Chinese Biomedical Space Odyssey Guide

Article source: Medical Rubik's Cube Pro

At 11:23 on April 29 this year, the Long March 5B carrier rocket was ignited into space from the Wenchang space launch site in Hainan, China
.

About 8 minutes later, the "Tianhe" core module of the Chinese space station was successfully sent into the scheduled orbit.

The core cabin is the most basic part of the entire space station, and other cabins will be docked and superimposed around the core cabin
.

According to China's space station construction plan, the space station construction task is divided into two phases of key technology verification and construction, with 6 missions in each phase

In addition to the successful completion of the first flight of the Long March 5B rocket and the launch of the "Tianhe" core module, the key technology verification stage will also implement two Tianzhou cargo spacecraft and two Shenzhou manned spacecraft launches this year
.

During the construction phase, the Wentian experimental cabin and the Mengtian experimental cabin will be launched one after another.

It is expected that the construction of China's space station will be completed around 2022, after which it will enter the application and development stage for more than 10 years, and a large number of scientific research tasks will be carried out in the experimental cabin of the space station
.

Soon, the "Tiangong" space station will also become the only space station operating in human low-Earth orbit
.

Because the US-led International Space Station (ISS) has been in service for more than 20 years, it will be decommissioned in 2024

The construction of a space station is undoubtedly of great strategic significance for a country
.

It will not only directly drive the progress of science and technology related to the entire aerospace science and technology industry chain, but also use scarce space resources for space exploration and cutting-edge scientific research

It is precisely because of the scarcity and preciousness of space resources that the US International Space Station has banned Chinese researchers from conducting space scientific experiments.
Therefore, Chinese researchers have not had the opportunity to conduct space exploration before, and the "Tiangong" space station will be plugged in for Chinese researchers.
"The Wings of Dreams"
.

Speaking of this, readers will definitely be curious, what kind of scientific research can be conducted on the Chinese Space Station? What are the experiments related to biomedicine? The editor will also give you a brief introduction here
.

Biomedicine research on the space station

Biomedicine research on the space station

According to statistics, the International Space Station has conducted about 3,000 scientific researches in various disciplines over the past 20 years or so, of which the highest proportion is from the fields of life sciences and biotechnology
.

Source: Nature

Even behind the blockbuster new drugs of individual celebrities, there are also contributions from space experiments
.

It's just that the chain of new drug research and development is too long, or for other reasons, it has not received widespread attention

K Medicine Gods

K drug (Keytruda) is a PD-1 monoclonal antibody.
As Merck’s flagship product, K drug has been approved for marketing in 22 different indications.
The excellent performance of K drug has also brought about PD-1 inhibition at home and abroad.
The upsurge of drug research and development
.

As a kind of macromolecular protein, K drug faces many technical difficulties in manufacturing, delivery and storage
.

For example, the manufacturing process of monoclonal antibody drugs is very complicated, usually requires multiple chromatographic steps for purification, which is expensive and time-consuming

These problems are expected to be solved by improving the monoclonal antibody purification technology to produce a highly uniform and stable monoclonal antibody concentrated crystalline suspension
.

Small molecule drugs and peptide drugs (such as insulin) are usually purified through a crystallization process, which can make the purification process faster and cheaper

In order to study the key variables that affect crystal growth, in 2019, Merck’s researchers cooperated with the International Space Station to conduct crystallization experiments using K drug on the SpaceX Commercial Supply Service 10 space mission, and use microgravity experiments to study the sedimentation rate and temperature gradient.
Impact on crystallization purification
.
It was found that under microgravity conditions, settlement and convection were reduced, and the resulting crystalline suspension had a lower viscosity and was more uniform than the ground control
.

Ultraviolet imaging of the ground control sample (left) and the space sample (right) in the Merck study (Source: Merck)

Later, the research team used a rotary mixer to control variables such as sedimentation rate and temperature gradient, induce nucleation and control crystallization, and successfully replicated a uniform crystal suspension in space in ground experiments
.

This is of great significance to the purification and storage of monoclonal antibodies.
It is expected to promote the transfer of drug K from intravenous injection to subcutaneous injection, and improve the quality of life of patients and nursing staff
.

Amgen Mouse Space Tour

In space, astronauts are under microgravity conditions for a long time, and their bodies will undergo a series of changes, which may induce some potential diseases.
The most prominent problem is osteoporosis
.

Bone is an important structure that supports the body and stores calcium.
Under normal circumstances, bone maintains the balance of bone mass under the interaction of bone formation by osteoblasts and bone resorption by osteoclasts
.
In a microgravity environment, because bones no longer need to resist the action of gravity, reduced load will lead to increased bone resorption, and accelerated bone loss makes astronauts more susceptible to fractures
.
Although physical exercise can alleviate these problems, it does not completely eliminate the risk of osteoporosis
.

In order to further understand the impact of the space environment on bone density, solve the physical health problems of astronauts, and develop new drugs for patients with osteoporosis on the ground, Amgen conducted three mouse space experiments in cooperation with NASA from 2001 to 2011
.
The three studies used different drug molecules and blocking targets.
Osteoprotective protein research was conducted in 2001, myostatin inhibitor research was conducted in 2007, and sclerostin antibody research was conducted in 2011
.

Sclerostin is a protein secreted by bones and is a key negative regulator of bone formation, bone mass and bone strength
.
The hypothesis of Amgen’s 2011 experiment was that the bones of mice injected with sclerostin antibodies before entering space would not be as badly affected by microgravity exposure as the placebo group
.

Researchers from Amgen gave two groups of mice about 10 weeks old the day before launching into space with sclerostin antibody and a placebo.
At the same time, the other two groups of mice left on the earth were given the same procedure.
Treatment
.

The instrument that carries the mouse space experiment (source: NASA)

Two weeks later, the mice that had adapted to free-floating in space returned to the ground
.
After analyzing various indicators of mouse bones in space and on the ground, Amgen researchers said that mice injected with sclerostin antibodies increased bone formation, improved bone structure, and even increased bone density
.

Show of results of sclerostin antibody space experiment (Source: American Astronautical Society)

These experimental data not only promote the development of osteoporosis treatments for astronauts, but also bring new hope to people with skeletal fragility (such as stroke, cerebral palsy and spinal cord injury) caused by "bone disuse"
.
The space research of osteoprotegerin helped the FDA to approve the listing of desulumab in 2010, and the space data of sclerostin antibody research promoted the FDA approval of romoxumab in 2019
.

A Preliminary Study of China's Space Research

A Preliminary Study of China's Space Research

The “Tiangong” space station will provide the greatest convenience to Chinese researchers in space research, especially the recyclability of “experimental samples” is a huge advantage, because some of the data will be obtained through observations in the space experiment capsule, and the experimental samples will be recovered.
The ground can also provide richer and more valuable information
.
This advantage is also conducive to expanding the blueprint of China's space experiment design
.

Space research is still a brand new exploration for us.
The experimental cabinets of the China Space Station, just like space magic boxes, are waiting to collide with various disciplines
.

According to Medical Rubik’s Cube, my country’s space medical research plan has begun to take shape and will follow the principle of easy to difficult.
Currently, it is trying to start from the following directions:

Microbiological Research

Under the special environmental conditions of space, the microorganisms carried by astronauts and space instruments and equipment may undergo certain mutations.
Scientists want to study what mutations occur in microorganisms, and how to prevent harmful mutations or use beneficial mutations
.

In fact, in May 2020, the Long March 5B carrier rocket and the new generation of manned spacecraft carried probiotics into space for three days of space experiments
.
The colony morphology of Lactobacillus rhamnosus M9 that has undergone space mutagenesis has become larger and more viscous than before, and the probiotic properties of the strain may have changed to some extent
.

For probiotic strains, the frequency of mutation on the earth is very low, and it is not easy to obtain probiotic strains with better acid resistance and better performance
.
With the rise of microbial therapy in recent years, and the important role of intestinal flora in various diseases have been continuously revealed, the use of space environment to accelerate the development of microbial therapy has great prospects
.

In addition, the China Space Station can also explore the screening and functional transformation of the popular intestinal flora in the medical field
.

Astronaut Health Research

Focusing on the health and immune system of astronauts is the second major direction of space medicine planning
.
Just like the previous case of Amgen, explorations in this direction (such as musculoskeletal drug research) are not only expected to ensure the health of astronauts and the smooth progress of space exploration, but also provide important assistance to the development of drugs for related patients on the ground
.

new medical research

The third dimension of space medical planning, and the most challenging task at present is "new drug research and development"
.

Space has an environment that is very different from the ground conditions, and it is undoubtedly an irreplaceable new resource for the research and development of new drugs
.
How to effectively use this precious resource to truly help overcome the challenges faced by ground drug research and development is the focus of China's space medicine planning
.

It is understood that China plans to transport three astronauts into space in June this year.
They will be the first "occupants" of the core module of the space station "Tianhe"
.
In addition, the natural medicine library verification samples provided by the Shanghai Institute of Medicine of the Chinese Academy of Sciences will also travel to the core cabin on the Shenzhou 13 manned spacecraft in September this year
.
China's space drug research and development has already begun.
.
.

other

Of course, the China Space Station's attempts in the fields of life sciences and biomedicine go far beyond the above three directions.
Explorations in biochips, 3D printed organoids, contrast agent research and development, and embryo research are also planned and ongoing
.
For example, the China Space Station is cooperating with the Institute of Aquatics of the Chinese Academy of Sciences, which has the world's most abundant zebrafish species, to plan to send embryos of zebrafish, a commonly used model animal for drug development, into space.
This is of great significance for deciphering the pathogenesis of diseases and guiding drug development
.

Prologue of Infinite Possibilities

Prologue of Infinite Possibilities

China’s new drug R&D has gone from being backward to now catching up.
It is gradually becoming the backbone of global innovative drug R&D.
The completion of the China Space Station will provide a new innovation carrier for the development of Chinese medicine and help the overall innovation and improvement of Chinese medicine.
The aerospace technology will benefit human life and health
.
The dream of drug research and development in space used to be far away, but as the completion of the Chinese space station is getting closer and closer, we are about to embrace that uncharted territory in our arms
.

Can hold the moon for nine days,

Can go to the five oceans to catch turtles,

Talk and laugh triumphantly
.

There is nothing difficult in the world,

Just be willing to climb
.

In the future, what kind of wonderful collaboration between space and biomedicine, and what kind of powerful force will it burst out? For advancing medical professionals, this is an unprecedented opportunity and the beginning of infinite possibilities
.

Note: The original text has been deleted

Reference materials:

[1] The Tianhe core module was successfully launched, and the Wentian experimental module and the Mengtian experimental module will also be launched next year (Source: The Paper)

[2] Astronauts have conducted nearly 3,000 science experiments aboard the ISS (Source: Nature)

[3] Reichert, P.
, Prosise, W.
, Fischmann,TO et al.
Pembrolizumab microgravity crystallization experimentation.
npjMicrogravity (2019)

[4] Published Results From Crystallization Experiments on the ISS Could Help Merck Improve Cancer Drug Delivery (Source: ISS National Laboratory)

[5] Andersen TL, Sondergaard TE, Skorzynska KE et al.
A Physical Mechanism for Coupling Bone Resorption and Formation in Adult Human Bone.
The American Journal of Pathology (2009)

[6] Why Do Astronauts Lose Bone Mass InSpace? (Source: Forbes)

[7] Rodent Research Contributes to Osteoporosis Treatments (Source: NASA Spinoff)

[8] This time, Tianhe brought the "matte doll" and "the alchemy furnace of the Taishang Laojun" to heaven (Source: Science Compound)