30 years since the Human Genome Project began – what's next?

For the future to truly be amazing with one sequencing the lab prep, chemistry, and equipment required needs to advance. Oxford Nanopore has some advancements here [2] but it's still a ways to go before you could have a sample prepared as easily as an ultrasound or x-ray.

[0] https://www.statnews.com/2017/06/20/human-genome-not-fully-s... [1] https://www.ecseq.com/support/ngs/are-there-regions-in-the-g... [2] http://nanoporetech.com/products/voltrax

- NIPT vendors (Natera, Ariosa (Roche), Verinata (Illumina), Sequenom (LabCorp) and others) have successfully commercialized carrier and prenatal screening for severe genetic defects.

- CareDx has commercialized pre- and post-screening for organ transplant rejection.

- Invitae, Color, Foundation (Roche) and others are scaling genetic testing, specifically clinical exome and panel sequencing (and solving the reimbursement problem in the process, by amortizing the cost of sequencing a patient's DNA across multiple physician-requested tests). Because variants need to be understood by physicians, this also enabled public/private data sharing partnerships for variant characterization (ClinVar).

- Grail (Illumina), Natera and others are on the verge of commercializing routine cfDNA cancer screening.

And here are more fundamental improvements which may yield more successes like the above:

- Oxford Nanopore has provided much needed competition to Illumina in lowering the barrier to portable sequencing and de novo whole genome sequencing.

- The ENCODE project has used ever more sophisticated assays to characterize functional regions of the genome.

- 10x Genomics has scaled and productized new ways to do single-cell transcriptomics, enabling breakthroughs in understanding functions of genes (by mapping differences in their expression across cell types and conditions) as well as development of CAR-T cell therapies (training and selecting the patient's own immune cells to fight cancer).

- UK Biobank has provided privacy-preserving access to a large cohort of annotated genomic data from the NHS, enabling more powerful association studies between genes and disease.

One of the bigger balancing acts in this industry is the monopolistic tendency of Illumina, Roche, and a few other big players to buy everyone up. This has clear anti-competitive effects but also incentivizes a lot of startups looking for that exit.

Jorge Conda [0] cited two reasons that genome sequencing (Different from 23andMe's GWAS, for example). First he cited the high upfront cost to buy the machines (Usually meaning you need to be a big hospital). The second fact was a bit more interesting, which is that doing one expensive test (Genome sequencing) which then your health care provider could do cheap queries against ("Which other users have your symptoms and similar mutations in key genes" for example) does not align with the current billing model.

I think that's the "What's next". Finding a way to effectively bring genomic care to the general population, to allow for better research into genetic conditions. If you're interested in how "big" this can be, here's a case where "This American Life" covered how just a few genetic differences was the difference between an olympic athlete and a muscular dystrophy patient [2].

There's also the bio-terrorism and pandemic response angle, which is why the DoD is investing in third-generation sequencing systems where portability has finally become more of a priority.

[0] https://en.wikipedia.org/wiki/Knome [1] https://a16z.com/bio-eats-world-podcast/ (About 13 minutes in) [2] https://www.propublica.org/article/muscular-dystrophy-patien...

Medically speaking, there isn't enough evidence to support the cost of doing WGS for individuals in most circumstances, or even storing large amounts of WGSs to do large-scale population-level analysis.

We've created a system where the only sane way for a biomedical company to behave is to patent, copyright, and hide as much medical information as possible. Further, we've made it REALLY hard to share such medical data in the first place.

Now, I get WHY we do this. There are a lot of good reasons (privacy and insurance issues come to the top of my mind). However, we should be working to eliminate those reasons as much as possible.

What we need to advance human understanding of medicine is a national database of medical data that's publicly available.

Ideally, We'd record every measurable aspect about a person in this database and update it throughout their lives (when did they get vaccinated? What allergies do they have? Did they get any cancers?)

That sort of a database would make it really easy to start mining for treatments, correlations, etc. It'd even have some positive benefits like removing the need for every doctors visit giving you a form with 50000 questions you've answered a million times before.

But I get why we don't do this. We don't do this for fear of police overly relying on genetic information to "prove" someone committed a crime (We found your DNA at the scene, you must be guilty). We don't do this out of fear of Insurance companies exploding their rates when any sort of marker comes up (Oh, you've got Gene XYZ that means you'll probably die sooner, so you get a higher rate or we won't insure you). We don't do this because of issues around discrimination (Oh, you have (had?) HIV? You must be gay and we hate gay people here).

But, man, do I wish we could somehow shape society so some day we could do it. It'd have the potential for so much good.

Although if you thought the genotype -> phenotype problem was hard, the microbiome -> phenotype problem is likely several orders of magnitude harder.

I acknowledge the lack of knowledge leading to the question. But it would be neat if possible.