Real

World Opportunities
at the Intersections Between Science, Law, and Big Data
(thanks to the ongoing revolution
in genomics and molecular biology)

Hawk Talk
Marist High School
Oak Lawn, IL

February 8, 2019

Kirk T. Hartley

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 Quick Questions for Students
How many of you have:

Watched CSI on tv?

Know about forensic use of DNA to prove the identity of a criminal, or to prove innocence?

Know someone who has had breast cancer – how many subtypes?
https://www.youtube.com/watch?v=7R6SEdaQqA

Know that scientists are growing little “organoids”?
https://www.youtube.com/watch?v=2CnkYtl99Cc

Know that scientists are working on regenerating limbs?
https://www.youtube.com/watch?v=HznzoH6tU1c

Know of testing drugs or “toxins” using “organ on a chip” technology?
https://www.youtube.com/watch?v=nCT0o7UA38U

Know of testing drugs or toxins using research undertaken “in silico?”
https://www.youtube.com/watch?v=vFo_4j_cZYQ

Know about “Big Data” and “Artificial Intelligence – AI”?
https://www.youtube.com/watch?v=uD8Dbozzod4

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 Overview of Talk

1)  Brief summary of factors driving ongoing revolution in genomics and molecular biology

2)  Examples of real world applications for and uses of genomic and other molecular sciences

3)  Examples of current and future intersections between genomics and law


4)  Closing message – many opportunities for multidisciplinary work and teams

5)  Questions and comments

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 Real World Opportunities Are Increasing Rapidly: Some Big Factors Are

Exponential Increases in Computing Power,
Exponential Decreases in Computing Costs,
and Massive Market for Cancer Treatments

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 Decreases In Computing Costs

The Impact of Technological Change on Employment and Skills: Theory and Empirical
Evidence - Scientific Figure on ResearchGate. Available from: https://
www.researchgate.net/figure/The-progress-of-computing-measured-in-cost-per-
computation-per-second-deflated-by-the_fig1_296348777 [accessed 6 Feb, 2019]

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 Increasing Investment in AI

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 Increasing Use of AI

www.forbes.com/sites/louiscolumbus/2018/01/12/10-
charts-that-will-change-your-perspective-on-artificial-
intelligences-growth/#15ad470b4758
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 What Is AI?

https://www.legaltechnology.com/wp-content/uploads/
2015/11/Artificial-Intelligence-AI-larger-graphic.png

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Big Data and Real World Evidence

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 “Real World” Data Defined for FDA Purposes
Definition set out in August 2017 FDA guidance document from FDA

•  Use of Real-World Evidence to Support Regulatory Decision-Making for Medical Devices 1 Guidance for
Industry and Food and Drug Administration Staff
–  https://www.fda.gov/downloads/medicaldevices/deviceregulationandguidance/
guidancedocuments/ucm513027.pdf

“Real-World Data (RWD) are data relating to patient health status and/or the delivery of health care routinely
collected from a variety of sources.”

Examples of RWD include data derived from electronic health records (EHRs), claims and billing data, data from
product and disease registries, patient-generated data including in home use settings, and data gathered from
other sources that can inform on health status, such as mobile devices.

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 Other Types of Real World Data from Devices and Sensors
“Fitbit” type devices

Watches that monitor heart rate

Clothing and other “wearables” that monitor hear rate

For diabetics, “continuous glucose monitors” that activate a wearable pump to inject insulin

Sensors in toilets – monitor human waste for protein levels, blood, etc

Implanted signaling devices and sensors

Biosensors for water, crops, plane wheels, forests and much more

https://cfpub.epa.gov/ncer_abstracts/index.cfm/fuseaction/display.highlight/abstract/8012

https://spectrum.ieee.org/tech-talk/energy/environment/plant-wearables-and-airdropped-sensors-
could-sow-big-data-seeds

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Cancers:
The Numbers Create
Vast Costs, Harms and Opportunities for New Thinking

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 Cancer's Toll, and Investment in Research
•  Patterson Clark wrote a February 17, 2014 article in the Washington Post, and included this
highly informative graphic on the human loss and research dollars:
•  http://apps.washingtonpost.com/g/page/national/the-years-lost-to-cancer/814/

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Estimated U.S. Cancer Survivor Data
Genomics and Big Data Offer Many Opportunities in
General and In Chicago In Particular

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 Business Terms - Chicago – Incubators

•  What is an incubator?
•  What is an IPO?

•  1871 - incubator for tech businesses in general – Merchandise Mart

–  https://1871.com/

•  20 different, smaller Chicago area incubators - summarized and linked

–  https://www.builtinchicago.org/2016/04/20/incubators-and-accelerators-chicago

•  Laboratory science focused - “The Incubator”
–  https://www.theincubator.com/

•  Healthcare focused – “Matter”

–  https://matter.health/

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 Many Opportunities for Entrepreneurs

• 

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 More Examples in Chicago

•  Outtakes from September 2018 article in Crain’s Chicago Business

–  https://www.chicagobusiness.com/john-pletz-technology/chicago-building-deep-bi

“It's been a very good year for life sciences companies in Chicago. In a matter of weeks, Iterum Therapeutics,
Xeris Pharmaceuticals and Aptinyx all went public, and AveXis, a startup with no revenue, sold for $8.7 billion.

A more tangible sign of the impact: Collectively, Iterum, Xeris and Aptinyx are worth $1.6 billion, based on their
market capitalizations.

Another: Illinois employment in the biopharma industry grew 9 percent between 2014 and 2016, compared to
2 percent nationally, Conrad says.

Illinois has the nation's fifth-largest concentration of life sciences workers.

.

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 University of Illinois – Computing and Genomics - Now Expanding
•  University of Illinois truly is one of the world’s top universities

•  New project in Chicago:

•  “The Discovery Partners Institute (DPI) is a joint education, research and innovation institute led by the University of Illinois
System, its three universities and partners.

•  The Chicago-based institute will:

•  Bring hundreds of the best minds from academia and industry together with thousands of brilliant students in an
interdisciplinary hub of unprecedented critical mass, to accelerate innovation and create life-changing products, taking
them to market faster than ever before
•  Serve as a magnet for entrepreneurs and venture capitalists, for inventors and investors, from across the state and nation,
while creating hundreds of new companies and educating thousands of new pioneering innovators that find their home
right here in Illinois
•  Retain and grow local and diverse talent, while attracting companies and talent from around the world, to live, play, work,
innovate and prosper in an iconic environment, embedded in the world city of Chicago. DPI will be a global destination for
innovation that will be visible from all corners of the world
•  Anchor an entire network of innovation hubs that connect great universities, national labs, companies and schools around
the state and beyond, creating an unparalleled innovation ecosystem at a grand scale without peer anywhere in the world.”

https://dpi.uillinois.edu/

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Examples of Real World Applications for and Uses of
Genomic and Other Molecular Sciences

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 Decreases in Cost to Sequence a Genome

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 Illumina – Global Leader in Genomic Sequencing

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 Increasing Genomic Sequencing

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 Increasing Genomic Sequencing

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 Increasing Genomic Sequencing

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 Fig. 1 Time line showing key events in the investigation of the cancer genome.

Michael R. Stratton Science 2011;331:1553-1558

Published by AAAS
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The Arrival and Impact of Precision Medicine

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 Precision Treatments for Cancers
Precision treatments target a particular genomic and molecular situation

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 Precision Treatments for Cancers
•  Most chemotherapy fails

•  Precision therapies depend on performing genetic sequencing and then using
computerized analysis of the sequence to identify the mutations and best
options for treatment of the specific mutations in that particular person

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Testing Drugs for Genomic Variables

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 Genomic Variables for Cancer Drugs
Genomic analysis of tumors and people can help us understand why an anti-
cancer drug works in persons A and C but not person B

Result: Genomic data can/should be used – after the fact - to identify cancer subgroups
where a drug will work well, and other subgroups for which it will not work well

Stewart DJ, Kurzrock R., Fool's gold, lost treasures, and the randomized
clinical trial. BMC Cancer. 2013 Apr 16;13:193. doi: 10.1186/1471-2407-13-193
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Using Genomic Testing to Approve Drugs More Rapidly

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 Recent FDA Drug Approvals Using Genomics and RWD/RWE
•  FDA approval of a “precision cancer” drug (gilteritinib) for use by persons after genetic testing established
a FLT3 mutation in acute myeloid leukemia (AML) – Nov. 2018
- approval based on trial of 138 patients with no placebo or control; all had relapsed or refractory AML
and a confirmed FLT3 mutation
http://app.info.fda.gov/e/es?
s=2027422842&e=166677&elqTrackId=78D8A052C380BCBFF284D754BEBE9730&elq=c01a2f7a0ab
74f73af38fce47e3fae6d&elqaid=6069&elqat=1

•  FDA approval of a “precision cancer” drug (larotrectinib)) for use by persons after genetic testing
established a NTRK gene fusion - Nov. 2018
- approval based on trial of 55 persons in trials with no control or placebo; all had various types of solid
tumors with a confirmed NTRK gene fusion
https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm626710.htm

•  FDA approval of eteplirsen, a molecular medicine designed to treat a lethal muscle wasting disease that
appears in boys under 10 (Duchenne muscular dystrophy); approval based on results of western blot tests
for a biomarker of desired effect, positive RWE/RWD observed in 10 of the 12 boys who received the drug
in a clinical trial involving effort based testing, plus only minor side effects and no alternative treatments

Aartsma-Rus A, Krieg AM. FDA Approves Eteplirsen for Duchenne Muscular Dystrophy: The Next
Chapter in the Eteplirsen Saga. Nucleic Acid Ther. 2017;27(1):1 -3 doi: 10.1089/nat.2016.0657

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Using Genomics and RWE/RDD
to End “Diagnostic Odysseys” for Undiagnosed Diseases

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 Using Genomics and RWE/RDD
to End “Diagnostic Odysseys”

•  Other examples of successful use of genomics and RWE/RWD lie in projects to end diagnostic odysseys

•  “Undiagnosed Diseases Program (UDP) was established at the National Institutes of Health (NIH) Clinical
Center to meet the needs of patients with undiagnosed diseases and to investigate the biologic
characteristics of the diseases.

•  During the first 2 years of the UDP, 1191 patient records were reviewed.

•  Of the 160 patients who were admitted for a comprehensive evaluation, 24% received a diagnosis. The
diagnoses included entirely new syndromes, rare diseases, and unusual presentations of common
diseases.”

•  “We also encourage and help UDN patients to make use of the Internet and social-media platforms to find
similar patients. In many situations, finding just one similar case can be critical in proving the causality of a
putative mechanism.”

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 More re Using RWE/RWD to Help End “Diagnostic Odysseys”

•  “The diagnoses fell into different categories:

•  “Although detailed financial information was not available for most of the patients, we analyzed data on
all billable medical procedures from a selected sample of 14 patients who had received all their health
care before and during the UDN evaluation within the same health care system.

•  Among these patients, the average cost of care before acceptance to the UDN was $198,651, and the
average cost of the UDN evaluation was $15,116 (7% of the total cost).

•  Among the patients who received a diagnosis, the average cost of care before acceptance was $305,428,
and the average cost of the UDN evaluation was $18,903 (6% of the total cost).

•  These cost estimates suggest that the UDN approach has the potential to cut short an expensive medical
diagnostic odyssey, and they are consistent with recent cost-effectiveness analyses for genome
sequencing.”

•  Splinter K, et al, Undiagnosed Diseases Network. Effect of Genetic Diagnosis on Patients with Previously
Undiagnosed Disease. N Engl J Med. 2018 Nov 29;379(22):2131-2139. doi: 10.1056/NEJMoa1714458.

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 Use of Sequencing to End “Diagnostic Odysseys”
Diagnoses According to Method.

K Splinter et al. N Engl J Med 2018;379:2131-2139.


Using Genomics and RWE/RDD
to Identify New Conditions and Diseases

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 Examples of New Syndromes Described by the Undiagnosed Diseases Network.
Identifying New Diseases/Syndromes

•  Same study also shows that genetic sequencing led to identification of

new conditions and diseases shared by other persons

K Splinter et al. N Engl J Med 2018;379:2131-2139.


Gene Editing – Now Arriving

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 CRISPR – Gene Editing

https://www.thedailystar.net/news/health/
gene-editing-molecular-miracle-1627630
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 Possible Applications of CRISPR

•  Text below quoted and extracted from: https://disruptionhub.com/9-amazing-applications-crispr/

Possible applications include:

•  “1. Fighting cancer - Perhaps CRISPR’s most celebrated application is in detecting and treating cancer.

•  2. Extracting HIV - At Temple University, a research team eliminated HIV-1 DNA from T cell genomes in
human lab cultures. What’s more, when these cells were exposed to the virus at a later date, they were
not re-infected.

•  3. [Antibiotics] Making diseases self destruct - At the University of Wisconsin Madison, food scientist Jan-
Peter van Pijkeren is developing an antibiotic that makes pathogens ‘commit suicide’. Through a DNA
slicing enzyme called Cas, CRISPR chops up the genes of invading bacterium. Then, a CRISPR laced
bacteriophage (which infects bacteria) is inserted into the pathogen, rewiring it to destroy itself.

•  4. Improving IVF - Carrying out gene editing within human embryos could help to improve chances of
pregnancy during IVF treatments. As well as benefitting IVF, scientists also hope to use CRISPR to reduce
miscarriages. CRISPR’s application to human cells is hotly debated, but in countries like Sweden it remains
legal. Earlier this year, Chinese scientists corrected genetic mutations in cells in three normal human
embryos.

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 More …. Possible Applications of CRISPR

•  5. Eliminating malaria - Various university teams are working on the elimination of malaria in mosquitos, in
the hope of stopping human infection. Through CRISPR Cas 9, scientists can snip out genes that are vital to
the spread of malaria within the mosquito population. In short, they could create mosquitos that were
resistant to malaria.

•  6. Protecting plants - Equipping plants with resistance genes could lead to reduced reliance on pesticides
and herbicides.

•  7. Producing food - Earlier this year, researchers at Tokushima University announced the creation of
seedless tomatoes using CRISPR. Seedless fruit could be a vital step towards more sustainable food
production, as they can be grown from scratch in laboratories.

•  8. Creating biofuel - A partnership between J. Craig Venter and Exxon Mobil has used CRISPR to improve
the energy production of algae. After eight years of research, their joint venture Synthetic Genomics Inc.
has successfully doubled the amount of oil produced by the aquatic organism via CRISPR gene editing..

•  9. Reviving extinct mammals - As future gazing as it sounds, a team at Harvard University has revealed
plans to bring back the woolly mammoth with CRISPR. By combining elephant genes with mammoth genes
recovered from fossils, the researchers hope to create hybrid embryos which could then be grown in an
artificial womb. The announcement came in February 2017, although the team says that the embryos
won’t be ready for the next two years.”

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Testing Drugs and Toxins Using
Organ on a Chip Technology

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Organ on a Chip
 Organs on a Chip
Evaluate Evaluate the entire system with complex biology

Control Control all aspects of the system

Expose Expose system to specific toxins

Evaluate Evaluate complex reactions and interactions

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 Organs on a Chip for Testing Drugs, Toxins etc
•  Working models

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 Organs on a Chip for Testing Drugs, Toxins etc
•  Working models for a range of organs
–  Beating hearts
–  Breathing lungs
–  Detoxifying liver
–  Working brains
–  Functioning reproductive systems

•  See generally Wyss Institute for Biologically Inspired Engineering at

Harvard University
–  https://wyss.harvard.edu/

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 Examples of Current and Future
Law and Science Intersections

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Using “Molecular Signatures”
to Identify Sources of Disease

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 Differences in mutation burden and
spectra between carcinogen and genetic models.

PMK Westcott et al. Nature 000, 1-4 (2014) doi:10.1038/nature13898

 Proof of Principle – Finding Signatures for Tumors Caused by a “Toxin”

•  As reported in a 2015 paper in Nature, researchers asked: can whole-exome sequencing and
computers identify signature differences between tumors caused by two well-known
“toxins” and tumors from an inherited (germline) mutation?

•  Yes, is the proof of principle answer for KRAS mutations and these two toxins

•  Westcott, The mutational landscapes of genetic and chemical models of Kras- driven lung
cancer, Nature, 2015 Jan 22;517(7535):489-92. doi: 10.1038/ nature13898.

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 Fig. 2 Mutational signatures associated with tobacco smoking.

Ludmil B. Alexandrov et al. Science 2016;354:618-622

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 “Mutational signatures associated with tobacco smoking in human cancer”

•  Alexandrov LB, Ju YS, Haase K, Van Loo P, Martincorena I, Nik-Zainal S, Totoki Y,
Fujimoto A, Nakagawa H, Shibata T, Campbell PJ, Vineis P, Phillips DH, Stratton MR.
Mutational signatures associated with tobacco smoking in human cancer. Science.
2016 Nov 4;354(6312):618-622.
•  “Abstract
•  Tobacco smoking increases the risk of at least 17 classes of human cancer.
•  We analyzed somatic mutations and DNA methylation in 5243 cancers of types for
which tobacco smoking confers an elevated risk.
•  Smoking is associated with increased mutation burdens of multiple
distinct mutational signatures, which contribute to different extents in different
cancers.
•  One of these signatures, mainly found in cancers derived from tissues directly
exposed to tobacco smoke, is attributable to misreplication of DNA damage
caused by tobacco carcinogens.”

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 Using Molecular Science to Understand and
Prove the Causes of Multigenerational Diseases

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 Toxic legacy. In a controversial finding, exposing a pregnant rat to a toxin had health effects
for three generations.

J Kaiser Science 2014;343:361-363

Published by AAAS

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 Turning DNA On and Off - Epigenetics – Multigenerational Diseases

•  Epigenetics means "above" or "on top of" genetics

•  Epigenetic changes to DNA can cause multigenerational diseases

•  Chemical changes on or “above” DNA can turn genes "on" or "off,” or amplify
or reduce the protein production that starts with genes
•  These modifications do not change the DNA sequence, but instead, they affect
how cells interact with or “read” genes
•  Epigenetic changes alter the physics of DNA and other factors

•  For a view at a manageable level, see this 2016 article, Epigenetics for
Dummies http://pmj.bmj.com/content/92/1085/183.full.pdf

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 DES – A Drug That Causes Multigenerational Diseases
•  Diethylstilbestrol (DES) - a man made estrogen first manufactured in a
laboratory in 1938

•  During 1940s -1971, prescribed to pregnant women to purportedly reduce/

prevent miscarriages and avoid other pregnancy problems

•  Excess numbers of cancers in “DES daughters” were the first outcome to

attract attention

•  DES cancers induced new law – courts implemented “market share” liability
–  some courts implemented “market share” liability”
–  shifted the burden of proof as to the maker of the injury causing product.
–  the shift arose because there were many makers and forms of the drug,
and it was sometimes difficult to identify the maker of the drug taken by
the mother. See Market Share Liability Adopted to Overcome Defendant
Identification Requirement in DES Litigation, Sindell v. Abbott
Laboratories, 26 Cal. 3d 588, 607 P.2d 924, available at:
http://openscholarship.wustl.edu/law_lawreview/vol59/iss2/10
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 DES - Multiple Harms Found After a Signal Disease
•  One harm was plain – a very rare vaginal cancer that usually struck after age 60
–  8 such cancers were found in young women in Boston in the late 60s
–  that subset of cancers formed the basis for the first big study, published in 1971
•  Long term studies followed, and ultimately showed multiple different harms
–  Data from Hoover paper published in the New England Journal of Medicine in October,
2011

•  Clear-cell adenocarcinoma (CCA) vagina or cervix 40.0 x

•  Neonatal death 8.0 x
•  Pre-term delivery 4.7 x
•  Loss of second-trimester pregnancy 3.8 x
•  Ectopic pregnancy 3.7 x
•  Stillbirth 2.4 x
•  Infertility 2.4 x
•  Early menopause (before age 45) 2.4 x
•  Cervical intraepithelial neoplasia (CIN2+) 2.3 x
•  Breast cancer (age 40 and higher) 1.8 x
•  First trimester miscarriage 1.6 x
•  Preeclampsia 1.4 x

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 Early Onset Breast Cancer in DES Daughters
•  Fecho v. Eli Lilly - federal court - Massachusetts before Judge Marianne Bowler

–  Four Fecho sisters were exposed to DES in utero and all suffered infertility as
well as signature DES reproductive tract abnormalities
–  All four sisters contracted breast cancer at or before age 50

–  The eldest, fifth Fecho sister was not exposed to DES, was able to have a
child, and remained cancer-free

–  Trial started in 2013; Eli Lilly settled the case soon after testimony by
plaintiff’s expert; the
jury reportedly was prepared to award $40-50 million in damages

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 Exposomics

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 “Exposomics” = Studying What Happens, While It Happens
•  “Exposomics” is a branch of science seeking to generate real time measurements during
“exposures,”

•  “Exposomic” studies seek to measure the molecular consequences during and after exposure

•  Exposomics will help to shape a “hot” area in litigation today, which consists of cases that
present issues about whether “low dose” exposures cause “serious harms,” such as cancers

•  Example of using exposomic studies to better understand autism

–  https://www.youtube.com/watch?v=tUFLLVeKMc0

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The Human Exposome Project Is Aimed at Collecting Genetic and
Epigenetic Data During and After Exposures
•  IARC’s Human Exposome Project has its roots in a 2005 article outlining improved
methods to seek better answers as to sources of diseases
–  http://humanexposomeproject.com/

•  “The human exposome is the environmental equivalent of the human genome. It

is a representation of the complex exposures we are subjected to throughout our
lives, including our diet, lifestyle factors, and social influences. It also incorporates
how our bodies respond to these challenges.”
•  Methods now used are better experiments than old days - new method exposes
the test creature AND measures impacts during and after the exposure
–  – blood, urine, proteins, DNA, RNA, microRNA, etc
•  Work underway in the US at places such as Baylor, Emory and Georgia Tech
•  Consider the impacts of automated sensors – e.g. wearable devices
•  Consider the impacts when implanted sensors yield even more data

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FDA - Saving Lives By Moving Faster on Science and Law Issues

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 Cancers – Estimate of Life Years Lost to Approval Delays
Multidisciplinary team estimated life years lost to delays in drug approvals:

“For new anticancer agents, the average time from drug discovery to marketing approval was 8 years in the
1960s, but had increased to 13.9 years from 2000 onwards, prior to recently decreasing for some drugs.

To estimate the number of life-years that could potentially be saved for every year by which time from drug
discovery to approval and funding could be reduced for these selected drugs (if all relevant patients were
treated once the drug was approved), we multiplied the incremental improvement in median survival by the
number of patients in North America and worldwide dying annually from the relevant malignancy, and then
multiplied this by the estimated time from drug discovery until approval.

Due to “breakthrough drug” legislation, the US Food and Drug Administration (FDA) recently granted rapid
approval for several promising new agents based on high response rates in phase I-II trials without requiring
the time and expense of phase III trials.

We have no major issue with the approaches taken in assessment of therapies for nonlethal conditions, but for
lethal diseases, we need “progress-centered regulation,” with the primary objective being the rapid, affordable
identification of new, effective agents.”

Stewart DJ, Stewart AA, Wheatley-Price P, Batist G, Kantarjian HM, Schiller J, Clemons M, Bradford JP, Gillespie L, Kurzrock R. The
importance of greater speed in drug development for advanced malignancies. Cancer Med. 2018 May;7(5):1824-1836. doi:
10.1002/cam4.1454

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 The importance of greater speed in drug development for advanced malignancies

“Cumulatively, across illustrative examples, more than 19,000,000 life‐years could potentially
have been saved worldwide if time from drug discovery to approval for these agents had been
reduced to 5 years, or more than 1,900,000 if (for example) only 10% of all relevant patients
were to be treated.”
The importance of greater speed in drug development for advanced malignancies, Volume: 7, Issue: 5, Pages: 1824-1836, First published: 30 March 2018, DOI: (10.1002/
cam4.1454)
 FDA Approvals of Gene Therapy Drugs
•  August 2017 - first ever gene therapy approved

•  “The U.S. Food and Drug Administration issued a historic action today making the
first gene therapy available in the United States, ushering in a new approach to the
treatment of cancer and other serious and life-threatening diseases.
•  The FDA approved Kymriah (tisagenlecleucel) for certain pediatric and young adult
patients with a form of acute lymphoblastic leukemia (ALL).”
–  https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm574058.htm

•  October 2017 – second gene therapy approved, also for a blood cancer
–  https://www.nytimes.com/2017/10/18/health/immunotherapy-cancer-kite.html?_r=0

•  Third approval occurred in December 2017 – for a rare, gene driven form of
blindness
–  https://www.nature.com/articles/d41586-017-04813-3

•  Scott Gottlieb - FDA - will do even more – he is a doc but understands legal
structures

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 Another Legal Issue: Health Insurance Barriers to
Adoption of New Medical Therapies

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 Health Insurance “Experimental Exclusion” Barrier to Using
New Technology Against Cancer
•  Both private and public insurers (e.g. Medicare) often refuse to pay for
“experimental” treatments

•  “experimental” clauses have defeated various forms of cancer therapies

•  “experimental” clauses have defeated use of molecular diagnostics

–  With the assistance of my daughters, I’ve done detailed research on the use of the
experimental exclusion

–  2018 research paper presents ideas for new approaches to the topic
•  http://conferences.asucollegeoflaw.com/personalizedmedicine/files/
2018/07/Hartley-ASU-Diagnostics-Workshop- Experimental_-Exclusions.pdf
–  2017 research paper presents more specifics about particular actions by health insurers,
and data from studies of insurance policy terms
•  http://conferences.asucollegeoflaw.com/personalizedmedicine/files/2017/05/Hartley-Final-ASU-
Diagnostics-2017.pdf

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Examples of ‘Experimental” Terms Used By Health Insurers
“Experimental – “Experimental Procedures “Experimental
Investigational or Any service or supply that is in the Procedures
unproven, not yet proven developmental stage or is in the process Procedures that
safe or effective.” of human or animal testing.” are mainly
limited to
laboratory
research.”

“They may not be proven Health care services, procedures, “not yet accepted
as effective or safe for therapies, devices, or supplies that the by insurance
most people.” insurance company considers plans as standard
medically unproven are considered treatment”
experimental or investigational
procedures.
“not yet accepted by “Any … [1] that has not received FDA “not in line with
doctors….” approval or [2] is not yet supported by generally
the clinical community because the accepted
scientific evidence available does not standards of
demonstrate the effectiveness of the care.”
service or technology ….”

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 Verdict Against Aetna Regarding Proton Beam Therapy

•  November 2018 trial verdict against Aetna for $25 million for refusing to pay for proton beam therapy for
a woman with brain cancer

•  “Orrana and her husband, Ron Cunningham, a retired Oklahoma City firefighter, had been together since
1987. He was determined to do whatever it took to get the love of his life the treatment she needed. The
couple mortgaged their dream home and set up a GoFundMe page to help pay the $92,082.19 to get the
therapy her doctors had prescribed at the MD Anderson Cancer Center in Texas.”

•  “[Jury foreperson] Schlotthauer said it was clear from expert testimony that proton beam therapy was not
experimental at all.
•  She said jurors were turned off by one Aetna medical director who acknowledged handling 80 cases a day
and by the fact that all three medical directors acknowledged they spent more time preparing for the
lawsuit than on Orrana's medical case.”

–  https://www.cnn.com/2018/11/10/health/aetna-verdict-oklahoma-orrana-cunningham/index.html

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 New Trump Administration Action To Refuse Payments for Gene Sequencing
for Persons with State 1 or 2 Cancer
•  New policy from CMs/Medicare “means that early-stage cancer patients will not be covered
for hereditary cancer risk testing.
•  Some have estimated that approximately 60 percent of cancer patients have stage I or II
disease.
•  Action is opposed by 63 entities/organizations that are involved with cancer, either making
products, tests, drugs, or patient advocacy groups.
•  One of the groups opposed is Triage Cancer, which is a not for profit focused on educating
doctors, nurses, patients and family members regarding the legal rights of persons with
cancer.

See:
the opposition letter from 63 entities
https://www.amp.org/AMP/assets/File/advocacy/
Group_Stakeholder_Letter_NGSNCD-FINAL-1-31-2019.pdf
News story at:
https://www.genomeweb.com/cancer/healthcare-stakeholders-ask-cms-not-limit-access-ngs-hereditary-cancer-risk-
tests#.XFdu4BnYrGI

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 New Legal and Social Policy Issues Will Arise from Very Early Detection Methods

•  The emerging science of liquid biopsies for cancer will, and other new scientific tests, will
lead to identification of more early stage cancers and other diseases

•  https://www.youtube.com/watch?v=ZJyvqhVWQyM

•  Early identification will lead to more debates about what to do, or not, when a cancer or
other disease is first found

•  When will/should health insurers pay, or not?

•  What is “good” or “best” course of action or treatment for patients?

–  “is “watchful waiting” a “good” idea; how will that evolve as tests become easier,
cheaper, and faster ?

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 Closing Message

New Opportunities
Multidisciplinary Teams

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 New Opportunities and Rules

•  Endless opportunities will arise to apply science, communication and other skills to specific situations

•  Some opportunities will be new professions for pay – e.g. CRISPR counselor (compare to genetic
counselor)

•  More 1 and 2 year specialized degrees will replace general law degrees and PhD programs

•  Other professions will see new continuing education requirements and/or new professional criteria
–  e.g. should all high school and college guidance counselors have to take yearly continuing education
courses to make sure they are really well informed about “real world” events
–  Similar issues will arise for teachers, school principals. lawyers and other professions
•  Do lawyers need some medical training if they do living wills?

•  Many opportunities will be pro bono or paid work for advocacy groups on issues involving diseases, such
as Triage Cancer, Imerman Angels (mentors for people with cancer) or others

–  https://triagecancer.org/
–  https://imermanangels.org/

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 Professionals Need Multidisciplinary Teams and Training

•  Most lawyers and judges have essentially zero knowledge of the

revolution in molecular biology in general or regenerative medicine in
particular

•  Many insurance companies have zero insight into

•  Many finance professionals are not aware of the molecular revolution

•  Many PhDs and doctors have essentially zero knowledge of
–  court rulings, laws and/or administrative rules
–  litigation

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 Some Lawyers Actually Want
Major Changes in Legal Rules and Systems
•  Some lawyers are creative and trying to create major change
–  Rules for a Flat World: Why Humans Invented Law and How to Reinvent It for a
Complex Global Economy, by Gillian Hadfield (Oxford Press 2016)
–  USC Law School - Professor of Law and Professor of Economics

•  Center for Law Science & Innovation
–  Arizona State University – Sandra Day O’Connor School of Law
–  Biodesign Institute
–  Gary E. Marchant, PhD genetics, plus public policy and law degrees
–  The Seventh Annual Conference on Governance of Emerging Technologies &
Science (GETS): Law, Policy and Ethics
–  May 2019

•  Marchant and Hartley – Genomics and Personal Injury Litigation (book in progress)

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 Law Schools Focusing on Science and Law Intersections

•  For many years, patent law was the place to go for law students with scientific training
•  Now, however, a few law school programs focus on science and law intersections
•  The leading edge is a decade old Center for the Study of Law, Science, and Innovation at The
Sandra Day O'Connor College of Law at Arizona State University. The ASU approach focuses
on multi-disciplinary intersections.
•  One of the program’s senior leaders is Gary Marchant, a Harvard trained lawyer with big law
experience in toxic torts, plus a PhD in genetics and a degree in Public Policy.
–  Years ago, Prof. Marchant foresaw current changes and began speaking
and writing book chapters numerous articles - with others - about the emerging issues
–  e.g. 2009 - The Ghost in Our Genes: Legal and Ethical Implications of Epigenetics
–  Full disclosure – I’m on the LSI’s outside advisory board and so may be biased
•  Other law and science programs, or classes, are emerging, especially in healthcare areas
–  University of Minnesota
–  Harvard
–  Georgia Tech

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 Scientists, Lawyers and Other Professionals
Need to Work Together
•  Forensic use of DNA revolutionized criminal law

•  Genomics and other molecular sciences will change civil law

•  To help create opportunities and change in laws and legal systems

–  Scientists and doctors do not need to become deep experts in law

–  Lawyers do not need to become deep experts in all medicine

•  Lawyers and scientists need willingness to think/work in multidisciplinary teams

•  Learn some genomic and other molecular science – it’s really cool

•  Learn about AI and other computerized systems

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 Thank You, and Questions or Follow-up

•  Thank you for attending today.

•  Thank you to Mr. Tucker and Ms. McArdle for encouraging interest in science.

•  Thank you to all the teachers who make learning interesting and relevant.

Kirk T. Hartley
LSP Group LLC – Law Science Policy
445 W. Erie Street
Suite 102
Chicago, IL 60654
(O) 312-857-5545
(C) 312-802-4471
khartley@lspgrp.com

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 GlobalTort Blog

•  GlobalTort blog is located at www.GlobalTort.com

•  Blog focuses on intersections between science, law, and other disciplines
•  Updated 3-5 times per week, most weeks

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