IN VITRO VS IN VIVO; THE PATH TO A CURE

In vitro vs in vivo; the path to a cure

By JJ KARWACKI Friday 20 March 2020

In medical research there are two ways to test the effectiveness of a treatment: one is in the test tube = in vitro; the other is in the body -= in vivo.

In the case of looking for an agent that can kill or even mitigate a virus, one first has to be able to artificially grow that virus outside the body in what is known as a cell culture. There are a number of strains of cells that grow well in special ‘test tubes’ (they are really flat plastic vials). When a virus is added to the cell culture it uses those cells to reproduce. That process can be viewed under a microscope. Using these infected cells, scientists can then add solutions containing drugs that they hope can kill the virus. All in all, this is a very fast way to screen for drugs that might show promise.

The next step is in vivo testing. Hopefully there is a non-human, animal substitute that the scientists can infect with the virus and then administer the drug to see if it kills (or at least mitigates) the virus.

If the drug in question doesn’t actually kill the virus, but say stops it from attaching to the target cell, they in vivo testing is the only way to go, since the cells used to culture any virus are not usually the actual target organ in the human body. Here animals are infected, then treated and their organs examined (usually after euthanasia) to see if the virus had entered the target organ or was stopped by the drug. Such procedures take longer to perform, so the experiment proceeds more slowly.

To be approved and marketed, any drug must be proven to be BOTH safe and effective. Safe = it has no severe side effects or at least acceptable side effects compared to the actual disease it is attacking. Effective means that it changes the outcome for the better if not actually curing the disease or in this case killing the virus.

Even when a drug seems to work well in a test tube or an animal model, one can never be sure that it will be effective in humans. But before it can be tested as a ‘cure’ in humans it has to be shown to be safe. This is most often done by paying people to take the drug and testing to see if it has any unexpected adverse effects. Infection with the virus is not used here, only the pure drug. This is where time can be saved if the drug under evaluation is already on the market. New candidate drugs consume a lot of time in this is-it-safe? step.

Next comes trying the drug in humans to see if it is effective. In some cases – although rarely – human volunteers can be infected with the actual disease or a similar less severe version and then treated to see if the drug does what the scientists hope it will do. In situations where the disease is too severe or risky to artificially infect humans (even volunteers), the drug is often tested under what is known as ’compassionate circumstances’. Humans with the disease who are close to dying are offered the (unproven) treatment in the hope that it will prolong their life. Even if the patient succumbs to the disease, scientists can often learn useful information from examining their organs.

When a new (known as novel) virus erupts on to the scene, scientists across the world attempt to find the items needed to do this stepwise progression to find a cure. Is the cell culture that I am familiar with and use daily in my lab, able to support this new virus? Is there a drug that I am familiar with that might be effective in treating it? Can people be recruited to test this treatment? Here is where modern technology of the internet comes into play. Isolated researchers can quickly report minor successes to others across the world. They can recruit other scientists to try to repeat any successes they might have had. The suggestion of the success with one drug might induce others to try similar drugs in hopes of improving the chances of success. Sharing information of successes and even failures via the internet can assist in speeding up the entire process even by steering others away from blind alleys (failed drugs).

Developing vaccines is a similar tedious and arduous progression of small steps. In the history of vaccines, many different paths have led to success. Cowpox was substituted for smallpox and proved effective in the 18th century. Polio was conquered first with a concoction of the actual virus that had been killed. This was the injected Salk vaccine. Some decades later Sabin developed a less potent strain of the virus (attenuated) that is administered live via the sugar cube. With the advent of genetic engineering, vaccines are being developed by inserting small (but important and unique) portions of the new virus’s genetic material into a harmless virus and using it as a carrier to invoke immunity in the patient. Here again, proving a candidate vaccine to be both safe and effective, much less the arduous science of inserting genetic material into another agent, is a time consuming process. HIV has been around since the 1970s and there is still not a safe and effective vaccine; but not for lack of effort.

Right now, there is no safe and effective treatment (drug) nor a vaccine for the COVID-19 corona virus. Hospitalization is purely for isolation and supportive treatment of the symptoms like intubation and respiratory assistance for those with severe lung infections.