Why We Need New Drugs, and Where They Might Come From

In 1928, Alexander Fleming discovered Penicillin quite by accident. Rarely in science are there “Eureka!” moments; more often, scientists are like lumberjacks. They do not know which swing will finally topple the mighty tree, but they keep swinging hard. Eventually, breakthroughs occur, but they require years of research and good luck. When Penicillin was discovered and developed into the first ever antibiotic, it was the equivalent of a redwood falling. Penicillin has saved millions of lives over the past half-century, and it launched an era of huge progress in the fight against bacterial infections.

But recently, Penicillin has become drastically less effective. Penicillin-resistant bacteria have become more and more common. In fact, selective pressure is causing resistant bacterial mutants to become immune the the majority of our drugs. We have a tendency to think that evolution occurs slowly over billions of years, but bacteria can evolve very rapidly. In the span of a few short years, many drugs can be rendered ineffective.

In the graph below, we see how MRSA has become more and more prevalent. The percentage of S. aureus which has become resistant to methicillin has been rapidly increasing. These increases are being seen across all bacterial infections which are treated with antibiotics.

How have we allowed this to happen? There are several factors which have contributed to the widespread antibiotic resistance we see today.

1. We over-prescribe antibiotics. Often, they are given to treat viral infections against which they will have no effect. This is the fault of both the patient for demanding antibiotics and the doctors for prescribing them.
2. Antibiotics are prevalent in trace amounts everywhere. For example, most of the animal products we eat are treated with antibiotics to promote the health of the animals and save money. But ingesting these antibiotics can help build up bacterial resistance in our own bodies.
3. When we misuse antibiotics, we don’t usually see the cost we impose on society. Every time you unnecessarily take an antibiotics, you promote the ability of bacterial infections to evolve. This will affect all of society, but you do not feel the immediate impact of your decision when you take the pill. This makes this problem similar to global warming; we don’t consider the potential consequences when we burn up fossil fuels.

We must come up with new ways to accelerate our drug discovery process. Alternatively, we must entirely rethink how we treat illness. This is not just limited to bacterial infections. We need to invent better ways to combat all forms of disease.

Accelerating Drug Discovery

The process of discovering, testing, and approving a drug for commercial use can take 20 years and over of 1 billion dollars. Obviously, decreasing both the time and the cost of developing these drugs can save many lives. There are some new technologies which are already helping to ramp up this process. For example, computational modeling of drugs has massively sped up the screening process for drugs. We can now take thousands of potential drug candidates and narrow them down to a couple viable options. But there are more ways we can expedite this process.

A recent estimate states that we now know the molecular cause of over 4,000 diseases — but we only have drugs for about 250. How can we do better? The FDA approval process is long and arduous. Even for compounds that have been approved in other countries, FDA trials can be drawn out for years. The FDA approval process can be responsible for about 25% of the cost of a drug and can delay the arrival of a drug over 10 years. There is even data that suggests that the FDA kills many more by not approving drugs than it ever saves by approving drugs (for more on the harmful effects of the FDA, see Cato, Forbes, The Independent Institute, and LifeExtension). By delaying good drugs that can save lives, and by doing little to stop bad drugs, the FDA is often an inhibitor to the medical process. We need to rethink the FDA if we want to streamline the drug discovery process. If we can change many FDA policies, we will see more drugs created for those 4,000 known targets.

Bacteriophages

Viruses get a bad reputation for causing disease, but it turns out we can actually use viruses as extremely helpful biological tools. Bacteriophages are viruses that infect and destroy bacterial cells. Phage therapy can be used to potentially treat pathogenic bacterial infections. Viruses carry genetic instructions, which we can program to destroy the target without harming human cells. Once the virus injects its genetic material into the bacterial cell, it will replicate within the cell, until it lyses and the virus is spread to new bacteria. One advantage to this approach is that bacteriophages are highly specific; the phage must have the correct protein to bind to the surface of the target cell, much like a lock and key. This way, the phage only infects the bacteria which we want to kill. Humans would remain unaffected, and more importantly, the helpful bacteria in our bodies would be unharmed. This specificity is better than most drugs on the market. However, this target-specific method is also a curse. We would have to develop a phage for each kind of bacterial infection, and it may be easier for resistant strains to mutate and dodge the phages. Creating mixtures of phages would be the most practical treatment, and they have been effective in penetrating biofilms, unlike antibiotics. There are no current phage treatments approved for use in the United States, but they have the potential to be further developed.

Probiotics

Much of this article has discussed antibiotics, but most bacteria are helpful or indifferent to our health. Probiotics is the concept that we can colonize the human body with bacteria that promote healthy functions.

Probiotics may help fight infection through competitive inhibition, out-competing bad bacteria for resources. Some probiotics also stimulate immune response, helping the body to fight off disease. Others may help produce useful vitamins. More research needs to be done on the efficacy of probiotics. Many of the products which currently claim to be probiotics are based on little or no evidence. There are no disease therapies currently involving probiotics, and we are unsure of their potential impact due to the lack of research. Discovering which probiotics are effective is difficult because there are millions of strains of bacteria to sort through.

Quorum Sensing

Bactiera communicate with each other by releasing signals called quorums. They have two different types of signals: one communicates only to bacteria of its own strain, and another that can communicate to a wide variety of cells. The discovery of quorum signalling showed that bacteria can behave differently when other bacteria are around. This allows them to move through phases together, coordinating invasive attacks on the host. It is also implicated in the formation of biofilms. There are no quorum sensing inhibitors potent enough to become drugs yet, but there is great hope that we will be able to slow the spread of resistant bacteria using this technology. If a few drug-resistant bacteria emerge, it will be difficult for them to proliferate effectively without the ability to signal other cells. Quorum sensing is yet another promising, innovative target for stopping the spread of disease.

Other Synthetic Biology Applications

Medicine is essentially a way to repair malfunctions in the human body. Synthetic biology re-engineers biological processes to prevent or repair those malfunctions; bacteriophages and quorum sensing are both types of synthetic biology. Since synthetic biology is still a relatively new field, creative scientists are coming up with many potential uses for the technology. Synthetic DNA may be able to stop mosquitoes from carrying disease. Modified bacteria may be able to target cancer cells. Synthetic genes encapsulated in liposomes may be be a better way to create vaccines. Engineering our own microbiome may help us to fight diseases. Synbio is one of the biggest buzz words in research today, and it will certainly be interesting to follow in the near future.

Dive Deeper

We thought we were running out of usable drugs, but recently, exploring the depths of the ocean have unveiled many more therapy options. So much of life on earth exists under the sea, and we’ve only explored 5 percent of the oceans. Already, drugs that have come from ocean life are being widely used, including 10 anticancer drugs. As we continue to discover new marine lifeforms and chemicals, we will create novel therapeutics that may not have been possible without our aquatic buddies.

We need to create new drugs now. We’re in a race against evolution itself. Can we innovate faster than disease? We’re unsure of exactly where the future of medicine lies, but I have faith that scientists will continue to find new treatments, whether they’re in our own cells or at the bottom of the ocean.

“The art of medicine consists in amusing the patient while nature cures the disease.” — Voltaire

For more posts about disease and biology, subscribe to Cell Your Soul. Feel free to comment below or message your feedback!