Organoids: Small in size, big in possibilities

How to test drugs and treat people better, faster, and for less money  

Writer: Thomas Drobkiewicz
Editor: Suzanne van Noordt
Art: Charlotte Capitanchik

What if I told you that we can put drugs through clinical trials faster and for less money, that we can screen drug-to-drug interactions and its threats, and that we can actually prepare personalized cancer therapies? Sounds like science fiction, right?

Well, there is a new technology that can be used in drug discovery, drug toxicity, and personalized medicine – organoids. This idea was proposed for the first time in 2008 by Dutch professor Hans Clevers. Organoids are 3D tissue cultures that can be as small as the head of a needle. You can think of them as small organs because they consist of all cell types and mimic the function of their organ equivalent. They are produced from human-induced pluripotent stem cells (HiPSC) and since their discovery, scientists have successfully created organoids of all major organs.

Okay, but you may still be wondering, “what is all this fuss about?” To begin with, the use of organoids can decrease the amount of time needed to develop new drugs. As an example, organoids are being used at Harvard University in the laboratory of Dr. Lee Rubin to develop medications for neuronal disorders. In his research, Dr. Rubin needs billions and billions of neurons. Using organoid technology, he can grow them in one flask in approximately 50 days, something he can never do by using 2D cell culture on 100 plates. Moreover, with saved time comes saved money, and because of that, this technique draws a lot of attention.

Secondly, let’s talk about drugs’ toxicity. You may think every drug in the pharmacy is safe. Unfortunately, some of them, in spite of passing all tests during clinical trials, come out to be toxic to humans. Some examples include Valdecoxib (a non-steroidal anti-inflammatory drug), Pemoline (used to treat ADHD), and Rapacuronium (used in anaesthesia). Organoids enable better toxicity testing on human tissues and can help to detect unexpected and long-term complications that are hard to detect in human clinical trials.

Moreover, in his 2015 TEDmed talk, Dr. Russ Altman was talking about how difficult it is to analyze drug-to-drug interactions. He and his student were looking for adverse effects of patients who took both Pravachol (an anti-cholesterol drug) and Paxil (an antidepressant) that wouldn’t occur while taking these drugs separately. What was surprising is that patients on both medications had higher blood glucose levels of about 20mg/mL. This difference is significant and can lead to diabetes. Thus, the interactions between drugs are very important, but remain unpopular because they would cost too much, and it does not affect many people. The point of Dr. Altman’s talk wasn’t to introduce the idea of organoids. He has simply shown a problem. Now think about it – we could use organoids to test drug interactions to resolve this problem, and patients would be given better treatment that doesn’t endanger them.

Organoids can also be used while deciding on the best therapy for the patient.

I am not talking about mild diseases like flu here. I am talking about probably the most controversial of them – cancer.

Every tumor is different and yes, we can grow its organoids too. These can be used to test what therapeutics would work best, and depending on the place, stage, and genetic mutation of cancer, different approaches should be considered by oncologists. Yes, we could use mice models to do this. However, they lack a human’s immune response and don’t reflect the real disease in the best way. Patient-derived organoids would give doctors the best information on what works best, possibly lowering the cost and shortening the time of therapy.

Let’s go back to the beginning. What if I told you, that we can put drugs through clinical trials faster and for less money, that we can screen drug-to-drug interactions and its threats, and that we can actually prepare personalized cancer therapies? Sounds like science fiction? Not anymore, not with organoid technology.

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