50 Years of Life Sciences Innovation: PMI's Top 10 Impactful Biotech Projects
The Project Management Institute (PMI) announced its 2019 Most Influential Projects list. This ranking cites the most impactful projects from the past 50 years, with the World Wide Web hitting the #1 spot followed by Apollo 11, and including such projects as Walt Disney World, Harry Potter, World of Warcraft and the Sydney Opera House.
The list is also broken out into subcategories, including biotech. Here’s a look at the biotech list.
#1. Human Genome Project. This ranked #5 on their overall list, and it indeed is one of the most influential life science projects, changing and informing healthcare and biology as we know it. One simple example is the overturning of the central dogma—which up until the completion of the project, was that one gene coded for one protein. Since there were about a hundred thousand known proteins, scientists had concluded there must be the same number of genes. However, it turned out that in human beings, there were about 30,000 genes and they are read in a variety of unexpected ways to code for those 100,000-plus genes.
The project launched officially in 1990 and drew on laboratories and institutions from around the world, including from the U.S. Department of Energy, the U.S. National Institutes of Health (NIH), the UK’s Sanger Centre (later the Wellcome Sanger Institute) and 17 university and laboratory sequencing centers.
#2. First IVF Baby. This year was the 41st birthday of the first so-called “test tube baby,” Louise Brown, who was born on July 25 in 1978. The process is in vitro fertilization. Now commonplace, the procedure was incredibly controversial at the time. Louise’s mother, Lesley Brown, hadn’t been able to conceive naturally as the result of blocked Fallopian tubes. She had been trying to conceive for nine years when she signed up for IVF, which was then an experimental procedure. She was one of 282 women who tried the procedure. At that time, doctors attempted 457 egg collections, but only 167 cycles led to fertilization. From 12 embryos that were successfully implanted, five became pregnant. Louise was the only live birth. Since then, about six million children have been born via IVF.
#3. CRISPR. CRISPR stands for clustered regularly interspaced short palindromic repeats, which is otherwise a fast and easy way to edit DNA. CRISPR-Cas9 allows researchers to easily identify specific gene sequences, clip them out and replace them. It has been cited as one of the most important and recent discoveries that could lead to new therapies and treatments for numerous diseases. In November 2018, it hit the spotlight with a major controversy when He Jiankui, a researcher in Shenzhen, China, announced he had utilized CRISPR-Cas9 to alter the DNA of embryos for seven couples. He used CRISPR to disable a gene called CCR5. CCR5 codes for a protein that allows HIV to enter a cell. In theory, the children born from the procedure should be resistant to HIV. The fathers all had HIV infections that were strongly suppressed by standard HIV drugs. The announcement was met by wide international condemnation, the eventual moratorium on using CRISPR germline editing, and He Jiankui being investigated by the Chinese government.
#4. Genetic Fingerprinting. Perhaps more accurately described now as forensic DNA analysis, genetic fingerprinting is a way of using DNA samples in criminal investigations to identify perpetrators (and victims). It was first introduced in 1984 by a researcher at the University of Leicester in the UK, Alec Jeffreys. The first practical application was in a 1985 immigration case, which was followed by a paternity case. The first criminal forensic case was applied to the case of two girls who were raped and murdered in the Enerby area of Leicestershire. There was a confession for one of the murders. They used the forensic test in an attempt to prove he committed the second, but unexpectedly, the test proved he was innocent of both murders. The police force then conducted blood draws and genetic profiles on the entire male population of that area. Again, no matches were found until a man named Colin Pitchfork bragged about how he had convinced a friend to provide the sample. He was a match for both rape and murders.
#5. 23andMe. 23andMe was founded in 2006 by Linda Avey, Paul Cusenza and Anne Wojcicki. It began by marketing a saliva-based direct-to-consumer personal genome test. However, the U.S. Food and Drug Administration (FDA) forced the company to pull it from the market because it was advertised as a medical device, which required FDA approval, which 23and Me did not have. The kits are still available, but health-related reports that came with it were no longer included. The company has since inked deals with major pharma companies, such as Pfizer, to use its genomics data in disease and drug research and development. In March 2018, the FDA approved 23andMe’s BRCA1 and BRCA2 genetics tests as the first-ever FDA approval for a DTC consumer genetic test for cancer risk, in this case, breast, ovarian and prostate cancer.
#6. Dolly. Although it seems like a distant memory, Dolly was the first mammal to be cloned from the cell of an adult. This was in 1996. Dolly was a sheep. Dolly was cloned by researchers at The Roslin Institute who were working to develop a better way to produce genetically modified livestock. The research was led by Ian Wilmut. Dolly was cloned from a cell acquired from the mammary gland of a six-year-old Finn Dorset sheep and an egg from a Scottish Blackface sheep. She was born to her Scottish Blackface surrogate mother on July 5, 1996. Oddly enough, because her DNA was taken from a mammary gland cell, she was named after country singer Dolly Parton.
#7. Engineered Organ. In 1999, Anthony Atala and his research group grew bladders in the laboratory and successfully implanted them into patients. Atala is the W.H. Boyce professor and director of the Wake Forest Institute for Regenerative Medicine and chair of the Department of Urology. Atala and his team took a bladder biopsy from each patient, isolated muscle and specialized urothelial cells, and grew them in the laboratory. They then implanted them onto a bladder-shaped scaffold where they grew for seven to eight weeks. They then attached the engineered bladder to the patients’ own bladder and followed the progress for up to five years. The bladder function improved without any of the side effects generally linked to implanting bowel tissue. The research paved the way for bioprinting of organs.
#8. Beyond Meat Burger. Beyond Meat developed a plant-based burger that mimics the taste of hamburger. The first plant-based burger was sold commercially in 2016. As of June 2019, the company had a $10 billion market cap and led the way for a variety of other companies to produce what are essentially genetically-modified vegetables that use a variety of ingredients, such as heme, to mimic the taste of beef. Although nutritionally about the same as beef—typically they have caloric levels similar to beef, with higher carbohydrate and salt levels with generally lower fat levels—the primary benefit is taking animals out of the protein production chain, which may have benefits for decreasing climate change.
#9. Golden Rice. The Golden Rice Project notes that Golden Rice “is the first purposefully created biofortified food.” The technology behind Golden Rice was donated in 2000 by its inventors, Ingo Potrykus and Peter Beyer. Golden Rice is a not-for-profit project that involved genetically modified rice to address vitamin A deficiency, which affects about 250 million children around the world. Potrykus was then a professor at the Swiss Federal Institute of Technology in Zurich, teamed with Peter Beyer from the University of Freiberg in Germany.
#10. Kymriah. Perhaps it would have been more appropriate to identify Immunotherapy or Immuno-Oncology as one of the projects, rather than Novartis’ Kymriah (tisagenlecleucel), even though Kymriah was the first CAR-T immuno-oncology therapy approved. The entire field of immuno-oncology has exploded in the last decade, revolutionizing cancer treatments and is beginning to make progress in other indications as well. The other approved CAR-T product is Gilead Sciences’ Yescarta (axicabtagene ciloleucel). They are approved for slightly different, but sometimes overlapping patient populations. Kymria is approved for pediatric and young adult acute lymphocytic leukemia (ALL) and for recurrently relapsing (r/r) aggressive lymphomas. Yescarta is approved for similar aggressive lymphomas.
CAR-T is a type of therapy where blood samples are taken from a patient, the patient’s white blood cells are processed to be supercharged to attack their cancer cells, then reinfused into the patient. It is a type of “living therapy” where the patient’s immune system is programmed to better attack the cancer.