Fighting HER2+ Breast Cancer with the Immune System

In the late 70s, scientists discovered that the body contains certain cancer-causing genes, which if mutated, lead to the development of cancer. This discovery unleashed a flurry of research in which scientists tried to identify genes that could be directly implicated in cancer. Scientists found one such gene – the HER2 gene – which is overexpressed in about 20% of breast cancers. This cancer was thus named HER2+ breast cancer. It is a particularly aggressive form of breast cancer; it typically does not respond to traditional chemotherapy, and patients with HER2+ breast cancer have a higher likelihood of cancer recurrence.

The HER2 gene codes for the HER2 is a receptor which, along with other receptors, plays an important role in regulating a variety of (sometimes contradictory) processes including cell growth, cell proliferation, and apoptosis (cell death when something in the cellular machinery goes very wrong). In normal cells, the activity of HER2 and the associated cell-signaling pathways is very strictly regulated.

The mutation causing this cancer leads to an overexpression of HER2 receptors, which in turn leads to the activation of signaling pathways that enhance cell survival and the suppression of the action of proteins that prevent the growth of damaged cells, both of which lead to the formation of tumors.

While most chemotherapy treatments have been ineffective at treating HER2+ type breast cancer, targeted immunotherapy in the form of trastuzumab has been effective in improving outcomes. Trastuzumab is a monoclonal antibody that binds to the HER2 receptor, which prevents HER2 from binding to the other receptors that are necessary for the activation of the signaling pathways that lead to tumor growth. The antibodies also activate the body’s immune system, which recruits cells that release cytotoxic chemicals into the environment surrounding the tumor cells, ultimately killing them.

While trastuzumab has improved the prognosis of HER2+ breast cancer patients – in some studies, the median overall survival has increased by nearly 5 years – many patients develop resistance against trastuzumab. This is often because the shape and structure of the HER2 receptor in tumor cells undergoes a change, due to which trastuzumab can no longer bind to HER2 and can no longer prevent it from activating signaling pathways. Further research into different targeted drugs is currently underway and in 2019, the Food and Drug Administration (FDA) approved another antibody, atezolizumab, to treat breast cancer.

References:
More on the discovery of the HER2 gene: https://www.gene.com/stories/her2/
How trastuzumab works: https://www-nejm-org.proxy.library.emory.edu/doi/full/10.1056/NEJMra043186
More on immunotherapies to threat HER2+ breast cancer: https://www.nature.com/articles/s41523-020-0153-3

15 Good Minutes: Nathan Jui

For Emory Assistant Professor Dr. Nathan Jui, the inspiration for his career in organic chemistry evolved in part from interests in cooking and building. Jui enjoys working on both of these in day to day life and sees similarities with his chemistry interest. Despite the complicated nature of his work, Jui believes that chemistry is similar on to these tasks as it similarly involves manipulating matter, just on a much smaller scale. In his research career, Jui uses this basic chemistry principle for groundbreaking scientific research in areas from cancer drugs to gene expression.

“Life is a bunch of molecules that interact with energy and do things that are really important,” Jui said. “But at the very bottom, basic level it’s all chemistry, and I thought it was really cool to be able to manipulate things on that fundamental level that can have impacts on all levels, from the materials that we deal with to the drugs that we take, to the way that we communicate with each other.”

Jui has been at Emory since 2014, where he runs a lab researching organic chemistry. He attributes his decision to come to Emory to the University’s strong reputation in chemistry, as well as its history of research and innovation. Jui’s lab is currently working on several groundbreaking projects. One notable area Jui is currently focusing on is in cancer research, where he and his team are looking into drugs that could override cancer cells’ ability to evade the immune system, utilizing the body’s natural machinery to destroy cancer. This stands in contrast to existing treatments such as radiation and chemotherapy, which essentially poison areas of the body to target cancer.

Another project Jui is currently pursuing is a new diagnostic tool to establish whether drugs will work in patients without requiring patients to try out the drug. This tool could be helpful in preventing unnecessary side effects from drugs by predicting efficacy before the drug is administered.

“We’re trying to use chemistry and a slew of other disciplines to help us make a tool that will figure out if drugs will work beforehand,” Jui said. “It’s a question we don’t have an answer to right now and that no one in the world has an answer to right now”

While Jui has yet to commercialize his research, he is working on several projects that he believes could eventually be commercialized. Jui says his field is open and collaborative by nature, oftentimes making commercialization unnecessary. However, in some instances, commercialization can be advantageous, although challenging.

“You have to make sure before commercializing a given project it’s going to work and it has to have a competitive advantage over everything else that’s been done in the same area with the same purpose,” Jui said. “So, the challenge is really getting something worth commercializing.”

Despite these challenges, Jui is optimistic that some of his innovations could eventually have commercial potential. He says that his relationship with Emory’s Office of Technology Transfer (OTT) will be a key component in this effort. Jui works with OTT on the patent and licensing processes for innovations discovered through his academic research.

“OTT is pretty responsive and pretty interested in commercialization of technology,” Jui said.  “And they’ve done it well in the past, and so hopefully some of the products I’m involved with will follow along those lines.”

Nathan Jui: https://www.juigroup.com/

Stems Cells as a Cancer Treatment

Within marrow tissue found in the center of bones, the body produces red and white blood cells, which are critical to transporting oxygen and fighting off infection. Certain types of cancers can cause serious damage to bone marrow, leaving patients without the blood cells needed to perform these important functions. Using stem cells from either the patient or a donor, doctors can now replace this tissue and allow patients to begin forming their own blood cells again. This procedure, which is known as a bone marrow or stem cell transplant, can be lifesaving for cancer patients.

Stem cells are cells within the body that can grow to serve as most other types of cells. They serve as a natural repair system for the body, allowing it to replace cells that are damaged beyond repair. Adult stem cells are commonly found in bone marrow and can be used to create new bone marrow tissue. Once implanted within bone marrow, the stem cells divide and modify themselves to form specific functions.

Stem cell transplants are most often used for patients with leukemia and lymphoma, cancers that directly attack bone marrow tissue. They can also be used to replace bone marrow damaged by very high doses of chemotherapy and radiation therapy used to treat other cancers. Once the patient receives an initial high dose of radiation or chemotherapy, they can then begin to receive the transplanted stem cells. The stem cells are injected directly into the patient’s bloodstream through an IV. Once inside the bloodstream, the stem cells then make their way to the damaged bone marrow tissue and begin to implant and grow. Over several months, the body begins to form new blood cells. It can take several months for red blood cell counts to be replenished, and up to two years for the immune system to fully recover.

Stem cell treatments fall into two specific categories depending on the source of the new cells. In autologous transplants, the cells come from undamaged tissue in the same patient. This technique is often used on cancers that do not directly attack the bone marrow tissue. Before chemotherapy or radiation therapy, bone marrow tissue is taken from the patient. Once this initial therapy is complete, the tissue then can be injected back into the patient, allowing the bone marrow to regenerate. Autologous transplants are preferable in many circumstances since the body recognizes the newly introduces tissue and does not mount an immune response as a result.

However, in cases of cancer such as leukemia that attack marrow tissue, patients may not have undamaged marrow tissue to collect. In these cases, a transplant from another donor becomes necessary. These cases are known as allogeneic transplants. In an allogeneic transplant, patients are matched with donors by human leukocyte antigen (HLA) type. HLA are proteins that exist on most of the body’s blood cells and help the body distinguish normal cells from foreign ones. Having a similar marker reduces the chances that the patient’s immune system will reject the cells, a condition known as Graft versus host disease (GVHD).

For an allogeneic transplant, a patient’s blood is first sampled to determine the HLA type. The patient is then matched with a donor, a process that can take several weeks. While the best donor is generally an immediate family member, 75% of patients do not have a suitable donor in their family and require an unrelated donor. These donors can be located through national registries such as the National Marrow Donor Program.

Stem cell transplants play an important role in treating cancers that damage bone marrow as well as in complimenting other types of cancer treatments by mitigating harmful side effects. Using modern technology, these transplants can be completed quickly and minimally invasively. Although the recovery process can be long, stem cell transplants allow many patients to eventually resume normal, healthy lives.

References:
https://www.mdanderson.org/treatment-options/stem-cell-transplantation.html
https://www.cancer.net/navigating-cancer-care/how-cancer-treated/bone-marrowstem-cell-transplantation/what-bone-marrow-transplant-stem-cell-transplant
https://www.webmd.com/cancer/cancer-stem-cell-treatment#1
https://www.cancerresearchuk.org/about-cancer/cancer-in-general/treatment/bone-marrow-stem-cell-transplants

Understanding Your Gut-Brain Connection

We are all familiar with the phrases “go with your gut,” “gut-wrenching experience,” or “butterflies in your stomach.” Although these phrases and idioms might be used in very different situations, they all suggest a connection between our gut and our emotions. Scientists have studied this connection for a long time and have identified how our brain can influence our gut. For example, simply thinking of eating can release stomach juices even without the presence of food. However, recent studies have suggested that the gut-brain connection might go the other way around too.

The Gut-Brain Axis (GBA) refers to the bidirectional communication between the central nervous system and the enteric nervous system. The enteric nervous system (ENS) is made of two thin layers of millions of nerve cells that line your gastrointestinal tract from the esophagus to the rectum.  The main role of the ENS is to control digestion from the swallowing point to nutrient absorption. The ENS connects our cognitive and digestive behavior through communication with our brain.

This communication is linked to various emotional shifts related to the gut. For example, ENS may trigger drastic emotional shifts for people dealing with irritable bowel syndrome (IBS), diarrhea, upset stomach, and even bloating. Studies have also found that a high percentage of people with IBS and functional bowel problems develop depression and anxiety. There are even recent studies that have linked microbiome diversity in the gut to mental health.

This understanding of our gut’s influence over our emotions has led to new treatment opportunities. For example, gastroenterologists have begun to prescribe antidepressants for IBS because some of these medications can give calming effects by acting on nerve cells in the gut. Mind-body therapies are also emphasized with the gut-brain connection. Gut-directed hypnotherapies, yoga, and meditation are proven to improve gastrointestinal issues, improve emotions, and decrease anxiety.

Research surrounding the gut-brain connection presents a holistic view of health where the different systems of the body are recognized as interconnected. Learning about this connection can help you assess your gastrointestinal issues, and to evaluate them alongside the emotions and stressors in your life. For all you know, “butterflies in your stomach” can be more than a simple idiom.

References:
Johns Hopkins: https://www.hopkinsmedicine.org/health/wellness-and-prevention/the-brain-gut-connection
Harvard: https://www.health.harvard.edu/diseases-and-conditions/the-gut-brain-connection
https://www.health.harvard.edu/blog/brain-gut-connection-explains-why-integrative-treatments-can-help-relieve-digestive-ailments-2019041116411
Duke: https://dukeintegrativemedicine.org/DHWBlog/understanding-the-basics-of-the-gut-brain-connection/

What are the Different Types of Stem Cells?

Adult stem cells exist in several parts of the adult body. These cells have the ability to become specialized cells only for the type of tissue in which they exist. For example, liver stem cells can regenerate liver tissue, and muscle stem cells can regenerate muscle fibers, but not the other way around. Adult stem cells are important for replacing dead cells in the tissue and assist in the healing process after tissue injury.

Embryonic stem cells, also called pluripotent, are responsible for the creation of thousands of different cell types that make up our bodies. Pluripotent stem cells are able to create all cell types in the human body, unlike tissue stem cells. However, embryonic stem cells are usually limited during the development period, and are eventually replaced by adult stem cells.

Induced pluripotent stem (iPS) cells are pluripotent cells that are derived from adult tissue using new scientific developments. Scientists have found that when adult stem cells are cultured in the right circumstances, they can revert their differentiation process and go back to the pluripotent state. This means that they can then be used to create any cell type in the body, when placed in the appropriate environment for specialized differentiation. iPS cells are studied extensively in the context of organ generation for transplants, as well as for various types of injuries and diseases.

Resources:

Stem Cells: What they are and what they do https://www.mayoclinic.org/tests-procedures/bone-marrow-transplant/in-depth/stem-cells/art-20048117

Stem Cells: https://www.closerlookatstemcells.org/learn-about-stem-cells/types-of-stem-cells/

 

The Brain-Blood Barrier and the Future of Medical Treatments

The blood-brain barrier is a biological structure that acts to maintain a homeostatic environment within the Central Nervous System(CNS). You can think of it as your brain’s wall of defense. The blood-brain barrier is known as a diffusion barrier because it is semipermeable. This means that it only allows some substances to enter the brain while preventing other harmful substances from circulating in the bloodstream and the brain. This can be thought of as a filtration or vetting system.

This semipermeable barrier is achieved through endothelial cells. Endothelial cells line the inside of every blood vessel in the body and form a one-cell-thick later called the endothelium.  The blood-brain barrier is a layer of endothelial cells that selectively allow entry of molecules needed for brain function. Unlike these other blood vessels in the body, the endothelial cells in the brain are tightly wedged together which creates the semipermeable boundary between the brain and bloodstream. The molecules that are permitted entry through this boundary are amino acids, oxygen, glucose, and water. This ensures that the right balance of hormones, nutrients, and water is flowing throughout the brain.

Research surrounding the blood-brain barrier and medical treatments has many challenges. Most drug treatments are unable to pass through the barrier, which is why drug development for brain diseases have poor success rates compared to the development of drugs in other areas of the body. In cancer, for example, the blood–brain barrier is largely responsible for the failure of brain of cancer treatments. The blood-brain barrier actively pumps selected molecules into or out of the brain and can prevent the drugs from entering the brain. In many instances where the cancer drugs do manage to cross the blood-brain barrier, they are promptly kicked back out by active efflux pumps<. Another issue with the blood-brain barrier and cancer treatments lies in the fact that the molecules that can easily slip across the barrier tend to be small and highly lipid-soluble. This presents a challenge since many lipid-insoluble biological drugs have improved outcomes for many other types of cancer.

Despite the challenges of the blood-brain barrier and cancer treatments, studies have proven that your brain’s wall of defense can also act as a potential noninvasive treatment tool for many neurological diseases. Through extensive studies, scientists have found that very small compounds or compounds that are lipid-soluble can pass through the endothelial cells of the blood-brain barrier with almost no effort. These compounds include antidepressants, anti-anxiety medications, alcohol, cocaine, and many other hormones. The passing of larger molecules such as glucose or insulin is also possible with the help of transporter proteins.

Blood-brain barrier research does not stop there. There are currently several ways that researchers are attempting to combat the challenges of the blood-brain barrier and medical treatments. One example of this is the development of cyclic peptides that can enhance the penetration of the blood-brain barrier. This is achieved by attaching the cyclic peptides to the surface of nanoparticles. This creates a drug nanocarrier for drug delivery through the blood-brain barrier, which is promising for the future effectiveness of drug delivery to the brain.

The future of medical treatments through the use of the blood-brain barrier continues to move forward. As scientists continue to explore this biological barrier, new and noninvasive treatments will arise to address cancer and other neurological diseases.

References:
NCBI: https://www.ncbi.nlm.nih.gov/books/NBK519556/
Science Daily: https://www.sciencedaily.com/releases/2019/10/191011095933.htm
Cure Alzheimer’s Fund: https://curealz.org/the-research/topics-of-interest/blood-brain-barrier/
Nature: https://www.nature.com/articles/d41586-018-06707-4
Pharma Tech: https://pharma.nridigital.com/pharma_jul20/breaking_blood-brain_barrier_neurology

History of Ventilators

Ventilators are machines that can help patients breathe, or, in some cases, breathe for them. Doctors use ventilators on patients in very severe cases, when it is determined that the patient does not get enough oxygen from regular breathing or through increased oxygen supply. While on a ventilator, the patient’s lungs have the opportunity to start healing and receive much needed medications, until breathing can be restored. Ventilators are now a standard part of critical care and have significantly evolved in their technology over the last 100 years.

The earliest attempt to support breathing mechanically can be traced all the way back to the late 18th century. These early visions of ventilators relied on negative pressure that is also seen in the most widely used ventilation device of the 20th century, the iron lung (for more information on iron lungs visit https://www.futurity.org/ventilator-history-2335052/). During the polio epidemic of the early 20th century, children with paralyzed lungs were placed in these machines, which expanded and contracted to force air into and out of the lungs. This technique required a patient to be fully encased in the iron lung with only their head sticking out. In the 1960s, researchers started developing positive-pressure machines, which force air directly into the lung. This technology caught on fast, and nowadays all modern ventilators rely on positive pressure. These machines require the insertion of a tube into the patient’s trachea, while the patient is sedated (intubation), making them more invasive than negative pressure ventilators.

Modern mechanical ventilators are much more portable than their predecessors and provide many adjustable features that can facilitate air flow and adjust the pressure and rate according to the patient’s needs. The goal is to optimize the process for each patient, to ensure as much comfort as possible and have a better outcome. While they are generally computerized microprocessor-controlled machines, patients can also be ventilated with a simple hand-operated bag valve mask in case of emergency.

Given the importance of ventilators in hospitals, we expect that future developments will allow them to integrate even further with other components of critical care. This will likely be assisted by electronic means of communication between different bedside devices for a more efficient interaction. Other possible features are the incorporation of ventilator management protocols into the basic operation of the ventilator, displays with organized information instead of rows of unrelated data, and smart alarm systems. Doctors hope that these improvements will lead to better outcomes for the patient and a higher level of care.

(For a further depth study on the past, present, and future of ventilators visit: http://rc.rcjournal.com/content/56/8/1170)

The Institutional Review Boards 101

New discoveries of therapies and drug mechanisms are not always the daily news headline, but today ethical guidelines exist to continue to keep a standard of the production of any new medication or treatment. However, the history of clinical research has not always been so ethical. For instance, the PHS Syphilis Study in Tuskegee, AL and the Willowbrook Hepatitis Experiments, are only two of many notorious examples of horrifically unethical clinical trials. The purpose of this article is to bring light into the role of the Institutional Review Boards (IRB) in relationship to on ongoing  clinical trials today to ensure safety for human participants.

In 1974, Richard Nixon passed the National Research Act. This act was created to ensure excellence of biomedical and behavioral research within the United States. These guidelines within the National Research Act emphasized a respect for autonomy, beneficence, and justice for research participants. As a result, the Institutional Review Boards (IRB) was formalized, for all DHHS-funded research, as a Committee. This committee would reside either within the research institution or be external (e.g., commercial IRB’s); and would be an ethical review board designated to protect the rights and well-being of human research participants.

The IRB must be independent from the institution for which it reviews research to avoid any inherent bias within the study, though it is often made up of faculty and staff of the institution. The IRB functions to review and monitor research involving any human subjects. This board has the power to approve, enforce any change, or reject research of a clinical trial. Moreover, patient safety is a priority in clinical trials and the IRB plays a fundamental role in this. Thus, the board will review the protocols and progress throughout the study. The main goal of the IRB is to confirm that the right steps are taken to protect the welfare and the rights of participants. The IRB also operates to verify the integrity and quality of the data being collected. IRB is also required by the Federal Drug Administration (FDA) regulations and may perform audits of the clinical trial study records.

Prior to a patient being recruited for a clinical trial, there must be both legal and ethical steps to ensure the patient fully understands what their part in the clinical trial will entail. The IRB will review documentation presented to participants to ensure procedures, risks, and benefits are discussed. This process is known as informed consent. Informed consent consists of verbal and written documentation that confirms the participants acknowledge and understand their part in the clinical trial in its entirety. A signed informed consent document is part of the process for ensuring that the institution is compliant. This process is designed to help patients thoroughly understand what to expect as well as the risks and benefits of participating. It’s important to note that the informed consent form is only one part of the informed consent process; there must also be an ongoing process, including updating the participant of any new information throughout the study.

In conclusion, while some of the history of clinical trials is disheartening, today the IRB continues to provide advocacy and protection for any participant within in a clinical trial and remains to be an integral component to the welfare and safety of human participants within clinical trials.

Resources:

The History and Role of Institutional Review Boards: A Useful Tension:  https://journalofethics.ama-assn.org/article/history-and-role-institutional-review-boards-useful-tension/2009-04

Being in a Clinical Trial: https://www.cancer.org/treatment/treatments-and-side-effects/clinical-trials/what-you-need-to-know/what-does-a-clinical-trial-involve.html

Clinical Trials: What Patients Need to Know: https://www.fda.gov/patients/clinical-trials-what-patients-need-know

Thinking about joining a clinical trial? Here’s what you need to know:  https://www.health.harvard.edu/blog/thinking-joining-clinical-trial-heres-need-know-2016090110187

Fats: The Good, The Bad, and The Ugly

Fats are confusing. There are some good ones, a lot of bad ones, and it is hard to keep track of the ones you want and the ones you don’t. Hopefully, this article will help keep things straight.

The body contains three types of lipids. Lipids are a class of organic compounds that are insoluble in water. One of the least talked about but most important types of lipids in the body are phospholipids. Phospholipids are the main constituent of cell membranes and play an important role in determining what enters the cell and what is left out.

The second type of lipids are called sterols. Cholesterol is a sterol and is used by the body in the synthesis of hormones. Cholesterol is, of course, infamous for its links to cardiovascular disease. However, there are two types of cholesterol – “good” cholesterol and “bad” cholesterol. This classification is based on the type of lipoproteins in which the cholesterol is contained. Lipoproteins are essentially large droplets of fats. The core of lipoproteins is composed of a mix of triglycerides and cholesterol and this core is enclosed in a layer of phospholipids. There are five different types of lipoproteins, but the two types that are most known are low density lipoproteins (LDL) or “bad cholesterol” and high-density lipoproteins (HDL) or “good cholesterol.”

Bad cholesterol, in high quantities, accumulates in the walls of arteries, where LDLs are oxidized.           Oxidized LDL causes damage to the walls of arteries. This damage leads to inflammation which leads to a constriction of arteries (leading to high blood pressure) and to further accumulation of cholesterol, leading to the formation of plaques. These plaques further narrow arteries, decreasing the flow of blood and oxygen to tissues.

High density lipoproteins, or good cholesterol, on the other hand plays an important role in reverse cholesterol transport, a process by which excess bad cholesterol is transported to the liver for disposal. Good cholesterol also has anti-inflammatory and vasodilatory properties and protects the body from LDL-oxidative damage.

Perhaps unsurprisingly, fried food, fast food, processed meats, and sugary desserts lead to increased bad cholesterol levels while fish, nuts, flax seeds and – you guessed it! – avocados lead to increases in good cholesterol levels.

The final type of lipids in the body are triglycerides. Triglycerides are the fat in the blood. Any calories that are not utilized by the body are stored in the form of triglycerides. The effect of high levels of triglycerides on the heart have not been as well understood. Excessive triglyceride levels are typically accompanied by high (bad) cholesterol levels and research in the past couple of years has indicated a relationship between high triglyceride and risk for cardiovascular disease.

The fats that we consume, however, are not in the form of triglycerides. The fats that we consume are broken down and converted into triglycerides and cholesterol. The major dietary fats are classified into saturated fats, trans fats, monounsaturated fats, and polyunsaturated fats.

Saturated fats are fats whose molecules have no carbon-carbon double bonds. Saturated fats are fats to be avoided because they increase LDL levels by inhibiting LDL receptors and enhancing lipoprotein production. Saturated fats are solids at room temperature and are found in fatty beef, lamb, pork, butter, lard, cream, and cheese.

Trans fats are also bad fats. They are typically found in margarine, baked items, and fried food. They suppress chemicals that protect against the build up of plaques in artery walls, increase bad cholesterol and decrease good cholesterol.

Monounsaturated fats and polyunsaturated fats are fats that have one (mono) and many (poly) carbon-carbon double bonds in their molecules respectively. These fats are liquids at room temperature and are found in salmon, nuts, seeds, and vegetable oils. Polyunsaturated fats are associated with decreased bad cholesterol and triglyceride levels.

Keeping track of which fats are found in which food can seem intimidating, but foods that lead to increased good cholesterol levels are foods that are typically considered healthy – nuts, seeds, fish, fruits, and vegetables, while foods that lead to excessive bad cholesterol are foods that we are taught to avoid in excess anyway – such as processed and fatty meats, processed food, and fried food.

Resources:
Contains both information on what various types of fats are and also food that contains the respective fats: https://www.hsph.harvard.edu/nutritionsource/what-should-you-eat/fats-and-cholesterol/types-of-fat/
A guide to choosing healthy fats: https://www.helpguide.org/articles/healthy-eating/choosing-healthy-fats.htm
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5577766/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5586853/

A History of the Hippocratic Oath

The Hippocratic Oath is arguably one of the most famous oaths of ethics in our history. Originating in Ancient Greece, it centers around medical practitioners swearing, “by all gods and goddesses,” physicians will uphold various ethical standards in their medical practice. Contrary to popular belief, the oath does not actually contain the renowned phrase, “First, do no harm,” an expression that has now become synonymous with the oath itself. Dated back to the fifth and third centuries B.C., the oath is often attributed to the Greek doctor, Hippocrates, though scholars have contended that it could, instead, be a work of the Pythagoreans. While its oldest remaining fragments date back to AD 275, the oath has been continually rewritten and adapted over the centuries to better suit the values and beliefs of evolving cultures and ethical standards.

Following the collapse of the Roman Empire and its religious ideals, today’s “multiethnic, multicultural, and pluralistic world” no longer worships ancient divinities such as Apollo or Asclepius (Indla, Radhika, 2019). As history progresses, the Hippocratic Oath has faced ideological challenges due to new and emerging technology, that did not exist in the era of Hippocrates. For instance, the Hippocratic Oath did not take into consideration a patient in a vegetative state, a patient suffering from pain, a patient requesting for an abortion, or addressing other autonomous rights of a patient. Considering that technology has and continues to advance the ancientHippocratic Oath has faced many modern-day dilemmas.

Consequently, the period following World War II, saw one of the Hippocratic Oath’s most significant revisions: the Declaration of Geneva. During this period, the tradition of medical graduates reciting the Hippocratic Oath became more than a mere formality. As such, the World Medical Association (WMA) altered the oath in the 1960s to state that providers would “maintain the utmost respect for human life from its beginning.” Making the custom a more secular obligation, that the oath is not to be taken in the presence of any divine figures, but before only other people. This served as a test of a practicing physician’s ethical, moral, and emotional standards, an especially remained an important notion after the atrocities of WWII.

As a result of this, in 1964 the Hippocratic Oath faced further revision. These alterations are most notably addressed by Dr. Louis Lasagna’s 1964 revision of the oath, which cites that “[doctors] do not treat a fever chart, a cancerous growth, but a sick human being, whose illness may affect the person’s family and economic stability.” Such changes represent the increasing humanization of the relationship between a doctor and a patient. Despite the controversies that have come with these changes, such alterations begin to represent the influence that cultural identities and contextual values demand on the form of the oath. In fact, in 1973, the US Supreme Court rejected the Hippocratic Oath as a guide to medical ethics by determining that the oath is unable to maintain changing medical ethics and codes. The final, most modified document of the Hippocratic Oath, known as “Pellegrino’s Precepts,” which functions as a set of principles. These precepts directly speak to doctors and are a “universal set of precepts about the nature of medicine” in contrast to the Hippocratic Oath.

In modern times, the Hippocratic Oath has essentially been replaced by more extensive and pragmatic ethical codes issued by national medical associations, such as the AMA Code of Medical Ethics, or the British General Medical Council’s Good Medical Practice. These documents offer a more comprehensive overview of the responsibilities and professional behavior expected of a doctor to their patients and to society, rather than to healing gods and other divinities. As such, in the United States, many of the medical schools use the Osteopathic Oath in place of the Hippocratic Oath. For instance, schools such as, New York Medical College, University of California, or Tulane, have had medical students vow to not discriminate against patients based on “gender, race, religion, or sexual orientation.” Hence, as time passes, many of today’s doctors face various ethical issues that are not included in the Hippocratic Oath. Therein lies the question, “is our society in a post-Hippocratic era?” With a modern society, continuing to evolve, physicians have begun question whether the Hippocratic Oath holds outdated principles. If so, how can medical students incorporate an evolving society to protect patients. Despite this, many providers argue that the Hippocratic Oath epitomizes ideologies of gratitude, beneficence, and humility.

While there is no direct punishment for breaking the Hippocratic Oath, a notable, modern equivalent is ‘medical malpractice’ which carries a wide range of punishments from legal action to civil penalties. Doctors who violate these principles are at risk of being subjected to disciplinary proceedings, including the loss of their license to practice medicine.

Overall, what began as an ethical principle in Ancient Greece saw itself transformed frequently through time as a result of contemporary ideals and beliefs. From a prominent idea to a mere formality, the importance of the Hippocratic Oath has fluctuated almost as much as its content. While it may no longer be the central ideal of medical ethics, its ideas have ultimately pioneered modern practices and formed the crux of what we now call medicine. Today, 100% of medical school graduates in the United States swear to some variation of the Hippocratic Oath; therefore, the responsibility to continue to pursue beneficence, compassion, and humility within the field of medicine maintains its utmost significance.

See the Emory Class of 2020 Hippocratic Oath at Emory School of Medicine!
“The Oath of Hippocrates”
As the ancient Greeks swore by their pagan gods, so do I solemnly affirm that as a student in medicine at Emory University, according to my ability and judgment, I will keep this oath and stipulation. I will consider dear to me those who have taught me this art and will impart the precepts and instruction of the profession to all those who qualify as students of the art and agree to the standards of the profession. I will follow that system of regimen, which according to my ability and judgment I consider for the benefit of my patients, and abstain from whatever is deleterious and mischievous. Into whatever house I enter I will go into it for the benefit of the sick, and will abstain from every voluntary act of mischief and corruption. Whatever in connection with my professional practice or not in connection with it, I see or hear in the lives of men and women which ought not be spoken of abroad, I will not divulge, as reckoning that all such should be kept secret. While I continue to keep this oath inviolate, may it be granted to me to enjoy life and the practice of the art, respected by all people in all times, but should I trespass and violate this oath may the reverse be my lot.”
– Emory School of Medicine Class of 2020

Resources