X-ray crystallography – The Laughing Wolf

This morning, I want to get a bit more into protein crystallography, vaccines, and why lockdown until vaccines are developed just won’t work. Meantime, my usual reminder that the mainstream media coverage is detrimental to the physical and mental health of you and those you love. Don’t give in to the deliberate and willful effort to incite panic and spread false information.

Vaccines have come a long way since cowpox and Jenner, or even the work of Pasteur. Part of that advancement is that we now have ways of studying the microbes down to a level where you can see the individual atoms that make up the subject of interest.

Proteins are the building blocks of life. In the case of some microbes (bacteria and viruses), they can be described as the building blocks of death. Understanding the structure of any protein helps scientists figure out what it does and how it does it.

One way to do so that I am most familiar with is protein crystallography. In simplest terms, you take a protein and grow a crystallized version of it. In most cases, there are several forms that can grow out of any single protein, so you have to isolate the particular structure that is needed. The crystals are usually grown in a drop of liquid that contains the protein, growth medium, and other factors related to the crystallization.

Once you have the crystal, you stabilize it and put it in the path of a “bright” (powerful) X-ray source and use sensors to record how the beam penetrates, doesn’t penetrate, or scatters. With a crystal of sufficient size, you can literally map out the physical structure down to the placement of the individual atoms. This data is then converted into a visual image of the protein in question.

Some of that imagery is quite spectacular. When I worked for NASA both times, I worked with the staff at the UAB Center for Macromolecular crystallography. At that center, they could and did grow crystals, on the ground and in space (which offers quite a few advantages, and analyze them. They had a system that could use that data to create a 3-D image that allowed you to examine the structure in detail, even rotate or isolate sections at need. With that information, treatments could be developed that would bind only with the desired target, allowing drugs to be developed that were more efficient and had fewer (or almost no) side effects.

What does this have to do with vaccines? For modern vaccines, everything.

To design a modern vaccine, you have to understand the structure of the organism against which you are vaccinating. First, all organisms mutate over time. Certain structures, however, have to remain the same or the organism is no longer viable and dies off. If you can identify those structures that can’t really change, you can design either a treatment that binds to that site; or, you can develop a vaccine that does the same thing to prevent it. For example, HIV had what was considered a high mutation rate which hampered development of vaccines. I know of at least one experiment that flew on the Shuttle to grow crystals to help identify the areas that could not change in order to develop a vaccine. Sadly, I don’t remember that effort being as successful as hoped. My memory is fuzzy, but I seem to recall that in the time available the crystals could not be grown to a useful size; but, again, my memory is fuzzy.

Again, understanding the structure is critical, as in many cases, you only want certain antigens or even a single antigen (a substance that produces an immune response by the body) to teach the body what it needs to fight against. When the vaccine is given, the antigen(s) in it cause the body to think it is being invaded and to develop an immune response that attacks the full/real pathogen when it enters the body.

Protein crystallography is one means of identifying the structure of a pathogen such as COVID-19. I know of one effort to use protein crystallography on COVID-19, and suspect there are more. So, between protein crystallography and other methods, targets for treatment and vaccine development can and have been identified.

For those wanting something more than this rather simplified explanation, may I suggest this paper, this paper, this paper, and this paper as starting points.

Now, we get to actual vaccine production. Despite the problems with the accuracy of information from China, we have genetic and structural information that identifies target antigens for vaccine development. These have to be isolated, grown in the laboratory, and then normally they would be tested on animals and then humans. The normal FDA approval process for drugs and vaccines has be circumvented, and the first of what will likely be several vaccines is now in human testing. Even with the shortened process, that still takes time, as in weeks to months to see how it works. If it does work and does not need refinement (this is where later vaccines will have an advantage), we can start giving it out, right?

Wrong.

Going from creating what could be as little as a few ounces needed for initial development and testing, you now have to manufacture hundreds, or even thousands, of gallons of a product that requires multiple stages to create while ensuring the highest possible quality. Even variations of the antigen being used have to be removed in many/most cases. Ramping up production will be a time consuming process. Again, we are talking months even with best case on development, production, and regulatory approval. In short, I think we are looking at somewhere between six to ten months in a best case scenario. I hope I’m wrong, but as noted before, you always plan for the worst, hope for the best, and take what comes.

Six to ten months in national lockdown is not going to work. The disaster that would be for the economy, not to mention to civil liberties, can’t be overstated. I can’t think of any rational person of any political persuasion who will stand for that.

Now, the above is greatly simplified. As above, if you want to know more about modern vaccine production methods, I recommend you start with this, with this, with this, this paper is a must read, this paper, and this paper. If you read those, I think you will better understand how miraculous both the current technology for studying things like COVID-19 is and the breathtaking pace shown in getting the first human trial underway. It literally could not have been done twenty years ago in my opinion, and quite possible even as little as ten years ago.

For those who want to know more about the work done at the UAB Center for Macromolecular Crystallography, I commend to you both what may still be available through NASA relating to Shuttle missions, and the papers and talks by Dr. Lawrence DeLucas, Charles Bugg, et al. For those who want to know more about the efforts to prevent paralysis from spinal cord injuries mentioned yesterday, you should look to the works of Borgens, Shi, et al at Purdue University.

Thus concludes today’s lecture. Yes, I have simplified things so that they are accurate though not necessarily precise. I wanted it on a level that could be widely understood. Hence the links to all the papers for those who want it in greater detail and precision.

Since the media isn’t going to say it, once again, COVID-19 is not Capt. Tripps. It is not the flu. Chill, distance, and use good hygiene. STOP THE PANIC!

Also, a reminder once again: if you are sick or think you are sick, DO NOT GO TO WORK OR TO VISIT PEOPLE. Stay the frack home. Don’t be Stupid, go to work/out, and insist on getting up close and personal to everyone you meet. Yes, Stupid is capitalized as I work with Stupid, who did just that. Don’t be Stupid.

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As always:

If you suspect you have COVID-19 or have been exposed: call your state health department and work with them so that you can be dealt with in a way that minimizes the chance of spreading the virus to those helping you and to the general public. Can’t get them? Call your local department or see if your health service has online/telemedicine screening set up; or see if one who has will let you use it even if you are not in their network. Do not go out in public, and don’t go to an ER or other facility without calling ahead. Be smart.

Use the interactive graphic to keep track of things. Is COVID19 an epidemic? Yes. Is it a Pandemic? Yes. Is there need for panic? NO. HELL NO. Should you be paying attention? Yes. Hell yes. Should you be preparing? Yes, better late than never. And good luck finding/getting stuff.

Want to avoid catching COVID19 here in the U.S.? Wash your flippin hands frequently, wash them thoroughly every time you use the bathroom, then follow with hand sanitizer after every washing, use hand sanitizer liberally when you can’t wash on a regular basis. Cover your mouth and nose when you sneeze, and stay away from those who don’t. Also, keep your bugger hooks out of/away from your eyes, nose, and mouth. Do NOT shake hands with anyone, and avoid touching or being touched by strangers. Or your strange friends.

Avoid travel if at all possible. If you have to travel, or go out for any reason, use lots of hand sanitizer and go to full flu protocols. If you have to use a public restroom, take full precautions including using paper towels and such to handle faucets, doors,etc. Believe it or not, this was highly recommended before now, and major grocery chains have long told employees to use those practices to avoid getting or spreading colds, flu, etc. Not many actually do it, but…

If you own a business, make sure your employees know the above protocols. Have someone who refuses to wash their hands or otherwise follow the protocols? Talk to them, write them up, and if necessary fire them as they now pose a risk of infection to you and your customers. Extreme? Yes, but while the CDC and others are working to slow it down, odds are it is already here and could hit hard and fast. Prepare for the worst and hope for the best.

I want to reiterate that there is no need for panic, but there is a strong need to be alert, be informed, and be prepared.

Good Sources Of Information On COVID-19

Instapundit (no longer doing roundups, but great articles from Glenn and his team)

South China Morning Post (decent, some salt may be needed)

Business Insider (decent, even if they did fall for some lies about Trump)

New England Journal of Medicine

Additional link to Johns Hopkins

More to come

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