cells & cellphones - looking deep at the molecular level

“Cell’s” response to a “Cell phone/

EMF” – Looking deep at molecular

level

Dr AVS SureshMD, DM, ECMO

Consultant Hemato-Oncologist

Chief Scientific Officer & Director, ClinSync

Natural radiation

Biological life has always taken place in a sea of naturally occurring EM radiation of ◦ cosmic, ◦ atmospheric and ◦ geomagnetic origin

Electromagnetic radiation of nearly all wavelengths.

Big

bang

(13.2

bn)

Earth

forms

(4.5 bn)

Prese

nt

day

1010 109 108 107 106 105 104 103 102 101 11011

Time (years)

Big

bang

(13.2

bn)

Earth

forms

(4.5 bn)

Prese

nt

day

1010 109 108 107 106 105 104 103 102 101 11011

Magnetotact

ic

bacteria

(2 bn)

Time (years)

Big

bang

(13.2

bn)

Earth

forms

(4.5 bn)

Prese

nt

day

1010 109 108 107 106 105 104 103 102 101 11011

Magnetotact

ic

bacteria

(2 bn)

Time (years)

Bird compass

(90 m)

Big

bang

(13.2

bn)

Earth

forms

(4.5 bn)

Prese

nt

day

1010 109 108 107 106 105 104 103 102 101 11011

Magnetotact

ic

bacteria

(2 bn)

Time (years)

Bird compass

(90 m) Early man

(6 m)

Big

bang

(13.2

bn)

Earth

forms

(4.5 bn)

Prese

nt

day

1010 109 108 107 106 105 104 103 102 101 11011

Magnetotact

ic

bacteria

(2 bn)

Time (years)

Bird compass

(90 m) Early man

(6 m)

Electrification

(1878)

Man Made

The effects of artificial (man-made) EM

radiation on living tissue can be broadly

divided into two categories:

◦ Thermal effects, i.e. the destructive effects of

gross thermal heating.

◦ Athermal effects or relatively ‘weak fields’ that

produce temperature increases below the

range of normal organism fluctuations.

Slid

e 9

IS an

equation

Never will be

an equation

Living and Nonliving Objects Differ Fundamentally

Man-made EM radiation

Simple man-made (artificial) externally applied weak EM radiation currently used to test for the effects of EM radiation would also seriously need to consider that:

◦ Any complex biological modulation systems are not readily duplicated by human produced weak EM radiation as currently used for testing purposes.

◦ Effects produced by man made EM radiation may be more due to increasing the general stress load on the organism rather than because of distortion of information.

Slid

e 11

Molecular and cellular level bioeffects

of Electromagnetic Fields The studies of interactions of EMF with

biological media have been always artificial.

Possible interactions with cell membranesproposed that cell membranes could act asnon-linear resonators strongly amplifiedsignals within a narrow range of frequencies.

Effect range from nerve excitations, electronically induced forces, the dielectric breakdown of cell membranes and other processes that directly involve electric fields.

Slid

e 14

Law of Superposition

System’s

Differential

Equations

Law Holds

LawDoesn’t Hold

Linear

Nonlinear

RRM: interacting proteins have the

same frequency but opposite phase

Slid

e 16

cell

Cell

membrane

p1 f1 p2 f2 p3 f3

DNA

Sinusoids of the same frequency but different phase

Why should we be worried so

much about the DNA The functionality of a given cell goes with

specific orders given by DNA

Periodic simple- AAAA

Periodic complex- CAT CAT

Complex- non informative--- AKJLHA

DHA SKDSK

Complex- informative- NOTE THIS

POINT

Why should we be worried so

much about the DNA The functionality of a given cell goes with

specific orders given by DNA

Periodic simple- AAAA

Periodic complex- CAT CAT

Complex- non informative--- AKJLHA

DHA SKDSK

Complex- informative- NOT THIS POINT

Postulate: proteins interact through oscillations of a

physical field possibly electromagnetic

charge transfer through the protein backbone is a sufficient condition for EM radiation/absorption

W= W(COOH)-W(NH2) = 0.13 Ry.

Vmax =

where e is the electron charge, and m is electron mass.

V < 7.87 x 10 5 m/sec

distance between amino acids could be considered at:

d= 3.8 Å

Fmax < V/(2d); Fmin =2 Fmax/N,

where N = total number of amino acids

Fmax < 1x1015 Hz, Lmin > 330 nm

Fmin > 1x 1013 Hz, Lmax < 30000 nm

meW2

Slide 19

Human DNA is ~2meters long and has ~3 billion base pairs

-230 -160 +1 (bp)-320 -192 -107 -68-100-166

HSPMYC A

HSP70

Sp1 AP-2 HSE Sp1 AP-2 HSE SRE

ATF

TATA

Sp1 AP-2

HSPMYC C

HSPMYC B

Heat Shock Domain

(thermal)

EMF Domain

(non-thermal)

.

EMF Specific Domain in HSP70

Lin et al (1999) J Cellular Biochem 75:170-176.

EMF-Specific DNA can be moved

counts

Chloramphenicol transferase

(CAT) Activity

0

10

20

30

40

50

60

Background

EM

Negative Control

Luciferase Activity

counts

0

10

20

30

40

50

60

Background

EM

Negative Control

Experimental Conditions Experimental Conditions

Lin et al (2001) J Cellular Biochem 81:143-148.

The next 2 important questions

So What?

Who cares?

There are 260 million known mutation

associated with cancer

But only 26 are proven to cause the

cancer beyond doubt

Primary

detection

Subsequent

responseMF

Common question:

Given that we are all exposed to the geomagnetic field of 50 mT, how can a 50 Hz 0.4 mT field make any difference?

The primary physics detector, only has

to detect

It is the subsequent biological response that

matters

The Point?

A scientist must keep an open mind

and be able and willing to let go of

their paradigms and their models –

otherwise we develop of a culture of

scientists interfering with science

Rhythmic signals and behaviour of

the human body

Life processes in any biological organism are

usually based on rhythmic oscillations:

Electrophysiological signals such as ECG, EEG, EMG

Hormonal/biochemical rhythms such as circadian

rhythms

Electrical and electromagnetic resonances in the body,

particularly at the cell level

Slid

e 27

To try to understand the epidemiological findings, lets consider

three physical interaction mechanisms and some biology

So-called Ion Cyclotron Resonance (ICR) models

and Ca2+ efflux from cells

Circadian rhythm and melatonin disruption

could potentially explain many of the health effects

Biogenic Magnetite

in animals & humans

Radical Pair Mechanism (RPM) at low fields

Mechanisms

Cryptochromes in birds and in man

Background:

Increased Ca2+ efflux from brain tissues with ELF modulated RF EMFs (Bawin et al. 1975, Blackman et al. 1979, 1980a, b, Adey et al. 1982), and with ELF electric fieldswithout an RF carrier (Bawin & Adey 1976).

Observations:

Increased Ca2+ efflux from brain tissue at particular frequencies of an applied magnetic field in the same vector direction as Earth’s natural DC field (Blackman et al 1985).

Overall findings:

Liboff (2006)1 cites 71 papers, on this apparent ‘window’ or ‘resonance’ phenomenon’ with only 11 reporting negative findings.

Today >150 papers in model systems: bone, cell culture, rat behaviour, neural cell culture, diatom motility, complex biological systems, plants, cell-free systems.

Explanation:

In a magnetic field, Ca2+ and other ions behave like a physics cyclotron and so response can be ‘tuned’ to the cyclotron frequency – hence ‘ICR’.

Status:

However, ICR may be an inappropriate analogy – unlike a real cyclotron, Ca2+

ions are not in a vacuum.

Ca2+ efflux and Ion Cyclotron Resonance (ICR) models

1Liboff 2006 Chapter 9. In Bioengineering and biophysical aspects of EMFs p261-292. Eds Barnes & Greenebaum. 1 edition (7 Nov 2006) CRC Press

DCBm

qf

2

1

r

mField BDC x

rmvBqvF 2

fr

v 2

For Ca2+, q=2, m = mass of Ca ion

e.g. at BDC = 50 mT, f = 40 Hz

Bawin et al. 1975 PNAS 247:74-81; Bawin & Adey 1976 PNAS 73:1999-2003 [10 – 15 V/m in air; 0.1 mV/cm in tissue]Gavalas-Medici & Day-Magdaleno 1976 Nature 261:256-259. Blackman et al. 1985 Bioelectromagnetics 6:327-37.

Physical interaction mechanisms and some biology

So-called Ion Cyclotron Resonance (ICR)




Biogenic Magnetite

in animals & humans


Mechanisms


Magnetite and other iron-mineral particles in animals and man

All possess biogenic magnetite or other membrane bound iron-mineral particles (magnetosomes) used for

navigation

(magnetic sensitivity exists in all major groups of vertebrate animals, as

well as in some molluscs, crustaceans and insects, including flies, chickens

and mole rats)

U = - μ.B where μ = v M

U = potential energy of dipole magnet in field B

m = magnetic moment

v = particle volume; r = radius

M = 4.8 x 105 J T-1 m-3

k = Boltzmann’s constant, 1.3807 x 10-23 J K-1,

and T the absolute temperature.

The energy required to rotate the particle 180° is 2U,

compare this to the thermal energy kT at 300° K

Potential energy of magnetic particle in the Earth’s field

- Compare this with the thermal energy kT

But the sensitivity is magnified with arrays & clusters of iron-based

minerals

Mag

net

ic F

ield

B

0

500

1000

1500

0 100 200 300 400 500 600

Diameter, 2r nm

Ra

tio

of

MF

en

erg

y t

o k

T

50

µT

0

10

20

30

40

50

60

0.4

µT

50 µT

0.4 µT

0

1

0 50 100 150 200 250 300

Particles of interest:

Single domain Superparamagnetic (sp)

Whole particle rotates Particle remains stationary but MF vector

flips

Pigeons

Solov’yov & Greiner 2007 Biophys J 93:1493–1509

- force of 0.2 pN sufficient to excite channels in nerve cell

Fleissner et al. Naturwissenschaften 94:631–642 (2007)

using μ-SXRF and μ-XANES.

Magnetite structures could

transduce 50 Hz MFs at 0.5 mT:

Vanderstraeten & Gillis (2010)

Bioelectromagnetics 31:371-

379

Similar structures in chickens,

European Robin and Garden

Warbler

Maghemite: 3

3

2 OFe

4

3

2

2 OFeFe

Magnetite:

In pigeons, the inclination sensitivity is 0.02 - 0.17 degrees, down to 0.01 mT (~10 nT) - Gould 2010 Current Biol 21;R226

<30 nm30 – 200 nm

5 mm─

Trigemina

l

nerve

10 mm

Physical interaction mechanisms and some biology

So-called Ion Cyclotron Resonance (ICR)




Biogenic Magnetite

in animals & humans


Mechanisms


Introduction to RPM – Zeeman splitting and Larmor

precession

hυ

En

erg

y+ 1/2

- 1/2

B-F

ield

(a) (b)

No field Applied field

Spin

direction

Precession of electron spin

vector with frequency

B-F

ield

At the GM field in Nottingham, 50 mT:- h is ~10-7 of thermal energy kT

The equivalent classical

model has the electron spin

vector precessing at the

Larmor frequency of 1.4

MHz at 50 mT

Pieter Zeeman

(1865-1943)

Zeeman Effect

1896

Joseph Larmor

(1857-1942)

Get resonant absorption (ESR) at frequency

= 1.4 MHz at 50 mT

In a static MF, get splitting of

spectral lines due to the electron

spin

RPM and the Low Field Effect

Singlet

productsTriplet

products

Electron

transfer

Magnetic nuclei

+ external field

Blue-light photon

(Different products)

S↔T mixing

S T

Woodward et al. 2009 Biochem Soc Trans 37(2):358-62

At low fields* get an increased rate of S-T conversionT-state radical pairs cannot recombine, so they react elsewhere, e.g. with DNA

*for GM field sensitivity, requires RP lifetimes ~1 us

If both radicals experience the same MF, no S-T mixing occurs

If each radical experiences a different MF, S-T mixing may occur

1 2

Unpaired electron

- radical 1

(precesses about B1)

Unpaired electron

- radical 2

(precesses about B2)

Both radicals see the Earth’s magnetic field, 50 mT, in

addition to any internal fields

At the low fields of interest, the radical pair needs to live for ~1 ms, for S-T mixing to evolve

B1 B2

EMF for Health Conditions

Fracture non-union – 65-75Hz

Congenital pseudoarthrosis – 15Hz

Osteoporosis – 72Hz

Hip arthroplasty – 50Hz

Arthritis – 50Hz

Tinnitus – 0.5-17Hz

Rotator Cuff Tendonitis – 71-75Hz

Venous skin ulcers – 75Hz

Multiple sclerosis – 4-13Hz

(Shupak, 2003)

PEMF Cellular Effects

Increases osteoblast intracellular calcium & alters

response to epidermal growth factor.(Shigaku,1990)

Stimulates production of type-I collagen,

osteocalcin, & osteopontin.(Cornaglia, et al., 2006)

Antiinflammatory effect via restoration of plasma

membrane calcium ATPase activity.

(Selvam, et al., 2007)

Conclusions

EMF had some effect on cells

What it will lead is not known

We can say that in last 140 years of electromagnetic emission from high tension lines, no observable adversities notes

No proven AE from cells at cellular level

The results are not enough to support the apprehensions

Care is always advisable

Conclusion

cells & cellphones - looking deep at the molecular level

Mobile