268 ‒ Genetics: testing, therapy, editing, association with disease risk, autism, and more

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Wendy Chung is a board-certified clinical and molecular geneticist with more than 25 years of experience in human genetic disease research. In this episode, Wendy delves deep into the world of genetics by first exploring the historical landscape of genetics prior to decoding the human genome, contrasting it with what we know today thanks to whole genome and exome sequencing. She provides an overview of genetic testing by differentiating between various genetic tests such as direct-to-consumer, clinical, whole genome sequencing, and more. Additionally, Wendy unravels the genetic underpinnings of conditions such as PKU, breast cancer, obesity, autism, and cardiovascular disease. Finally, Wendy goes in depth on the current state and exciting potential of gene therapy while also contemplating the economic implications and ethical nature of gene editing.
We discuss:
0:00:00 - Intro
0:00:38 - Wendy’s interest in genetics and work as a physician-scientist
0:03:25 - The genetics of phenylketonuria (PKU), a rare inherited disorder
0:17:28 - The evolution of genetic research: from DNA structure to whole genome sequencing
0:28:43 - Insights and surprises that came out of the Human Genome Project
0:35:09 - Overview of various types of genetic tests: direct-to-consumer, clinical, whole genome sequencing, and more
0:40:50 - Whole genome sequencing
0:46:59 - Germline mutations and the implications for older parents
0:52:31 - Whole exome sequencing and the importance of read depth
0:56:21 - Genetic testing for breast cancer
1:04:12 - What information does direct-to-consumer testing provide (from companies like 23andMe and Ancestry.com)?
1:09:42 - The GUARDIAN study and newborn genetic screening
1:21:57 - Treating genetic disease with gene therapy
1:26:28 - How gene therapy works, and the tragic story of Jesse Gelsinger
1:33:05 - Use cases for gene therapy, gene addition vs. gene editing, CRISPR, and more
1:43:03 - Two distinct gene editing strategies for addressing Tay-Sachs and fragile X syndrome
1:47:40 - Exploring obesity as a polygenic disease: heritability, epigenetics, and more
1:55:55 - The genetics of autism
2:10:24 - The genetics of cardiovascular disease
2:15:28 - The financial costs and economic considerations of gene therapy
2:21:37 - The ethics of gene editing
2:31:55 - The future of clinical genetics
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About:
The Peter Attia Drive is a deep-dive podcast focusing on maximizing longevity, and all that goes into that from physical to cognitive to emotional health. With over 70 million episodes downloaded, it features topics including exercise, nutritional biochemistry, cardiovascular disease, Alzheimer’s disease, cancer, mental health, and much more.
Peter Attia is the founder of Early Medical, a medical practice that applies the principles of Medicine 3.0 to patients with the goal of lengthening their lifespan and simultaneously improving their healthspan.
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[@PeterAttiaMD]

In this episode, we discuss: 0:00:38 - Wendy’s interest in genetics and work as a physician-scientist 0:03:25 - The genetics of phenylketonuria (PKU), a rare inherited disorder 0:17:28 - The evolution of genetic research: from DNA structure to whole genome sequencing 0:28:43 - Insights and surprises that came out of the Human Genome Project 0:35:09 - Overview of various types of genetic tests: direct-to-consumer, clinical, whole genome sequencing, and more 0:40:50 - Whole genome sequencing 0:46:59 - Germline mutations and the implications for older parents 0:52:31 - Whole exome sequencing and the importance of read depth 0:56:21 - Genetic testing for breast cancer 1:04:12 - What information does direct-to-consumer testing provide (from companies like 23andMe and Ancestry.com)? 1:09:42 - The GUARDIAN study and newborn genetic screening 1:21:57 - Treating genetic disease with gene therapy 1:26:28 - How gene therapy works, and the tragic story of Jesse Gelsinger 1:33:05 - Use cases for gene therapy, gene addition vs. gene editing, CRISPR, and more 1:43:03 - Two distinct gene editing strategies for addressing Tay-Sachs and fragile X syndrome 1:47:40 - Exploring obesity as a polygenic disease: heritability, epigenetics, and more 1:55:55 - The genetics of autism 2:10:24 - The genetics of cardiovascular disease 2:15:28 - The financial costs and economic considerations of gene therapy 2:21:37 - The ethics of gene editing 2:31:55 - The future of clinical genetics

[@QwinnieLu56]

Great interview. Wendy is so knowledgeable and tactful in the way she conveys the information and views.

[@stephm4047]

Wendy Chung is extremely precise in the way she explains things and at the same time very clear. That was really a great podcast. 👍🏻

[@howsale838]

This is another great interview. She discussed complex information so clearly.

[@stevenst56]

Wow, probably the most valuable 2-1/2 hours I’ll spend this week, thanks!

[@anchi267911]

Such an amazing woman and work, what a field to put your life into... she and her team are saving lives. True heroes of society noone talks about. Thank you Peter, again for an amazing podcast and insight. Wish I could have listened to something like this while studying pediatrics/genetics in medschool.

[@westfield90]

So informative. I wish I were younger again and had gone to medical school

[@stepannovotny4291]

Yikes! Wendy Chung is one of the most eloquent people I've ever listened to ...could listen for hours! I'm listening to this at 1.5X normal speed and she is STILL completely comprehensible, despite the complexity of the subject.

[@evilmung]

Please interview Gabor Maté MD, author of The Myth of Normal, When The Body Says No, In The Realm of Hungry Ghosts, How To Hold On To Your Kids, Scattered Minds. As well as Bessel van der Kolk MD author of The Body Keeps the Score.

[@kendalrepass9057]

QUESTION!!! On the patient with autism secondary to PKU, did PKU treatment change the ASD?

[@eliteboxfitness]

Thanks for the information. An intriguing area of life. Congrats on th new role also

[@traceybutler5420]

This is absolutely fascinating...I spent 30 years in the business of cancer and it is mind blowing we have this technology yet are held hostage by a fictious book that is misinterpreted and grasping onto life. I love this!

[@mariaoropallo2386]

I was waiting for this! Thank you!

[@elefante1986]

Wonderful podcast, and the episode with Prof. Wendy Chung is probably the best so far - incredible knowledge and ease of communication on such complex topics. Will Jennifer Doudna and/or Emmanuelle Charpentier be guests?

[@yoongkeoklee857c]

Thank you for the insightful interview - Accidental inventions: Wonder if you could speculate what we learn from gene therapy (viral vehicles, "barbaric" ventricular injection etc) could lead to other uses unintended originally, perhaps like the history of mRNA vaccines - Human errors: It's interesting to know that mis-calls in genetic tests do happen Now that we are sequencing the whole genome at 30 or even 100x, I wonder how much of the noise in test results can be attributed to human/logistic issues

[@DavidConnerCodeaholic]

Well this was an inspirational sequel. Good luck!

[@bryanbennett1659]

Congrats on the new role!

[@zxsw85]

Congrats on the congrats!

[@splitkostanjeuma]

About the question regarding the necessity of using breast cell DNA for sequencing in the detection of risk of cancer. How would a liquid biopsy identify that the BRCA DNA fragment it caught in the blood isn't from some other type of cell where the mutation isn't an increased risk of cancer?

[@amiensarabellis8391]

Does the NIH All of Us research study fit into any of this? And if so, how?

[@contextwithjohnmalone]

I've seen commercials for the home colon cancer test and in fine print they state that this test doesn't confirm if you have colon cancer or not. So why pay the money for the test to only have to see a gastroenterologist anyway? I've been blessed that both sides of my family kept amazing records of our heritage as well as family medical backgrounds. Who had thyroid issues and didn't. Who had cancer and didn't. Etc, etc. This way I know where I come from instead of taking a genetic test to be told that I'm 78% Italian and 22% Labradoodle 🤣 I've heard that those tests aren't 100% accurate.

[@tutupuff6359]

Are these newborn genetic tests mandatory or optional?

[@happynjoyousnfree]

I love that she mentioned how the diagnosis of autism has changed over time. Everyone and their dog is autistic since it became a spectrum disorder. When I first started working with autistic children, these kids were non-verbal or if they could talk, they had very disordered speech--clearly disabled, in other words. Changing the definition was driven by a desire for more patients, period, and it means that the TRULY autistic are not going to get the help they need or should have.

[@MeanBeanComedy]

Or maybe the mild-autists should be classified with a separate condition.

[@happynjoyousnfree]

@@MeanBeanComedy that's what used to be the case, but now it's been changed as a total money grab.

[@tonaruch8623]

Wait, i thought if a couple (with a parent with braca1 mutation) selects an embryo with no brca1 mutation I thought this sets their future progeny to not have the brca 1 mutation further. At 2:24:50 she disagrees?

[@zibtihaj3213]

So shouldn’t gene therapy be THE wave of the future in terms of health/longevity ?

[@lalaragimov]

I really do hope that people bend medical ethics because currently it is stopping progress. Being careful is important, but it's being taken to the extreme. If it can save or significantly improve a life, it should be done, as long as the patient is aware of the risks. Also there's nothing wrong about creating superhumans. I would love to be one :)

[@lh5520]

Why did Derek have to tease the podcast with you 😭 I can’t keep waiting

[@4thGen4runner__]

What would be the best path in college to focus on stem cell therapy?

[@thomabow8949]

You may benefit from biomedical engineering at a high tier research college that has a tissue engineering lab.

[@4thGen4runner__]

@@thomabow8949 thank you! I greatly appreciate it!

[@imtryinghere1]

Selling Marijuana to a lab tech who works in a stem cell lab at a research university

[@Geroscientist]

make sure you learn about the difference between differentiated and undifferentiated cell therapy. The latter has been only hype and wishful thinking, the former actually has early clinical data suggestive of cell activity

[@petercallison5765]

"Obesogenic", that is a new one to me.

[@PaulLadendorf]

Hey Peter. Why won't you debate Paul Saladino?

[@Maiden4eva1995]

Pointless. The guy is a charlatan.

[@BestLifeMD]

What opinion would they be debating?

[@imtryinghere1]

Paul Saladino is not a Nobel prize winnef.

[@BallietBran]

Pulsechain Gang ♥️ 💪

[@sandybayes]

Fascinating! I wonder how AI is assisting with identifying genetic related diseases vs a standardized computer identification model? It would be interesting to see where the field is at currently to move the whole genetic field ahead. It would certainly be an interesting historical perspective.

[@ChessMasterNate]

I completely disagree with the rejection of modifying the germ line. That is exactly what you want to do. Fix it and the next generation does not suffer. And the next, and so on. There is no guarantee that we won't get bombed to the Stone Age or antiscience nutters gain power, and we lose not just the legal ability, but the technical ability to fix a genetic defect. If we had already fixed most of it, we would still profit from it. It could even increase the likelihood of the species surviving in some very difficult future. It also likely means that healthcare becomes much more affordable. The cost increases are certainly unsustainable. If, with a few modifications, there was no arteriosclerosis, no diabetes, no heart disease, no Alzheimer's, no Parkinson's, greatly reduced cancer, no sarcopenia, greatly reduced deafness and blindness in the elderly, and none of these genetic diseases that harm or kill children. How is that not a win? If we don't correct the germ line, there will be an accumulation of terrible genes, as nothing will be weeded out, everyone will be just fine, even as their genes get worse. We will be reliant on the technology. But if the germ live is repaired, we would not have to spend increasingly large sums of money for modifications. We would have all the improvements our ancestors made. Most of the arguments against are some form of someone else will get it, not those with less money. Well, that is pretty weak. They would not have it for sure if we did not allow it. So it is just jealousy. And, there are few technologies around that have been available to the rich exclusively that have been around for 30 years, and are not physically large. Human growth hormone, maybe. Not much. Even the poor could save up and do whole genome sequencing. It is now only $300. $450 for 30 times read.

[@firstlast-em2yq]

At 1:14:08 what was said is so scientifically dangerous and erroneous that it will lead to helping no one. Hispanics and Latinos are not genetically linked. Please keep the following in mind: Race and Hispanic or Latino origin are distinct and separate concepts. The labels "Hispanic" and "Latino" are not related to biology or skin color. Individuals of Hispanic and Latino origin do not fit into specific biological, anthropological, or genetic categories and can belong to any race, including white, black, or Asian. Any study that associates biological, anthropological, or genetic criteria with individuals of Hispanic origin is a systematic distortion of statistical outcomes, resulting from an unaccounted factor in its derivation.

[@user-wc3sd8nu6j]

I think she is a 100% wrong on ethics (2hr 24). There is every reason why removing genetically inherited disease in a heritable manner is desirable and ethically sound.

[@ybntoye2376]

Who are you?

[@JamesSmith-sw3nk]

Genetics are relative. 😁

[@micksc1]

"that's a good question" can she please point out the bad questions?

[@stephm4047]

😂😂😂 I was interpreting these « that’s a good question » as something like « that’s a difficult question » 😅