Episode 11 Where the Science Began: A tribute to Dr. Ralph Holman
Who identified EPA and DHA omega-3? Ever wonder why omega-3 fats are called “omega-3”? How did we learn what fats were essential? In this episode, we take a walk back to hear Dr. Ralph Holman’s story, from poverty to pioneer; how his quest to solve problems built the foundation of omega-3 science. Living legends today sought his wisdom and his mentee, Dr. Doug Bibus, tells the story. Smuggling, brandy, sardines, love, ocean ships, character, and simple living are part of this American dream.
- Ralph Holman’s background (3:17)
- Dr. Holman’s discoveries at the University of Minnesota (4:27)
- Holman Omega-3 test (11:36)
- How Dr. Holman came to name omega-3s (16:00)
- The beginning of Dr. Holman’s research on lipids (18:28)
- Dr. Holman’s personal background (20:56)
- Ralph Holman’s impact on Doug Bibus’ life & career (25:06 )
Resources Mentioned in this Episode
Any statements on this podcast are the opinion of the scientific guest and/or author and have not been evaluated by the FDA. The information we may provide to you is designed for educational purposes only and is not intended to be a substitute for informed medical advice or care. This information should not be used to diagnose, treat, or prevent any health issues or conditions without consulting a health care professional. If you are experiencing a health issue or condition, we suggest you consult with your health care professional.
Hello, and welcome to The Science and The Story: Behind Omega-3, a podcast brought to you by Wiley Companies where we explore one of the most researched nutrients on the planet. Listen in as global omega-3 experts and researchers translate the science, reveal personal insights and share their stories of discovery while navigating the sea of omega-3 science
Thanks for joining us today. Now, here’s your host, Greg Lindsey.
So we welcome to the program Dr. Doug Bibus. Dr. Bibus, thank you so much for joining us today. We invited you here to talk about your esteemed mentor, Dr. Ralph Holman, and a future episode I want to look into more about your career. But today, I understand you started as Dr. Holman student and eventually came to manage his laboratory. Can you tell us how you met Dr. Holman? And then what’s your first memory of meeting him was? Yeah, great question. Thanks so much for allowing me to talk about Dr. Holman, one of my absolute all time favorite people. I was teenager actually, in the mid 80s. And I had a scholarship to
get the kid I guess, to work in a local laboratory. So I got randomly placed into this guy named Ralph Holmans lab and had no idea who he was. And I think I had like my football jersey on being cool for the first day of my job as a 15-year-old. And so I met Dr. Holman there. And I remember the first time I met him, I was trying to use like a nitrogen evaporator or something in the laboratory, and I couldn’t quite get it. So I went back to his office knocked on the door. And this very soft-spoken man came out and helped me figure out how to turn on the natural evaporator and so that was really the first time that I met Dr. Holman.
So Dr. Bibus, can you tell us who was Ralph Holman? Yeah, Ralph Holman was, you know that the headline you’d see on wiki would be something like a famous American biochemist. You know, Ralph Holman, was really pioneer, one of the great pioneers in nutritional research that emulated from, you know, the 1940s era into the 1970/80s era. Ralph grew up in Minnesota grew up in Minneapolis, Ralph’s dad drove a trolley car and Minneapolis, they grew up during the Great Depression. So Ralph talked a lot about never having money,
and not having enough money to go to college. Certainly, Ralph was rough story is really a story of the American dream about somebody that went from really a struggle to fame, in terms of success. And Ralph later went on, obviously, to be a great chemist.
And the long and short some of the significant things. He was the guy that named Omega-3, did a lot of the functional, basic pathophysiology about omega-3 fatty acids.
Can you tell us what were the main discoveries of his, I guess, lifelong program at the University of Minnesota? Yeah. So Ralph was one of the first people in his team to characterize EPA and DHA didn’t have GCS or aspects at the time, but they used a technique called Alkaline isomerization. And they had physical readouts or traces that will capture absorption of what they determined or molecules with five double bonds and six double bonds and three double bonds and they later use that technology this would have been in the 50s to determine the conversion of 18 three omega-3 from plant-based sources to EPA DHA is one of his fundamental discoveries. Ralph also discovered the competition between omega-6 and omega-3 for the longest centuries enzymes. Obviously, a lot of things happen once they got GCS. They developed GC technology that allowed them to actually measure EPA and DHA and at the time, it was in the early 1970s, Dr. Jorn Dyerberg was making his discoveries on fascinating folks in Greenland to eat a whole lot of fat, but didn’t die from cardiovascular disease. I know Jorn came to the lab. And so we have these peaks on our chromatograms. But we can’t quite figure out what those peaks are. And Ralph I think was working maybe Bill Christie was in the laboratory at the time. Bill’s probably one of the best lipid Alpha chemists in the world. And they said no, these are EPA and DHA. So that was the big six. I know Ralph’s family is from Sweden originally so human Jorn shared some Nordic similarities
You know further along the line, Ralph also was in 1984, he had a paper hatch at all the definitively determined that alpha linoleic acid was essential at that time. So George Burr in November worked with essential fatty acid deficient animals. And in the late 20s, they were the ones that figured out that omega-3 were essential, but because linseed oil they used as the omega-3 component because linseed oil contained bits of linoleic acid, it wasn’t definitively proven, I guess that 18 Three was the kurta factor or the essential nutrient at that time. So the hatch paper from the 80s was about a girl with a gunshot wound. And she was maintained on parenteral nutrition with just mu like acid as the essential fat.
And so this girl, over time was a growing kid, you know, and she over time, she started to develop episodic paralysis and visual problems and cognitive problems. And they sent a blood sample to Ralph Holman’s lab, at the University of Minnesota. And she had really, really low levels of omega-3. So they, fed back, I think soybean oil into her motion, or a source of 18, three, omega-3 and all those symptoms resolved. So that’s a classic clinical case of
omega-3 deficiency. But that was a really profound study at the time, and that put omega-3 on the map in terms of the sensuality. But yeah, he other things, looked at the dynamics of omega-3 during pregnancy, looked at the levels of omega-6 and omega-3 during the span of a pregnancy from first trimester, second trimester to third trimester and third trimester, you see a big deficit of DHA in studies that did back in the 80s, and 90s. And that was part of some of those studies. So the need for DHA throughout pregnancy was partly established in some of the work that Ralph did his lab. So we, our laboratory was about 40 minutes from the Mayo Clinic. So we had a whole lot of access to collaborative efforts with the Mayo Clinic and a lot of clinical cases over the years.
So Ralph really became interested in the economy of omega-6 and omega-3 and living systems and diets.
He was one of the first people to feed fish oil in the 80s. When I was there, we got fish oil from Japan tahini, which is now a mega protein on the East Coast. And the fish oil had like visible solids, and it just really had a strong smell. So we would, we would feed people, doses of that and we’ll look at the legation of the EPA DHA, and then looked at cholesterol levels effects on cholesterol, one of our German subjects, he would always drink whiskey or brandy.
because the taste was pretty foul, but then we get a lot of complaints about the smell of fish throughout the building. That was the state of the art back in the day. So we were really grateful just to have access to fish oil. And of course, that’s changed dramatically since that time. So then we, you know, went on to look at different diseases and sick people. The list was probably 60 or 80 different disease types would get 20 to 100 samples, and he would establish these graphics looking at increases or decreases in omega-3 and omega-6 and the take home was you know, the illness really decreased omega-3 and omega-6 status. Whether or not that was a cause or functional disease was
a question but certainly being sick was a stress on your essential fatty acid status. And then kind of the next phase is research. We went on and looked by population studies around the world looking at different populations and different foods they ate looking at the omega-3 and omega-6 levels and certainly,
people in Nordic countries eating fish had really high levels. You know, their total omega-3 score omega-3 in their blood is like 15%. At high levels in America, we were at a three or 4% pretty low. Good studies and from Vladivostok, Russia looking at pregnant moms and offspring’s. Those ladies had much higher levels of DHA than American moms. We had a cohort for male from Utah as well. But yeah, interesting things. We looked at populations in Los Nigeria as well. They
they weren’t eating a whole lot of fish, but they were eating a lot of sources of omega-3, and they had relatively high levels of wanting and omega-3 it was… it was fun science, you know people would send us tubes from all over the world and samples from all over the world and the Vladivostok Russia study we actually smuggled
The supplies out of Seattle, we tried to send them with DHL, and they got to Moscow. And we have a request for a $10,000 Signing check. Oh my god. Yeah. So.
So a creative Russian friend of mine said, you know, we used to send things to the Port of Seattle and for $5 A kilogram bill, take a view. So we had boxes of test tubes and things needed for those studies. So good times, good memories.
Really, you know, a lot of his research pointed the finger that Americans just don’t eat enough omega-3 and causes this for a lot of diseases.
So, Ralph was particularly interested in DHA. And he had a quote that said, you know, your brain is full of DHA and helps us see the beauty of life and not having adequate amounts of DHA filter that beauty.
And then he also there was a Holman Omega-3 test, is that right? Yeah, we so we spent a lot of time looking at omega-3 status, and we would get people calling us and saying, can you can you measure my blood for omega-3. So he and I both worked on
developing this, and then, you know, we were doing, we were doing blood draws, but people had to go to the hospital and get a blood draw, and ship it to us. So, you know, by the time a sample got to us, it costs probably $200- $300, at least in fees for them.
Maybe measure and report back to them. But so we start working with fingerstick technology in the early 90s. And that was an improvement. And then all along, you know, the technology and gas chromatography were improving to the point where you could really accurately track things down to two micromolar microgram levels. So we were good at measuring small amounts of things accurately, using small samples to get things accurately.
And then we went to went to cards. Neonatal testing was using bloodspot cards, and dried blood spot technology,
along with several other groups at the time, we figured out how to stabilize our system. And now we use bloodspot cards for all kinds of things. So we’ve had bloodspot cards come we were doing studies in turtles coming from Madagascar. Wow. Yeah. So professional soccer players in Europe, all over the place. Yeah, so the dried blood spot technology is really wonderful for, for transmitting, and collecting samples and doing samples, recently done breast milk studies in Guatemala. And so the cards can use to go out into the fields and into the mountainous areas and pluck samples, and then bring them back into larger cities, and then return samples, a
lot of fun. But, you know, you rattled off just so many amazing discoveries. When did all of this work, I guess, between which years did all of this work take place? Yeah. So, you know, Ralph, Ralph finished
his PhD in the mid 40s. And he enlisted in the military. But he had five feet or some something that excluded him from doing that. And so a lot of this research when he was a young man was in the 50s and 60s, because that was the fundamental stuff of discovering different isomers and legation the saturation,
the disease where the pregnancy work, started in probably the late 70s, early 80s. There and then went into the 90s populational studies were, we’re
early 90s into the 2000s. So I think Ralph, kind of officially hung it up, laboratory life up around 2000 to 2003, somewhere in there.
He never stopped working though. He was always writing and publishing papers and, and Ralph, he loved the omega-3, he was just so upset that they didn’t, he said people have to eat this nutrient. It’s really important and, and he was so frustrated that it wasn’t happening. So I got a call one day or email with a picture from our local Heidi grocery store. And he was so proud that the salmon had said a great source of Omega-3. And it’s this sort of bad in the 1990 timeframe, but he actually wrote a paper called The slow discovery of the importance of Omega-3 and it was kind of his rant about how we’ve known all these wonderful things about omega-3 fats and nobody was acting on this information. The truth is changes in dietary guidelines and stuff are often really slow.
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We you mentioned Dr. Bibus earlier that Dr. Holman actually named omega-3s. So why omega? And why three? Yeah. So Ralph, these are some of the tidbits, you know, I was around Ralph a lot every day. And I knew him as a really, really nice guy and very compassionate mentor. But, but then I started discovering all these tidbits, I go on my National Academy of Science number 100. Yeah, I named those omega-3 fats, he did. So he, in the early 60s, I guess it was the Delta system that was used, that counted from the carboxylic acid and the molecule in Delta still use today. But every time a fatty acid would elongate, the saturator would add a double bond, or it would have a double bond or carbon and that numbering system would change. So he wanted to main fatty acids from the tail end of the metal end of the molecule where, where that end of the molecule never change. So you do the word for the term end. And Ralph said, I learned about this in Sunday school – I am the Alpha, and I am the Omega at the beginning. So from the Bible. So kind of cool. And, of course, there’s a lot of, you know, a lot of religions, especially Christianity, there’s a lot of references to fish, and the importance of fish as Christianity. But so that’s where Omega came from. And the three is the three carbons in it’s the distance to the first double bond. So omega-3, the first Obata, there’s three carbons in and the Omega-6 occurs, six double bonds in omega 999 carbons in so and that turtle tail portion never changes in terms of its structure. So it’s a familial trade, if you will follow. So that’s where it came from, was a paper published, they used it in a paper in 1963 that describe the competitive nature of omega-6 and omega-3, and he has a little sidebar that says, you know, here’s this new nomenclature, by the way that we’re using this paper. That’s fascinating. So yeah, well, we used today was just something that he put together. That’s, that’s fantastic. Just needed a solution. That’s kind of how Ralph was throughout his life. He, he solved problems, you didn’t necessarily look for an easy way out or hire somebody or
so kind of ties in with his work. Do you know why Dr. Holman studied lipids instead of maybe protein or carbohydrates? Yeah. So in that period of time, Ralph started studying actually carbohydrates at the University of Minnesota. And carbohydrates were the
bomb at the time of metabolism and what they were in. And Ralph was studying metabolism of sugar in radishes. And he would get heavy carbon from heavy sugars with C 13. From engineers lab at the University of Minnesota. They’ll in their work with mass spec, surely Mass Effects and looked at radioisotopes and things like that. Ralph was getting sources of that every day for his radish plants, you can go essentially, and they would filter off carbon dioxide, I’m sorry, from a super long chromatographic tube that would be for storytime to building so. So heavy, heavy air, if you will, which would filter to the bottom and we would isolate that. But Ralph walked in the lab one day, and everything was dark in near his lab, and he was like what’s going on because it was one of those seven day a week kind of labs. And he said all the instruments were off and everything was off. And so Ralph soon found out that telomere and his group was requisition for the Manhattan project to work on the nuclear bomb so they were absconded in the middle of the night. They were taken. Very secretive.
So Ralph was a young man you know, Ralph had struggled to get to college financially and people at Bethel University helped him financially with a job to make it there. So he was he was really blessed and then he got an offer to work down the central fats of Georgia November. He decided I want to work on fats, boring, you know,
but it was you know, it was really undiscovered material there and the discovery of essential fats was great about that same time. So in George Burr turned out to be a big feature and Ralph Holmans life.
He an exceptional human being- just like Ralph was to me and countless other postdocs and faculty members in Ralph had a picture of George Burr on his desk for the rest of his life after, after his graduate school time, but Ralph began working with George in November and worked on aspects of the essential fats at that time.
That would have been in the early 40s And that launched his career. He went to Texas. I think for a little bit he asked me when a postdoc to the Karolinska Institute in Sweden,
crystallized the poxy drinks while he was there. So he worked with Sumi Bergstrom blanking the name of the other Nobel laureate that he worked with. apologize about that.
But back in those days, you didn’t take an airplane to Europe, you took a boat. So I think it was 14 days across the ocean, or 11 days, something like that. So he gave me his travel trunk – it has stickers all over it, the big wooden trunk where people would put their stuff so we have that in the farm to the laboratory
of Dr. Holman. Obviously, he was your mentor. Can you tell us what are other things you’d like us to know about Dr. Holman? Yeah, Ralph was just a really good guy unassuming. Ralph, very simply, I think growing up in the depression and Ralph knew the value of $1 because he
just lived a very simplistic life. He enjoyed eating fish every day, he was proud of the fact that he ate two cans of sardines every day, with his lunch. Sometimes he would spice it up with sardines and tomato sauce and mustard.
But that was his lunch. And he loved his wife, immensely, Karla home and he, he talked about her all the time, and they just had this magical relationship and, and Karla was a graduate of Rutgers. Karla had a master’s in library science. And for a woman at that time, that was really a great achievement. But they worked well together. They had a great son, Ted, who still lives in the Minnesota Minneapolis area. But Karla was always very patient with Ralph, Ralph worked that night, he worked in the day he was always working,
writing papers, things like that the Karla got sick and Ralph spent every day as you’d expect with her in a nursing home. And when Karla eventually passed away, Ralph would continue to go to the nursing home – Sacred Heart nursing home in Austin, Minnesota every day to visit people because he said some of these people just don’t have anyone. But he really felt a strong sense of compassion, to just smile and say hello to a lot of people. That was really kind of the person Ralph was. Science was part of his life and big part of his life. But he didn’t have a kind of ego or behavior, indicative of a lot of success. Ralph drove a regular car, you know, in the house with maybe 1000 square feet on the main floor. He built it. He loved orchids.
So he grew a couple hundred orchid plants from all over the world. And he grew up, he built a greenhouse in the back of his house. So they had just amazing plants. And we actually studied fragrances coming off of orchids. That was well, solid guy. And then Ralph was financially very successful and Bethel University, gave him a start to his college career. I think they made it free. He worked as a janitor to pay it. And then so the Ralph was very grateful. He said, I would have never made it without Bethel’s help so he gave them his money, you know, most of his money and assets to Bethel University. So now there’s scholarship programs for the great kids that go to school there to go to science meetings, and there’s a Ralph Holman laboratory part of a building named after him. So his legacy goes on with the people that gave him the chance.
Do you think that he understood the value of his work and contribution upon his death? Yeah, it’s a great question. I you know, I think he did.
Well, he had friends all over the world, you know, but you didn’t have a ton of friends locally outside of his church obviously, but I don’t think he thought about that.
His social ecosystem was spanned countries you know from his involvement in science offers the National Academy of Science member and which is prestigious is 1500 or so at the time across the world.
You know, he knew he had done great things but he was more concerned about making sure people ate omega-3 fats and get the right kind of nutrition
tried to reduce suffering and human suffering by diets, adequate, healthy and omega-3 fats. We’ll dig into this more on another program when we talk about the great work that you’re doing. But if you can just kind of sum up the impact he had on your professional life, or maybe personal life both early on, and then as you’ve gravitated through your illustrious career. Yeah. You know, I think I learned the most about just being a good person from Ralph, and using science as a tool to help people.
Obviously, I learned a lot of great things in the lab analytical techniques. And I was, I was so lucky, you know, my mom pushed me to take this position as in the mid 80s, as a teenager, take this position, I don’t want to work in a lab. You know, I don’t want to think about this. She said just do it. But Ralph was the lottery ticket for me, and in having two amazing parents. It’s a lottery ticket for me as well. It really opened a lot of doors and acceptance, and I realized how much Ralph was liked and cared about, like so many people.
What a fascinating tribute to your mentor. And I want to thank you so much for being on our program today to talk about Dr. Homans work and talk about him. So people would know a little bit more about him both professionally and personally. I’m excited to have you back to talk about some of your great work that you’re doing. So would you be kind enough to come back and talk about some of your work? Yeah, absolutely.
Looking forward to that. I want to thank you again today. And I want to thank our growing listener base for joining the program today. And as always, be healthy, be well and fight the good fight.
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Any statements on this podcast are the opinion of the scientific guests and or author and have not yet been evaluated by the FDA. The information we may provide to you is designed for educational purposes only as not intended to be a substitute for informed medical advice or care. This information should not be used to diagnose, treat or prevent any health issues or conditions without consulting a health care professional. If you are experiencing a health issue or condition we suggest you consult with your healthcare professional.