[Kim Byungmin's Science Village] The Law of DNA Twisted in One Direction... Decoding Nature's Cipher

Does a 'Miracle Drug' Exist?

Kim Byung-min, Science Writer

When you visit a pharmacy, you encounter many drug names. Among them, some names are already familiar, while others are chemical names you see for the first time. Even I, who studied chemistry, find many names unfamiliar, so I imagine most people would find them very strange and difficult. It made me think that pharmaceutical companies must struggle to name their drugs. For example, a drug like 'Benachio' immediately evokes the symptoms it is meant to treat just by hearing its name. This sometimes brings a smile when considering the naming intention.

Pharmaceutical companies either hide the drug's ingredients like a code or name them so that the ingredients are immediately recognizable. For instance, the 'A' in Aspirin stands for 'Acetyl,' and 'spir' refers to spiraeic acid, such as salicylic acid from meadowsweet. The main ingredient of Aspirin is acetylsalicylic acid. Ibuprofen, well known for its antipyretic, analgesic, and anti-inflammatory effects, is a case where the chemical name is openly revealed. The syrup form, Brufen, contains the same ingredient. The drug substance ibuprofen is the chemical name of the organic compound.

However, on the pharmacy shelves, there are health supplements with somewhat unfamiliar names following this naming convention. These are amino acid names that make up the proteins in our bodies, but they have the Roman alphabet letter 'L' prefixed to the name. In other words, the substance 'L-arginine' is used directly as a brand name.

The reason I can freely mention specific product names in this article is that the names are common chemical names. But is the term 'L' used only for arginine? In fact, it applies to ibuprofen and most organic compounds as well.

Moreover, this has a meaning beyond simply distinguishing chemical substances. For example, ibuprofen contains two components, L-ibuprofen and D-ibuprofen, in equal amounts. However, only D-ibuprofen has antipyretic and analgesic effects. Then, what about the other one?

The two substances have the same chemical elements. They have the same types and numbers of atoms, but their bonding differs, resulting in different properties. In chemistry, such substances are called isomers.

Among isomers, there are stereoisomers that even have the same atomic bonding. At first glance, they look like identical twins. But upon closer inspection, their arrangements differ. Simply put, they are like mirror images with reversed left and right spatial configurations.

The 'A' in Aspirin stands for Acetyl
Ibuprofen's L and D components have the same elements
But different chemical bonding makes them isomers
Like identical twins with different arrangements
Only one chiral form exists in nature
The secret of DNA's helix remains unknown

We see a reflection of ourselves in the mirror that resembles us, but in fact, it is a reversed left-right image. These molecules cannot overlap. Just as a right-hand glove does not fit the left hand. In chemistry, these are called mirror-image isomers or chiral molecules. 'Chiral' originates from the Greek word for hand. It refers to the fact that our two hands are reversed left and right and cannot overlap. Here, L and D are abbreviations of the Latin words Levo and Dextro, meaning left and right, respectively.

Why is this important? The two substances have very similar physical and chemical properties, making them hard to distinguish and separate. However, when such substances enter the body as drugs, the situation changes. For example, L-ibuprofen causes stomach irritation and liver burden.

Most artificial organic compounds are produced as both mirror-image isomers. So drugs are no exception. Most drugs exert their effects by interacting with enzymes in our bodies. Like a key fitting a lock, the structure must fit well for the effect to occur.

In the case of ibuprofen, the right-handed mirror-image isomer has the therapeutic effect. Therefore, unnecessary isomers are filtered out, and only the effective D-ibuprofen is extracted to make the drug. Dexibuprofen can achieve the same effect with half the dose of ibuprofen and without side effects.

Interestingly, natural substances produce only one chiral form, not artificial ones. They do not produce the opposite mirror-image isomer. Ultimately, the other isomer of the effective one either has no effect or acts as a toxin.

Looking at DNA, it twists in a helix in only one direction. This is because the sugar molecules that make up DNA are also one chiral form. It is mysterious and impressive, but humanity still does not know exactly why nature produces only one side.

Unaware of this, humanity experienced one of the worst events in the history of modern medicine. In 1959, the German pharmaceutical company Gr?nenthal developed a sedative called 'Thalidomide.' Thalidomide was called a miracle drug because no side effects appeared in animal and clinical trials, and it rapidly spread across Europe.

Gr?nenthal knocked on the door of the huge U.S. pharmaceutical market and applied for approval from the U.S. Food and Drug Administration (FDA). The reviewer at the time was Francis Oldham Kelsey (1914?2015), an American pharmacologist.

Kelsey was a prodigy who entered college at age 15. After working in research, he joined the FDA. His first approval review was for thalidomide, submitted by the German company. However, he rejected the application due to insufficient experimental data from the pharmaceutical company and inadequate review of the potential effects on fetuses if taken by pregnant women.

Kelsey, who rejected the most famous drug at the time, endured lawsuits for damages, various threats, and criticism from the pharmaceutical company. He also faced harsh criticism within the FDA. When he joined the FDA, the atmosphere was not favorable to hiring female researchers. His supervisor mistook him for a man just by his name, which allowed him to join.

One can imagine the hardship Kelsey endured. While he rejected approval six times over more than a year, the true nature of thalidomide was revealed. It was a drug that caused birth defects even with a single dose. Ultimately, about 12,000 children with birth defects were born in Germany in one year. Thalidomide was known for its excellent effect on morning sickness in pregnant women and spread rapidly by word of mouth.

The problem lay in thalidomide's molecular structure. One chiral molecule had the effect of relieving morning sickness, but the other inhibited blood vessel formation. As a result, the limbs, which are terminal tissues of the fetus, could not grow. The fact that only 17 birth defects occurred in the U.S. was thanks to Kelsey's adherence to scientific principles.

German sedative 'Thalidomide'
FDA Kelsey's courage in rejecting approval six times in one year
Serious side effects from one chiral molecule
Hoping no issues with COVID-19 vaccines and treatments

Recently, over 200,000 new COVID-19 cases have been reported daily in the U.S. The U.S. Department of Health and Human Services is expected to approve COVID-19 vaccines developed by two major pharmaceutical companies soon. The White House launched the vaccine development project called 'Operation Warp Speed' at the start of the pandemic. Given the project's name, unprecedented rapid approval of new drugs is not surprising.

Both pharmaceutical companies are reportedly ready to distribute vaccines within 24 hours of approval. Developing new drugs usually takes a long time. Of course, vaccines differ from treatments. However, the long time taken for new drug approval is due to thorough verification and testing for side effects. Therefore, the rapid moves of major pharmaceutical companies are indeed concerning. It feels like stepping into unknown territory.

I also hope that vaccines and treatments have no side effects. I hope this period, when everything has stopped, passes quickly. At the same time, I think that to achieve herd immunity, a sufficient population must be vaccinated. We still do not know how many doses are needed for effectiveness because we have no prior experience.

Moreover, from the perspective of social justice and the public good, vaccine benefits must be distributed fairly. Vaccination starting in developed countries could cause new social inequalities. In poor countries that do not receive benefits, COVID-19 could become endemic. This endemic disease might return to us in mutated forms at any time.

The arrival of vaccines is certainly hopeful. However, it is time to look at the hidden aspects of this hope in a multidimensional way, along with social justice. Everyone hopes for a miracle drug, but in a world and drugs made by humans, there seems to be no miracle. The other face of drugs is poison, and humanity always carries two faces...

Adjunct Professor, Nano Convergence School, Hallym University