Three Bioinformaticians Raise Tough Questions about Genomic Medicine

Theral Timpson

Today we launch our series on bioinformatics, and I thought I’d jot down a few thoughts that have come from the interviews.  Three bioinformaticians have influenced my thinking and the interviews this year.

Christophe Lambert, Golden Helix

Christophe Lambert is the CEO of Golden Helix, a bioinformatics company based in Boseman, Montana.  Montana?  Yes, Montana. The closest thing Christophe has to a neighbor in our field is Lee Hood when he’s at his ranch.  Lambert is Canadian who ended up doing his under graduate schooling in Bozeman. Going to Duke for his Ph D, Lambert returned to this unlikely place for biotech and formed his own company, becoming one of the first bioinformatician entrepreneurs.  Golden Helix was founded in 1998, the same year that Ingenuity got its start as a spinout from Stanford.  Lambert says he started the company writing code in his bedroom and talking about it out loud to his wife, who nodded in approval knowing nothing of the content.

I came across Lambert this year by reading one of his excellent blog posts, which was reposted here at Mendelspod.  (If you have a blog you’d like published at Mendelspod, please contact me.)  I was currently interviewing for our series on NGS, and had been looking for a bioinformatician to comment on the sequencing tools space.  With Lambert, I found much more.  He’s thought systematically about the future and the business of genomic medicine. In another of his blogs I noticed that Lambert used the thinking tools of the business management guru, Eli Goldratt, the same tools that my partner Ayanna and I have used to build up Mendelspod and produce our shows.

Lambert writes about Goldratt’s work on supply chain theory and how it influenced his thinking about his own business and the adoption of genomic medicine into the clinic.  “As long as the end consumer has not bought, nobody has sold,” Lambert quotes Goldratt.  This truth struck Lambert forcefully.   The end consumer of genomic medicine isn’t buying, except in very special cases.   So, as a bioinformatics company doing the work of analyzing and interpreting human genomes, was Golden Helix really selling?  Lambert laments the commoditization of bioinformatics at a stage when it’s still the bottleneck, and still in its infancy. In today’s interview, he talks about how small the bioinformatics market really is into the research space.  A small market?  I thought bioinformatics was a booming space.

Lambert is a big picture guy and I highly recommend his blogs. Perhaps working in Montana has forced him to do more thinking for himself.

So what is keeping the adoption of genomic medicine from happening in the clinic?  What is keeping the end user from buying?

Nathan Pearson, Ingenuity Systems

Last week we were at Ingenuity interviewing the newest member of their team.  Going by the new title, Principal Genome Scientist, Nathan Pearson moved to Silicon Valley away from the leader in the genomic interpretation space, Knome.  Nathan is known for sharing the stage for a TED talk with Ozzy and Sharon Osbourne after Nathan and the team at Knome analyzed the rock star’s genome.  Calling itself the Human Genome Interpretation Company, Knome was one of the first in the space, offering detailed analysis of genome sequences back when they were available only to the rich and famous.  What does the move to Ingenuity mean, I ask Nathan in our upcoming interview.  In essence--not directly--he tells me that the science is not ready for Knome to achieve its vision.  And why isn't the science there yet? What needs to be done? To make the biggest difference, Pearson says he had to go upstream where Ingenuity is making headway in better curation and analysis software.   

Judging by the way Pearson has voted with his feet, we are still early in the research phase of genomic medicine.  The accounts of patients being diagnosed and treated with information got from their genome are few and far between, such as the story of Lilly Grossman presented at the recent Future of Genomic Medicine Conference.  In our upcoming interview with Pearson, he talks of the work he thinks needs to take place at Ingenuity and other settings before companies such as Knome or the new companies on the block (Personalis, Omicia, or SV Bio) are able to make a difference.

Sultan Meghji, Appistry

So the science isn’t there yet.  But is there more holding back this revolution in medicine?  Sultan Meghji thinks so.  A regular guest at Mendelspod, Sultan has been advising us on the bioinformatics shows we produce.   He says that the culture around medicine is holding us back as well.   Meghji is the VP of Product Strategy at Appistry, a big data company that recently licensed the Broad’s GATK software for commercial release.

Sultan is also a big picture guy. Sultan suggested three questions for each of the series. He’s very much a three point, Ciceronian rhetorician. I’ll list them here, but it’s the first question for the Clinical Genome Series that I want to pursue here.


  1. What is nanopore based sequencing going to mean for bioinformatics?

  2. What technology is going to allow us to manage data per patient?

  3. What will the next generation of storage/data transfer look like? Are we going to go beyond the cloud?

The Clinical Genome

  1. How do we change the culture in the medical ecosystem toward personal or genomic medicine?

  2. How do we get the medical ecosystem more consumer driven?

  3. How do we bring the cost down 90%?

In an upcoming show, we’ll have Eric Topol on the program to talk about his terrific book published last year, The Creative Destruction of Medicine. In the book, Topol tackles the big data challenges, sequencing everyone’s genomes, wireless sensors data capture and more. But what he and others don't pursue directly is a discussion about the culture of medicine, from a social perspective. Sultan is one of the few who are eager to go there.

“Forty-five percent of Americans don’t even believe in evolution, let alone genomic medicine,” Sultan likes to say. He’s got a point. His impatience with irrational thinking is shared by many working in this industry.

Politically, we read a lot about whether science in general is more accepted on the left than the right. Recently I watched a Canadian program where Michael Shirmer, a well known skeptic, countered this argument. He’s been on a bit of a crusade to say that the left, that progressives have their science denial moments as well as conservatives. He pointed out on the program that many conservatives are willing to accept the science of evolution when it comes to medicine and technology but not when their beliefs are challenged. He points to the fact that conservatives have widely embraced vaccination, even if they want to believe that mankind began in the Garden of Eden.

Is religion holding back the adoption of genomic medicine? Sultan brings up the case of the explosive adoption of prenatal diagnostic testing, (NIPD) and the concerns of Catholics and other religious groups that more parents will choose selective abortions. Here, as with the use of GM foods, the advance of genomic medicine clashes with many of our notions of spirituality. Most of the readers of this blog are scientists, and according to Lee Silver, author of the terrific Challenging Nature: The Clash Between Biotechnology and Sprituality, molecular biologists are the least religious of us all. But it's the average American out there who will be the patient of genomic medicine. How can scientists best sell their discoveries?

(I recommend Silver's book. In dry scientific style, he does his best to first define what is science and what is religion and question again and again the places where the two clash.)

Sultan says he constantly encounters an “irrational resistance to knowledge,” and sees a further segmentation of society along these lines. I can’t help but think that the ethical concerns about NIPD must be dealt with by society as a whole, for it doesn't look like knowledge is going to stop coming any time soon. New technologies such as NIPD do bring up valid ethical concerns that must be considered by us all. (In a recent interview I asked sci-fi author, David Brin, whether we should slow down the progression of science.)

As I said, Sultan is a big picture guy. And these are the questions on his mind as he goes about developing better, more practical bioinformatics tools for the clinic. Lambert says until the end user is buying, bioinformatics companies are not selling. Pearson says the science must improve. And Sultan says we cannot just look at the science. We have to confront the big ethical questions.

Just yesterday I saw articles about three person IVF becoming a reality in England. What will it mean for a child to have three or more parents? Some say that using mitochondrial replacement techniques on humans would violate a widespread international agreement against making changes in human DNA that can be passed down from one generation to the next. Those of us in the industry love to go to conferences such as the Future of Genomic Medicine and hear about the latest story where a genome sequence opened up new possibilities for health. We must also grapple with the larger societal questions that this new technology brings up if we want to see it become a reality.