David and Jen on their wedding day, and Jen undergoing treatment for her rare sarcoma.
It was 15 years ago this month, but I'll never forget those words. When my wife Jen and I asked her oncologist about our plans to start a family, he calmly replied, "Well, I wouldn't do so unless Dave is prepared to be a single father."
About 50 percent of all people with cancer have a rare type, like the one Jen was fighting.
Time stood still. The danger crystalized — we were in a battle for my beautiful bride's life, and the odds were not in our favor.
We felt every emotion expected. Anger, sadness, confusion, frustration, and especially fear. But we made a very intentional choice to take that fear, put it to the side, and do everything we could to live our lives together to the fullest.
We focused first on Jen's health and learned everything we could about MFH Sarcoma. I was with her every step of the way — for hundreds of medical appointments, six intense surgeries, and twenty different types of chemotherapy. During such a challenging time, our choice to reject fear allowed us to live our best lives. Our careers blossomed, we enjoyed several international vacations, and Jen inspired thousands of fellow patients through her blog and speeches.
When we researched treatment options we learned that Jen was not alone. About 50 percent of all people with cancer have a rare type, like the one Jen was fighting. However, rare cancers don't get the funding they desperately need so effective treatment options are hard to find. The lack of funding felt unfair — and urgent. We didn't worry about everything that can go wrong when starting a new venture. Instead, we jumped in head first and convinced a small group of friends and family to ride stationary bikes with us to raise money for rare cancer research.
Jen Goodman Linn, riding a stationary bike for Cycle for Survival.
(Courtesy David Linn)
From those humble beginnings, Cycle for Survival grew steadily. After starting from scratch, Jen and I ran Cycle for Survival on our own for two years. We quickly realized that if we wanted to help as many people as possible, we needed the best partners. In 2009, we agreed that Memorial Sloan Kettering Cancer Center would take over the ownership of Cycle for Survival and Equinox officially became the Founding Partner. Flash forward to today, and Cycle for Survival has raised more than $220 million! I'm proud that 100% of every donation, yes every penny, goes directly into life-saving rare cancer research within six months of the annual indoor cycling events, which now take place in 17 cities nationwide.
While Cycle for Survival's trajectory was heading straight up, Jen's health struggle was devastatingly swinging up and down. With her incredible spirit and tenacity, Jen would beat the cancer through chemo and surgery, but then it would frustratingly come back again and again. After going into remission six times, it returned with such a vengeance in 2011 that even the world's leading doctors were forced to say, "I'm sorry, there's nothing more we can do."
Those were the most difficult words I've ever heard, by far. I hope no other family has to hear these crushing words.
When Jen died soon after, I didn't know what would happen to me, to my life, and to Cycle for Survival. I do remember making two very important choices at the time. First, I chose to get out of bed and put one foot in front of the other. It wasn't easy. Tears, pain, and grief would hit at any hour of the day or night. I did have a great support network of family and friends who kept me moving forward. One friend in particular changed the route of her morning runs so that I would join her and start getting back to exercising.
My second key choice was to stay involved with Cycle for Survival. At times, it was an excruciatingly difficult decision because I felt the depth of my loss each and every time I stepped into one of the events. However, it was also rewarding and energizing because I could see firsthand how many people it was helping, even though it was too late for Jen.
I began to travel across the country with the Cycle for Survival staff. My hope was to spread the word about rare cancers; along the way I met a lot of wonderful people who shared their stories with me. What I soon realized is that each of us faces obstacles in our lives. For me, it was losing the person who I wanted to spend my life with. For others, it might be challenges with their kids or in their professional lives. The common theme is that we don't have control over the fact that we have to face these challenges. But the biggest lesson I've learned is that we very much do have a choice in how we react.
I made the choice to do everything I can to help rare cancer patients and their families and it has been transformative and healing for me. The small group who rode in the first Cycle for Survival event has grown into a powerful movement of nearly 40,000 riders making a real difference. If Jen were diagnosed today, there are new treatments available– including genomic sequencing, targeted therapies, and immunotherapies – that could help her. Those weren't even options a short time ago. That's the result of funding research.
A recent Cycle for Survival event shows the passion and power of the community.
(Courtesy David Linn)
I also want to share one more choice I made. Remember that friend who changed the route of her morning runs so I could start exercising after Jen died? Well, over the years friendship grew into love, and we're now building a home together and can't wait to see what the future holds for us.
So with all that in mind I ask – when you face those inevitable challenges in your life, how will you choose to react? Remember that even in the midst of hopelessness, you can find choices. Those will be the decisions that define and guide you.
A string of the code that comprises a DNA molecule, pictured at Miraikan, the National Museum of Emerging Science and Innovation in Japan.
New Alzheimer's Therapies
Mary Carrillo, Chief Science Officer at the Alzheimer’s Association
Alzheimer's Association
One of the biggest health stories of 2021 was the FDA’s accelerated approval of aducanumab, the first drug that treats the underlying biology of Alzheimer’s, not just the symptoms. But, Alzheimer’s is a complex disease and will likely need multiple treatment strategies that target various aspects of the disease. It’s been exciting to see many of these types of therapies advance in 2021.
Following the FDA action in June, we saw renewed excitement in this class of disease-modifying drugs that target beta-amyloid, a protein that accumulates in the brain and leads to brain cell death. This class includes drugs from Eli Lilly (donanemab), Eisai (lecanemab) and Roche (gantenerumab), all of which received Breakthrough Designation by the FDA in 2021, advancing the drugs more quickly through the approval process.
We’ve also seen treatments advance that target other hallmarks of Alzheimer’s this year. We heard topline results from a phase 2 trial of semorinemab, a drug that targets tau tangles, a toxic protein that destroys neurons in the Alzheimer’s brain. Plus, strategies targeting neuroinflammation, protecting brain cells, and reducing vascular contributions to dementia – all funded through the Alzheimer's Association Part the Cloud program – advanced into clinical trials.
The future of Alzheimer’s treatment will likely be combination therapy, including drug therapies and healthy lifestyle changes, similar to how we treat heart disease. Washington University announced they will be testing a combination of both anti-amyloid and anti-tau drugs in a first-of-its-kind clinical trial, with funding from the Alzheimer’s Association.
AlphaFold
Olivier Elemento, Director of the Caryl and Israel Englander Institute for Precision Medicine at Cornell University
Cornell University
AlphaFold is an artificial intelligence system designed by Google’s DeepMind that opens the door to understanding the three-dimensional structures and functions of proteins, the building blocks that make up almost half of our bodies' dry weight. In 2021, Google made AlphaFold available for free and since then, researchers have used it to drive greater understanding of how proteins interact. This is a foundational event in the field of biotech.
It’s going to take time for the benefits from AlphaFold to transpire, but once we know the 3-D structures of proteins that cause various diseases, it will be much easier to design new drugs that can bind to these proteins and change their activity. Prior to AlphaFold, scientists had identified the 3-D structure of just 17 percent of about 20,000 proteins in the body, partly because mapping the structures was extremely difficult and expensive. Thanks to AlphaFold, we’ve now jumped to knowing – with at least some degree of certainty – the protein structures of 98.5 percent of the proteome.
For example, kinases are a class of proteins that modify other proteins and are often aberrantly active in cancer due to DNA mutations. Some of the earliest targeted therapies for cancer were ones that block kinases but, before AlphaFold, we had only a premature understanding of a few hundred kinases. We can now determine the structures of all 1,500 kinases. This opens up a universe of drug targets we didn’t have before.
Additional progress has been made this year toward potentially using AlphaFold to develop blockers of certain protein receptors that contribute to psychiatric illnesses and other neurological diseases. And in July, scientists used AlphaFold to map the dimensions of a bacterial protein that may be key to countering antibiotic resistance. Another discovery in May could be essential to finding treatments for COVID-19. Ongoing research is using AlphaFold principles to create entirely new proteins from scratch that could have therapeutic uses. The AlphaFold revolution is just beginning.
Virtual First Care
Jennifer Goldsack, CEO of Digital Medicine Society
Digital Medicine Society
Imagine a new paradigm of healthcare defined by how good we are at keeping people healthy and out of the clinic, not how good we are at offering services to a sick person at the clinic. That is the promise of virtual-first care, or V1C, what I consider to be the greatest, and most underappreciated, advance that occurred in medicine this year.
V1C is defined as medical care accessed through digital interactions where possible, guided by a clinician, and integrated into a person’s everyday life. This type of care includes spit kits mailed for laboratory tests and replacing in-person exams with biometric sensors. It’s built around the patient, not the clinic, and provides us with the opportunity to fundamentally reimagine what good healthcare looks like.
V1C flew under the radar in 2021, eclipsed by the ongoing debate about the value of telehealth more broadly as we emerge from the pandemic. However, the growth in the number of specialty and primary care virtual-first providers has been matched only by the number of national health plans offering virtual-first plans. Our own virtual-first community, IMPACT, has tripled in size, mirroring the rapid growth of the field driven by patient demand for care on their terms.
V1C differs from the ‘bolt on’ approach of video visits as an add-on to traditional visit-based, episodic care. V1C takes a much more holistic approach; it allows individuals to initiate care at any time in any place, recognizing that healthcare needs extend beyond 9-5. It matches the care setting with each individual’s clinical needs and personal preferences, advancing a thorough, evidence-based, safe practice while protecting privacy and recognizing that patients’ expectations have changed following the pandemic. V1C puts the promise of digital health into practice. This is the blueprint for what good healthcare looks like in the digital era.
Digital Clinical Trials
Craig Lipset, Founder of Clinical Innovation Partners and former Head of Clinical Innovation at Pfizer
Craig Lipset
In 2021, a number of digital- and data-enabled approaches have sustained decentralized clinical trials around the world for many different disease types. Pharma companies and clinical researchers are enthusiastic about this development for good reason. Throughout the pandemic, these decentralized trials have allowed patients to continue in studies with a reduced need for site visits, without compromising their safety or data quality.
Risk-based monitoring was deployed using data and thoughtful algorithms to identify quality and safety issues without relying entirely on human monitors visiting research sites. Some trials used digital measures to ensure high quality data on target health outcomes that could be captured in ways that made the participants’ physical location irrelevant. More than three-quarters of research organizations, such as pharma and biotech, have accelerated their decentralized clinical trial strategies. Before COVID-19, 72 percent of trial sites “rarely or never” used telemedicine for trial participants; during COVID, 64 percent “sometimes, often or always” do.
While the research community does appreciate the tremendous hope and promise brought by these innovations, perhaps what has been under-appreciated is the culture shift toward thoughtful risk-taking and a willingness to embrace and adopt clinical trial innovations. These solutions existed before COVID, but the pandemic shifted the perception of risks versus benefits involved in these trials. If there is one breakthrough that is perhaps under-appreciated in life sciences clinical research today, it’s the power of this new culture of willingness and receptivity to outlast the pandemic. Perhaps the greatest loss to the research ecosystem would be if we lose the momentum with recent trial innovations and must wait for another global pandemic in order to see it again.
Designing Biology
Sudip Parikh, CEO of the American Association for the Advancement of Science and Executive Publisher of the Science family of journals
American Association for the Advancement of Science
As our understanding of basic biology has grown, we are fast approaching an era where it will be possible to design and direct biological machinery to create treatments, medicine, and materials. 2021 saw many breakthroughs in this area, three of which are listed below.
The understanding of the human microbiome is growing as is our ability to modify it. One example is the movement toward the notion of the “bug as the drug.” In June, scientists at the Brigham and Women’s Hospital published a paper showing that they had genetically engineered yeast – using CRISPR/Cas9 – to sense and treat inflammation in the body to relieve symptoms of irritable bowel syndrome in mice. This approach could potentially be used to address issues with your microbiome to treat other chronic conditions.
Another way in which we saw the application of basic biology discoveries to real world problems in 2021 is through groundbreaking research on synthetic biology. Several institutions and companies are pursuing this path. Ginkgo Bioworks, valued at $15 billion, already claims to engineer cells with assembly-line efficiency. Imagine the possibilities of programming cells and tissue to perform chemistry for the manufacturing process, inspired by the way your body does chemistry. That could mean cleaner, more controllable, and affordable ways to manufacture food, therapeutics, and other materials in a factory-like setting.
A final example: consider the possibility of leveraging the mechanics of your own body to deliver proteins as treatments, vaccines, and more. In 2021, several scientists accelerated research to apply the mRNA technology underlying COVID-19 vaccines to make and replace proteins that, when they’re missing or don’t work, cause rare conditions such as cystic fibrosis and multiple sclerosis.
These applications of basic biology to solve real world problems are exciting on their own, but their convergence with incredible advances in computing, materials, and drug delivery hold the promise of game-changing progress in health care and beyond.
Brain Biomarkers
David R. Walt, Professor of Biologically Inspired Engineering, Harvard Medical School, Brigham and Women’s Hospital, Wyss Institute at Harvard University
David Walt
2021 brought the first real hope for identifying biomarkers that can predict neurodegenerative disease. Multiple biomarkers (which are measurable indicators of the presence or severity of disease) were identified that can diagnose disease and that correlate with disease progression. Some of these biomarkers were detected in cerebrospinal fluid (CSF) but others were measured directly in blood by examining precursors of protein fibers.
The blood-brain barrier prevents many biomolecules from both exiting and entering the brain, so it has been a longstanding challenge to detect and identify biomarkers that signal changes in brain chemistry due to neurodegenerative disease. With the advent of omics-based approaches (an emerging field that encompasses genomics, epigenomics, transcriptomics, proteomics, and metabolomics), coupled with new ultrasensitive analytical methods, researchers are beginning to identify informative brain biomarkers. Such biomarkers portend our ability to detect earlier stages of disease when therapeutic intervention could be effective at halting progression.
In addition, these biomarkers should enable drug developers to monitor the efficacy of candidate drugs in the blood of participants enrolled in clinical trials aimed at slowing neurodegeneration. These biomarkers begin to move us away from relying on cognitive performance indicators and imaging—methods that do not directly measure the underlying biology of neurodegenerative disease. The identity of these biomarkers may also provide researchers with clues about the causes of neurodegenerative disease, which can serve as new targets for drug intervention.
