A Brain to Spare

Organoids take over the Biomedical Field

By BotsAndBrainz

There are at least 50 emails to answer, an experiment to run, lab samples to be ordered, and the supervisor is asking for a manuscript on the latest research findings – and I haven’t even prepared for the conference yet. By the way, which printer did I send my poster to? Sometimes life would be easier if I had a second brain. Or three. Hell, with the one I’m carrying, I’m in need of 50 spares – this one is easily distracted. Where was I again? Oh yes, spare brains. Well, I’m in luck. Because brains come in a dish instead of a skull these days. Sounds sci-fi? Well then, welcome to reality, because I’ll be talking about organs grown in the lab today. And these so-called “organoids” are very, very real.

First of all, if you’re imagining a proper brain the size of a grapefruit, floating in an aquarium filled with a liquid of a faint green hue, covered in veins pulsating with blood – I’m very sorry to burst your bubble. Though the field has made some astounding leaps forward in the past couple of years, the organs that are being produced right now are still no larger than a pea. But what they lack in size, they make up for in diversity. Currently it’s possible to produce mini-organs of all types: stomach, lungs, liver, intestines… Need a new eyeball? No problem. Thinking scientists can’t create something as complex as a tiny kidney in a dish? Well, think again. You can even get a breast organoid these days! The sheer number of possible organoids is enough to make you and your second brain dizzy. (Here’s a list)

The organoids scientists are creating (such as my future spare brain) are produced by using stem cells. There are two options to get from stem cell to cerebral organoid:

  • Embryonic Stem Cells (ESCs)

There’s the type most of you have possibly read about in the papers, when stems cells are be collected from embryos. These ESCs can grow into any organ you have in your body. They’re donated by couples who’ve been trying for a baby through in-vitro fertilization. For this method, a relatively large number of sperm and egg cells are combined outside of the female uterus in a lab dish. Later, once the cell clump is large enough to survive a transplantation, it is surgically moved into the mother-to-be. But not every cell clump survives to grow that large. Also, most women do not want to give birth to a relatively large number of kids all at once. The leftovers of the in-vitro fertilization method are stored at -80°C and later used to gain stem cells for research in the organoid field.

  • Adult stem cells (ASCs)

The other type of stem cell used to make organoids is less ethically debatable: Adult stem cells can be found in each and every organ of our body, at all times and stages of our life. They’re collected when a doctor cuts off tiny bits of tissue of a certain organ. The ASCs can then produce exactly the organoid they were taken out of – and unlike the pluripotent ESCs – ONLY into that one specific organ type. But despite this limitation ASCs are a lot more useful for medical research since they share the exact same genetic code with the person they were extracted from. If you’re a researcher studying a disease-causing genetic mutation an organoid is the closest you can get to studying the disease in action outside of the human body! You get to test new medical drugs on this “patient in the dish” while the patient in the hospital bed is safe from any experiments going awry. It also offers up the possibility for personalized medicine. Drugs are usually created for patient groups. The larger the group of people suffering, the higher the chance time and energy will be put into treatment research. Most of the time patients with statistically common diseases win out over patients with rare disorders. Organoids change that completely. In 2016 a patient from the Netherlands with a disease-causing genetic mutation so rare only one other person besides him in the entire world carries it, was helped after a medical drugs tested straight on organoids from his own body worked successfully. Pretty cool!

But why would scientists create organoids (“the name essentially translates to organ-like cell clump” I was told by the leading expert in liver organoid field Dr. Meritxell Huch from Cambridge University, UK) if they’re so tiny that no one in their right mind would ever consider them for a real organ transplant? How can something so miniscule be useful? That question is easy to answer if you’re aware of the following trade secret in biomedical research: At the end of the day, what scientists are truly after, is a better model organism.

Usually they are forced to use lab animals – who live the type of life you wouldn’t wish upon your greatest enemy. The animals play the role of the model organism, and drugs are tested on them to prevent human patients from being hurt by side-effects. Unfortunately, the lab mouse only ever be the best model for another mouse. When scientists move on to the next phase in a clinical trial – the human testing stage – there is no guarantee that a drug which works great in a lab mouse will heal a human patient. It’s frustrating work, not only for the scientists, but for anyone with a functioning moral compass. Here’s where the organoids come in. Organoids do not involve lab animals at any stage of the research process. With them, animal testing will soon be a thing of the past (or at least greatly reduced).

Currently almost 3 million animals are being used for lab research every year in Germany alone. Excluding invertebrates, such as fruit flies, of course. I frankly don’t want to know the true number if those were counted, too. A lot of the lab animals are used to test whether a new medical drug will work to treat a disease. “Let’s say you want to test 30 different drugs. In order to say for sure whether the drug is safe and works, you need to use about 50 mice. That adds up to 1500 animals in total!” Dr. Huch explained to me during our Skype call. “But to produce 1500 liver organoids, you only need a single animal or patient sample.” Talk about economical!

 

Unfortunately there are still some problems to keep in mind while you’re writing your banner “NO MORE LAB ANIMALS; POWER TO THE ORGANOIDS!”. Organoids grow up in a completely sterile environment, and have no immune system to protect them in the outside world. They also come only in singles instead of as part of a big, complex body like the human body where many organs need to interact to keep the entire machine going. But when organoids are already being used as a biological Band-Aids at such an early stage in the research process, you know you’re onto some sexy science. So organoids might still be too small to solve the problem of organ shortages for transplants. After all, these tiny organs might be no larger than an uncooked legume. But in terms of what they can do, organoids should be seen as the next Big Thing in medical research. I’m betting my second brain on it.

 

BONUS ROUND

Check out this cool Ted Talk on Organoids by Dr. Hans Clevers!

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