Imagine living in a time where reaching the age of 48 was considered a milestone. If you were born in 1900, that was the average life expectancy. Fast forward to today, and a child born now can expect to live to around 79 years old. This remarkable increase in lifespan over the last century is a testament to advancements in medicine and public health. However, there’s still much work to be done, especially in the realm of drug development.
Currently, we understand the molecular basis of approximately 4,000 diseases, thanks to recent scientific breakthroughs. Yet, we have effective treatments for only about 250 of these conditions. This gap highlights a significant challenge: transforming our deepening knowledge of biology into practical, effective therapies.
The process of developing a new drug is akin to navigating a treacherous journey. Imagine setting off with various modes of transport—some might succeed, but many will face obstacles like storms or hidden dangers. Similarly, in drug development, only a few compounds make it through rigorous testing to become approved treatments, often taking over a decade and costing billions of dollars.
Despite these challenges, there have been notable successes. Take cystic fibrosis, for example. The genetic mutation causing this disease was identified in 1989, and it took until recently to develop a drug that targets this specific defect. Although this drug doesn’t work for everyone with cystic fibrosis, it marks a significant step forward.
Another inspiring example is Hutchinson-Gilford progeria syndrome, a rare condition causing rapid aging in children. In 2003, researchers discovered the genetic mutation responsible and quickly moved to develop a potential treatment. Just four years later, a clinical trial began, offering hope to affected children and their families.
To accelerate drug development, we must leverage technology and foster collaboration. The cost of sequencing the human genome has plummeted, making it feasible to explore genetic information for therapeutic insights. Additionally, repurposing existing drugs—originally developed for other conditions—can lead to new treatments, as seen with the progeria trial.
At the National Institutes of Health (NIH), the newly established National Center for Advancing Translational Sciences aims to bridge the gap between scientific discovery and practical application. By partnering with academia, government, industry, and patient organizations, we can explore innovative approaches to drug development.
One promising avenue is using human cells to test drug safety and efficacy, reducing reliance on animal testing. For instance, “lung on a chip” technology allows researchers to simulate lung function and evaluate potential treatments in a controlled environment.
As we stand on the brink of 21st-century biology, the potential to transform our discoveries into life-saving solutions is immense. By investing in high-risk, high-reward research and fostering interdisciplinary collaboration, we can tackle diseases that have long eluded effective treatment.
The journey to better drugs is complex, but with determination and innovation, we can overcome the challenges. By harnessing the power of modern science and technology, we have the opportunity to make significant strides in improving human health. Let’s seize this moment to turn our knowledge into action and create a healthier future for all.
Examine the case studies of cystic fibrosis and Hutchinson-Gilford progeria syndrome. Identify the key steps taken in the drug development process for these diseases. Discuss with your peers how these examples illustrate the challenges and successes in modern drug development.
Create an interactive timeline that outlines the drug development process from discovery to approval. Include key milestones, challenges, and innovations that have shaped the industry. Present your timeline to the class and explain how each stage contributes to the overall journey of a drug.
Participate in a debate on the role of technology in accelerating drug development. Consider the benefits and potential drawbacks of technologies like genome sequencing and “organ on a chip.” Use examples from the article to support your arguments and engage in a constructive discussion with your peers.
Work in groups to brainstorm potential existing drugs that could be repurposed for new therapeutic uses. Research their current applications and propose novel conditions they might treat. Present your findings and discuss the feasibility and potential impact of your proposals.
Conduct a research project on one of the future directions mentioned in the article, such as using human cells for testing or interdisciplinary collaboration. Analyze the current state of this approach, its potential benefits, and the challenges it faces. Share your insights with the class through a presentation or report.
Thank you. Let me ask for a show of hands: how many people here are over the age of 48? Well, there do seem to be a few. Congratulations! If you look at this particular slide of U.S. life expectancy, you are now above the average lifespan of someone born in 1900.
But look at what happened over the course of that century. If you follow that curve, you’ll see it starts low, with a dip for the 1918 flu, and here we are in 2010, with an average life expectancy of a child born today at age 79. And we are not done yet—that’s the good news. However, there is still a lot of work to do.
For instance, if you ask how many diseases we now know the exact molecular basis for, it turns out it’s about 4,000, which is pretty amazing because most of those molecular discoveries have just happened recently. It’s exciting to see what we’ve learned, but how many of those 4,000 diseases now have treatments available? Only about 250.
So we have this huge challenge, this significant gap. You would think it wouldn’t be too hard to take this fundamental information we’re learning about basic biology and build a bridge across this gap between what we’ve learned about basic science and its application. Unfortunately, it’s not that easy.
In reality, trying to go from fundamental knowledge to its application is more complicated. There are no shiny bridges; you sort of place your bets. Maybe you’ve got a swimmer, a rowboat, a sailboat, and a tugboat, and you set them off on their way. Then the rains come, lightning flashes, and oh my gosh, there are sharks in the water. The swimmer gets into trouble, the sailboat capsizes, and the tugboat hits the rocks. Maybe if you’re lucky, someone gets across.
What does it really look like to make a therapeutic? A drug is made up of small molecules—hydrogen, carbon, oxygen, nitrogen, and a few other atoms—all cobbled together in a shape. It’s those shapes that determine whether that particular drug will hit its target and land where it’s supposed to.
When developing a new treatment for conditions like autism, Alzheimer’s disease, or cancer, you need to find the right shape in that mix that will ultimately provide benefit and be safe. You start with thousands, maybe tens of thousands of compounds, and you weed down through various steps that cause many of these to fail. Ultimately, maybe you can run a clinical trial with four or five of these, and if all goes well, 14 years after you started, you will get one approval, costing upwards of a billion dollars for that one success.
We need to look at this pipeline the way an engineer would and ask how we can do better. That’s the main theme of what I want to discuss this morning: how can we make this process go faster and be more successful?
Let me tell you about a few examples where this has actually worked. One recent success is the approval of a drug for cystic fibrosis, but it took a long time to get there. The molecular cause of cystic fibrosis was discovered in 1989 by my group, working with another group in Toronto, identifying the mutation in a specific gene on chromosome seven.
This year marks a significant milestone, as it is the year where we have the first FDA-approved drug that precisely targets the defect in cystic fibrosis based on all this molecular understanding. The downside is that this drug doesn’t treat all cases of cystic fibrosis, and it won’t work for everyone, including one individual who has been waiting for a next-generation treatment.
It took 23 years to get this far—too long. How do we go faster? One way is to take advantage of technology, particularly the human genome. The ability to look at a chromosome, unzip it, and read the DNA code has dramatically decreased in cost over the last decade. It is now less than ten thousand dollars to have your genome sequenced, and we’re headed for the thousand-dollar genome soon.
Let me tell you about another disorder: Hutchinson-Gilford progeria syndrome, a rare condition that causes dramatic premature aging. Only about one in every four million children has this disease. Due to a mutation in a specific gene, a toxic protein is produced that causes these individuals to age at about seven times the normal rate.
In 2003, we discovered this and aimed to correct it. By understanding the molecular pathways, we could pick a compound that might be useful and test it in cell culture. In just 72 hours, that progeria cell became almost like a normal cell.
But would it work in a real human being? This led to a clinical trial just four years after the gene was discovered, involving 28 children who volunteered. One of them, Sam Burns from Boston, is here today to share his experience living with progeria.
Sam, please come up and tell us about your experience.
[Sam speaks about how progeria limits him in some ways but also how he finds ways to pursue his interests and activities. He expresses gratitude for the progress in research and hopes for a cure in the near future.]
Thank you, Sam. Your story highlights the drive of researchers and the importance of their work.
The drug now in clinical trial for progeria was not originally designed for that condition; it was developed for cancer but turned out to have the right properties for progeria. Wouldn’t it be great if we could do that more systematically?
We could encourage companies to explore drugs that are known to be safe in humans but have not succeeded in their original applications. This could lead to repurposing old drugs for new uses, teaching them new tricks.
At NIH, we have started a new National Center for Advancing Translational Sciences to foster partnerships between academia, government, the private sector, and patient organizations to pursue these goals.
Another idea is to test drugs for effectiveness and safety without putting patients at risk. Instead of relying solely on animal testing, we could use human cells. For example, researchers have developed a “lung on a chip” that mimics lung function and can be used to test drug compounds for safety and efficacy.
In summary, we are at a remarkable moment in research. We need resources for high-risk, high-cost research with enormous potential payoffs. We need new partnerships to repurpose compounds and, most importantly, we need talent from diverse disciplines to join this effort.
This is the time for 21st-century biology, and we have the chance to turn our discoveries into solutions that can eliminate diseases. Thank you all very much.
Drug Development – The process of bringing a new pharmaceutical drug to the market once a lead compound has been identified through the process of drug discovery. – The drug development phase involves rigorous testing to ensure the efficacy and safety of the new medication.
Biology – The scientific study of life and living organisms, including their structure, function, growth, evolution, distribution, and taxonomy. – Advances in molecular biology have significantly enhanced our understanding of genetic diseases.
Health – The state of complete physical, mental, and social well-being, not merely the absence of disease or infirmity. – Public health initiatives aim to improve the overall health of communities through education and preventive measures.
Therapies – Treatments intended to relieve or heal a disorder, often involving a systematic approach to address specific health issues. – Gene therapies are being developed to target genetic disorders at their source by correcting defective genes.
Treatments – Medical care given to a patient for an illness or injury, often involving a combination of therapies and medications. – The new cancer treatments have shown promising results in clinical trials, offering hope to patients with advanced stages of the disease.
Technology – The application of scientific knowledge for practical purposes, especially in industry, including the development of tools and devices that improve healthcare. – Wearable technology is revolutionizing patient monitoring by providing real-time health data to clinicians.
Collaboration – The action of working with someone to produce or create something, often seen in research and development projects in the healthcare sector. – Collaboration between pharmaceutical companies and academic institutions has accelerated the pace of drug discovery.
Genetic – Relating to genes or heredity, often used in the context of genetic research and the study of inherited traits and disorders. – Genetic testing can provide valuable insights into an individual’s risk for certain hereditary diseases.
Research – The systematic investigation into and study of materials and sources in order to establish facts and reach new conclusions, particularly in scientific fields. – Ongoing research in immunology is crucial for developing vaccines against emerging infectious diseases.
Safety – The condition of being protected from or unlikely to cause danger, risk, or injury, especially in the context of medical treatments and procedures. – Ensuring the safety of new medical devices is a top priority during the regulatory approval process.
