucial role in the development of the polio and COVID-19 vaccines. In addition, studies on this cell line have led to groundbreaking discoveries that were awarded with three Nobel Prizes to date! All these HeLa cells came from Henrietta Lacks, a woman who had been dead for 13 years before living cells were sent into space.

Blood Cancer UK, 24.10.2023 The stolen legacy of Henrietta Lacks

But where do these immortal HeLa cells come from?

In 1951, Henrietta Lacks a 31-year-old African-American mother of five, went to Baltimore’s Johns Hopkins Hospital to be treated for an unusually aggressive form of cervical cancer. She grew up in Clover, Virginia, and later moved with her growing family to Turner Station in Baltimore County, Maryland. She was a tobacco farmer, loved cooking, dancing, horseback riding and was also known for caring and helping members of her community who were looking for work. While Henrietta Lacks was undergoing radiation therapy at Johns Hopkins Hospital, some of her cancer cells were taken from her cervix without her knowledge or permission and grown in a laboratory. Where any of the other cells would die, Henrietta Lacks' cells doubled every day. They became the first immortal human cell line, nicknamed HeLa after the first two letters of her first and last names. Although she ultimately passed away on October 4, 1951, at the age of 31, her cells continue to impact the world and biomedical research. Johns Hopkins Hospital was the only hospital in the area at the time that would treat African Americans. The collection and use of Henrietta Lacks' cells for research was an acceptable and legal practice in the 1950s. Fortunately, laws protecting research subjects have evolved since then.

Henrietta Lacks’ cells were the first cells that could be easily shared and multiplied in laboratories around the world. Johns Hopkins Hospital never sold or profited from the discovery or distribution of HeLa cells and does not own the rights to the HeLa cell line. Rather, Johns Hopkins has made HeLa cells freely and widely available for biomedical research. Since 1951 Johns Hopkins Hospital has supported changes in the law to protect human research subjects (e.g. requirements related to an informed consent). Despite the fact that Johns Hopkins Hospital never made profit with HeLa cells, other Biotech companies have made billions selling them. As a result, the descendants of Henrietta Lacks settled a lawsuit against the biotech company last year.

While Henrietta Lacks’ story has been known in the research community for some time, it raised further awareness after the publication of the best-selling book The Immortal Life of Henrietta Lacks (Crown, 2010).

Does one cell line fits it all?

The HeLa cell line has been well established in the scientific community for over 50 years. However, like gender bias in clinical trials or HF biomarkers, the use of only one single cell line from a single individual is likely to have its limitations. But the convenience of being able to work with the same cell line around the world seems to outweigh any potential concerns about always using the same cells from the same person.

What the gender bias in medicine has to do with the solar-powered press garbage bin in Basel

When the city of Basel installed the first solar-powered press garbage bins in the centre in 2020, it probably provoked a worldwide novelty. For the first time, garbage bins became a political issue. Whether this is because Basel doesn't have too many problems, or because the cans actually spoil the cityscape, or the fact that a garbage bin might have a bias too remains to be seen. But the fact is: Solar-press garbage bins remain an emotional issue in Basel.

In short, the intention to add 940 new solarpowered press bins to the 160 bins already in use sounds good. They compress waste to fit in 240 litres of garbage instead of just 40 or 110 litres. This reduces costs because they don't need to be emptied as often as the conventional bins. However, the city has already decided to move the existing solar-powered press garbage bins from the city centre and old town to the suburbs. They do not contribute to the enhancement of the cityscape, and they need to be emptied just as often as the conventional ones. Therefore, politicians decided to order a significantly fewer number of new garbage bins, to only 823 for 4.86 million CHF instead of the planned 940 garbage bins at a cost of 5.6 million CHF.

Don’t worry, the savings weren’t that great as 37’000 CHF were already spent on improving the user-friendliness of the bins. People with physical disabilities, elderly and children found it quite difficult to use the bins. The insertion hatch on the brand-new garbage bins had to be lowered by 20 cm to make it much easier for everyone to use them.

Basler Zeitung, 03.12.2020, 17:38, Basel kauft 1000 Solar-Press-Abfallbehälter

Take the outside view for decision-making

These different examples demonstrate why it can be beneficial and important to take the outside view when making decisions. If you design and develop a garbage bin that works perfectly for you, it may not be ideal for the rest of population or the city centre. There are indeed similarities with clinical trial design. If you only enrol a certain group of subjects to achieve your desired outcome, you will introduce a bias into your development. Or if you're developing a diagnostic test where cutoffs are just one snapshot, it might not give the best for the diagnosis and prognosis for patients. Moreover, one cell line doesn't fit it all and might not be sufficient to answer all questions.

The outside view forces us to consider the experiences and outcomes of similar situations. This gives a more comprehensive picture of what to expect. By looking at past experiences, we can gain a better understanding of the likelihood of success or failure, allowing us to make more informed decisions rather than focusing solely on the details of the current situation. One of the key benefits of taking an outside view is that it helps to reduce bias and improve the accuracy of predictions (e.g. studying uterine cancer in man). When we focus only on the details of the current situation, we are more likely to be influenced by our emotions, personal biases and preconceptions. As a result, we may be making decisions based on incomplete or inaccurate information, which can have negative consequences (e.g. overmedication of women, suboptimal prognostic value, or inaccessibility for people with physical disabilities). By considering the experiences and outcomes of similar situations and of other people, we can better understand the context and potential challenges, allowing us to approach the situation with greater emotional resilience, make more informed decisions and achieve better results.