On May 8, 1980, the 33rd World Health Assembly announced that the world was free of smallpox.
The WHO officially started the initiative against the disease in 1959, but the fight
against smallpox stretches back centuries.
Fortunately, we were able to win against the disease thanks to one man’s astute observation.
Humans had battled smallpox for generations.
Every year, the disease caused epidemics that would kill thousands and cause immeasurable
immeasurable pain and suffering.
Its victims suffered from fever, body ache, and painful pustules all over their body.
If they survived, their body would be covered with ugly scars.
There was only one prevalent cure.
Developed multiple times in different regions, certain medics would knowingly inject the
matter from a scab of an infected person into someone at risk of contracting the disease.
The method was effective for its time, but posed its own problems.
Practitioners were knowingly infecting people with the disease, albeit a diluted dose of
it.
If the dose was too high, then the patient would get the disease in full force and could
die.
Even if all went right with the treatment, one would still suffer through a mild attack
of the disease.
In 1769, Edward Jenner, an apprentice surgeon, noticed something interesting.
He observed that milkmaids never seemed to suffer from smallpox, though they were susceptible
to a similar, but milder disease called cowpox.
This, it would seem, made them immune to smallpox.
This was common knowledge at the time, but Jenner put it to the scientific test.
Jenner began by infecting an 8-year-old boy with cowpox.
The boy fell ill from it, but eventually recovered.
Jenner then exposed him to smallpox… and nothing happened.
The boy lived out a happy life going forward, entirely smallpox free!
Jenner had stumbled across one of the greatest discoveries in human history – vaccination!
This gave humanity’s fight against smallpox a major boost.
Even so, it took us another 200 years to finally defeat the disease.
In 1977, the last case of naturally occurring smallpox was recorded.
Since Jenner’s first rudimentary vaccine, we’ve successfully combated diseases like
measles, polio, and whooping cough.
Today, from the day we’re born, there is a timetable of vaccination recommended or
prepared for us to protect our health and those we love from deadly and highly infectious
diseases.
Whether we take those shots gratefully or with tears and screams, they have become an
important component of humans leading a healthy life.
However, the general public rarely understands what goes into the making of a vaccine, or
how long it takes to develop.
To gain some clarity, let’s look at how vaccines help our immune systems fight diseases.
When an invader—a pathogen like a virus, bacteria, or parasite - enters the body from
outside, the immune system begins a highly coordinated attack that takes place in two
phases.
Phase one is the general attack phase.
In this part, cells of the immune system like neutrophil, macrophages and dendritic cells
will try to kill off the pathogen.
If the pathogen manages to evade the immune system’s first line of defense, the body
calls upon more specialized immune cells – the B-cells and T-cells.
The B-cells recognize the pathogen, analyze it, and then undergo rapid division.
These B-cells inform the T-cells how to make weapons against the pathogen.
These weapons are antibodies.
The antibodies tag the pathogen, which signals other immune cells to destroy it.
Once the pathogen is beaten, the immune system, particularly memory T-cell and B-cells, keep
a record of the pathogen so that when it returns, the immune system can eliminate the threat
before it has a chance to wreak havoc.
This is what we call acquired immunity.
Giving the immune system the ability to remember past infections is the primary aim of making
a vaccine.
Simply put, a vaccine is a biological formula that enables the immune system to fight off
diseases by activating acquired immunity.
It is a cardboard cut-out of the enemy upon which the immune system can practice, so that
when the real thing comes along, it knows exactly what to do.
This gives the immune system a memory of the pathogen without the immune cells ever having
to actually face the threat of infection.
This is why Jenner’s vaccine worked so well.
It did two things that are critical for any vaccine: first, it activated the immune system
without causing the fatal disease; and second, it stimulated the immune system to develop
a lifelong memory of the disease.
The more traditional inoculation used to combat smallpox before Jenner’s vaccine can’t
be considered a vaccine, since the virus used in the preventative measure is still capable
of causing the disease, despite also providing immunity.
To create an “ideal” vaccine, scientists must fully understand the biology of the pathogen.
This is the first step in creating a vaccine.
Basic research in the lab studies everything and anything about the pathogen: its shape
and structure, the molecules on its surface, its genetic material, the pathogen’s molecular
machinery, how it reproduces, etc.
Basic research also looks at how the immune system responds to the disease.
Performing this research shows scientists where the pathogen’s Achilles’ heel might
be.
It teaches them how to choose the best strategies to take the pathogen down.
There are several of these possible strategies.
The first is the live attenuated vaccine.
This is the route Edward Jenner took with smallpox.
The pathogen is living, but in a weakened state.
It does not cause the disease directly, yet it is still capable of activating the immune
system.
Most attenuated live vaccines are produced by growing the pathogen in very specific conditions,
like a very salty solution or in different animals, so that it can no longer grow in
humans.
It can take multiple years to create a live attenuated vaccine.
These vaccines provide something close to lifetime immunity with only one vaccination.
Another strategy is using the dead pathogen.
Vaccines against the flu, for example, use dead copies of the virus.
These vaccines still manage to stimulate the immune system, since it is a foreign object
and has the molecular structure of the virus, but it produces a weaker immune response.
For this reason, it usually requires a booster, but it is still a safer option than a live
attenuated vaccine.
The next set of strategies only use a few molecules.
These molecules, called antigens, are what trigger the immune system’s alarm bells
and drive it into action.
In many cases, these antigens are enough to stimulate the immune system, but only mildly.
With advances in biotechnology and genetic engineering, scientists are able to create
safer and more effective vaccines.
They are creating hybrid viruses and bacteria that can stimulate the immune system, just
like a live attenuated vaccine, but they pose very little danger of causing the disease.
Many newer vaccines use this strategy, since it allows scientists to target specific diseases
more precisely.
Lastly are the DNA vaccines, which are composed of DNA that code for antigens.
The immune cells take up this DNA, read it, and produce the antigens.
The immune system then reacts to these antigens by producing antibodies against them.
When a pathogen that has the same antigen enters the body, the immune system is armed
Vaccines usually have other proteins and chemicals that enhance their efficacy, as well as preservatives
to increase the vaccine’s shelf life.
These concoctions are vigorously tested and refined before being used on humans.
The first step to see if a vaccine works is animal testing.
Animal testing shows whether the vaccine works in the body, how it works and how long it
takes to work.
This is a mandatory step before moving onto the final and most crucial part of vaccine
development—the clinical trials.
Even if the vaccine works on a lab animal, it might not work on humans.
Clinical trials happen in three phases.
Phase One looks at safety in a small group of volunteers.
Once the vaccine passes Phase One, Phase Two checks whether the vaccine really works.
. In Phase Two and Phase One, the effect of
the vaccine is compared to a placebo.
If the vaccine works significantly better than the placebo, scientists know that the
vaccine works.
In Phase two, scientists look at whether the vaccine can stand up to the pathogen that
causes the disease.
In Phase 3, scientists look at whether the vaccine can stand up to the real thing —
safety, efficacy and immune response.
The number of volunteers are the largest in Phase 3, which ensures that any “proof”
that the vaccine works is as objective and bias-free as possible.
At various stages of these three phases, vaccines can be sent back to the drawing board to make
modifications.
The subsequent iterations will once again need to be tested.
Clinical trials follow the double-blind method.
Here, neither the volunteer nor the administrator knows whether the true vaccine or a placebo
is being given, which removes human bias from the picture.
Only when a vaccine passes all these stages can it be released to the market.
At this stage, manufacturers will have to figure out scalability, packaging and transport,
acquire patents for their vaccine formulation and get approval from various government agencies
like the Food and Drug Administration, the FDA, in the USA.
This process can take up to 10 years or more.
It is impossible to calculate how long basic research will take to provide a vaccine.
Very few vaccine formulations reach the clinical trial phase.
Out of 100 vaccine formulations, 94 will result in failure, and it can take millions of dollars
to produce one vaccine.
However, basic research on vaccines and the advancement of specialized technology has
allowed us to ramp up our vaccine production and devise safer and more efficacious treatment
options.
The H1N1-swine flu vaccine was developed relatively fast, since basic research on the influenza
viruses provided scientists with enough information to battle the virus effectively.
In 2020, the world is facing a highly infectious virus for which a vaccine appears to be the
only long-term solution.
Organizations and pharmaceutical companies have significantly ramped up their development
of vaccines, but the road ahead is long.
Vaccine developers have to ensure that the vaccine is safe and effective, which requires
time and caution.
That being said, past research on other coronaviruses has allowed vaccine developers to begin clinical
trials on a number of candidates.
Without information gathered by basic research, timely development of a vaccine against COVID-19
virus would be nearly impossible.
Vaccines have made it possible for humanity to escape the scourge of regular or seasonal
epidemics.
Whereas diseases like smallpox once led to the downfall of major civilizations, global
society can now move quickly to develop a cure.
Since Jenner’s rudimentary vaccine against smallpox, science has advanced so that we
are now better equipped than ever before to save as many lives as possible.
We still have a long way to go, but, as a species we’re moving towards a better and
healthier tomorrow.