Quest to control our genes by the power of thought
The power to control living cells by treating molecules like switches or transistors has been established in principle. Synthetic biologists think we might be on the verge of reorganizing life itself, but will we really reach a point where our minds can order our genes to behave? Award-winning bio-engineer, Prof. Martin Fussenegger, talk to Dermot Martin for Laboratory News on the New World of Bioinformatics Technology.
“Being able to control gene expression through the power of thought is a dream we have been pursuing for over a decade. “
Professor Martin Fussenegger, 2014
In two generations, the world has been totally transformed thanks to the silicon revolution and the rapid rise in chip technology. A new wave of this revolution has started with the development of computerization using the basic building blocks of life. We can now make simple changes from the complex molecules that control our DNA function.
The control and manipulation of gene expression through the intelligent design of biologically modified logic gates is one of the most fascinating developments in modern biology. We are now at the entry level into a world of infinite potential to improve our lives. The long-term goal of harnessing the control of human body function at the molecular level has implications for both the good and the bad in the human experience.
The tiny plastic implant developed by Marc Folcher and Professor Fussenegger could be used to capture unconscious brain waves. Photo: Marc Folcher, EPF Zurich
Mind over matter?
Martin Fussenegger heads a team in the Biosystems and Scientific Engineering Department at the Universities of Zurich and Basel. They create switching or “wetware” systems using complex molecules with Boolean logic familiar in the software world of digital design. He has already given a glimpse of a future in which our brains could control genes using the power of thought.
In 2014, Fussenegger’s group performed an astonishing experiment, harnessing human brain waves and wirelessly transferring them to an array of genes to regulate the expression of a gene based on the type of thought.
In the experiment, the team used an EEG headset, recording brain waves transmitted over Bluetooth to a controller, which in turn controlled an electromagnetic field generator to power an implant in a mouse with an induction current. An integrated LED lamp in the near infrared wavelength range lit in the implant illuminating a culture chamber containing genetically modified cells. When this light illuminated the cells, they began to produce the desired protein.
“Being able to control gene expression through the power of thought is a dream we’ve been chasing for over a decade,” Fussenegger said at the time.
Seven years later, where are we in the process?
Need to focus on the goal
DM: The application of logic gates to biological molecules was achieved by creating the digital equivalent of a central processing unit in a biological system. In 2014, your famous experiment demonstrated the potential. Where are we today with this work?
MF: The biological and electronic worlds are radically different but conceptually similar. Biological systems are analog in nature as they are based on ions flowing through isolated membranes while electronic systems, such as processors, are digital … using electrons flowing through insulated metal wires. Biological systems cannot be digital (give yes-no answers) because our metabolism requires the mid-level responses that are typical of analog systems.
However, the potential of molecular CPUs can be seen at three levels:
The first is in vivo. Unlike silicon processors. the computing power of in vivo The processors will be unlimited. We are rightly proud of having multi-core processors combining a few processors, all of which can only handle one operation at a time, but at very high speed.
Imagine a world in which a single living cell can perform thousands of analog metabolic operations per second. If that were to represent a single-cell mainframe, the tissues designed to handle logical operations could represent multi-billion mainframe processors. It’s a fantastic sight!
Second, our lives are increasingly dominated by electronic devices. These devices can control, manage, and profile a lot of things, but because they are incompatible with biological systems, they cannot interface directly with our genes or with human metabolism. In order to have electronics that communicate with genetics and genetics relate to electronics, we need to design compatible interfaces to allow this.
Third, we have to write genetic software like computer code.
In just ten years, synthetic biology, the rational and predictable engineering of mammalian cells, has led to an increasingly diverse portfolio of tools for rationally programming the behavior of human cells. It is an evolutionary process but bioengineers assembled genetic circuits whose behavior was identical to the most elementary electronic computational elements (logic gates, half-adder, full adder, band-pass filter). This led to the belief that genetic software could be assembled like computer code to program cellular behavior.
To give examples of what this might mean; What if we could program cells to sense changes in blood sugar and respond with the production of insulin? Or, how about if stem cells could be programmed to differentiate into beta cells?
DM: How far are we from such a functional system?
MF: It’s hard to predict. I would opt for between 10 and 20 years, but it is important to realize that this is a direction of travel that is starting to gain momentum. No matter how long it takes, it will one day be a reality.
DM: I suspect the practical use and our better understanding of CRISPR [gene editing] has been a leap forward on the path of biological informatics and the potential delivery of new therapies for diseases. Is it true?
MF: CRISPR turns out to be another very valuable tool in our kit box. It’s a very efficient tool, but anything that CRISPR can do was also possible before. Gene editing was previously possible with so-called zinc finger nucleases. It’s just that with CRISPR the work has become more efficient. Additionally, the off-target effects of CRISPR are not yet fully understood.
DM: Have your experimental laboratory techniques created innovative procedures for use in the laboratory?
MF: He made difficult mammalian cell engineering accessible to everyone. Complex genetic engineering was limited to a few specialist groups, but CRISPR made it possible that even undergraduates could handle this in lab classes. The effect is that the pool of genetic engineers has grown beyond what we thought imaginable. The more genetic engineers we train with better toolkits, the faster we can change the world for the better.
DM: What is the biggest obstacle to the success of a processor in vivo?
MF: Digital electronic systems work well in a very isolated environment and only need a power supply. A processor in vivo must operate within a living system, which has millions of analog housekeeping operations to master and at the same time must grow and can repair itself. The bio-CPU must be isolated from the maintenance activity of a cell and this is a major challenge. Also, the molecular world is analog to ensure the right dosage of molecule, and these systems are very robust and self-healing, but they are not very precise. Biological systems can have variations of 5-10% and they are extremely slow compared to electronic systems.
DM: Do you think there is enough funding and training for this research?
MF: The problem is not the degree of funding or investment. It’s more about the structure of the funding. The main weakness is that we organize universities into departments like a school with compartmentalized themes (chemistry, biology, physics, etc.). Research at this level is becoming increasingly interdisciplinary with molecular biologists working alongside electrical engineers. We need funds to be directed to dedicated research units that focus on the objective and not on a single discipline.
References and further reading:
Nature Communications, published online November 11, 2014, doi: 10.1038 / ncomms6392call_made
Recommended online viewing: https://biox.stanford.edu/video/synthetic-biology-what-should-we-be-vibrating-about
Interviewed: Martin Fussenegger is Professor of Biotechnology and Bioengineering at the Department of Biosystems Science and Engineering (D-? BSSE) at ETH Zurich in Basel and at the University of Basel.
Author: Dermot Martin is a writer and reporter specializing in science, technology and medical research