"Grandpa, it's time to eat some afternoon tea to lower blood sugar——"
"Well, today's cookies I want to accompany black tea."
In the future, drugs may look different from what everyone thinks: a cookie, a cup of tea, can also become a medicine to treat diseases.
Good medicine may not be bitter, afternoon tea can also cure the disease, with the development of the field of synthetic biology, such medical treatment may become a part of the future.
If one day aliens come to Earth and leave behind a spaceship, how do we understand the complex principles behind the spaceship?
The first step – tear it apart.
Alien: Ah, right, right
Starting from the thinking of engineering, any great invention is inseparable from the most basic parts, from a small screw to a wire, which is the foundation of modern science and technology. When we can fully understand the function and logic of each component, we can assemble these seemingly ordinary parts and create a variety of modern technologies such as bicycles, maglev trains, artificial intelligence and so on.
Disassembling complex structures into parts is the first step to understanding complex machines, and the same is true of wanting to understand our bodies. We may not feel it, but in order to maintain the basic order of the human body, our body is like a 24-hour factory, and the cells in the body are methodically executing complex commands every moment.
Human Factory artist Fritz Kahn (1927)
There are many "signal receivers" on the surface of cells, called receptors, that can receive signals from other cells. When the correct signal binds to the receptor, a portion of the gene in the cell is turned on/inhibited, which is then catalyzed by enzymes to produce a series of chemical reactions that convert one substance into another.
Such a process of "receiving signals-acting" is called a signaling pathway, and the chain reaction within a cell that converts one substance into another is called a metabolic pathway. Through signaling pathways, our bodies are able to regulate the functioning of metabolic pathways that prompt the body to respond to complex environments.
The coagulation waterfall of working cells is a common metabolic pathway
Source: Animation Working Cell
Over the past few decades, human understanding of the mechanisms of these complex signaling pathways has deepened. In 1990, an important study, the Human Genome Project, was launched to sequence human genes.
When we have a good understanding of the cell's signaling pathways, as well as the genes and proteins involved, we can try to use engineering and programming methods to "design" the metabolic pathways in the cell.
Synthetic biology thinking is similar to engineering thinking
图源：Molecular Systems Biology
Synthetic biology applies engineering thinking to biology—using proteins and genes as basic components, designing signaling pathways, and manufacturing synthetic biology. At present, there are two ways to try:
1 Top-down: Use existing life forms — bacteria, single-celled organisms — as a basis, and give them some additional functions, or replace some genes
2 Bottom-up: Using inanimate objects and known cellular pathways, a completely new life form is designed
Many of the intractable diseases of humans are also related to the abnormalities of cellular signaling pathways – for example, diabetics cannot produce insulin and regulate blood sugar; cancer patients cannot stop the growth of cancer cells. If there is a problem with the communication and execution of the cells, some functions of the body cannot be realized. Synthetic biology designs cells with programmed ideas, and when the complex factory of the human body fails, the synthetic cells through special designs are like external experts, and can come to accurately support, repair or replace the problematic metabolic pathways to treat diseases.
Chocolate, ice cream, bread – For gluttonous but healthy people, the result of consuming too much sugar is usually obesity. Normally, when the blood sugar is high, the body secretes a protein hormone, insulin. Insulin can assist cells in absorbing sugar from the blood, turning it into energy for cells to function, while excess sugar is stored as fat.
However, for diabetic patients who do not secrete enough insulin, or whose insulin cannot be fully utilized, the sugar content of the blood cannot be used by the cells, and the blood sugar content is too high, bringing fatigue, irritability, frequent urination and other problems.
Scientists have developed a new type of cell that can produce insulin, like a plug-in for insulin production that is independent of the body. By implanting cells in mice, it is equivalent to building an "insulin production plant" that can produce insulin and lower blood sugar when needed.
Insulin production plant in the human body
Source: Nature Chemical Biology
Wait, the physical environment is so complex, how do we ensure that a foreign cell does not cause unexpected side effects?
To control cells to work only when they need to, scientists used synthetic biology to create an amino acid "key" that is not found in nature, and such a key can be stored in a special biscuit. Usually, keyless synthetic cells rest in the body, do not respond to any signals, and do not produce insulin. Once the biscuit is eaten, the artificial amino acids in the biscuit are sent directly to the "insulin factory" cells by a special synthase messenger that is not found in the body.
When blood sugar drops and the amino acids in the biscuits are fully metabolized, the artificial cells once again go to sleep.
"Just count you the most noisy"
Using synthetic biology methods, scientists have designed a set of insulin production mechanisms that are independent of the metabolism of the organism itself. From amino acid keys to synthase messengers to synthetic cells, this whole system operates without interacting with the organism's own signaling pathways. Amino acids and synthetic cells should be combined inside and outside, successfully repairing the problematic amino acid production line.
Under normal circumstances, cells grow and divide at the mercy of special signals, divide only when needed, and initiate a self-destruct process when they are not needed.
However, there are always some cells that are particularly rebellious, and when the cells begin to ignore the instructions of external signals and begin to divide and grow without tissue, it becomes a cancer cell. Cancer cells have the potential to appear anywhere in the body, ignoring any instructions to stop growing, tricking immune cells into growing wildly, and growing wildly in the body.
Fainting "cancer cells"
Source: Animation Working Cell
Because the body cannot distinguish between cancer cells and normal cells, cancer treatment is now very difficult, and the indiscriminate attack of the treatment plan will also accidentally injure many normal cells, causing a burden on the body.
Ah, how hard it is - if only the cancer cells could be labeled "cancer cells"!
Well? In fact, it is not impossible —
Fingerprints need to be identified if the bad guys are to be found, and different kinds of cancer cells also have different microRNAs (microRNAs) "fingerprints" than normal cells.
Through synthetic biology techniques, we can design biological pathways to install a "virus software" on cells. Based on the composition of microRNAs, let each cell determine itself – am I a cancer cell?
Self-discipline gives freedom?
Image source: Mustard SpeakeGreen
If the microRNA composition of the cell matches the cancer cell, then the "auto-destroy" pathway will be activated and the cancer cell will execute the suicide command. But if the composition of the target microRNA does not match the cell, then the cell will not respond in any way.
In this way, we can effectively distinguish cancer cells from healthy cells, and use synthetic biology to trick cancer cells into the "suicide road".
At present, synthetic biology is still an emerging field, and artificially modified living cells are the most complex "drugs" designed by humans.
There are more than 10,000 recorded diseases in the world, and most of them do not have good treatments. In the future, synthetic cell drugs will face more clinical trials and commercial potential. On the path of humanity's fight against disease, synthetic biology will provide us with endless possibilities.
At the same time, the development of synthetic biology has also brought new policy and ethical issues. After all, acting on the medical field was only the most conservative and beautiful idea before the technology matured — it may have countless other uses to change our lives. This is also the questioning and scrutiny that most nascent technologies have always faced.
Synthetic biology is only a tool in our hands, and any creation carries the subjective projection of people; the development of technological means also requires the active support and rational treatment of people and society. So the future of synthetic cells ultimately remains a question: How do we want to apply it? What kind of future do we want it to usher in? *★
Review: Hu Zhiguo, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences
∧∨ flip up and down to see the reference content
· https://www.nature.com/articles/s41589-021-00899-z
· https://www.frontiersin.org/articles/10.3389/fbioe.2019.00175/full
· https://www.nature.com/articles/s41568-019-0121-0
· https://www.frontiersin.org/articles/10.3389/fphar.2020.00119/full
· https://www.sciencedirect.com/science/article/abs/pii/S0958166919301545
· https://m.ofweek.com/medical/2021-11/ART-11106-8420-30535389.html
· https://www.genome.gov/about-genomics/fact-sheets/Biological-Pathways-Fact-Sheet#:~:text=A biological pathway is a,spur a cell to move.
· https://www.frontiersin.org/articles/10.3389/fbioe.2018.00070/full
· http://sheitc.sh.gov.cn/gydt/20220114/aeef580e0bd54c178d17484ce0ce0600.html
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Source: Shanghai Science and Technology Museum
EDIT: Hidden Idiot