Women were excluded from drug trials. They suffer from more adverse drug reactions.

Plus, getting another PhD at 89, naturally curing HIV, cultivating microbes in the gut-zoo, and giving birth without males

Hello!

How have you been? The days are getting shorter in the northern hemisphere and it is getting colder. I started this newsletter as a means of providing information about COVID-19. These days, I have other ulterior motives. The purpose of this newsletter is to share what I’ve found interesting about life and nature. It is also a means of figuring out how we can try to live better within the constraints of our inherited genes and our surroundings. But more than anything else, it is an attempt to identify and accept differences in brains, bodies, and experiences.

On the one hand, there are universal aspects to life. For all of the complexity and unpredictability of human life, it is still pretty incredible that you can make life-altering discoveries that impact cancer, brain diseases, and ageing in people by taking apart one-celled baker's yeast and pond scum. Some of the same pathways in complex human organs can be found in those simpler organisms.

On the other hand, biology is a science of exceptions. Mutations are the differences that makes life possible in every niche on this planet. I’m not just interested in someone else’s definition of normal, I’m also interested in the outliers.

One thing I’m learning about psychology is that for most of its history it has mainly dealt with “fixing” people. It is only in the last two decades that the field of positive psychology has emerged to deal with wellbeing and mental health (more than focusing on mental illness).

To anyone thinking all the major discoveries in human biology have been made, think again. We’ve discovered new organs, new functions for known organs, new senses and reflexes, how people are evolving, how we are getting new diseases. Pulp the school textbooks. They’re wrong.

With this, I want to start this newsletter with a very inspirational true story.


“..and when I retired from medicine and I was approaching age 70, I decided to enter the world of physics.”

Manfred Steiner was inspired by Albert Einstein. He always wanted to be a physicist. But after World War II, practical considerations took precedence. Steiner got a doctorate in medicine in Vienna in 1955. After moving to the US, he earned a Ph.D. in biochemistry from M.I.T. and joined the department of hematology at Brown University as an assistant professor. He worked his way up the ranks to become department chair. Steiner helped establish hematology departments elsewhere and had a stellar academic career.

After retirement, Steiner decided to focus on physics, taking classes with undergraduate students at the age of 70. He earned his Ph.D. in physics at the age of 89 and is now looking to publish work from his doctorate work. This inspiring story reminds me of a passage by the great Japanese artist, Hokusai. We are— all of us— works in progress.


Women were excluded from drug trials. Now they suffer more from adverse drug reactions.

This is the subject of my column in Hindustan Times this week, and the first of a series I hope to do on why the drug development pipeline isn’t perfect.

Adverse drug reactions are a leading cause of death; women are twice as likely as men to suffer from them. Up until recently most drug trials in the US (where many drugs originate) were conducted on white males.

Until 1993, the FDA considered women a special subgroup of patients, leading to their exclusion from most clinical trials. This despite the fact that women took 80% of the drugs on the market. Even as late as 2001, two-thirds of drug trials had few women.

Men and women clear drugs from bodies differently. If a drug is not cleared rapidly, it can result in an adverse drug reaction resulting from overdose. The dosage of Zolpidem for women was halved in 2014, but only after millions of women had taken the drug at a higher dose. Zolpidem is a sleep-aid, which caused prolonged and excessive drowsiness in women who were prescribed the initial recommended doses. In 2009, an American woman who had taken the drug hit two people while driving the following day.

Here’s one more example.

Paracetamol- which everyone pops from anything from mild aches and pains to flu- is a safe drug for most. But it is also one that is cleared in women more slowly than in men. Also, a consensus report strongly advised against pregnant women taking paracetamol unless directed.

What can be done about all the drugs that are already on the market? Women were excluded from clinical trials for many of these drugs, and those trials are unlikely to be repeated again. AI tools can sort through the FDA database to find differences in adverse reactions.


Spontaneous cure of HIV

I want to share a fantastic true-story. It is worth reading in entirety, but here is how it starts—

One evening in March 2020, a doctor walked out of a hospital in the Argentine city of Esperanza cradling a styrofoam cooler. He handed it to a young man who’d been waiting outside for hours, who nestled it securely in his car and sped off. His destination, a biomedical research institute in Buenos Aires, was 300 miles away, and he only had until midnight to reach it. That day, while his sister was inside the hospital giving birth to her first child, Argentina’s president had ordered a national lockdown to prevent further spread of the coronavirus, SARS-CoV-2, including strict controls on entering and leaving the nation’s capital. If the brother didn’t make it, the contents of the cooler — more than 500 million cells from his sister’s placenta — would be lost, along with any secrets they might be holding.

The woman was a scientific curiosity. Despite being diagnosed with HIV in 2013, she’d never shown any signs of illness. And traditional tests failed to turn up evidence that the virus was alive and replicating in her body. Only the presence of antibodies suggested she’d ever been infected.

Since 2017, scientists have been collecting blood samples from this woman, who is being called the “esperanza patient” (esperanza means “hope” in Spanish) to protect her identity. Clinical details of this patient were published in Annals of Internal Medicine. It appears that this woman has cleared the virus from her body completely- technically called a sterilizing cure. Examining how exactly she managed this and what is unique about her immune system could kickstart HIV research.

Less than 1% of 38 million people infected with HIV are known as elite-controllers because they can keep the virus under control in their bodies, but vanquishing it to the point that is is no longer detectable is another matter altogether.HIV has been practically cured twice in the past, but both times remission has required a bone-marrow transplant from donors with a rare genetic superpower that makes their cells resistant to the virus.

There is only one other patient in medical history who has ever cleared HIV to levels that we can call a spontaneous cure. A woman in California named Loreen Willenberg has kept the virus out of her body for nearly three decades without the need for drugs. No one knows how she or the Esperanza Patient accomplish this milagro yet.


Your gut is a zoo. Here's how to cultivate the right lifeforms.

If you don’t mind reading one more newsletter from yours truly, I've written about the new, emerging science of engineering gut microbiomes for health and longevity. This is a topic close to my own gut and something I know and care about deeply. At the World Revealed I’ve been taking up one cutting-edge field of science every month (previous topics include synthetic biology and xenotransplantation).

Remember, if you don't feed your gut microbes, then your gut microbes eat you.

I mean this literally. They eat the mucin in your intestinal wall, leading to inflammation and then all kinds of bad stuff all over the body.

There’s a lot of research in people that shows carbohydrates are good for you (and your gut microbes). Just be sure they’re varied, complex carbohydrates from fruits, vegetables, legumes, and whole grains, and you have no existing metabolic disorders.

As opposed to fad diets, using prebiotics to feed microbiomes has an evidence-base. From studies in germ-free mice a little over a decade ago to observational studies in populations to clinical trials in people now. The next step will be multi-year clinical trials with large patient cohorts.

Being able to precisely and predictably engineering gut microbes through diet for health, longevity, and mood is going to be an active area of science for at least the next 10 years.


Kids without males

A pair of female condors gave birth to birds without the need for males. The offspring were males and that is because in birds, males have similar ZZ chromosomes and females are ZW and dissimilar (another way birds are different from mammals like us in which males are XY and females are XX).

By Chuck Szmurlo - Photo taken by Chuck Szmurlo with a Nikon D70 and a Nikon 70-200 f2.8 lens. Edited by Fir0002, CC BY 3.0

This form of reproduction is extremely rare in birds and has been observed only in a few other birds like domestic turkeys and chickens that had no access to males. In this case, the condors kind of just ignored the males.


That’s it for this week. If you like what you’ve read, then why not spread the love by sharing or signing up?

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Until next time…

Anirban