No two sand grains in the vast African Sahara, no two celestial bodies in the immense universe, no two leaves in the Amazon rainforest, or no two mortal human beings are exactly the same. As the American mythologist Joseph Campbell (1904-1987) once said, “There are something like 18 billion cells in the brain alone. There are no two brains alike; there are no two hands alike; there are no two human beings alike.” Thus, he asks us to find our ‘own path.’
However, to perceive, interpret, and manage the world, we have no choice but to oversimplify it by imposing our rude mental order to unruly super-diverse nature. We, for example, recognize just two kinds of people: sick or sound. And then we have kinds of sickness, each with its own symptoms; similar discomforts that affect everyone similarly. And when your sickness is diagnosed, there is pre-made medicinal provisioned to be prescribed with a pre-determined dose for the condition, not for ‘you’ in your unique current condition.
This oversimplification, or ignoring differences in genetic makeup, is where the side-effects are born. Side-effects are a more common outcome of modern treatment procedures than may be thought. In an attempt to find for each person his “own path,” personalized genetic medicine is developing to avoid serious drug side-effects.
Now doctors can ask for genetic testing to know which drugs, by what doses, would work best in the body of that particular individual. Eventually, the remedy may be in the genes of the holder body. Otherwise, the doctors are compelled to try various drugs once at a time to find the effective one, which is doomed to include errors. Needless to say, how agonizing and dangerous the process could be to the patient.
For example, some gene variants, or alleles, may make your body less-or unresponsive to a certain drug and require you to take a larger dose or turning to substitutes. Currently, testing for genetic mutations to prescribe appropriate medications with more precise doses has become conventional for patients with various tumors such as melanoma and lung cancer.
Consider, for example, simvastatin, which is a commonly prescribed drug to manage high blood cholesterol. Having a rare variant of the gene SLC01B1, however, not only makes simvastatin ineffective on you but also may lead to some severe damage to your muscles. Even the standard doses of some medications could raise the chance of stroke or heart attack in about 5 percent of people. Knowing your genetic makeup could be as life-saving as knowing your blood type.
Pharmacogenomics, the study of gene-drug matching or how genes may affect a person’s response to drugs, is the most accessible part of the future desired by personalized medicine, where all treatments would be tailored to the individual’s unique genetic makeup. Human genome sequencing cost has been continually going down in recent years, and a whole-genome could be sequenced for about 600 US$. And in cases where you need just a partial sequencing with a few hundred genes, it can be done by one third for that price and in a couple of days.
Genetic testing has become an effective method in the toolkit of modern medicine. It is being used routinely to identify those with a high risk of getting diseases like Alzheimer’s, Parkinson’s, and breast cancer.
Personalized Medicine
Precision medicine has its roots in the Human Genome Project, which was accomplished in 2003 and produced a map of more than six billion nucleotides of the human genome. Having all the genes sequenced, it seemed at first easy to find links between each gene variant and a specific disease.
To make it a cost-effective approach, it was enough to sequence a small stretch of the patient DNA to find defective variants. Pharmaceutical companies, hoping to find a treasure trove, rushed to invest massively in this new approach.
However, this view to gene-disease dynamics has turned out too simplistic since then, and it seems there is not such a one-to-one allele/disease correspondence. It’s been made clear that each condition is indeed the consequence of many gene variants (alleles) added up, each having a slight effect raising the risk.
Then, the differences are not only between individuals. Even a single individual is subject to change through his life due to many so-called ontogenetic processes. As they say, you cannot step into the same river twice. This is the reason your dentist requests a new radiograph every two years. This is the case about genes, too, as they don’t express simultaneously, incessantly, and consistently all your life. After all, many so-called late-onset diseases are because of genome changes over our lifetime.
So, what’s the solution? Should a new medicinal suit be ‘tailored’ for a patient every time? The supporters of precision medicine seem determined to embrace the complexity to any level it takes. To reach a comprehensive view, we should not limit our scope only to genetic differences but examine the entire genome and supplement it with other kinds of information such as family history, microbiome (the microbes that live inside and on the human body), and epigenome (some proteins that attach to DNA and turn genes on or off) by studying large cohorts of patients who take a specific medication.
This way, the researchers hope to be able to determine the combination of factors leading to a certain disease. This is indeed an ambitious plan for the customization of healthcare.
Building a Future
To such a future is contributing Ali Khademhosseini, an Iranian-American biomolecular researcher at Terasaki Institute for Biomedical Innovation (TIBI), Los Angeles. Khademhosseini, 45 and a recipient of many prestigious awards, among them the 2019 Mustafa Prize for his work on ‘micro-fabricated hydrogel for biomedical applications,’ takes a bioengineering approach towards precision medicine. He and his team work to improve using custom-fit implants and devices, biomaterials, organs-on-chip, and other strategies that increase precision medicine accuracy and make it more applicable.
Some of the devices Khademhosseini and his team have engineered so far include wearable sensors for real-time monitoring, webcam technology to measure medications’ effects on the heart, development of inflatable stents to be applied in endovascular treatments, and patient‐specific bioinks to be used in 3D printing scaffolds of various implant tissues.
In a recent paper on organ-on-chip, which is a microphysiological system for assessing toxicity and therapeutic effects of a potential drug, he and his team utilize ‘multiorgan‐on‐a‐chip systems for advancing nanotechnology’ that may play a part in the future of precision medicine. In another recent paper in the journal of Advanced Drug Delivery Reviews, they explain how micro and nanoscale technologies in oral drug delivery can “enable fabrication of oral drug carriers as well as human tissue-on-a-chip models for precision medicine applications.”
This is not an easy accomplishment, and Khademhosseini and his team have discussed in their many contributions to the field the main challenges of engineering precision medicine.