Biomedical innovations have forever changed human society. Thanks to breakthroughs in basic research and applied clinical science, humanity now enjoys an increased life expectancy, improved quality of life and better health care. Yet, like a double-edged sword, innovative biotechnologies have not only brought hopes to patients and their families, but in many cases have also unexpectedly caused harm and led to social discourse. In this article, I would like to delve into some of the most remarkable biomedical advancements made in the 21st century and comment on the blessings and curses they have brought to our society.
The Progress We’ve Made…
“It is a history book – a narrative of the journey of our species through time. It is a shop manual, with an incredibly detailed blueprint for building every human cell. And it’s a transformative textbook of medicine, with insights that will give health care providers immense new powers to treat, prevent and cure disease.” -Francis Collins, ‘The Language of God’
Since the late 1990s, advancements in the knowledge of basic science, especially in molecular genetics, stem cell biology, and cancer research, have cultivated numerous breakthroughs in medicine and health care. For example, the insight gained from the Human Genome Project has contributed tremendously to our understanding of human genetics and has aided in the identification of specific mutations linked to various forms of cancer, creation of gene-targeting therapies, and significant advancements in fields such as forensic science, anthropology, evolution and much more. Similarly, the discovery of stem cell by Ernest McCulloch and James Till (University of Toronto) and the breakthroughs in laboratory technologies capable of generating and culturing stem cells by James Thomson (University of Wisconsin-Madison) and Shinya Yamanaka (Kyoto University and Gladstone Institute) have revolutionized basic biomedical research and therapeutic science. Currently, stem cells have become a powerful tool for basic research labs and pharmaceutical companies to gain insights into gene functions and assess the safety and effectiveness of new drug candidates. Additionally, billions of dollars of funding are pouring into basic and clinical research globally with a focus on utilizing stem cell therapies in regenerative medicine, raising hopes for curing diseases such as diabetes, muscle degeneration and blindness. Besides advancements in genetics and stem cell technologies, breakthroughs in targeted cancer therapies have also revolutionized the field of oncology and patients’ survival. An excellent example is Trastuzumab (targeted HER2 receptor) that has significantly improved the overall survival rate of HER2+ breast cancer patients since its FDA approval in 1998. Likewise, many other targeted cancer immunotherapies aim to increase survival rate of patients such as pembrolizumab (anti-PD1) and ipilimumab (anti-CTLA4), and have indeed already showed promising results in multiple forms of cancers alone or in combination with other therapies. The combination of targeted therapy, earlier detection methods, and public advocacy for cancer prevention has led to an overall 27% decline in cancer motility rate as of 2016 compared to 1991.
Without a doubt, the aforementioned biomedical advancements have led to the creation of better treatments options for patients, extending lives and bringing hope to numerous families. Yet, they have also brought unexpected problems, and in many cases even caused physical and financial damages. For the remainder of the article, I will reflect on some of the serious problems associated with medical innovation.
The Safety & Ethical Concerns of Stem Cell Therapy & Gene Therapy
“Emerging biotechnologies pose public health challenges because of both the known and unforeseen risks they carry, the uncertain medical benefits they offer, the speed at which they have been disseminated and their unproven mode of application.” -World Health Organization
In contrast to the rapid development of novel biomedical technologies, regulations and internationally agreed guidelines for the application of these new technologies have fallen far behind. Despite the great therapeutic potential of stem cell therapies in regenerative medicine and in the treatment of autoimmune and genetic disorders, the technology is still too premature for clinical usage. In fact, currently the only approved stem cell therapy is bone marrow/hematopoietic stem cell transplantation for blood cancers such as leukemia, while very few other stem cell treatments have ever reached the earliest phase of clinical trials. Despite the lack of evidence-based proof that stem cell injections may benefit patients, globally there is a worrisome increase in private clinics that offer such ‘stem cell therapies’; these are mostly marketed online and claim to treat or alleviate symptoms for heart problems, multiple sclerosis and Crohn’s disease. The failure of governmental health agencies to effectively regulate these ‘private clinics’ has led to a booming industry of stem cell tourism, where individuals travel internationally to access these stem cell clinics. Consequently, cases where stem cell injection led to unexpected severe medical incidences are rising at an alarming rate. For instance, in 2017, A.E. Kuriyan et al. reported a case where injection of adipose tissue-derived “stem cells” by “stem-cell clinics” led to severe vision loss in three patients in New England Journal of Medicine. Because of the huge health risks, in May 2019, Health Canada officially announced crackdowns on “stem-cell clinics” that advertise unproven stem therapies. Though the effectiveness of these regulations is yet to be seen, still it is a step towards the right direction, setting a good example for stricter regulations on a global scale.
Like stem cell therapies, gene editing has also become a technique posing huge challenges on global supervision and regulation. Thanks to the human genome project and the development of gene-editing technologies such as CRISPR-cas9, targeted gene editing can be carried out with a fairly small amount of money and minimum scientific training. While this ease of use may be a huge convenience for academic research labs and pharmaceutical companies working towards advancements in science or medicine, it also raises severe safety and ethical concerns regarding its widespread use. In November 2018, Chinese researcher He Jiankui shocked the world by modifying the CCR5 gene of two embryos with CRISPR-cas9 and implanting them back to the mother in an unconvincing excuse to prevent paternal transmission of HIV. There is no dispute that He’s experiment is irresponsible and unethical, yet Pandora’s box has now been opened and devil has been released. Not surprisingly, in June 2019, Russian scientist Denis Rebrikov announced his plans to follow the path of He, creating more gene-edited babies. The unsettling act of He has not only put the future of the gene-edited twins in uncertainty, but also opened a dangerous and unforeseeable path for the entire human species. The application of gene editing for clinical usage may be extremely useful; especially in the treatment of genetic disorders; however, the application of genetic editing on human beings is like walking on an ethical tightrope – one wrong step could lead to widespread misuses of this powerful technology. Thus, we need to reach ethical consensus, correct current flaws in regulations and set up effective monitoring system. What type of conditions will be considered as gene enhancement versus treatment? Should the cost of gene therapy be subsidized by public health system? How can we prevent off-target effects? Until we can figure out the answers to these safety and ethical concerns, the huge risks of using gene editing for therapeutic and reproductive purpose cannot be justified by the benefits it brings.
As we officially enter the 21st century ‘information age’, privacy and usage of personal data by large corporations such as Facebook and Google have led to heated public debates. Moreover, in much of the same manner, the safety of personal genetic information has also emerged as a serious problem. Thanks to the rapid development of genomic sequencing techniques, the cost to sequence human genome has dropped substantially from 10 million USD to just 1,000 USD. Today, people can purchase and use DNA tests for various purposes, such as learning about their ancestry (23andme kits), as well as testing for high-risk cancer linked mutations (BRCA1 and BRCA2 test kits). Despite the rapid commercialization of genomic sequencing tests, there is a surprising lack of legal infrastructure to protect the consumers’ genetic privacy. Rules regarding the definition and usage of genetic data differ from state to state and country to country. Complete anonymity of genetic information, though guaranteed by the testing companies, is nearly impossible to achieve. Recently, a study (Kim J. et. al, Cell 2018) showed that combining an anonymous DNA sample with some basic information – such as someone’s approximate age – can allow researchers to narrow down the individual’s identity to fewer than 20 people within a database of 1.3 million people. Even more striking is the fact that we can easily infer or identify a whole family’s genetic information and associated health risks from just one member’s genetic test as family members share a significant amount of genetic information. A recent example that really highlights the availability of genomic information was the arrest of the “Golden State Killer” using an open online genetic database in 2018. By uploading pieces of the killer’s DNA data to GEDmatch, a free online database where anyone can share their test result from DNA testing companies (like 23andMe), law enforcement agencies were able to identify several individuals who shared similarities with the killer’s DNA and were likely distant relatives. With this information, they were able to identify the killer and solve a crime that took place nearly 32 years ago. The case of “Golden State Killer” is a positive example where genetic information could be used for good purpose and benefit the society. Yet, the illustrated power of genetic data sends chills down our spine, knowing how much damage it could cause if misused. Health insurance companies could easily use pieces of one person’s genetic information to infer health risk of the entire family, and deny or make discriminative insurance policies against certain populations. Moreover, there are still so many unanswered questions: who can own and access these genetic information – the individual, genetic testing companies or the government? Would it be acceptable to use a person or demographic group’s genetic information for commercial / academic research values? Should a government mandatorily collect and regulate citizens’ genetic information for national security? How would these regulations affect international collaborations on genome research?
Biotech & Pharmaceutical Companies: A Broken System
Last but not least, consumer and patient access to biomedical and pharmaceutical innovation has also faced numerous issues in recent years. Fraudulent marketing of medical technologies is one of these problems. Perhaps, the most notorious example of this is Elizabeth Holmes and her company Theranos. From 2003 to 2018, Theranos and its founder Elizabeth Holmes was able to deceive patients/consumers and defraud investors, raising billions of dollars on a “breakthrough medical device” that could run multiple diagnostic blood tests on a very small amount of blood. Theranos continued to offer consumers questionable blood tests until in 2015 when its unreliable testing was exposed by The Wall Street Journal reporter John Carreyrou. Yet, because of the false test results, thousands of consumers suffered not only economic loss but also mental and physical distress by paying for unnecessary medical examinations and treatments for conditions they do not have. Numerous cases of such frauds pose great pressure on governmental agencies to scrutinize new medicines and medical devices to ensure that their effects are in concordance with their marketing.
False marketing is only the tip of the iceberg of the problems with biotech and pharma companies. Another serious problem with new medical treatment is that they usually come with a hefty price that few patients can actually afford. For example, the first FDA approved therapy involving genetic modification called Tisagenlecleucel/Kymriah (anti-CD19 CAR T cells for treating acute lymphoblastic leukemia and diffuse large B cell lymphoma) costs 475,000 USD for a single treatment. Though Novartis only charge patients if they respond to the treatment, patients (often children and young adults) are still daunted by the high price. In fact, the clinical usage of another type of anti-CD19 CAR T cells, Axicabtagene ciloleucel/Yescarta developed by Kite Pharma, was initially rejected by the National Institute for Health and Care Excellence (NICE) of UK due to the high price. Though Yescarta was finally approved by NICE in 2018 after negotiation to a lower price, the case raises a complicated question – how should the price of new medicines/technologies be regulated or subsidized so that they can be afforded by most patients while still bringing enough profits for pharmaceutical companies to continue their research? Without a proper solution, the benefits brought by these life-saving innovations will remain out-of-reach for most people.
Biomedical innovation acts as both an angel and the devil; it gives hopes to numerous patients and their families. Yet, as history has shown us time and time again, when misused it can also bring disaster. As basic research and science continue to progress, more novel technologies will be developed and applied in every aspect of our lives. Our society will continue to be shaped by these innovations, for better or for worse. It is up to us to treat these innovations carefully, reflect and learn from our mistakes, and apply them in the correct way.