Who builds CRISPR machines

UZH magazine

Martin Jinek is one of the protagonists of the Crispr revolution. The biochemist made a significant contribution to the development of the Crispr-Cas9 gene scissors, with which genetic material can be changed easily, quickly and precisely.

From Stefan Stöcklin

Martin Jinek is a reserved and polite person. But when he comes to He Jiankui, the biochemist is unmistakable: "He carried out irresponsible experiments that harm children and science." By manipulating early embryos, the Chinese researcher last year irrevocably changed human genome for the first time. With genetic scissors called Crispr-Cas9, which Martin Jinek helped develop. It allows genetic material to be changed easily, quickly and precisely. That is why the Crisp-Cas9 technology has established itself in science within a very short time.

He Jiankui's intervention is a taboo break. Jinek followed the conference in Hong Kong at which the misguided Chinese researcher explained his experiments to the professional community - calmly and with obvious pride. “I listened with a mixture of disbelief and disapproval,” Jinek recalls. And is still annoyed by the irresponsibility and audacity of the scientist. Although an independent verification is still pending months after the performance, hardly anyone doubts that He, who has since been submerged, carried out the experiments as claimed.

Breakthrough in California

Martin Jinek's office on the Irchel campus is sparkling clean, the few books are neatly lined up. In one corner is a bass guitar with an amplifier, one of the few distractions the researcher allows himself. Otherwise, the room appears sober, reduced to the essentials, a space for new ideas and exciting experiments. As a researcher, Jinek's reputation is closely linked to the Crispr-Cas9 gene editing method. It is true that his name is not mentioned first when the revolutionary method is mentioned. Jennifer Doudna, Emmanuelle Charpentier and Feng Zhang are considered to be inventors. But Jinek carried out crucial experiments as a postdoc in Doudna's Californian laboratory and published them in 2012 in the journal “Science”. The publication paved the way for a broad application of the method, which is now used worldwide to manipulate human, animal, plant or bacterial cells, primarily for research purposes - and secondarily for the treatment of genetic diseases.

The work fueled the scientific career of Jinek: He is the winner of several prizes, at 39 years Associate Professor at the Biochemical Institute, networked worldwide, group leader of a team of 14 and a sought-after expert in specialist committees and media. No wonder he is “extremely satisfied with the way things have gone”. He can get over the fact that the former boss Doudna and other people are more in the spotlight. “That's how science works,” he says. In addition, the relevant experts in the field know very well how crucial his contribution was effectively.

Martin Jinek was not born with a scientific career. He comes from a provincial town in the northeast of today's Czech Republic. He was already interested in natural science subjects at school, but so were languages, especially English. This was unusual in the former Czechoslovakia in the mid-1980s and owed to the father, who politically oriented himself more towards the west than towards the east and encouraged the son to learn English. The knowledge enabled the 17-year-old to successfully apply for a high school scholarship in Reading, UK. The English boarding school was then the springboard for the gifted student to the renowned Trinity College in Cambridge, where he studied chemistry and natural sciences.

Biological machines

“I'm interested in the chemistry of living cells, more precisely the molecular mechanisms of biomolecules,” says Jinek in accent-free English. If one imagines the important biomolecules of a cell as a kind of machine which, thanks to its atomic structure, can perform certain tasks, then knowing their spatial structures provides insight into how they work. Structural changes are particularly revealing when different molecules interact with one another. For example, the genome molecules DNA and RNA with proteins, because genetic information is activated or deactivated during these processes. "Only by knowing the structures can we understand the processes in cells," says Jinek.

During his first research work as a student in Kyoshi Nagai's laboratory in Cambridge, Martin Jinek dealt with the structures of biomolecules and their functions: "Nagai sparked this passion in me." Later, during his doctoral thesis in Elena Conti's laboratory in Heidelberg, he studied the activity of enzymatic proteins. Then the nucleic acid RNA moved into focus, because the single-stranded molecule is biologically more interesting than the double-stranded DNA, Jinek believes. In Jennifer Doudna's laboratory, he worked on another project without success before he became aware of the Crispr topic. Jinek scrutinized the system from a structural biology perspective and landed his big coup in 2012. Immediately after this scientific climax, he joined the UZH Biochemical Institute as an assistant professor. Since then he has built up his own group step by step and publishes at a high rate. "The interactions between RNA and proteins, which are also important for Crispr, remain my hobbyhorse," says Jinek.

The researcher, who lives in Basel and commutes to his place of work, seems well organized and weighs up his answers. Both in temperament and outward appearance, Jinek is the pure opposite of an absent-minded professor who loves chaos. There is not only order in the office, the laboratories also make a great impression. As can be heard, Jinek and his team occasionally organize laboratory cleaning days. When asked what constitutes good science, he refers to his teachers. “From them I learned to ask the right questions. And to tackle these questions with the right experiments. " A motto that he has internalized and tries to pass on to his employees. Apparently with success, because he is considered a good mentor.

Cure genetic ailments

Hey Jiankui, you might say, asked the wrong questions. Because the Crispr-Cas9 system is not yet reliable enough to rule out undesirable genetic effects. "The interventions are not only dangerous for the children, they were medically unnecessary," says Jinek. The protection against HIV intended by He could have been achieved differently in this case. Breaking ethical taboos is more problematic, because genetic manipulation is passed on to future children of those affected. Germ line therapies are banned in most countries, including Switzerland. "We should adhere to this ban," says Jinek.

The researcher does not feel responsible for the colleague's crossing of boundaries. "Scientific knowledge can always be misused," he says. And refers to the useful medical applications that are made possible thanks to the gene scissors. In addition to his basic research, Jinek is working with various colleagues on optimizing the Crispr system to cure certain cancers and genetic diseases. In these cases, the planned interventions only affect somatic cells and therefore not subsequent generations. Martin Jinek is convinced that “Crispr-Cas9 brings medical progress”. For him it is clear: the genetic scissors will hold their own, despite the errant He.