Post by Krystyna Joyce
$1000 Travel Grant to ISSCR Annual Meeting 2023 for Young Professionals
April 5, 2023
Cutting edge technology for vascularized kidney organoids
February 17, 2023In honor of International Women’s Day on the 8th March, and World Organoid Research Day on 22nd March, we have been privileged to interview two extraordinary women about their experiences working in science: Dr Hynda Kleinman, one of the co-inventors of Matrigel, and Dr Meritxell Huch, of one the Directors at the Max Planck Institute of Molecular Cell Biology and Genetics (MPI-CBG).
Dr. Kleinman has published over 440 papers and been awarded 10 patents, 3 of which have been successfully commercialized. Matrigel is used worldwide and was among the top 15 NIH patents bearing royalties for many years. She has received numerous national/international awards for her scientific accomplishments.
For her pioneering work on developing organoid models, Dr Huch has published over 70 papers and been awarded 5 patents, 4 of which on organoid technology which have been successfully licensed and brought royalties to the Dutch academy of sciences. She has received several awards, including the Hamdan Award for Medical excellence, the Women in Cell Science Prize from the British Society, the EMBO Young Investigator Award, and the BINDER Prize.
How did you get into 3D/organoid culture research?
Dr Kleinman: I am the co-inventor of Matrigel. We developed Matrigel for the purpose of analyzing the ratios of its contents. By chance, we had a site visit, and the head of the committee was a cell biologist. So, we put different cells on Matrigel thinking that those results would be of more interest to the site visiting team.
We got remarkable and rapid differentiation, such as capillary formation by endothelial cells, melanin production by melanoma cells, and gland formation by salivary gland cells. We even did sweat glands and hair follicles using immature cell clumps as well as many other organs and cell types.
Dr Huch: I was in Hans Clevers lab when small intestinal organoids were first generated. I started working in the lab in the very early days when the organoids started to work, and then became very quickly interested in translating the technology to other organs.
That brought me, back in 2010, to be the first one to develop non-intestinal organoid models for other endoderm derived tissues including stomach, liver and pancreas.
How has the field changed since you started working in this area?
Dr Kleinman: It has grown immensely. I am impressed with the range of cells and mixtures of cells used as organoids and the ability to develop differentiated organs with one stem cell. I also like that in some cases, such as the brain, the developed organoids are being put back into the animals and displaying functional activity.
Dr Huch: Back then, more than a decade ago, we didn’t call them organoids but adult stem cell cultures, which should give you the idea of how much the field has changed. There was no such a thing like an “organoid field”: we were making it.
We certainly thought that these models could be helpful and applicable to different areas, but we never knew how much impact it was going to have in so many different fields from basic biology to toxicology or medicine. To think that just a decade ago, growing primary epithelial cells in a dish was considered pretty much impossible. We were making history by breaking stablished dogmas.
However, I must admit that we never imagined we were contributing to the birth of an entire field.
When did you become interested in science? Was this fostered through your education and academic career?
Dr Kleinman: By the time I was 10, I knew I wanted to have a career in science. It was 1957 and my parents, knowing the odds, and were worried I wouldn’t be successful as a female scientist. Instead at age 14, I was sent to Hickox Secretarial School after my regular high school classes to learn typing and other skills for an alternative career. From the ages of 12-22, I went to an all-girls junior high/high school and college so there was support for my scientific interests.
I went to a mostly male graduate school at MIT in 1969 and faced many challenges based on my gender. I put my head down and did whatever I had to do to graduate, including doing a Master’s degree before my Ph.D which was not required of the male graduate students.
Dr Huch: since I was little I have always wanted to understand how things worked. For instance, as a teenager I was always fascinated to understand how medicines worked. I guess this motivated me to study Pharmacology and from there, since it brought more questions than answers, I moved on to a career in science.
Can you tell us about your current research in the 3D/organoid culture space, and what you enjoy about it?
Dr Huch: We exploit organoid technology to learn on basic molecular and cellular mechanistic understanding of how tissues regenerate and how these change in disease. We not only keep developing better models that recapitulate better the tissue of origin but we also apply them to model diseases and to study disease mechanisms.
What I love is looking through the microscope and seeing these amazing multicellular structures form and develop. I still find it fascinating that we can take a piece of tissue and expand it for months in a dish while still retaining its identity. This really broke the dogma that primary epithelial cells could not be expanded.
What are some of the main challenges you have overcome as a female researcher in this space?
Dr Kleinman Being from an older generation – I was born in 1947 – I faced many challenges from male colleagues, including exclusion from meetings, lack of promotions to higher positions, salary inequities, rude and offensive behavior, etc.
For example, I was once invited to interview for a higher position. I was told when I walked in the door that I looked too young for the job even though I had grey hair and a daughter in college at the time. Then, I was told I lacked experience even though it was 20+ years since my Ph.D graduation. They made additional efforts as discrediting me. I was the ‘token’ woman in the process before they hired an already chosen male candidate. If that happened today, I would walk out.
Nevertheless, I have used my network of colleagues, ability to communicate, confidence, powers of persuasion, and a big mouth to face and overcome these challenges, and despite this, I have enjoyed my life as a scientist and been very lucky to be successful and to find so many warm like-minded friends.
Dr Huch: Although being from a younger generation (I was born in 1978), I found it challenging being a young female in the liver field in the 2000s, basically the hepatology field is very well established, which seemed to be a more difficult and challenging space. Instead, in the organoid field, I have not noticed the same thing. I cannot tell if this is because I have been in the field since its birth or simple because it is a young field with young people, or for any other reasons. But I am grateful for the fantastic colleagues, male and female, in this field.
Can you share an anecdote about 3D and life in the lab?
Dr Kleinman: Matrigel had a rough evolution and was rejected constantly! The invention report was rejected by the NIH Patent Office for “lack of usefulness”, and I personally went to show the attorney data to move forwards. The patent was eventually filed but rejected by the US Patent Office. We responded to the comments, and it was eventually accepted and got the lucky patent number 4,829,000 in 1986. Then the paper describing Matrigel and some of its uses was rejected by 3 journals: Cell, Journal of Biological Chemistry, and Biochemistry. We wrote a rebuttal to those comments and the paper was finally accepted by Biochemistry.
Dr Huch: After months of constant failure trying to grow stomach epithelium in 3D, I put a deadline to myself. I said if by Christmas 2008 it does not work, I’ll quit. Then, on the 8th of Dec 2008, I got the very first stomach organoid culture to grow, and that changed my life forever.
It not only set me off for a career in organoid research but it also played some role in the birth of the field.
If there’s one thing you could have other scientists understand about 3D/organoid culture, what would it be?
Dr Kleinman: Organoids have huge potential for studying genes, factors, or drugs for diagnostics and therapeutics as well as for tissue engineering/repair/regeneration either as delivery systems or tissue replacement. Try anything!
Dr Huch: That organoid cultures are not the answer to everything. Scientists have to choose according to the principle of which is the “best model” that addresses their question. And, if organoids happen to be the best model, then use organoids, but if they are not, then do not use them.
What do you enjoy doing in your spare time?
Dr Kleinman: I love to read, cook, garden, walk, and stay in physical shape. I was an avid runner but have recently due to arthritis been biking and swimming. I have biked self-supported with my husband across the USA, around half of Lake Michigan, around coastal Sardinia, Tuscany, and Puglia (southern Italy), and in group-supported rides through Slovenia and Croatia.
Dr Huch: I really enjoy spending time with my family, and, when there is some extra time, listening and playing classical music and reading classic literature.
What advice you would give a new female researcher starting out in their career?
Dr Kleinman: Training, training, and more training in the tools needed to advance your career, either through course participation or online reading. This includes things such as: public speaking, mentoring and being mentored, communication skills, negotiation, listening, networking, presentation/slide making, writing, patent law, clinical trials, and more. These tools also are helpful in your life outside of the lab.
Get awards either through self-nomination or ask your colleagues to nominate you. Join professional societies, serve on committees, and use social media platforms to communicate with colleagues and showcase your successes.
I would also advise female scientists to have a life outside of the lab for work-life balance and your sanity.
Dr Huch: I would give two pieces of advice: 1. Follow your dreams, and 2. Do not allow the criticism to bring you down, just take it as an opportunity to grow.