October 10, 2019

A map of humankind from the inside out—the Human Protein Atlas

By Conor McKechnie and Dodi Axelson

A map of humankind from the inside out—the Human Protein Atlas

We humans have been mapping things since the beginning of time. In this episode, Dodi takes Conor on an explorer’s journey—destination: the Human Protein Atlas project. Strap on your seatbelt; it might get bumpy visiting explorers, chemists…and even sociologists.

DODI : Conor, you're fond of saying to your team every day's a school day.

CONOR : Yeah, I know. Oh my God. I say that all the time. But you know what, I'm deadly serious. Every day is a school day.

DODI : And do you remember how you learned things when you were younger?

CONOR : No. How much younger? I mean maybe fast, I'd like to think, but probably not. I might have been a bit dumb.

DODI : Super young. We're talking kindergarten, like learning the ABCs young.

[Classic ABCs song]

DODI : Yeah, that young. You know, the ABC's are so foundational. Everybody knows them, but there are also countless versions of the ABC song.

[Another version of the ABCs song]

CONOR : So, lots of different songs because music helps us learn. It helps us, you know, memorize things. Is that right?

[Same song as previous]

DODI : I think it does. And then when it comes to more advanced learning, music can also help like the periodic table, for example.

[Periodic table song]

CONOR : Okay. Even with the song, that's a tough one, but somehow, you're going to tell me why that matters.

DODI : I am going to tell you, and with Conor McKechnie

CONOR : and with DODI Axelson, this is Discovery Matters.


CONOR : So Dodi, periodic table. It's about classification. ABCs is about kind of helping us build the blocks of how we make words. You could say the periodic table is about understanding the blocks of chemistry and how we build compounds. Is that where you're going with this?

DODI : That is exactly. So the ABC's language keeps on growing, language keeps on giving. So does the periodic table.

AMANDA HALFORD : The periodic table is a way to classify all the elements that have been discovered in our universe. And it has a really long history. My name is Amanda Halford.

DODI : Amanda is our General Manager of Commercial for the U.S., Canada, Europe, and Global Services. And at her foundation, she's a chemist. When she says that the periodic table has a long history, she means long.

[Calming song]

AH : I mean, we can go all the way back to Aristotle who's tried to classify things by earth [earth sounds], wind [wind sounds], fire [fire sounds] and water [water sounds]. The alchemists, they were classifying things by sulphur, mercury and salt. And the first element was actually only discovered in around 1649. So, you can see that for a long time we really didn't know what the things were around us, and we had no way of naming them or understanding how they act in.

CONOR : I love the fact that she went to Aristotle. I mean, that's just brilliant. So, the periodic table helps us make sense of the world in the way. Linnaeus helped us make sense of, you know, biological genus and species and so on. Is that what we're doing?

AH : Well, that's what it's helped us do. It's helped us understand all of the things around us and how they function and how they contribute to life. And it's helped us understand what happens when you mix them together. How you create new compounds, which have given as many of the things we have today. Just look at the clothes that you wear, the textiles, the dyes, your mobile phones, full of some of the newer elements that we have been able to develop with this technology. So yes, it's helped us to understand the world around us and create new things that are useful for us today.

[Piano music]

AH : So let's go back. It was 150 years this year that the periodic table was first presented by Dmitri Mendeleev to the Russian chemical society. So back in 1869, he presented the first few of the periodic table and he'd sort of made it his life's mission to organize the study of chemistry. He really wanted to put some structure around it to help us understand, and he came up with the periodic table. Which consisted of the rows, in the horizontal way, and the groups that are the vertical columns. So, he collected up the known elements by certain properties, and that was their electrons, the number of electrons that were in their outer shell and so he collected this, the group of known elements. And he saw the gaps. And so he predicted, he had the hypothesis that these gaps actually represented elements that were not know, said that they existed around us, but we just hadn't discovered them.

DODI : And it seems the periodic table is also serving as a model for organizing other parts of our nature. So this got me thinking about another piece of history, that of explorers.

[Marching music]

CONOR : So explorers like Columbus and Marco Polo, is that who you mean?

DODI : Exactly. Specifically, the maps they used. Maps and atlases.

CONOR : The really interesting thing about the maps that Columbus used and that Marco Polo used and so on was not what they had mapped but what they hadn't mapped. It was the gaps. It was filling in the gaps that drove them.

DODI : And I've been wondering if we as human beings with our maps and atlases and periodic table like is that just a basic need to do that?

MATHIAS UHLÉN : I don't think we need to do it, but I think a human being has a, a natural curiosity and natural lust for adventure and going into new territory. I think at least some people are very, very keen to do that. And are you know, driven by that. My name is Mathias Uhlén. I'm a professor at the Royal Institute of Technology but also at the Karolinska Institute here in Stockholm.

CONOR : So help me here because we now got a professor of life sciences what that's got, what's that got to do with maps and gaps and atlases and filling in knowledge.

DODI : So 20 years ago, Mathias was given a grant by the famous Swedish philanthropic family, the Wallenbergs, and he used that money to start something kind of similar to the periodic table, but for the human body. He called it the protein atlas project. And you're going to see how the maps in atlas is come in here. And basically what the protein atlas project does is go through all the proteins in the human body.

MU : These 20 000 proteins is what we tried to map and try to understand where are they in the body. And then also ultimately how do they interact with each other. And then of course in the end also to try to understand the function of them, but our part of that is very much the mapping part. And that is where are these proteins, which ones are in the brain and which ones are in the liver and so on. And that's what we are doing, we have our own technology to do it. And all the information that we gather is then goes out on the public database, called The Human Protein Atlas, which is now visited by many, many, well 300 000 researchers every month. So it's, it's a good basis for these researchers that wants to understand human biology, but also if they want to develop drugs for different diseases, it's very good to look in the protein atlas. Because when you go to pharmacy in Sweden, in Stockholm, in Göteborg or in New York, and you go in and you, you buy a pill or you get, you know, some sort of injectables, they are all, more or less all of them directed to proteins. So, knowing about the proteins is to know about diseases, knowing about drugs and also know about future drugs.

DODI : And Mathias says in the last 20 years, there's been a kind of silent revolution.

MU : A lot of the drugs now that are selling very well are these very directed drugs. Which actually is proteins themselves and you inject them into to patients and they have a very direct and very dramatic sometimes function for and to cure diseases.

DODI : Discovery matters is here to tell you that we're a fan of seedinglabs.org. Seeding labs donates research equipment to deserving institutions that would otherwise lack access to scientific instruments. You like them, don't you Conor?

CONOR : I do. It’s just an absolutely fantastic organization. And if you have lab instruments which are nearing the ends of their useful life, or you have one languishing somewhere that doesn't get used, you're able to donate it to researchers in the developing world and in lower resource settings who otherwise might not have access to scientific equipment to support them in their research.

DODI : So don't languish. Donate. Seedinglabs.org. Let's get back to Discovery Matters.

CONOR : So where did this idea come from for Mathias, the idea of a protein atlas?

DODI : So remember I said Mathias started this project 20 years ago and it turns out he's been mapping for a while. Before this project he was part of what's known in acronym speak as the H G P. You know what that is, don't you?

CONOR : I do, I hate, I hate acronyms, but the Human Genome Project I love. A huge effort by a group of international scientists that mapped all of the human genes.

DODI : Exactly. So in the early two thousands, when the human genome project was about to finish up, Mathias was thinking, you know, “okay, so what's next?” And what he figured out was that he wanted to try and understand the genes that had been determined by that project.

MU : This was considered so difficult. So I don't think that anyone dared to do it, but we had this idea that we can do this through a very factory-style way. And that's what we proposed to the Wallenbergs Foundation. And fortunately for me, they thought it was a good idea, but they didn't trust me completely. So they said, you know, we give you three years to prove that you can do this in a pilot. And after three years then they continued and they’ve been very generous, and have supported this now for 20 years.

DODI : So again, we're talking about gaps that drive science forward. And antibodies became a focus for Mathias. So that is a concrete example of a particular forward motion in finding a cure or treatment that Mathias can track back to is protein atlas research.

MU : Which is a proteins that are sort of targeting, it's a defense molecule in the human body and all the work is based on that. And we have done, started I think four now companies which are actually trying to make antibodies for different diseases. So, we have just starting a clinical trial now in China for gastric cancer where we have an antibody to fight gastric cancer. We have started, we have here in Stockholm an antibody-like molecule towards Alzheimer's, that we're hoping to go into clinical trials with. We also have through this knowledge, developed some cocktails that we think is good for something called fat liver disease, which is a very common disease in the Western world. Where the liver stops functioning. So, there are several examples of these kind of spin-outs that we're working on.

DODI : This protein atlas research is popular. In fact, every single pharmaceutical company is using this protein atlas.

CONOR : What? Every single one? How can he be so sure that everyone, everywhere is using this atlas?

MU : Because we know. We’re tracking the people that goes into our, and we see that there are researchers from all the pharmaceutical companies going in every day.

CONOR : Wow. That's just incredible. So when can Mathias expect this map, this protein atlas to be complete? Because that's what we were looking for, isn't it? We'd like to fill in the gaps. When will we be able to say there are no more gaps. We understand all the proteins and what they do.

MU : We have, you know, a different, how should I say, different flagship products that are kind of finished. So four years ago we finished a first map of all the tissues, tissues and organs. Where are the proteins in the different parts of the human body? Two years ago, we went into the cell and made a cell atlas where we say, where are the proteins in the smallest, you know, living part, the cell. And then we've also made a cancer atlas about one year ago. So we’re constantly adding information to this. But I don't think it will ever be finished, and I hope that even after we maybe have stopped this product together with the Wallenberg Foundation that others will take on and then develop this further. Because obviously this is what happened with the periodic table back in the, you know, a 150 years ago you started to fill in the missing pieces, but I guess in this case it was kind of finished. But I think when it comes to the periodic table of human beings, it will take a hundred years to, you know, to make it complete.

DODI : Conor, you're frowning just a little bit.

CONOR : Yes. I mean the, with complete knowledge, I mean, in so far as it will ever be complete comes great responsibility. So is there this ethical question that we often throw around, which is what might we do if we knew everything that every single protein did in terms of using that to better human life in ways that maybe we shouldn't?

DODI : Yeah, Mathias and I talked about that kind of situation. He actually doesn't think that will happen.

MU : I hope not. I'm not a very big proponent of trying to change us and make us better. I think that, clearly when human being, when we have a deficient protein, we call it genetic diseases. Then of course it could be nice to be able to go in and correct it and make that, you know, gene protein correct again for that. But in order to make super humans, I think life is a, and human beings are so complex that it's going to be very hard to do that.

DODI : Mathias thinks that even if we have a map or an atlas of ourselves, he's not sure if we'll ever deeply understand every single bit about ourselves. We are forever mysterious. And one good example of this is Mathias is now planning to put out a brain atlas, in the very near future.

MU : We will describe exactly what are the proteins which are in different parts of the human brain and, and others have shown how they interact and there's a lot of, you know, thousands of groups mapping and trying to understand the function of each one of them. And yet we know very little about the brain. And I think it's kind of nice. We still, it's still kind of a mystery, how the brain works, and certainly, there's a lot of mysteries that we'll be unsolved for a long time. But that's of course nice because it means that there’s a lot of things to, to do research for in the future.

CONOR : A brain atlas. Wow.

DODI : I know it's super trippy and Mathias is not stopping with the brain. He has a couple of other mapping milestones that he wants to explore this year in 2019 alone.

MU : A lot of the drugs, but also a lot of the diagnostics are towards the blood proteins and blood cells. And a lot of the new biologicals are directed towards blood cells and immune oncology and immunotherapy and so on. So, another very big launch this year is a blood atlas, where we will be mapping both the cells and the proteins in the human blood. And then we also have a third launch. And that is together with Chalmers in Göteborg, Jens Nielsen’s group there. Where they have done a metabolic atlas. And that is what are the small molecules which are generated by enzymes in the body and where are they in the different parts of the body and which ones are produced.

DODI : I think one day we're going to remember Mathias Uhlén the way we remember Mendeleev today. Because there's so much significance, not just in identifying things and identifying relationships between them, but also seeing where the gaps are going to be filled later on. It's fascinating.

CONOR : Okay! This is absolutely incredible. So in less than 20 minutes, we've gone from the history of the periodic table to how it can help us make sense of the world. And then in turn inspire projects such as Mathias' protein atlas. You started with the ABCs. It's extraordinary. What a, what a journey.


DODI : Everything, everything starts with that fundamental basic logic, right? So how, how to put things together to make words into communicate ideas. That starts with the ABCs. Then when you start looking at math and physics and chemistry, you know, there's that famous comic.

CONOR : Where the entirety of science is built on a series of different foundations. So math's underlies it all on which on top of which you can build physics on top of which you can build chemists and chemistry and on top of which, you know, biologists and there beyond that. You know, psychologists and dare I say it, sociologists.

DODI : You did just dare say it and because we dare go there on Discovery Matters…

CONOR : Did I just link math’s to sociology?

DODI : You did! You did. So maybe we should, you know, Conor can be reached at Conor. Dot….


CONOR : Yeah, you can tweet me complains…

DODI : …for complaints, send them directly…

CONOR : Tweet me in anger @Conorato. I promise to be nice to anybody who's an ist. Or maybe not the misogynists. I won't be nice to you.

DODI : Don't be nice to them.

DODI : So Discovery Matters is pleased to take you from the very foundations to wherever our curiosity takes us.

DODI : Discovery matters is produced in collaboration with Soundtelling. Our executive producer is Andrea Kilin production and music by Thomas Henley. Thank you for listening.

CONOR : And we will see you next time on Discovery Matters.


Our executive producer is Andrea Kilin. Discovery Matters is produced in collaboration with Soundtelling. Production and music by Thomas Henley.