Saturday, August 23, 2014

Crystal Balls, Ebola, and Pharmaceutical Development in 2020

It is always safe to make predictions about what the future will be like in ten years, because if it turns out that you were wrong, the odds are no one will remember. If it turns out that you were right, you can seize the opportunity to remind everyone of your remarkable prescience. With that as prologue, I will start by revisiting a prediction I made sixteen years ago about a date still six years from now. In April of 1998, at a conference entitled NEXTMED:  The Future of Medicine, I made a prediction for the year 2020 (20/20 vision was a popular theme in the futurist business back then). Actually I made several predictions, but I have carefully selected the one which has the best chance of proving accurate. In my talk I included the Ebola virus as an example of the progress I foresaw in our ability to respond to future threats:

Immunology at the Rainbow’s End: A Push-Button Vaccine Machine

It is a few years off, but obviously the science of predicting protein structure from a gene sequence is moving rapidly; and, well within the time frame spanned by this talk, it will be a reality. At that point, the window will slam shut on the possibility of our being overrun by a third-world virus, another HIV or, worse, a more widespread and contagious Ebola. Within days of the first cases being picked up, a blood sample of a victim would be sufficient to do a full genomic analysis of the pathogen, the pathogen’s proteins would be fully analyzed both for their function and their antigenicity, the most antigenic regions would then be synthesized with an appropriate adjuvant, and a very effective vaccine would be coming off the production line a week or two later.
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In power point style, the prediction can be broken down this way:

-       1. rapid sequencing of viral genomes from early patient samples
-       2. rapid analysis of  a viral pathogen’s proteins for function
-       3. rapid determination and selection of antigenic regions of viral proteins
-       4. Rapid scale-up to produce an effective vaccine within weeks after antigen selection

So, does it look as though I am going to be correct by 2020 or (deadlines for this sort of forecasting ought to be at least a bit flexible) within a few years thereafter? Part one of my prediction seems to have already arrived: Illumina’s sequencing machines, known for already delivering the one thousand dollar human genome (in 30 hours), have also been used in research that demonstrates the ability to identify a viral pathogen’s genome in a clinical sample. 

What about the ability to determine the function and antigenicity of the pathogen’s proteins?  We are getting very close.  Although viral genome analysis can already identify the proteins on the viral envelope, the routine ability to determine the antigenicity of the viral proteins requires continued progress in in silico biology.  In silico biology, which is the ability to model biological systems on a computer, is more than simply bioinformatics or computational biology. The field is moving rapidly: two years ago, a group from Stanford University and the J. Craig Venter Institute published a report of an extraordinary scientific breakthrough, the computer simulation of an entire organism, M. genitalium, a mycobacterial parasite that is the cause of a sexually transmitted disease. However, in silico antigen prediction is more complicated, because it requires not only modeling the virus but also modeling the human immune system. Nevertheless, in silico approaches to antigenicity prediction have already been published.  We are not all the way there yet, but I am feeling good about the accuracy of prediction three for the year 2020. 

That leaves prediction four--rapidly scaling up to produce a candidate vaccine.  Rapid scale-up of novel protein or antibody production to meet an emerging new viral epidemic may be the most difficult challenge of all. Pilot production is easy, but scale up still requires time.  Check back with me in six to ten years, especially if I am proven right.  I’m always glad to take credit when I am occasionally proven right.  Meanwhile, back to the present for next week’s post.

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