From Swiss Federal Institute of Technology in Zürich [ETH Zürich] [Eidgenössische Technische Hochschule Zürich] (CH): “Computer algorithms are currently revolutionising biology”

From Swiss Federal Institute of Technology in Zürich [ETH Zürich] [Eidgenössische Technische Hochschule Zürich] (CH)


Artificial intelligence can help predict the three-​dimensional structure of proteins. Professor Beat Christen describes how such algorithms should soon help to develop tailored artificial proteins.

Computer algorithms have been a helpful tool in biomedical research for decades, and their importance has been growing steadily over that time. But what we’re now experiencing is nothing short of a quantum leap; it overshadows all that came before and it will have unforeseen effects. Artificial intelligence (AI) algorithms have made it possible to use nothing but the linear sequence of the building blocks of proteins – amino acids – to deliver extremely accurate predictions of the three-​dimensional structure into which this chain of amino acids will assemble.

Grasping the importance of this development hinges on knowing that biology on a cellular level is actually always about spatial interactions between molecules – and that it’s the three-​dimensional structure of these molecules that determine those interactions. Once we understand the structures and interactions in play, we understand the biology. And only once we understand the structure of molecules can we engineer medications capable of influencing the function of these molecules.

Proteins are thread-​like molecules that assemble to form a specific three-​dimensional structure. (Visualisation: Shutterstock)

Up to now, there have been three experimental methods for determining the three-​dimensional structure of proteins: X-​ray structure analysis, nuclear magnetic resonance and, just in the past few years, cryo-​electron microscopy. The addition now of AI as a fourth precision method is due not just to improvements in AI algorithms and the vast computing power that is available today. For AI to make accurate predictions, it also needs to be trained using a wealth of data of exceptional quality. What makes the abovementioned quantum leap possible is considerable progress and effort in both data science and experimental protein research.

Competition between private and public research

Currently occupying most of the spotlight is the AlphaFold AI program developed by DeepMind, a sister company of Google. At present, DeepMind is undoubtedly the most important player in predicting protein structures. But what gets lost in the public discussion is that DeepMind is by no means the only player in this area; in particular the team led by David Baker from the University of Washington (US) is conducting some outstanding research.

Overall, this competition between private and public research has surely served to inspire and invigorate the field, even if, as one would expect, private players keep many of their insights to themselves to protect their own business interests. But highly competitive research has also led to vast improvements to the AI algorithms that are in the public domain, which the entire scientific community can now use and develop. I expect this trend to continue. AI algorithms will soon provide us with highly precise structures for all known proteins. This will enable us to design precision medications on the computer.

In the future, it should be possible to start from a three-​dimensional molecular scafold designed on a computer and employ AI to calculate a sequence of amino acids that will precisely assemble into the desired structure with the desired molecular function.

Once this sequence of amino acids has been determined, my area of research comes into play. My work deals with the development of artificial genes and genomes, and it also employs computer algorithms. Based on sequences of amino acids, we calculate how protein information can be encoded into sequences of genetic building blocks – in other words into DNA. And we do it in a way that provides a simple means of synthesising these genes for practical applications.

Reversing the information flow

This means we are on the verge of being able to calculate an artificial gene for any given three-​dimensional protein structure designed on a computer, and then synthesise that gene. In biotechnology, this paves the way for manufacturing artificial proteins in microorganisms – including new pharmaceutical agents, vaccines or enzymes for use in industry.

Ever since the earliest lifeforms emerged several billion years ago, to this day biological information has always been stored in the form of DNA. Inside biological cells, this information is transcribed– first into RNA molecules, and then translated into proteins. Until now, there has been no mechanism for reversing the flow of information such that protein information is translated back into DNA information. AI will soon change all that. For biologists such as myself, this is an incredibly spectacular development, one that will have a profound impact on biotechnology and medicine.

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ETH Zurich campus
Swiss Federal Institute of Technology in Zürich [ETH Zürich] [Eidgenössische Technische Hochschule Zürich] (CH) is a public research university in the city of Zürich, Switzerland. Founded by the Swiss Federal Government in 1854 with the stated mission to educate engineers and scientists, the school focuses exclusively on science, technology, engineering and mathematics. Like its sister institution Swiss Federal Institute of Technology in Lausanne [EPFL-École Polytechnique Fédérale de Lausanne](CH) , it is part of the Swiss Federal Institutes of Technology Domain (ETH Domain)) , part of the Swiss Federal Department of Economic Affairs, Education and Research [EAER][Eidgenössisches Departement für Wirtschaft, Bildung und Forschung] [Département fédéral de l’économie, de la formation et de la recherche] (CH).

The university is an attractive destination for international students thanks to low tuition fees of 809 CHF per semester, PhD and graduate salaries that are amongst the world’s highest, and a world-class reputation in academia and industry. There are currently 22,200 students from over 120 countries, of which 4,180 are pursuing doctoral degrees. In the 2021 edition of the QS World University Rankings ETH Zürich is ranked 6th in the world and 8th by the Times Higher Education World Rankings 2020. In the 2020 QS World University Rankings by subject it is ranked 4th in the world for engineering and technology (2nd in Europe) and 1st for earth & marine science.

As of November 2019, 21 Nobel laureates, 2 Fields Medalists, 2 Pritzker Prize winners, and 1 Turing Award winner have been affiliated with the Institute, including Albert Einstein. Other notable alumni include John von Neumann and Santiago Calatrava. It is a founding member of the IDEA League and the International Alliance of Research Universities (IARU) and a member of the CESAER network.

ETH Zürich was founded on 7 February 1854 by the Swiss Confederation and began giving its first lectures on 16 October 1855 as a polytechnic institute (eidgenössische polytechnische Schule) at various sites throughout the city of Zurich. It was initially composed of six faculties: architecture, civil engineering, mechanical engineering, chemistry, forestry, and an integrated department for the fields of mathematics, natural sciences, literature, and social and political sciences.

It is locally still known as Polytechnikum, or simply as Poly, derived from the original name eidgenössische polytechnische Schule, which translates to “federal polytechnic school”.

ETH Zürich is a federal institute (i.e., under direct administration by the Swiss government), whereas the University of Zürich [Universität Zürich ] (CH) is a cantonal institution. The decision for a new federal university was heavily disputed at the time; the liberals pressed for a “federal university”, while the conservative forces wanted all universities to remain under cantonal control, worried that the liberals would gain more political power than they already had. In the beginning, both universities were co-located in the buildings of the University of Zürich.

From 1905 to 1908, under the presidency of Jérôme Franel, the course program of ETH Zürich was restructured to that of a real university and ETH Zürich was granted the right to award doctorates. In 1909 the first doctorates were awarded. In 1911, it was given its current name, Eidgenössische Technische Hochschule. In 1924, another reorganization structured the university in 12 departments. However, it now has 16 departments.

ETH Zürich, EPFL (Swiss Federal Institute of Technology in Lausanne) [École polytechnique fédérale de Lausanne](CH), and four associated research institutes form the Domain of the Swiss Federal Institutes of Technology (ETH Domain) [ETH-Bereich; Domaine des Écoles polytechniques fédérales] (CH) with the aim of collaborating on scientific projects.

Reputation and ranking

ETH Zürich is ranked among the top universities in the world. Typically, popular rankings place the institution as the best university in continental Europe and ETH Zürich is consistently ranked among the top 1-5 universities in Europe, and among the top 3-10 best universities of the world.

Historically, ETH Zürich has achieved its reputation particularly in the fields of chemistry, mathematics and physics. There are 32 Nobel laureates who are associated with ETH Zürich, the most recent of whom is Richard F. Heck, awarded the Nobel Prize in chemistry in 2010. Albert Einstein is perhaps its most famous alumnus.

In 2018, the QS World University Rankings placed ETH Zürich at 7th overall in the world. In 2015, ETH Zürich was ranked 5th in the world in Engineering, Science and Technology, just behind the Massachusetts Institute of Technology(US), Stanford University(US) and University of Cambridge(UK). In 2015, ETH Zürich also ranked 6th in the world in Natural Sciences, and in 2016 ranked 1st in the world for Earth & Marine Sciences for the second consecutive year.

In 2016, Times Higher Education World University Rankings ranked ETH Zürich 9th overall in the world and 8th in the world in the field of Engineering & Technology, just behind the Massachusetts Institute of Technology(US), Stanford University(US), California Institute of Technology(US), Princeton University(US), University of Cambridge(UK), Imperial College London(UK) and University of Oxford(UK) .

In a comparison of Swiss universities by swissUP Ranking and in rankings published by CHE comparing the universities of German-speaking countries, ETH Zürich traditionally is ranked first in natural sciences, computer science and engineering sciences.

In the survey CHE ExcellenceRanking on the quality of Western European graduate school programs in the fields of biology, chemistry, physics and mathematics, ETH Zürich was assessed as one of the three institutions to have excellent programs in all the considered fields, the other two being Imperial College London(UK) and the University of Cambridge(UK), respectively.