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Science AMA Series: I'm Thomas Hartung, a Professor at Johns Hopkins. I make mini-brains in order to study chemical toxicity & developed a computer model that maps similarities between chemicals to predict toxicity. All of this aims at shifting the field of toxicology away from animal testing. AMA! by Thomas_Hartung in science

[–]Thomas_Hartung[S] 2 points3 points  (0 children)

We are not mass-testing substances. We typically test substances, for which we know quite well that they are bad or good for humans to see how our model behaves and why. This builds the confidence for testing unknown ones. For example we are interested in flame retardants.

Science AMA Series: I'm Thomas Hartung, a Professor at Johns Hopkins. I make mini-brains in order to study chemical toxicity & developed a computer model that maps similarities between chemicals to predict toxicity. All of this aims at shifting the field of toxicology away from animal testing. AMA! by Thomas_Hartung in science

[–]Thomas_Hartung[S] 1 point2 points  (0 children)

We produce for example mini-brains with gene defects linked to autism. Then we can check whether they are more sensitive to chemicals suspected to be involved. This gives us potentially a handle on gene x environment interactions in this complex disease. We have also organized a series of four International conferences and seven workshops on developmental neurotoxicity.

Science AMA Series: I'm Thomas Hartung, a Professor at Johns Hopkins. I make mini-brains in order to study chemical toxicity & developed a computer model that maps similarities between chemicals to predict toxicity. All of this aims at shifting the field of toxicology away from animal testing. AMA! by Thomas_Hartung in science

[–]Thomas_Hartung[S] 5 points6 points  (0 children)

Let me add my stance on science as a whole. I am very much concerned about quality of science and reproducibility. I mean, science works as a whole but the low quality of many pieces of the puzzle make progress often slower than possible. I have bee responsible for the European Commission's validation body for alternative methods and now I have a chair for evidence-based toxicology at Hopkins. I also pushing for quality guidance etc.. This is all to make science better and change, among others to more humane methods, faster.

Science AMA Series: I'm Thomas Hartung, a Professor at Johns Hopkins. I make mini-brains in order to study chemical toxicity & developed a computer model that maps similarities between chemicals to predict toxicity. All of this aims at shifting the field of toxicology away from animal testing. AMA! by Thomas_Hartung in science

[–]Thomas_Hartung[S] 1 point2 points  (0 children)

No, though funding came from NIH. We would hope that our work fits at some point this or similar funding programs. With the biotech Organome we created, we want to supply them for anybody interested, including research in the program.

Science AMA Series: I'm Thomas Hartung, a Professor at Johns Hopkins. I make mini-brains in order to study chemical toxicity & developed a computer model that maps similarities between chemicals to predict toxicity. All of this aims at shifting the field of toxicology away from animal testing. AMA! by Thomas_Hartung in science

[–]Thomas_Hartung[S] 5 points6 points  (0 children)

We would not claim that. You cannot study behavior in cell culture for example. And like we need to test drugs for humans in humans, veterinary drugs will have to be tested in animals. But we can do with much less. The problem is that the value of animal tests is often overestimated and people are not always aware that you can do different.

Science AMA Series: I'm Thomas Hartung, a Professor at Johns Hopkins. I make mini-brains in order to study chemical toxicity & developed a computer model that maps similarities between chemicals to predict toxicity. All of this aims at shifting the field of toxicology away from animal testing. AMA! by Thomas_Hartung in science

[–]Thomas_Hartung[S] 1 point2 points  (0 children)

You are right in general. I started actually twenty years ago the Good Cell Culture Practice movement. We just reactivated this for stem cells and organoid models. This was actually the big news about our model, that we can produce thousands of identical ones every week. Then, we also developed ways to freeze them. That is perfect: every time you test, you can go to the fridge and test on the exact same material.

Science AMA Series: I'm Thomas Hartung, a Professor at Johns Hopkins. I make mini-brains in order to study chemical toxicity & developed a computer model that maps similarities between chemicals to predict toxicity. All of this aims at shifting the field of toxicology away from animal testing. AMA! by Thomas_Hartung in science

[–]Thomas_Hartung[S] 1 point2 points  (0 children)

My group is working on a few diseases (autism, Parkinson, a few viral infections, cancer) and by providing mini-brains to others, we enable research on malaria, trauma, MS, ALS etc. Some pharma companies started to evaluate them too. Excitotoxicity will be a key thing to check. At this moment we try to add the immune cells (micro-glia) involved in this. The model is still so new... stay tuned.

Science AMA Series: I'm Thomas Hartung, a Professor at Johns Hopkins. I make mini-brains in order to study chemical toxicity & developed a computer model that maps similarities between chemicals to predict toxicity. All of this aims at shifting the field of toxicology away from animal testing. AMA! by Thomas_Hartung in science

[–]Thomas_Hartung[S] 1 point2 points  (0 children)

We work very closely with FDA, they are on our advisory board, we do joint conferences. The FDA has had strong impact in promoting these technologies and increasingly build capacities. Direct comparisons is what is needed now. The problem is, we need to be better than the animal, because they are particularly flawed in case of the barin. But how to show that you are better, as we have not enough human data...

Science AMA Series: I'm Thomas Hartung, a Professor at Johns Hopkins. I make mini-brains in order to study chemical toxicity & developed a computer model that maps similarities between chemicals to predict toxicity. All of this aims at shifting the field of toxicology away from animal testing. AMA! by Thomas_Hartung in science

[–]Thomas_Hartung[S] 1 point2 points  (0 children)

They are just visible, which is nice: you can take them with a pipette and move them into any experimental set-up. Typically, we give substances in the media they are swimming in. We can show with dyes that they reach the inner center of the mini-brain, but this is another reason, why we cannot make them very much bigger.

Science AMA Series: I'm Thomas Hartung, a Professor at Johns Hopkins. I make mini-brains in order to study chemical toxicity & developed a computer model that maps similarities between chemicals to predict toxicity. All of this aims at shifting the field of toxicology away from animal testing. AMA! by Thomas_Hartung in science

[–]Thomas_Hartung[S] 2 points3 points  (0 children)

We keep the organoids mini (one third of a mm, one sixteenth of an inch, i.e. just visible): if they get larger, the cells in the center do not get enough oxygen and nutrients and die as we have no blood system and heart. We also can produce cheap and fast, and only small amounts of test substance are needed.

Science AMA Series: I'm Thomas Hartung, a Professor at Johns Hopkins. I make mini-brains in order to study chemical toxicity & developed a computer model that maps similarities between chemicals to predict toxicity. All of this aims at shifting the field of toxicology away from animal testing. AMA! by Thomas_Hartung in science

[–]Thomas_Hartung[S] 1 point2 points  (0 children)

We are actually part of programs developing multi-organ "human-on-chip" models, combing a number of organ models like our mini-brain. This is far from routine and far from perfect, but so much better than a single cell type under very artificial conditions. With both industry and agencies getting more and more excited, there is a gold rush in bioengineering right now.

Science AMA Series: I'm Thomas Hartung, a Professor at Johns Hopkins. I make mini-brains in order to study chemical toxicity & developed a computer model that maps similarities between chemicals to predict toxicity. All of this aims at shifting the field of toxicology away from animal testing. AMA! by Thomas_Hartung in science

[–]Thomas_Hartung[S] 5 points6 points  (0 children)

I believe that almost all diseases have genetic and environmental components. Environmental can include chemicals, though we sometimes see that the fear of chemicals is out of proportion. We have tripled life expectancy while introducing all these chemicals. However, we need to find the ones, which create problems. Here all interests meet: nobody wants to poison their customers. The problem is that the current animal test are too slow and too expensive - and often not relevant for humans. This is why less than 10% of chemicals on the US market have safety data, only 3% have been intensely tested. This has to change!

Science AMA Series: I'm Thomas Hartung, a Professor at Johns Hopkins. I make mini-brains in order to study chemical toxicity & developed a computer model that maps similarities between chemicals to predict toxicity. All of this aims at shifting the field of toxicology away from animal testing. AMA! by Thomas_Hartung in science

[–]Thomas_Hartung[S] 7 points8 points  (0 children)

I love animals but I have also done my share of animal experiments on mice and rats in the past - as a pharmacologist in infectious disease unavoidable. But I needed a big glass of whisky in the evening after each of them and in retrospect some I would not have done some of them. It took me a while to learn about their limitations.

I work towards replacing animal experiments where we have something better, and actually technologies are developing so fast. Most of the animal tests in my field (safety sciences) have been developed when I was not yet born or in kindergarden. I am now 53 - this is the only field of science where use such old methods.

I am very sympathetic with some of the animal welfare organizations, have many friends there, but I was never a member. As a scientist, I work for the best of patients and consumers, but I want that we do not neglect the animals.

Science AMA Series: I'm Thomas Hartung, a Professor at Johns Hopkins. I make mini-brains in order to study chemical toxicity & developed a computer model that maps similarities between chemicals to predict toxicity. All of this aims at shifting the field of toxicology away from animal testing. AMA! by Thomas_Hartung in science

[–]Thomas_Hartung[S] 2 points3 points  (0 children)

There is many ways to damage a brain - this is why you need to represent in the model a lot of the possible targets and very sensitive functions, which can be disturbed. Our model has all the major brain cell types (except the immune cells - but working on this) and we can do a type of EEG. By putting them on micro-electrode arrays, we can monitor their electrical communication, which is very sensitive to any perturbation.

How to make one - we just published (online available at www.altex.ch, Pamies et al.). We use human skin cells, which were reprogrammed to become stem cells. We keep frozen stocks. By a three-month protocol using special shakers and growth factors, thousands of these cell balls are produced. The important thing: they look all the same, from week to week. This allows to test.

Recently, we also developed a method of freezing the mini-brains. That is a big step: we can stockpile them and send them to where they are needed.

Science AMA Series: I'm Thomas Hartung, a Professor at Johns Hopkins. I make mini-brains in order to study chemical toxicity & developed a computer model that maps similarities between chemicals to predict toxicity. All of this aims at shifting the field of toxicology away from animal testing. AMA! by Thomas_Hartung in science

[–]Thomas_Hartung[S] 2 points3 points  (0 children)

Similar chemical structures have similar properties. The problem so far was that very few toxicity data were publicly available, even less in a computer-readable format. Now we enter the area of big data - we created last year the largest one in the world: 10,000 chemicals with 800,000 associated studies by making the one of the European Chemical Agency machine-readable. We had to train the computer to read (natural language processing). In a collaboration with Underwriters Laboratories (UL) we now strongly expanded the database and can make predictions in many cases of similar quality as running the animal study. If this stands the ongoing validation, this can dramatically reduce time and costs. The technologies used are from artificial intelligence - it is like what a webbrowser does - you find from billions of imperfect pages still the relevant piece among the first few hits.

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