recombinant DNA drugs « Janet K. Ray

Just in time for your Thanksgiving dinner (live or zoomed) or those fun holiday social media debates, I’ve made a little vaccine cheat sheet!

Three top vaccine contenders recently released phase three results: Pfizer/BioNTech, Moderna, and AstraZeneca/Oxford University.

All three studies meet the gold standard of science research: huge study groups, randomly assigned and double-blinded trials. In a double-blind trial, neither the study groups nor the people running the trial know if a volunteer receives a placebo or the actual vaccine.

All three of the first-out-of-the-gate vaccines are bioengineered. All three use genetic information to teach the immune system to attack the COVID-19 virus.

The Pfizer and Moderna vaccines are very similar, so we’ll start with them.

How Do They Work?

Both vaccines use a molecule of RNA, coated in an oily micro-bubble.

RNA is closely related to DNA, the molecule that carries the genetic code. When our cells need to make something (like a protein), a copy of the DNA gene for that protein is made on an RNA molecule.

Think of it this way: grandma’s cookbook contains all her recipes. You make a copy of one cookie recipe on a notecard and carry it back home, where you create the cookies. DNA is the cookbook; RNA is the notecard.

Both the Pfizer and the Moderna vaccines use RNA with the “recipe” for one of the protein spikes on the COVID-19 virus.

When injected, the oily micro-bubble fuses with a muscle cell. The cell uses the RNA “recipe” to make spike proteins, which are released into the body.

A spike protein alone won’t make you sick, but it will teach your body to attack anything presenting the protein – like an actual COVID-19 virus.

Although RNA vaccines have been studied for years and are approved for animal use, if approved, these vaccines would be the first for human use.

Do They Work?

Apparently, magnificently.

The Pfizer vaccine was reported to be 90% effective and the Moderna vaccine 94.5% effective.

What does that mean in actual humans?

In the Moderna study, for example, 95 of the 30,000 volunteers got sick with COVID. Of the 95 sick people, ninety people received the placebo and only five received the vaccine, giving us an effectiveness rate of 94.5%.

An especially promising bit of news is that the five who got the vaccine and also got sick experienced only minor symptoms.

Severe symptoms were only found among the 90 people who got the placebo. This finding suggests that Moderna’s vaccine reduces the severity of disease in vaccinated people who still get sick.

To put a 90-95% effectiveness rate in perspective: in order for the FDA to consider a vaccine for use, it must demonstrate a 50% efficacy rate. Seasonal flu vaccines are 40-60 % effective. The measles vaccine is 97% effective.

Are They Safe?

Neither the Pfizer trial (44,000 participants) nor the Moderna trial (30,000 participants) uncovered any serious side effects. Both studies included volunteers of all ages and multiple ethnicities. But research doesn’t stop there. Safety studies continue as vaccines are rolled out to the general population.

Before launching their large phase three study, Pfizer tried out four versions of their vaccine in smaller groups. Pfizer selected the version that produced the fewest cases of mild and moderate side effects, such as fever and fatigue.

Once Approved, How Will the Vaccines be Distributed?

Gus Perna is the army general in charge of “Operation Warp Speed”, the plan to distribute enough vaccine for 300 million Americans in the most timely and efficient way. General Perna is an army logistics expert. (Check out Perna’s “60 Minutes” interview on November 6 for the details).

A problem to be solved with both the Pfizer and the Moderna vaccines is transportation and storage.

Pfizer’s vaccine needs to be really cold, stored at -112 degrees Fahrenheit. Pfizer is making special ultra-cold shipping boxes and storage containers for use until the vaccines are given. (For reference, your home freezer is 0 degrees Fahrenheit).

Moderna’s vaccine is a little less finicky, requiring “only” -4 degrees Fahrenheit. Additionally, Moderna’s can be stored in a regular refrigerator for 30 days after shipping.

The latest vaccine announcement comes from AstraZeneca and Oxford University.

How Does it Work?

Although the AstraZeneca vaccine is also bioengineered, it differs in delivery from the other two. The AstraZeneca vaccine uses a “vector” – a biological delivery truck – to deliver the genetic information needed to teach the immune system how to fight the actual COVID-19 virus.

The vector used is an adenovirus. This adenovirus causes colds in chimpanzees but is harmless to humans.

The adenovirus’ DNA is modified to contain the code for a COVID-19 spike protein. The adenovirus given in the vaccine “infects” human cells, delivering the gene for the spike protein. The cells in turn churn out the spike protein.

And just as with the other two vaccines, the spike protein teaches your system to fight future infections by the actual virus.

Adenovirus vaccines have been studied for decades, and European regulators recently approved a Johnson & Johnson adenovirus vaccine for Ebola.

Does it Work?

The AstraZenaca vaccine is reported to be about 70% effective. During the phase three trial, two versions were used. One version was 62% effective, one was 90% effective, for an average of 70%.

Is this enough data for AstraZeneca to ask for FDA emergency authorization? We don’t know yet.

Is it Safe?

AstraZeneca’s phase three trial was briefly halted due to possible reactions by two volunteers. However, the symptoms were found not to be directly related to the vaccine and the trials resumed.

That’s your cheat sheet for the first three vaccines.

So, what’s next?

Mark your calendars for December 10, 2020. Pfizer’s vaccine is on the FDA’s docket for emergency authorization consideration. If approved, get in line – healthcare workers, you’re first.

Regardless of your Thanksgiving dinner plans, consider this lovely little prayer, penned by Amanda Held Opelt, sister of Rachel Held Evans:

“These vaccines represent the tireless work by scientists & researchers who have already led lives of rigorous study and discipline. Lord, for these women & men, many of whose names we may never know, we give thanks.”

Happy Thanksgiving, 2020 style.

And as You speak

A hundred billion creatures catch your breath

Evolving in pursuit of what You said

If it all reveals Your nature so will I

(Hillsong United So Will I)

The hospital ward had beds for as many as fifty children.

Dr. Banting and his associate quietly stepped inside. Bed after bed was occupied by a child, comatose and dying from diabetic ketoacidosis. Grieving parents sat bedside, awaiting the inevitable.

The year was 1922. Medical researchers Fredrick Banting and his assistant Charles Best had been studying type 1 diabetes for the past two years. Using dogs, Banting and Best isolated insulin and treated (induced) diabetes in the animals.

We’ve known about type 1 diabetes for centuries. The condition is well documented in ancient Egyptian, Hindu, and Chinese medical records. Aretaeus of Cappadocia, a second-century Greek physician, described diabetes as “the melting down of flesh and limbs into urine”.

When the pancreas no longer produces insulin, people with type 1 diabetes cannot metabolize carbohydrates. Without insulin, patients waste away and suffer greatly, no matter how much they eat. The death rate for type 1 diabetes, prior to insulin therapy, was 100%.

By the nineteenth century, we realized the role of carbohydrate metabolism in diabetes. Doctors attempted to control the disease with diet – prescribing only meat or fat for suffering children. On severely calorie-restricted diets, children lost weight and were critically malnourished.

Still, instead of death in a few weeks, children might survive a year.

Encouraged by their success with dogs in the lab, Banting and Best injected an emaciated 14-year-old boy with insulin obtained from a cow in January 1922. Daily injections over the next twelve days dropped his blood sugar until it was no longer detectable in his urine.

Soon after, Banting and Best walked into the solemn and quiet ward in a Toronto hospital, filled with comatose children. Banting and Best went bed to bed and injected each child with insulin.

As they injected the last child, the first child woke up.

One by one, all the children awoke from coma.

A room filled with impending death became a place of hope.

The 1923 Nobel Prize in Medicine was awarded to Fredrick Banting and John Macleod, in whose laboratory Banting and Best worked. Banting shared his prize with Best.

The Eli Lilly Company improved the process for obtaining insulin from animals and sold the patent to the University of Toronto for $1.00.

For the next six decades, insulin for human use was obtained from the pancreases of pigs and cows, a difficult and expensive process.

Everything changed in 1982. Using new genetic technology, the gene for making insulin was snipped out of human DNA and inserted into the DNA of a bacteria. The new transgenic bacteria were cloned. Entrepreneur Bob Swanson and his partner biologist Herbert Boyer grew vats and vats of the bacterial cells, all of which churned out huge quantities of insulin.

HUMAN insulin.

For the first time, human insulin was produced in enormous quantities and made available to people with diabetes.

Human insulin was the first genetically engineered drug approved by the FDA. Today, hundreds of medical conditions are treated with recombinant DNA drugs.

Objections to genetically modified organisms (GMOs) play on fears of the unknown. All too often, biotechnology is rejected without fully understanding the underlying science.

Fear of GMO technology results in absurd nonsense like the marketing of “NON-GMO” labeled salt. Salt contains no DNA to modify.

The top five contenders in the race for a COVID-19 vaccine use genetic information to teach our immune system to fight a viral infection. Already the anti-GMO movement is joining forces with anti-vaccine groups. Already vaccines developed using biotechnology are suspect.

Drugs developed using biotechnology have saved countless lives. A new generation of bioengineered vaccines are ready to join to the fight.

November is National Diabetes Awareness month.

Thank you, Drs. Banting and Best.

And thanks to the pioneers in recombinant drug therapies.