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I know that there are some efforts from scientists working with bladder cancer to perform liquid biopsy from urine for detection and monitoring of the cancer such as this one.

I've been searching online - but the "wastewater" search term gives me tons of hits about "microbiome" and several types of pathogens.

But I'm really interested in sequencing the sewage to find and analyze human DNA. I have been wondering about liquid biopsies to get an estimate of the cancer status of a population.

I immediately think of several problems:

1. Technical Feasibility

  • Would we expect to find enough human nuclear DNA within the samples (taken across several days)?

2. Law and Bioethics

  • Is it legal in the US or European Union?
  • It could be difficult to get informed consent of all people who are connected to a certain sewage system. You may get informed consent from all residents but what about visitors?
  • It could be difficult to opt out of such study the wastewater without a) moving to a different place b) using a septic tank.
  • I only found this elaborating other privacy issues: its just about Cov-19 and drug testing; both of which are not able to identify individuals at a genomic level.

I'd appreciate your experience and thoughts and references!

[Edit] as suggested in the comments: I have posted part 2 of the question to the law stack exchange here

ilam engl
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    Given the availability of sets of human reference-haplotypes I think it should theoretically be possible to gather some additional information to common mutations like SNPs even from sub-optimal waste-water. Just you have to be aware how incredibly polluted human DNA would be by incomparably higher DNA-concentrations from other species like microorganisms. Still, as it is possible to identify the whole range of micro-organisms from soil-samples using NGS, one can easily evaluate whether sequenced stretches are uniquely human. Anyways, why not directly get high-quality human DNA samples? – KaPy3141 Jun 30 '21 at 10:45
  • I once met a lady working at a waste water plant and she told me about the different samples they take. I found it fascinating and wondered about other applications that would only consider human DNA in particular as acquisition of participants for a study is probably one of the bottlenecks. The question became 'hot' for me now as I'm doing an applied genomics course where we must invent a project with the requirement to do "very smart" and cheap sampling (his words). The project must be feasible and we are required to calculate a budget. --> why would not use high-quality human DNA :) – ilam engl Jun 30 '21 at 14:23
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    The U.K. tests wastewater for COVID currently https://post.parliament.uk/monitoring-wastewater-for-covid-19/ – Tim Jun 30 '21 at 23:38
  • @Tim That is a totally different story as this is not looking into human DNA which can identify people... Thats the most personal data the any of us have to offer. Given you could make a Data Base of this human DNA. There are many ways this data could be matched to a region/community (where you poop) and to a network you belong to, possibly identifying you. That makes labeled DNA data. Given your computer science back ground I'm sure you can see why this is a totally different story and ethically concerning. Downstream one could even identify your relatives... – ilam engl Jul 01 '21 at 10:47
  • @ilamengl The bit about the practicalities of DNA sequencing are on topic. However, the edits which ask for a discussion on the law/ethics side of this are off-topic here. It also reads a bit like a discussion question rather than one with a specific, objective answer. – user438383 Jul 01 '21 at 11:45
  • @user438383 they are 2 yes no questions in the post: The concrete answer to question is 1: yes it is legal - 2: No it is illegal. Question 2 can be answered as follows: 1: yes it is possible (see answer below) or 2: no its not – ilam engl Jul 01 '21 at 11:46
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    @ilamengl Either way, questions about the law and ethics are off-topic, and so is having multiple questions. Stick with the original bit about the scientific aspect of sequencing from waste-water and if you are interested in the legal aspect, maybe ask a question in https://law.stackexchange.com/ – user438383 Jul 01 '21 at 11:48
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    @user438383 given that people who have written proposals for scientific project had to think about those things and ask their local bioethics commission I feel like I got more chances here than in law... – ilam engl Jul 01 '21 at 11:52
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    @ilamengl Any "philosophical or ethical questions related to biology" are explicitly off-topic here, per the site help page. – jakebeal Jul 01 '21 at 13:09

3 Answers3

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As it turns out, you are not the first to have this idea. Prior research claims that it is, at least in principle, possible to conduct epidemiology of cancer by sequencing on wastewater DNA for biomarkers.

The ethics of this approach also need not be problematic because narrowly targeted sequence amplification focused on biomarkers like SNPs will not typically produce enough information to identify an individual.

The practicality of this approach is a major open question, however, given the small and variable nature of the signal.

jakebeal
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  • Grate idea and grate paper -They are however using mtDNA. I am still wondering about the first part of my question is is ethically and legally possible to extract human cellular DNA. – ilam engl Jun 30 '21 at 17:11
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    If you can get mtDNA, then in principle you can get other DNA as well. The key issue remains signal levels. – jakebeal Jun 30 '21 at 17:40
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    @ilamengl a sewer grate? Sorry, couldn't resist. – Boluc Papuccuoglu Jun 30 '21 at 23:59
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    @BolucPapuccuoglu LOL a Freudian slip. – ilam engl Jul 01 '21 at 10:38
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    @jakebeal thanks for answering the technical part. About the other part of the question: are you aware of any US or European laws that would prevent scientists from sequencing human DNA from the sewer without consent given it would be hard to get consent? – ilam engl Jul 01 '21 at 10:39
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    @ilamengl that might be a better questions for [law.se] – AncientSwordRage Jul 01 '21 at 10:44
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As already hinted in the answer by @jakebeal, the low concentration (high dilution) of human DNA in waste water would mean that we need huge sequencing depth in order to detect something. This is not the case when dealing with urine or feces. This is also not the case when sequencing bacteria in waste water, since we are dealing then with the strains that can live and multiply in water, i.e., they are present in important quantities. Moreover, we are interested in them only when they are present in high quantities, when they are potentially harmful.

Roger V.
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    The research group of the paper jakebeal linked used filters -> less water more cells... – ilam engl Jul 01 '21 at 12:48
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    @ilamengl it seems that their main achievement is precisely overcoming the problem that I described in my answer. It is a strong claim - if this is really the case, we might expect this done commercially in a few years. Note that they didn't do sequencing, and that they look only at mitochontdrial DNA (a small part of the DNA contained in a human cell). – Roger V. Jul 01 '21 at 12:55
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    @ilamengl it is human mtDNA. I think the catch is that they have a library allowing to amplify mtDNA. I am not sure, whether the same can be done for all of the nuclear DNA. If not, you have to shotgun sequence everything that is found in the water, which is the premise of my answer. – Roger V. Jul 01 '21 at 13:13
  • Again, I am aware that it is human mtDNA because I've actually read the article ;p but we both know that we cant find the same kind of info as within the nuclear portion of human DNA – ilam engl Jul 01 '21 at 14:56
  • @ilamengl if one is looking for a specific biomarker (e.g., a specific type of cancer) one is concerned only with this DNA fragment. I don't know what is special about mtDNA in this respect. – Roger V. Jul 01 '21 at 15:01
  • What if I wanted to find novel SNPs? And maybe their distribution within the population? – ilam engl Jul 01 '21 at 15:09
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    @ilamengl in most cases one can sample such data in less complicated ways. – Roger V. Jul 01 '21 at 15:54
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Reputedly Osama bin Laden was tracked this way

... according to Water and Wastes Digest citing Time Magazine, but few of the details are known. Given that 10 milligrams of feces is sufficient to amplify desired markers from DNA, you would need only consider the number of people living "upstream" to determine how much material you should need to collect overall, and how many sequences you would need to run to find the right one. Maybe with some clever efforts to separate material into microwells you might be able to isolate one or more cells from the target of the search away from all others.

Mike Serfas
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