Im a geneticist. I study the connection between information and biology essentially what makes a fly a fly, and a human a human. Interestingly, were not that different. Its a fantastic job and I know, more or less, how lucky I am to have it.
Ive been a professional geneticist since the early 1990s. Im reasonably good at this, and my research group has done some really good work over the years. But one of the challenges of the job is coming to grips with the idea that much of what we think we know is, in fact, wrong.
Sometimes, were just off a little, and the whole point of a set of experiments is simply trying to do a little better, to get a little closer to the answer. At some point, though, in some aspect of what we do, its likely that were just flat out wrong. And thats okay. The trick is being open-minded enough, hopefully, to see that someday, and then to make the change.
One of the amazing things about being a modern geneticist is that, generally speaking, people have some idea of what I do: work on DNA (deoxyribonucleic acid). When I ask a group of school kids what a gene is, the most common answer is DNA. And this is true, with some interesting exceptions. Genes are DNA and DNA is the information in biology.
For almost 100 years, biologists were certain that the information in biology was found in proteins and not DNA, and there were geneticists who went to the grave certain of this. How they got it wrong is an interesting story.
Genetics, microscopy (actually creating the first microscopes), and biochemistry were all developing together in the late 1800s. Not surprisingly, one of the earliest questions that fascinated biologists was how information was carried from generation to generation. Offspring look like their parents, but why? Why your second daughter looks like the postman is a question that came up later.
Early cell biologists were using the new microscopes to peer into the cell in ways that simply hadnt been possible previously. They were finding thread-like structures in the interior of cells that passed from generation to generation, were similar within a species, but different between them. We now know these threads as chromosomes. Could these hold the information that scientists were looking for?
Advances in biochemistry paralleled those in microscopy and early geneticists determined that chromosomes were primarily made up of two types of molecules: proteins and DNA. Both are long polymers (chains) made up of repeated monomers (links in the chains). It seemed very reasonable that these chains could contain the information of biological complexity.
By analogy, think of a word as just a string of letters, a sentence as a chain of words, and a paragraph as a chain of sentences. We can think of chromosomes, then, as chapters, and all of our genetic information what we now call our genome (all our genetic material) as these chapters that make up a novel. The question to those early geneticists, then, was: Which string made up the novel? Was it protein or DNA?
You and I know the answer: DNA. Early geneticists, however, got it wrong and then passionately defended this wrong stance for eight decades. Why? The answer is simple. Protein is complicated. DNA is simple. Life is complicated. The alphabet of life, then, should be complicated and protein fits that.
Proteins are made up of 20 amino acids there are 20 different kinds of links in the protein chain. DNA is made up of only four nucleotides there are only four different links in the DNA chain. Given the choice between a complicated alphabet and a simple one, the reasonable choice was the complicated one, namely protein. But, biology doesnt always follow the obvious path and the genetic material was, and is, DNA.
It took decades of experiments to disprove conventional wisdom and convince most people that biological information was in DNA. For some, it took James Watson and Francis Crick (http://www.pbs.org/wgbh/aso/databank/entries/do53dn.html), using data misappropriated from Rosalind Franklin https://www.nature.com/scitable/topicpage/rosalind-franklin-a-crucial-contribution-6538012/), deciphering the structure of DNA in 1953 to drive the nail in the protein coffin. It just seemed to obvious that protein, with all its complexity, would be the molecule that coded for complexity.
These were some of the most accomplished and thoughtful scientists of their day, but they got it wrong. And thats okay if we learn from their mistakes.
It is too easy to dismiss this example as the foolishness of the past. We wouldnt make this kind of mistake today, would we? I cant answer that, but let me give you another example that suggests we would, and Ill argue at the end that we almost certainly are.
Im an American, and one of the challenges of moving to Canada was having to adapt to overcooked burgers (my mother still cant accept that she cant get her burger medium when she visits). This culinary challenge is driven by a phenomenon that one of the more interesting recent cases of scientists having it wrong and refusing to see that.
In the late 1980s, cows started wasting away and, in the late stages of what was slowly recognized as a disease, acting in such bizarre manner that their disease, bovine spongiform encephalitis, became known as Mad Cow Disease. Strikingly, the brains of the cows were full of holes (hence spongiform) and the holes were caked with plaques of proteins clumped together.
Really strikingly, the proteins were ones that are found in healthy brains, but now in an unnatural shape. Proteins are long chains, but they function because they have complex 3D shapes think origami. Proteins fold and fold into specific shapes. But, these proteins found in sick cow brains had a shape not normally seen in nature; they were misfolded.
Sometime after, people started dying from the same symptoms and a connection was made between eating infected cows and contracting the disease (cows could also contract the disease, but likely through saliva or direct contact, and not cannibalism). Researchers also determined the culprit was consumption only of neural tissue, brain and spinal tissue, the very tissue that showed the physical effects of infection (and this is important).
One of the challenges of explaining the disease was the time-course from infection to disease to death; it was long and slow. Diseases, we knew, were transmitted by viruses and bacteria, but no scientist could isolate one that would explain this disease. Further, no one knew of other viruses or bacteria whose infection would take this long to lead to death. For various reasons, people leaned toward assuming a viral cause, and careers and reputations were built on finding the slow virus.
In the late 1980s, a pair of British researchers suggested that perhaps the shape, the folding, of the proteins in the plaques was key. Could the misfolding be causing the clumping that led to the plaques? This proposal was soon championed by Stanely Prusiner, a young scientist early in his career.
The idea was simple. The misfolded protein was itself both the result and the cause of the infection. Misfolded protein clumped forming plaques that killed the brain tissue they also caused correctly folded versions of the proteins to misfold. The concept was straightforward, but completely heretical. Disease, we knew, did not work that way. Diseases are transmitted by viruses or bacteria, but the information is transmitted as DNA (and, rarely, RNA, a closely related molecule). Disease is not transmitted in protein folding (although in 1963 Kurt Vonnegut had predicted such a model for world-destroying ice formation in his amazing book Cats Cradle).
For holding this protein-based view of infection, Prusiner was literally and metaphorically shouted out of the room. Then he showed, experimentally and elegantly, that misfolded proteins, which he called prions, were the cause of these diseases, of both symptoms and infection.
For this accomplishment, he was awarded the 1997 Nobel Prize in Medicine. He, and others, were right. Science, with a big S, was wrong. And thats okay. We now know that prions are responsible for a series of diseases in humans and other animals, including Chronic Wasting Disease, the spread of which poses a serious threat to deer and elk here in Ontario.
Circling back, the overcooked burger phenomenon is because of these proteins. If you heat the prions sufficiently, they lose their unnatural shape all shape actually and the beef is safe to eat. A well-done burger will guarantee no infectious prions, while a medium one will not. We dont have this issue in the U.S. because cows south of the border are less likely to have been infected with the prions than their northern counterparts (or at least Americans are willing to pretend this is the case).
Where does this leave us? To me, the take-home message is that we need to remain skeptical, but curious. Examine the world around you with curious eyes, and be ready to challenge and question your assumptions.
Also, dont ignore the massive things in front of your eyes simply because they dont fit your understanding of, or wishes for, the world around you. Climate change, for example, is real and will likely make this a more difficult world for our children. Ive spent a lot of time in my career putting together models of how the biological world works, but I know pieces of these models are wrong.
I can almost guarantee you that I have something as fundamentally wrong as those early geneticists stuck on protein as the genetic material of cells or the prion-deniers; I just dont know what it is. Yet.
And, this situation is okay. The important thing isnt to be right. Instead, it is to be open to seeing when you are wrong.
Dr. Thomas Merritt is the Canada Research Chair in Genomics and Bioinformatics at Laurentian University.
See original here:
Discover: Science is often wrong and that's actually a really good thing - Sudbury.com
- Protein folding - Wikipedia [Last Updated On: August 18th, 2024] [Originally Added On: September 11th, 2019]
- Protein Folding: The Good, the Bad, and the Ugly - Science ... [Last Updated On: August 18th, 2024] [Originally Added On: September 13th, 2019]
- Protein Folding - Chemistry LibreTexts [Last Updated On: August 18th, 2024] [Originally Added On: September 14th, 2019]
- Protein Structure and Folding [Last Updated On: August 18th, 2024] [Originally Added On: September 19th, 2019]
- Structural Biochemistry/Proteins/Protein Folding ... [Last Updated On: August 18th, 2024] [Originally Added On: September 28th, 2019]
- Proteopathy - Wikipedia [Last Updated On: August 18th, 2024] [Originally Added On: October 1st, 2019]
- Folding@home - Wikipedia [Last Updated On: August 18th, 2024] [Originally Added On: October 1st, 2019]
- Denaturation and Protein Folding | Introduction to Chemistry [Last Updated On: August 18th, 2024] [Originally Added On: October 4th, 2019]
- Protein Folding - Anfinsen's Experiment ~ Biology Exams 4 U [Last Updated On: August 18th, 2024] [Originally Added On: October 4th, 2019]
- Protein Structures: Primary, Secondary, Tertiary, Quaternary ... [Last Updated On: August 18th, 2024] [Originally Added On: October 4th, 2019]
- Protein Folding - an overview | ScienceDirect Topics [Last Updated On: August 18th, 2024] [Originally Added On: October 6th, 2019]
- Thermodynamics of spontaneous protein folding: role of ... [Last Updated On: August 18th, 2024] [Originally Added On: October 8th, 2019]
- Molecular Biology 02: 'Thermodynamics of protein folding' [Last Updated On: August 18th, 2024] [Originally Added On: October 8th, 2019]
- The Science Behind Foldit | Foldit [Last Updated On: August 18th, 2024] [Originally Added On: October 8th, 2019]
- Diseases Folding@home [Last Updated On: August 18th, 2024] [Originally Added On: October 8th, 2019]
- DeepMind timeline: The history of the UK's pioneering AI firm - Techworld.com [Last Updated On: August 18th, 2024] [Originally Added On: October 10th, 2019]
- Geroscience and it's Impact on the Human Healthspan: A podcast with John Newman - GeriPal - A Geriatrics and Palliative Care Blog [Last Updated On: August 18th, 2024] [Originally Added On: October 10th, 2019]
- Yumanity Therapeutics Initiates Phase 1 Clinical Trial of Lead Candidate YTX-7739 for the Treatment of Parkinson's Disease | Small Molecules | News... [Last Updated On: August 18th, 2024] [Originally Added On: October 10th, 2019]
- Tenure-Track or Tenure-Eligible Position in the Laboratory of Chemical Physics job with National Institutes of Health | 28302 - Chemical &... [Last Updated On: August 18th, 2024] [Originally Added On: October 10th, 2019]
- Food for the soul: Traditional gyza makers and eaters in Utsunomiya try to keep the dumplings rolling - The Japan Times [Last Updated On: August 18th, 2024] [Originally Added On: October 19th, 2019]
- UT molecular evolution professor named 2019 American Physical Society Fellow - UT The Daily Texan [Last Updated On: August 18th, 2024] [Originally Added On: October 19th, 2019]
- 9 must-have Instant Pot accessories for healthy eating - CNET [Last Updated On: August 18th, 2024] [Originally Added On: October 19th, 2019]
- Researchers Find Fish Wearing Natural 'Bullet-Proof Vest' to Thwart Piranhas in Amazon - News18 [Last Updated On: August 18th, 2024] [Originally Added On: October 19th, 2019]
- Christopher Dobson: chemist whose work on proteins advanced research into neurodegenerative diseases - The BMJ [Last Updated On: August 18th, 2024] [Originally Added On: October 19th, 2019]
- Two years in the making, Pizza Hut tests a round pizza box - Fast Company [Last Updated On: August 18th, 2024] [Originally Added On: October 23rd, 2019]
- Fava Is All About Balance - East Bay Express [Last Updated On: August 18th, 2024] [Originally Added On: October 23rd, 2019]
- Amazon fish wears nature's 'bullet-proof vest' to thwart piranhas - Reuters [Last Updated On: August 18th, 2024] [Originally Added On: October 23rd, 2019]
- RNA Folding Insights Lead to New Therapeutics and Synthetic Biology Technologies - Technology Networks [Last Updated On: August 18th, 2024] [Originally Added On: October 23rd, 2019]
- The Hidden Inactive Ingredient: Biological Products in Recombinant Pharmaceuticals - P&T Community [Last Updated On: August 18th, 2024] [Originally Added On: October 23rd, 2019]
- Insights into Parkinson's Onset May Lie in New Model of Cell Aging and Damage - Parkinson's News Today [Last Updated On: August 18th, 2024] [Originally Added On: October 23rd, 2019]
- Antibiotics with novel mechanism of action discovered - Drug Target Review [Last Updated On: August 18th, 2024] [Originally Added On: October 25th, 2019]
- The top AI lighthouse projects to watch in biopharma - FierceBiotech [Last Updated On: August 18th, 2024] [Originally Added On: October 25th, 2019]
- UCI vision scientist Krzysztof Palczewski elected to National Academy of Medicine - UCI News [Last Updated On: August 18th, 2024] [Originally Added On: October 26th, 2019]
- Rett Syndrome Tied to Altered Protein Levels in Brain in Early Study - Rett Syndrome News [Last Updated On: August 18th, 2024] [Originally Added On: October 26th, 2019]
- Bulls-Eye: Imaging Technology Could Confirm When a Drug Is Going to the Right Place - On Cancer - Memorial Sloan Kettering [Last Updated On: August 18th, 2024] [Originally Added On: October 26th, 2019]
- IBM vs. Google and the Race to Quantum Supremacy - Citizen Truth [Last Updated On: August 18th, 2024] [Originally Added On: November 7th, 2019]
- Microprotein ID'd Affecting Protein Folding and Cell Stress Linked to Diseases Like Huntington's, Study Finds - Huntington's Disease News [Last Updated On: August 18th, 2024] [Originally Added On: November 7th, 2019]
- IBM vs. Google and the race to quantum supremacy - Salon [Last Updated On: August 18th, 2024] [Originally Added On: November 11th, 2019]
- That Junk DNA Is Full of Information! - Advanced Science News [Last Updated On: August 18th, 2024] [Originally Added On: November 16th, 2019]
- Argonne Researchers to Share Scientific Computing Insights at SC19 - HPCwire [Last Updated On: August 18th, 2024] [Originally Added On: November 16th, 2019]
- How to Make the Most of Your Old Tech - New York Magazine [Last Updated On: August 18th, 2024] [Originally Added On: November 16th, 2019]
- 2 tricked-out pies to be thankful for: pear with cranberries and pumpkin with ginger praline - The Gazette [Last Updated On: August 18th, 2024] [Originally Added On: November 17th, 2019]
- From Mediterranean Lentil Salad to Cinnamon Raisin Bread: Our Top 10 Vegan Recipes of the Day! - One Green Planet [Last Updated On: August 18th, 2024] [Originally Added On: November 22nd, 2019]
- What is Biophysical Analysis? - The John Innes Centre [Last Updated On: August 18th, 2024] [Originally Added On: November 22nd, 2019]
- Thermodynamic probes of instability: application to therapeutic proteins - European Pharmaceutical Review [Last Updated On: August 18th, 2024] [Originally Added On: November 22nd, 2019]
- In science, its better to be curious than correct - The Conversation CA [Last Updated On: August 18th, 2024] [Originally Added On: November 22nd, 2019]
- New Study Reveals US Airlines With the Healthiest Food Options - TravelPulse [Last Updated On: August 18th, 2024] [Originally Added On: November 29th, 2019]
- Study Reveals Hepatitis A Originated in Insects - Advanced Science News [Last Updated On: August 18th, 2024] [Originally Added On: November 29th, 2019]
- How Home-Baked Bread Is Defying the Industrial Food System - YES! Magazine [Last Updated On: August 18th, 2024] [Originally Added On: November 29th, 2019]
- Black Friday Is Absolutely Massive. Here Are a Bunch of Deals We Couldn't Call Out Individually - Gear Patrol [Last Updated On: August 18th, 2024] [Originally Added On: November 30th, 2019]
- A conserved ATP- and Scc2/4-dependent activity for cohesin in tethering DNA molecules - Science Advances [Last Updated On: August 18th, 2024] [Originally Added On: November 30th, 2019]
- Ancient Worm Reveals Way to Destroy Toxic Cells Potential New Therapy for Huntingtons and Parkinsons - SciTechDaily [Last Updated On: August 18th, 2024] [Originally Added On: December 11th, 2019]
- Biologics Market Size Expand at a CAGR of 3.9 With $399.5 Billion By 2025 - MENAFN.COM [Last Updated On: August 18th, 2024] [Originally Added On: December 11th, 2019]
- Exploring the Diversity of Parkinson's Proteins - Technology Networks [Last Updated On: August 18th, 2024] [Originally Added On: December 11th, 2019]
- Early detection of brain degeneration on the horizon with innovative sensor - UNM Newsroom [Last Updated On: August 18th, 2024] [Originally Added On: December 16th, 2019]
- Holiday cookies from around the world | Features - yoursun.com [Last Updated On: August 18th, 2024] [Originally Added On: December 22nd, 2019]
- The Art of Origami is Now A Key Tool That Helps Doctors Save Lives - Nature World News [Last Updated On: August 18th, 2024] [Originally Added On: December 23rd, 2019]
- Nanopores can identify the amino acids in proteins, the first step to sequencing - University of Illinois News [Last Updated On: August 18th, 2024] [Originally Added On: December 23rd, 2019]
- Wow your New Year's Eve guests with a puff pastry appetizer - KARE11.com [Last Updated On: August 18th, 2024] [Originally Added On: January 1st, 2020]
- The 10 most compelling product innovations of 2019 - Fast Company [Last Updated On: August 18th, 2024] [Originally Added On: January 1st, 2020]
- Our best recipes from 2019 | Food and cooking - STLtoday.com [Last Updated On: August 18th, 2024] [Originally Added On: January 1st, 2020]
- The best WIRED long reads of 2019 - Wired.co.uk [Last Updated On: August 18th, 2024] [Originally Added On: January 1st, 2020]
- Structure of Drosophila melanogaster ARC1 reveals a repurposed molecule with characteristics of retroviral Gag - Science Advances [Last Updated On: August 18th, 2024] [Originally Added On: January 1st, 2020]
- Gocycle to partner with nutrition brand Fuel10k to promote benefits of e-bikes - Bike Biz [Last Updated On: August 18th, 2024] [Originally Added On: January 16th, 2020]
- The Importance of Understanding TargetProtein Interactions in Drug Discovery - Technology Networks [Last Updated On: August 18th, 2024] [Originally Added On: January 16th, 2020]
- How DeepMind is unlocking the secrets of dopamine and protein folding with AI - VentureBeat [Last Updated On: August 18th, 2024] [Originally Added On: January 16th, 2020]
- How To Grow (Almost) Anything - Hackaday [Last Updated On: August 18th, 2024] [Originally Added On: January 19th, 2020]
- U of T's Peter Wittek, who will be remembered at Feb. 3 event, on why the future is quantum - News@UofT [Last Updated On: August 18th, 2024] [Originally Added On: January 19th, 2020]
- The DeepMind algorithm to solve two complex problems of biology - The Times Hub [Last Updated On: August 18th, 2024] [Originally Added On: January 19th, 2020]
- High Focus on Product Innovation & Development to Assist the Growth of the Folding Cartons Market between and . 2017 2025 Dagoretti News -... [Last Updated On: August 18th, 2024] [Originally Added On: January 24th, 2020]
- Folded, frozen, and faster: JUST Egg is now more convenient, and cheaper, to enjoy - FoodNavigator-USA.com [Last Updated On: August 18th, 2024] [Originally Added On: January 24th, 2020]
- Phyllo, cheese, heaven: Balkan women have been making these treats for centuries - The Gazette [Last Updated On: August 18th, 2024] [Originally Added On: January 26th, 2020]
- Phyllo, cheese, heaven: Balkan women have been making these treats for centuries - Waterbury Republican American [Last Updated On: August 18th, 2024] [Originally Added On: January 28th, 2020]
- The keto diet: Its highs and lows plus 5 recipes - The Gazette [Last Updated On: August 18th, 2024] [Originally Added On: February 12th, 2020]
- Study Shows How Soap Molecules Alter the Protein Structure - AZoM [Last Updated On: August 18th, 2024] [Originally Added On: February 12th, 2020]
- CryoEM of CBD Tau Suggests Another Unique Protofibril - Alzforum [Last Updated On: August 18th, 2024] [Originally Added On: February 16th, 2020]
- Working In Science Was A Brutal Education. Thats Why I Left. - BuzzFeed News [Last Updated On: August 18th, 2024] [Originally Added On: February 17th, 2020]
- The Evolution of the Eye, Demystified - Discovery Institute [Last Updated On: August 18th, 2024] [Originally Added On: February 28th, 2020]
- L-serine could be used to treat ALS, after promising study results - Drug Target Review [Last Updated On: August 18th, 2024] [Originally Added On: February 28th, 2020]
- One of Our Best Biochemists, She Was Never Awarded By India! - The Better India [Last Updated On: August 18th, 2024] [Originally Added On: March 17th, 2020]