A Response to the “Space Drugs” article in The Scientist Magazine

The paraphrasing statement at the beginning of the article is as follows:

“Researching and developing drugs in microgravity could lead to better treatments. But will it ever be worth the cost?”

This statement is missing the mark in terms of summarizing the article. One of the main interesting aspects of crystallizing protein – which the article had a large emphasis on – is more directly related to manufacturing and production, as opposed to the treatment aspect. For example, crystallization is helpful for purification of enantiomers. This would have been extremely useful for the thalidomide tragedy in terms of its treatment but the issue was the purity of the racemic mixture.

Greco is reported to be working with a light-activated bacteria, named bacteriorhodopsin. I thought it was a little funny that the article stated that they were having difficulty with consistent quality, so they decided to turn to microgravity environments. The reason why I found it funny is because there are so many factors that affect sedimentation of proteins, which seemed to be the problem, according to the article. Sedimentation is an issue in the field of flocculation optimization. Some of the factors that affect stability of colloidal systems involve the charge of the particles or proteins at their “slipping plane” (aka surface charge) which can be controlled via the shielding of charges, the ionic strength of the diluent, concentration, amongst others. It is interesting to me that a microgravity environment might be the variable that they are seeking to control in order to optimize sedimentation. I agree that a microgravity environment may help with crystallization but what about all of the other variables that do as well that do no require a rocket, its fuel, and the International Space Station? I think in some contexts a microgravity environment is warranted in the pharmaceutical realm – but not for sedimentation purposes. I am not questioning Greco’s decision because I don’t have all of the details. I am just commenting based on what I read in the article.

Something interesting I learned in the article is that the International Space Station still feels 90% of the gravitational pull by the earth but it itself is in free fall. In a sense, it is doing exactly what the “vomit comet” experience is providing.

I found it fascinating that the article references a group who obtained far more homogeneous distribution of crystallized particles in a microgravity environment. The article then states how this property is ideal of drug delivery. In the world of drug delivery, the consistency in the particles would be ideal for controlling the structure-activity relationships. The effect of the output is better controlled when the input is more precise. With that said, it is not clear to me in the realm of drug delivery who is using crystalline protein to deliver a functional protein – assuming the crystalline protein is the protein you are intending to deliver. Generally speaking, if you deliver some therapeutic agent with a drug delivery system in a controlled manner, the carrier system is hydrophobic so that it can inhibit being dissolved and inhibit the immediate release of its contents. If the protein is in a crystalline form, does it irreversibly denature. Perhaps the exposure-response profile would be drastically altered? I have a lot of questions about the drug delivery aspect of the crystalline protein that is being made in space. In my opinion, the article should have elaborated a great deal in that regard (I am biased, however, because I have a lot of interest in drug delivery itself so it only makes sense that I would want the article to expound upon that topic).

Regarding having rodents go to space to undergo musculoskeletal degeneration seems absurd. I feel there are so many other ways that would be more humane. For example, why start with a non-disease state and force them into a disease state when we could do that genetically on earth. I do not know enough to state that there are not experiments that warrant this because I am not an expert in musculoskeletal disease models. More discussion about this would have been nice. Especially because we are talking about animals. I feel more respect should be given by educating others why it is needed, if such a topic is going to be discussed. I think more damage is had by leaving that rodent comment – which really was just one sentence in essence.

The discussion of endothelial responses changing in a microgravity environment is not surprising nor is it necessarily important. There are so many experiments outlining how 3D microenvironments, 2D microenvironments, and how the cells respond to stress-strain changes of what they are adhering to. I feel to have this discussion in the article, it should not breeze over this. The article stating that there are changes and making it sound like that is interesting when it is uninteresting is not great.

I really liked the discussion of the companies involved in these areas. The discussion of “cube labs” was interesting. The discussion of how it may be more profitable to outsource to space was fascinating. I have learned a great deal about the current status of pharma endeavors in space. Thanks for the great article!

These thoughts are mine and mine alone and not endorsed by any entity I am affiliated with.

Best,

Pharmacoengineering.com