Science Archives - Philosophy of Biology and Health

Dawn of a biotechnology renaissance… and is our society ready for it?

Novel biotechnologies and biomedical innovations are of great interest to me. Not just the science and technology but also the economics, policy, and ethical considerations. Over the past year, I have dedicated much of my blog posts to exploring novel innovations in biotechnology – the miracle of mRNA technology, COVID-19 vaccines, and the future mRNA marvels to come from such advancements. I have sought to answer critical questions such as: how we as a society have fared worse in the COVID-19 pandemic, despite the breakthroughs in technology, compared to the Spanish Influenza 100 years earlier. I explored challenges posed by the pandemic, often in real time, across ethical, business, legal and socio economic considerations. I warned early on about the chasm to go from vaccine development to vaccinations. I made a compelling case for global vaccine collaboration. I even estimated the economic business case for such global vaccine collaboration within a few million dollars of what was estimated by respected organizations such as the Rockefeller Foundation (Rockefeller Foundation).

My interest in biotechnology and biomedicine preceded the pandemic and will continue to extend well beyond. More broadly as I have been reading about the incredible advancements in biotechnology over the past four years, I have begun to develop a rather bold hypothesis:

I believe that we as a society stand at the dawn of a biotechnology renaissance. An upcoming period that has the potential, over the next decade or two, to more rapidly and meaningfully improve the health and well-being of humanity than in any other point in human history!

I will continue to elaborate on and evaluate this hypothesis in future blogs. Most importantly, whether or not we realize the full potential of these incredibly promising advancements in biotechnology will depend on whether we as a society are prepared to ethically and equitably manage these potentially life-changing biomedical innovations for the good of society at large.

As one example, recently I was struck by the positive early results to use cell therapy, not just to treat but to potentially cure type 1 Diabetes. Vertex Pharmaceuticals, a biopharmaceutical company, made headlines when its novel stem-cell therapy reversed Type 1 Diabetes in a single patient. Type 1 Diabetes has traditionally been a chronic disease in which the body cannot produce enough insulin. While the exact cause of the disease isn’t fully known, Type 1 Diabetes is considered to be caused by an autoimmune reaction – where the body’s immune system attacks the insulin-making beta cells of the pancreas (CDC). Often, people with Type 1 Diabetes are genetically predisposed. Epigenetics and outside life influences, such as a viral infection, can increase the likelihood of the disease. Once the gene is activated, the disease progresses. However, thanks to the research done by Vertex, a cure might finally be feasible.

In their first patient, a man who’d been suffering from Type 1 Diabetes for decades, Vertex’s therapy saw a resulting 91% daily drop in the required insulin doses previously necessary. They deemed it a potential “functional cure” – not necessarily a one-time cure, but one that allows the disease to be managed without consistent medication. The therapy is conducted through a series of synthetic islet cell transplants (Vertex). Islets are clusters of various cells – including beta cells – within the pancreas that help secrete Insulin. In Type 1 Diabetes, these cells are unable to naturally create the hormone. In traditional Islet transplants, Islets are isolated from 2 donors using various enzymes by a radiologist, who is able to guide these cells into the pancreas of the recipient. The goal is that these transferred cells achieve insulin independence and are able to create insulin on their own. Often, these transfusions are unsuccessful as the host body rejects the foreign Islet cells.

To solve this challenge, Vertex’s cure has Islet cells that are synthetically manufactured with novel immunoprotective devices. These devices are designed to evade recognition from the body’s immune system. This allows the cells to successfully transfer into the patient’s body. Transplantations are conducted via an injection, with an infusion of these synthetic insulin-producing cells” (clinicaltrials arena). Within 90 days post transfusion, the test patient was able to once again produce and maintain their insulin levels, effectively “curing” this disease. The potential of a stem-cell therapy as a cure for diabetes has the potential to be life-changing for millions of Type 1 Diabetes patients.

These advancements are incredibly exciting. Even curing one patient of Type 1 Diabetes is a huge accomplishment, one that I cannot wait to see replicated in future clinical trials. I will be eagerly following this novel biotechnology, its clinical trial outcomes, and broader application.

Beyond the exciting science, thinking about this advancement through my other PBH lenses raises some important questions. While this new cell therapy is still under development, I read that another breakthrough therapy from the same company for Cystic Fibrosis is priced at approximately $300,000 per patient per year (Fiercepharma). While Cystic Fibrosis is a rare disease affecting approximately 30,000 patients in the US, a chronic disease such as Type 1 Diabetes affects over 1.8 million people in the US, and millions globally. So, as I eagerly follow the incredible science and technology behind this promising new therapy, I will also be thinking about other important questions in my subsequent readings, research, and blogs:

How can novel biotechnologies like gene and cell therapies be made more affordable, especially as they help cure not just rare diseases but more common, chronic diseases?
How will patients and healthcare systems afford all these incredibly promising new therapies?
How can we – society at large – make sure that these incredible biotechnology advancements help reduce, and not increase, healthcare inequalities in our society?

Critical Disconnect, PBH Assessment, and Emerging Lessons

I have shared in earlier blogs my excitement and optimism for biomedical innovation across broadly applicable biotechnologies such as gene therapy, immunotherapies, mRNA vaccines. I have also discussed the critical role biomedical innovation has played in the global response to the pandemic: from rapid genome sequencing of the virus, to novel diagnostics, monoclonal antibody therapy, of course the first mRNA vaccines, and hopefully soon, antiviral pills. All this biomedical innovation at this rapid pace has been breathtaking to follow.

Why then do we, in the US, have more people dead from this pandemic in 18-months than we had US casualties in all of World War II? What good is all this innovation if more people died from COVID-19 than did from the Spanish Flu pandemic a 100 years ago?

Concept and Illustration by Rama Bhagwat

When I launched this blog site in spring of 2020, in the early days of the pandemic, I had articulated my underlying premise that our great societal challenges can not be solved by science alone. While scientific innovation is often necessary to solve these great challenges, it is not sufficient. Effective solutions need to be multidisciplinary and based on science, ethics, policy & law, and economics; my four PBH Lenses. Over time I added leadership as another important dimension to envision and then implement effective solutions.

Can I apply my PBH framework to the US response to the COVID-19 pandemic? I think it is worth testing.

This is indeed a sobering assessment. How can it be constructively used? We are still in the midst of the pandemic, especially in low and middle income countries. As I have said before, we are not truly safe, unless all of us are protected from this virus. Since the past is prologue, surely COVID-19 will not be the last global pandemic. We have already had MERS, SARS, Zika and Ebola threaten the health and well-being across countries and continents just in the past couple of decades. I believe the honest PBH assessment of our response to the current pandemic can help identify important learnings and lessons. The lessons that can help us, as a society, to be proactive – avoiding potential pandemics, limiting them to local epidemics – while also being better prepared for the inevitable next pandemic or global public health crisis.

Broadly speaking, I find myself organizing the PBH lessons learnt into two buckets:

Keep doing, further strengthen, and build on what we are doing well especially in the areas of scientific and biomedical innovation, and economics.
Aggressively and diligently fix those areas that have been lacking, especially in the areas of ethics and policy and law. The need to strengthen our public health infrastructure, capacity, and governance should be high on the list. So should the need to adopt Bioethics as a core value around which we build our public health systems.

Perhaps I will elaborate in more detail the specific lessons from the pandemic in a subsequent post. For now, I am happy that I was able to apply my PBH framework for this assessment, and that it has pointed me in the direction of potential answers to the question I raised. The reason the US has had more deaths from COVID-19 than from the Spanish Flu, in spite of all the incredible biomedical innovations over the past century, is that, we as a country, have neglected the PBH lenses of Ethics and Policy & Law while over indexing on Science and Economics. Narrow focus on science and economics alone cannot make up for the weakness in ethics, policy & law. This assessment makes the case for more comprehensive and lasting solutions, that cover ALL PBH dimensions, to effectively address our great societal challenges such as the global pandemic.

Finally on the PBH Leadership dimension: who is accountable for this tragic disconnect? I think, as a society, this Critical Disconnect represents a collective failure of leadership. Previously, in my Perspectives on Leadership, I have written of my admiration for Presidents Lincoln and FDR, who built coalitions and steered the country, and even the world, during times of crises. Can we even imagine the outcome of the Civil War or World War II without the leadership of a President Lincoln or FDR? As we face new, complex and deadly challenges, my unanswered question is: where are the Lincolns and FDRs of our time? Are we doing enough to educate and develop the next generation of multidisciplinary, transformational leaders who can comprehensively address the Critical Disconnect, and prevent it from recurring? To do so would be the most valuable lesson of all.

Gene Therapy – Connecting Three Exciting New Developments

Three very different, recent developments related to Gene Therapy caught my attention. One was a company specific announcement, another a national funding decision, and the third a global policy recommendation. In the spirit of PBH, I will share how I connected these distinct developments – from Cambridge, MA; Bethesda, Maryland; and Geneva, Switzerland – and along the way discuss their broader implications.

In the last week of June, two biotech companies – Inetllia and Regeneron – announced a landmark development in the application of CRISPR Cas-9 technology in humans. They had demonstrated the first safe and effective in-vivo application of this novel technology in a Phase 1 clinical trial to treat Transthyretin (ATTR) Amyloidosis. This is the first ever clinical data suggesting that we can precisely edit target cells within the body to treat genetic disease with a single intravenous infusion of CRISPR. (Intellia). How incredibly exciting!

Transthyretin (ATTR) Amyloidosis is a “monogenic disease,” meaning it is caused by the mutation of a singular genetic mutation. A genetic mutation hinders the correct protein folding process for the protein Transthyretin. Now, this is taking me back to my Science Olympiad events on Designer Genes and Protein Modeling – Proteins have four key structures: the primary and secondary structures focus on the base amino-acid chain and resulting alpha helix or beta strand bonds formed along the chain. The tertiary structure folds the excess amino-acid chains into the final protein, cementing its properties and purposes. The connection of multiple protein tertiary-structures to each other is what makes up the quaternary structure.

The hereditary ATTR Amyloidosis occurs when a person is born with mutations in the TTR gene. This causes the liver to produce the protein Transthyretin with a tendency to misfold, thus changing its tertiary structure and inhibiting the protein’s function. Accumulation of the misfolded protein leads to the buildup of amyloid deposits in the body causing complications in the patient’s nerves, bone marrow, heart and kidney. If untreated, life expectancy of patients is 2-15 years after the onset of symptoms.

Intellia’s therapy (NTLA-2001) to treat ATTR Amyloidosis targets the Transthyretin (TTR) proteins. The therapy includes a lipid nanoparticle – similar to the mRNA vaccines (PBH) – and a two part gene editing system: a guide RNA specific to the disease causing gene, and the Cas-9 mRNA that encodes the enzyme that does the precision editing.

*Illustration by Rama Bhagwat – based on information at Intelliatx.com*

While additional clinical trials are underway, this exciting development opens the door to the possibility that in-vivo, single dose, gene therapy may be able to treat or cure other monogenic diseases. In order for this to come to fruition, we now have a proven safe and effective CRISPR Cas-9 platform, what is needed then is basic scientific research to identify the specific genes that cause each of the monogenic diseases.

This brings me to the second development: On July 15th, 2021 – less than a month after this breakthrough in in-vivo gene therapy – the NIH announced almost $80 million in new funding to support research efforts to discover the cause of single-gene diseases and disorders. There are 7000 Mendelian gene diseases affecting several hundred million individuals in the world. The current pace of identifying the genes that cause each of these diseases is about 300 a year. This new NIH funding has the potential to significantly accelerate the pace of these discoveries. The speedy discovery and availability of data surrounding specific mutations and mutagenic causes of disorders will be vital for researchers to better understand, identify, and ultimately develop new gene therapies, faster.

Yes, economic and affordability factors ultimately need to be considered. Especially given the vital role public funding, such as NIH grants, has played in the development of the science that is the basis of so many of these innovations. I will continue to learn and think about ways that these exciting innovations are made broadly affordable and accessible. Perhaps sharing my thoughts and learnings in a subsequent blog.

Beyond science, policy and economics, the other big question is – what are the ethical guardrails for gene editing in humans? There seems to be a growing consensus around the ethics of somatic gene editing, but what about human germline gene editing? More than a year ago, as I discussed in my earlier blog, A Look Back… Eugenics to CRISPR (PBH), I began to explore the ethical implications of novel gene editing technologies. As new advancements are made, and as our understanding evolves, there is an even more urgent need for global collaboration to evaluate and establish ethical guardrails and legal standards for the application of gene editing.

That brings me to the third recent development out of Geneva, Switzerland. On July 12, 2021- the WHO released its first global recommendations on human gene editing for the advancement of public health (WHO). The recommendations are based on over two years of consultations and hundreds of diverse perspectives. They cover both somatic gene editing – modifying a patient’s DNA to treat or cure disease – much like the Intellia therapy; as well as germline and heritable human gene editing. More needs to be done to generate a global consensus, build capacity across countries and establish some mechanism of enforcement. However, this WHO announcement is an important step towards ensuring that humanity can benefit from the immense potential of gene editing to diagnose, cure and treat disease, while still protecting our universal human values.

I hope this blog has brought to life the connections I saw across these three very different developments. Reflecting on these developments, I began to better understand how these various pieces fit into kind of a jigsaw puzzle, or an ecosystem. As I pictured this ecosystem, I observed a couple of virtuous cycles further accelerating the discovery and development of gene therapies.

Finally, these developments reinforce my belief in the need for, and the power of, public-private partnerships and global collaboration to address shared challenges especially in the area of bioethics, and for the prudent advancement of innovations that can improve the health of all our peoples. As a high school student, I am excited about these promising developments. I continue to be fascinated by what I am learning and the personal insights I am able to gain as I research and reflect on these developments through multidisciplinary lenses. This is my PBH at work!

Racial Inequalities in Healthcare, Drug & Vaccine Development

In the summer of 2020, the country surged with support for the Black Lives Matter (BLM) movement, in protest of the systemic racism that unfortunately still occurs in our country. Through peaceful protests, widespread donations and petitions, and increased media coverage, the world’s eyes were opened to the various social and political disparities that affect many minority groups. In this blog, I will look through my Philosophy of Biology and Health (PBH) lenses to discuss the health disparities faced by many people of color (POC) in terms of disease prevalence and under representation in the clinical trials used to develop drugs and vaccines.

Health disparities between different demographic groups is commonly defined as the “attainment of full health potential” for individuals, and is measured through differences in incidence rates, mortality rates, severity of the disease, and future side effects (NCBI). While health disparities can occur due to a variety of demographic factors such as gender, sexuality, age, and socioeconomic status, one of the predominant determinants of this disparity is race.

Like so many other healthcare related challenges, this discrepancy has become much more evident in light of the COVID-19 pandemic. Currently, as of February 18, 2021, the CDC reported that the risk of COVID-19 infection, hospitalization and death was substantially higher for many racial and ethnic minority groups. The table below summarizes the current CDC findings.

These health disparities did not begin with the current pandemic, they have long represented a challenge to our healthcare system across many disease areas. As an example, a 2018 study showed that asthma, a lung-condition that causes inflammation of the lungs, is 42% more likely to impact African Americans than white individuals. While white individuals had a 7.7% chance of receiving the disease, African Americans had a rate of 10%, and Native American groups were even higher at a rate of 12% (Lung.org). Regarding overall respiratory disease prevalence in the United States, African Americans and Hispanics made up 12% and 16% of the population, respectively (Journal of Women’s Health). Type 2 Diabetes is another disease that illustrates this disparity. Those of Hispanic heritage, both white and black, were reported to be 1.56 and 2.64 times more likely to contract adult-onset Type 2 Diabetes, respectively, in comparison to their non-hispanic counterparts (NHIS). Perhaps cancer represents the most significant health disparity based on race. African Americans are the most likely racial group to contract Breast, Lung, Colon, and Prostate cancer (RCCA). In addition to contracting the disease, African Americans have been found to have higher mortality rates across these different forms of cancer, on average, in comparison to other racial or ethnic demographics (Cancer.gov).

That these trends have been in place for so long is very disturbing to me. I think a lot needs to be done to understand the causes of these disparities and also to effectively address them. As a start, pharmaceutical companies should make sure that the clinical trials that are conducted to test the safety and efficacy of new treatments – drugs or vaccines – are representative of the population suffering from that underlying disease. In the United States, new drugs and vaccines must go through a series of clinical trial phases in order to be approved. These trials allow scientists, researchers, and doctors to test the safety and efficacy of the new medicines. Each study is conducted with clinical trial participants, usually patients previously diagnosed with the disease and sourced from various hospitals and medical programs. Upon completion, companies and scientists submit their research to the FDA for safety approval. The end goal is a medication that can be used across all patients of the disease, safely and effectively.

I have spent hours going through data on the FDA and related websites. I had assumed, before I began researching some of the data, that a critical requirement for the design of clinical trials would be the fair representation of the underlying patient population by race and ethnicity. However, over the past decades, many drugs and vaccines have been developed and approved based on clinical trials that do not correctly represent the racial and ethnic diversity of the underlying patient population. This is especially problematic for diseases that disproportionately impact POC and underrepresented racial minorities. For example, despite respiratory illnesses being predominant in African American and Hispanic populations, as of 2015, only 1.9% of clinical trials included a representative number of minority subjects (The Editors). In other respiratory disease studies, African Americans made up only 5% of the clinical trial subjects and Hispanics only made up 1%.

Another challenge is perhaps that the effectiveness of approved drugs and vaccines is not reported based on the race and ethnicity of the patients treated. Also, the adverse event data that are reported to the FDA to document the undesired effects of the medications do not require companies to report this information by race and ethnicity.

As I think about this issue from the PBH lenses, I believe there is much that can be improved to make our drug and vaccine development process more representative of the racial diversity of the affected patient population, and as a result make the new drugs and vaccines more effective and safer for all people. A few starting thoughts on potential improvements that I will continue to explore in the future include:

FDA updating guidelines and requiring companies to design clinical trials that represent the racial diversity of the affected patient population
Eliminating barriers (social, economic, trust, awareness, etc.) to the low representation of POC in clinical trials
FDA requiring companies to report the effectiveness and adverse events of their drugs and vaccines by race and ethnicity

Bridging the Chasm: From Vaccines to Vaccinations

8 months ago when I started this PBH blog, my underlying premise was that scientific breakthroughs and science alone, while necessary, are not sufficient, for solving many of the health-related challenges facing our society. I believe that nowhere is this more true than in bridging the chasm from the discovery and development of the COVID-19 vaccines, to the vaccinations in large numbers sufficient to achieve herd immunity. Effectively addressing significant challenges, such as the COVID-19 pandemic, requires multi-faceted solutions that include considerations across Science, Ethics, Policy & Law, and Economics.

In my last blog, I shared my excitement about the tremendous accomplishment of utilizing novel mRNA technology to develop safe and effective COVID-19 vaccines in record time. Recent headlines have tempered that excitement. It has been disheartening to see the recent reports about vaccines not being used, sitting in freezers, or even going to waste. As of mid-January, on average across the US, only 35% of the distributed vaccines have been administered (CBS News). California, which according to the John Hopkins Covid Tracker has nearly 40,000 new daily cases and over 700 daily deaths, has only administered 26% of the vaccines they have received. Georgia has only administered 20% of the vaccines received. How is this acceptable in our country, one of the richest and most developed in the world?

Many other countries are doing a lot better at vaccinating their citizens (OurWorldData). As of mid-January, Israel, for example, has vaccinated approximately 25.8% of their population, as compared to 3.7% in the United States! Even the United Kingdom is doing much better, at 5.9% of their population.

More people are dying in the US, in a single day, than died from the terrorist attacks on 9/11. That day transformed the way the US deals with intelligence gathering and terrorism threats. This pandemic must be the crisis that transforms healthcare in the US. Clearly just scientific and technological advances, such as mRNA vaccines, are not sufficient. My hypothesis is that we need a multifaceted approach. We need continued contributions from science and technology to now develop effective, 1-dose vaccines that are more stable and easier to store and distribute.

From a Policy & Law Lense, short-term, I think that the United States needs to develop a much stronger and more streamlined vaccination plan. Currently, there is little coordination between federal and state governments on the most effective method for COVID-19 vaccinations. Each state is responsible for administering their allocated vaccines, developing priority groups, maintaining lock-downs, and scheduling the second-dose appointments. Developing a national plan that’s congruent across all states and territories, developed by heads at the HHS, FDA and CDC, and consistently implemented using say the national guard in each state would provide the structure needed to maximize the timely use of all available vaccine doses. Looking at learnings from countries like Israel and the UK, both the countries seem to have benefited from a national health system. Perhaps it is time for the US to establish an effective national health system.

From an Ethical Lense, we need to continue to make sure that the vaccines for this pandemic are available for free to all citizens. Some recent reports claim that elite medical schools have received an excessive number of vaccines, and people socially well-connected and rich have found ways to receive the vaccine early. Could the HHS or CDC establish a special office, not just to provide consistent ethical guidelines for vaccine distribution, but also to track their implementation, and, through the influence of the federal government that is supplying these vaccines, ensure compliance to these fair and ethical vaccination policies across all states? Beyond the US, the world must come together to make it easier for all countries to have the option to manufacture the COVID-19 vaccines in their own country, at a lower cost. An important step will be to make a one-time ethical and humanitarian exception for the IP associated with the COVID-19 vaccines.

From an Economics Lense, it is good that this first round of vaccines is being given for free in the United States. Given the shared public health implications of this pandemic, we need to ensure that the COVID-19 vaccines will continue to be available for free even if we find out that our entire population needs to be vaccinated for multiple years to come. Governments need to budget for this while also working with pharmaceutical companies to reduce the cost to manufacture the vaccines and the price the governments have to pay for them. Hopefully, economies of scale and increased competition with multiple safe and effective vaccines will help reduce the price over time.

These are my early thoughts based on reactions to recent news headlines. The COVID-19 pandemic has given us a real-life view into why focusing solely on scientific and technological innovations doesn’t automatically solve our greatest health challenges. By looking at all four of my PBH lenses – Science, Ethics, Policy & Law, and Economics – I am optimistic that with time and dedication, the United States and the world can bridge the chasm from vaccines to vaccinations, and a safer, healthier society.

The Miracle of mRNA Technology

As a highschool student with a strong interest in genetics and immunology, the developments of the past few weeks have been exciting and provided much needed hope. Biological sciences to the rescue of humanity – YES! The first two vaccines to receive emergency use authorization by the FDA are both mRNA vaccines. I hope that this marks the beginning of the end of this pandemic that has had such a devastating impact on all of our lives across the globe. For this PBH (philosophy of biology and health) blog post, I want to focus on the Scientific Lens to explain the cause of my excitement. Also, as I zoom out and think about these developments from a broader, multidimensional PBH perspective, I want to share some new questions that have come up.

On December 11, 2020, the FDA authorized for use the Pfizer and BioNTech’s mRNA COVID-19 Vaccine (FDA). The first doses were administered to healthcare workers from December 14, 2020. Just the following week, on December 18th, 2020, Moderna’s mRNA vaccine also received FDA emergency use authorization (FDA). The mRNA vaccines were developed in record time and faster than the traditional vaccines that are yet to be approved by the FDA.

Both of these vaccines have gone through extensive trials, proven to be safe and highly efficacious after two doses. However, many people are still wary about what the new mRNA vaccine entails. A recent survey (WebMD) found that only 60% of the American population are “certain” or “probably certain” they will get the vaccine. To achieve herd immunity, professionals believe 75%-85% of the population will need to be vaccinated. What’s causing this reluctance and lack of faith in modern medicine? Yes, wild conspiracies and fear mongers influence this opinion. However, I think one of the primary causes for this uncertainty is a lack of knowledge about this new vaccine technology. So, what really is the mRNA vaccine, and how does it differ from a conventional vaccine?

Conventional vaccines have been utilized since 1796, when english doctor Edward Jenner produced the first vaccine for the Smallpox disease. This primal vaccine was used by introducing cowpox into a young boy. As cowpox doesn’t produce symptoms for humans, the boy’s immune system was able to learn and fight off the non-threatening virus. When introduced to smallpox, the boy was not affected as now his body had the antibodies to fight off the disease. This was a huge breakthrough for the scientific field, and for over the last 200 years this method has been used to some extent. Now, common vaccinations for diseases such as Chickenpox, measles, and the flu use various forms of this method. Overarchingly, they work by introducing a harmless, denatured version of the virus into the body, allowing the immune system to build the proper antibodies and immune response to fight it off. Then, when exposed to the pathogen in the real world, the body already has it’s defense system built up and prepared to effectively stop the spread of the disease.

mRNA stands for messenger RNA, and it is an important part of the DNA replication process. In DNA replication, the first stage is called transcription. An enzyme called DNA helicase “unzips” the double-stranded DNA, leaving one side of the genetic material exposed. mRNA reads the genetic code of nucleotides A, T, G, and C, creating a complementary strand of mRNA utilizing the nucleotides T, U, C, and G respectively. This strand of mRNA leaves the nucleus and nuclear envelope, carrying the new RNA codes to the cell’s ribosomes. These ribosomes read the mRNA instructions, build the corresponding amino-acid chains, thus producing the specific proteins. Scientists are now able to leverage the role of mRNA to develop new medications and treatments. Synthetic mRNA, precoded for a specific protein, can be distributed to many cells in the body. From there, human biology takes over. The synthetic mRNA is taken up by the ribosomes, continually building up the amino acids and proteins, allowing them to be expressed in the body. This technology has the potential to be applied for many different medical uses, with the most current and notable one being the COVID-19 mRNA vaccines (Moderna).

Early in the outbreak, scientists sequenced the COVID-19 virus and published its genetic code. Scientists discovered that this virus is characterized by “spike proteins” on its surface. Scientists used these protein spikes as the target for vaccines and treatment, as opposed to injecting a fully-structured denatured virus. While BioNTech and Moderna worked on their vaccines separately, there are a lot of similarities in the underlying science. Using the genetic code of the COVID-19 virus, scientists use complementary RNA base-pairs to build strands of synthetic mRNA, with the instructions to build the specific viral spike proteins. The synthetic mRNA strands are delicate, and need assistance entering human cells. They are packaged in a specially designed oily coating, created with lipid nanoparticles. Once injected into the body, these oily capsules bind to some cells and break apart, inserting the mRNA material into the cytoplasm. These mRNA strands make their way to the cell’s ribosomes, where the mRNA sequence is read repeatedly to produce the viral spikes. These viral spikes are then pushed to the surface, protruding from the cell membrane as either displayed fragments or full spikes.

Once the cell ultimately dies, the mRNA is destroyed, disallowing it from spreading and taking over other cell functions. This acts as a safety feature for the vaccine, ensuring that only a select few cells are taken over. Upon the individual cells’ destruction, the protein spikes and debris float throughout the body, unable to do real harm. However, the foreign material attracts the attention of the body’s immune system – specifically antigen-presenting cells and T-cells. The antigen-presenting cells take in the spikes and present at its surface, while helper T-cells can send a signal to the rest of the immune system. This calls another type of immune cell: B-cells. These B-cells can hit and lock into the protein spikes, and with activation from helper T-cells can begin forming antibodies to identify the virus. Lastly, killer T-cells are activated, and trained to recognize and kill the virus upon contact. Memory B and T-cells store this information, offering protection in the long term. This shortens the reaction time of the immune system upon exposure to the virus, allowing it to utilize the “alarm” system and its antibodies to destroy the virus before it can continue to replicate. In this way, the vaccine utilizes the new mRNA technology to protect the vaccinated individual and break the chain of transmission.

These two COVID-19 vaccines are the first ever mRNA based product to be approved by the FDA. This miracle of being able to use the human body as a factory to custom manufacture targeted proteins has the potential to protect humans from other infectious diseases and genetic disorders. I am very excited about the potential this new genetic technology has to do so much good for human health!

From a PBH perspective, as I zoom out beyond the Scientific lense, these promising new scientific developments also raise some important questions and considerations:

What are some of the other most promising applications of this new mRNA technology?
How can we make these new, promising mRNA vaccines cheaper and more accessible beyond the rich, developed countries?
Should the intellectual property (IP) associated with the COVID-19 mRNA vaccines be made freely available to developing and poor countries, at least until this pandemic ends?

There will be other opportunities to address these questions. But for now, I want to take a moment to marvel at this miracle of science!

Philosophy of Biology and Health: A Look Back…Eugenics to CRISPR

I believe that as we continue to make amazing progress in scientific breakthroughs, we have so much potential to improve the health of hundreds of millions of people, even billions of people in our world. However, as a society, do we have a good, common understanding of the purpose of science, the values that guide our decisions, and the effect it has on the health and well-being of our society? How has it been in times past? Historically, how have societies thought of the philosophy of biology and health?

Until the late 18th and early 19th century, there wasn’t a clear distinction between a “philosopher” and a “scientist.” Up until this period they went hand in hand with one another; philosophy helping create the scientific method and science allowing for a sound way to test philosophical theories. The Philosophy of Science is thought to have begun with early western philosophers, including the likes of Plato and Aristotle. In modern times, the Philosophy of Science has shifted. The roles have seemingly reversed. Scientific innovations are being made at breakneck speed and scale; considerations of purpose, values, and social impact seem to come as an afterthought.

In this regard, given my interest in biology and especially genetics, I find the example of Eugenics over the last century very instructive. In the early twentieth century, some in the American scientific community became preoccupied by the idea of creating a “stronger” society through “preferred” breeding. While not nearly as extreme as the horrors that occurred in Nazi Germany, there is a dark history of abusing scientific ideas and innovations under the pretext of social good even in the US. In the early 20th century, the ideas of Gregor Mendel – the father of genetics – and his work regarding inheritance and the human genome were still fairly new. His most popular work – providing an insight into the nature of dominant and recessive genes – became popular in American culture and the beginning of eugenics. Society began to compare people to livestock and promoted the benefits of selective breeding. This meant encouraging “fit” parents, based on societal norms, to have more children. On the flip-side, new laws were put into place restricting the reproduction of the “unfit” in society, including the poor, criminals, the mentally ill, and some racial minorities. Rather than treating, educating, and rehabilitating these people, society chose to follow the ideas of Darwinism – survival of the fittest. As a result, tens of thousands of Americans were unjustly sterilized. In order to further encourage selective breeding, states such as Indiana and Iowa hosted “best baby” contests at state fairs – crowning the winner based on ethnicity, mental capacity, and physical fitness.

While a seemingly harmless idea with the goal of bettering society, the execution abused scientific knowledge and unethically stripped people from basic human rights. Despite the blatant ethical issues with these practices, very little was done to protect people from such policies. For example, in Buck v. Bell, the SCOTUS ruled the practice of authorized sterilization as legal and in compliance with one’s constitutional rights. I went back and reviewed the case syllabus to learn the reasoning behind this ruling. Buck v. Bell followed Carrie Buck, a “feeble minded white woman” who came from a line of other“illegitimate feeble minded” women. The court supported the decision of authorized sterilization on two counts. One factor was “that experience has shown that heredity plays an important part in the transmission of insanity, imbecility, &c.” In their opinions, legalizing authorized sterilization of any patient that displayed these hereditary traits was for the “best interests of the patients and of society”. The second factor was that the operation proceeded only after “months of observation,” therefore allowing for due process of the law and not interfering with one’s constitutional rights (Justia US Supreme Court). Despite the clear ethical issues with such programs and how they promoted racial and scientific ignorance, laws, and society deemed it appropriate to continue. It wasn’t until after the horrors that occurred in Nazi concentration camps during World War II that these ideas began to change.

Despite the halt of such programs in the second half of the 20th century, the advent of new scientific breakthroughs in the 1970s proved another test for society’s philosophy of biology and health. In 1978, Louise Brown became the first human conceived through IVF, thanks to scientific advancements made by Patrick Steptoe and Robert Edwards. The science itself was created for a good cause: allowing even those suffering from infertility to reproduce and have children and families. Over the decades, over six million babies have been born as a result of IVF! However, this new technology raised new concerns about ethics, social discrepancies, gender discrimination, and abuse. People were worried that these reproductive technologies would lead to editing life for cosmetic reasons: such as gender, intelligence, looks, or athleticism. In April of 1992, the Assisted Reproductive Technology Act was put into place to help regulate and control the use of such technology. Even the inventor of IVF Robert Edwards, later in 2004, spoke to the Parliamentary Committee on Science of Technology about the fine line between using genetic and reproductive technology for good rather than eugenics. Society, it seemed at least for the time being, had found a good balance to benefit from biology while limiting its ills. At least until the next scientific breakthrough!

In 2018, Chinese scientist He Jiankui made the first genome-edited babies using new CRISPR technology. The twin girls had been genetically modified to reduce their risk and ability to contract HIV. Despite being a breakthrough in biotechnology, it also sent the science world into a frenzy. When should one be allowed to use such technology on other humans, based on ethical and moral codes? Should gene-editing be limited to cure disease, or could it also be used for preventive and cosmetic purposes? Should there be common global standards? Old ideas of superior breeding and using technology to create a stronger society – based on genetics – have led to both contemporary biological innovations and new ethical issues. This is only one example of how old ideas have throughout history reappeared and sparked ethical and moral questions as technology has evolved. New questions regarding the Philosophy of Biology and Health are still left unanswered. Challenges for my generation to take on and resolve!